Japanese Society of Toxicology Acta Medica Okayama 0388-1350 51 10 2026 Integration of QSAR modeling and in vitro validation for identification of food-derived Nrf2 activators against arsenic-induced toxicity 533 547 EN Ngo Thanh Huong Laboratory of Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Susumu Kodama Laboratory of Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Atsushi Ono Laboratory of Toxicology, Division of Pharmaceutical Sciences, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Arsenic exposure is a major public health concern due to its toxicity and carcinogenicity, largely mediated by oxidative stress, and activation of the Nrf2 signaling pathway is considered a promising strategy to mitigate such damage. In this study, a quantitative structure–activity relationship (QSAR) model was developed to identify potential Nrf2 activators from food-derived compounds. Machine learning algorithms, including Random Forest (RF), Support Vector Machine (SVM), Linear Discriminant Analysis (LDA), and a stacking model, were developed and optimized. The optimized RF, SVM, and LDA models were subsequently integrated into a stacking framework, which was selected as the final predictive model for virtual screening based on its robust and balanced predictive performance. The stacking model achieved the highest accuracy during five-fold cross-validation (0.77) and demonstrated competitive performance on the independent test set (0.742 �} 0.040), with balanced precision, sensitivity, and F-measure. Consequently, the stacking model was selected as the final model for virtual screening. A total of 70,926 compounds retrieved from a food-derived database were filtered based on physicochemical criteria, and QSAR-based virtual screening predicted 920 compounds as potential activators of the Nrf2 signaling pathway, from which 5,7-Dimethylchrysin (FooDB ID: FDB015537) and Demethylvestitol (FooDB ID: FDB012218) were selected for experimental validation. In vitro assays using HepG2 cells demonstrated that 5,7-Dimethylchrysin significantly enhanced cell viability against sodium arsenite (150 ��M)-induced cytotoxicity, with an effective concentration (EC50) of 0.54 ��M, whereas Demethylvestitol exhibited only limited protective effects. Furthermore, luciferase reporter assays confirmed that 5,7-Dimethylchrysin activated antioxidant response element (ARE)-driven transcription in a concentration-dependent manner, producing a 1.5 to 2.4-fold increase at concentrations ranging from 0.78 to 6.25 ��M. Overall, these findings highlight the effectiveness of integrating QSAR modeling with experimental validation to identify food-derived compounds with protective potential against arsenic-induced toxicity, with 5,7-Dimethylchrysin emerging as a promising candidate for further investigation. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2075-1729 16 10 2026 Purification, Structural Characterization, and Genomic Insights of an Anti-MRSA Peptide from Mangrove-Derived Brevibacillus sp. A34 1697 EN Thanyamai Thongin School of Pharmacy, Walailak University Namfa Sermkaew School of Pharmacy, Walailak University Apichart Atipairin School of Pharmacy, Walailak University Sucheewin Krobthong Center of Excellence in Natural Products Chemistry (CENP), Department of Chemistry, Faculty of Science, Chulalongkorn University Chanat Aonbangkhen Center of Excellence in Natural Products Chemistry (CENP), Department of Chemistry, Faculty of Science, Chulalongkorn University Jumpei Uchiyama Department of Infectious Diseases, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan Nuttapon Songnaka School of Pharmacy, Walailak University The widespread prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in community and healthcare settings has driven the urgent search for novel antibacterial agents. Mangrove sediments are an underexplored source of antimicrobial-producing bacteria. This study characterized an antimicrobial fraction and the genome of the mangrove-derived isolate Brevibacillus sp. A34. The active fraction was purified via ammonium sulfate precipitation, cation-exchange chromatography, and reversed-phase chromatography. De novo MS/MS analysis assigned the octapeptide LLLLLLAH (905.19 Da), designated as A34 AMP, which was further confirmed by chemical synthesis. This active peptide inhibited all four tested S. aureus strains, including three MRSA strains, with a minimum inhibitory concentration (MIC) of 62 µg/mL. At 2�~ and 4�~ MIC, A34 AMP exhibited a concentration-dependent bactericidal effect within 20 h. Increased SYTOX Green uptake and morphological alterations supported a membrane permeabilization mechanism, and antimicrobial activity was retained following thermal, pH, protease, and surfactant treatments. Genome mining identified 23 putative biosynthetic gene clusters, including an 11-module nonribosomal peptide synthetase (NRPS) cluster linked to A34 AMP through three-dimensional adenylation-domain modeling. Collectively, these findings highlight A34 AMP from Brevibacillus sp. A34 as a promising bioactive anti-staphylococcal peptide scaffold. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0308-8146 526 2026 Flavor encapsulation capacities of amphiphilic polyvinylpyrrolidone as a carrier for amorphous solid dispersions 150819 EN Haruna Sato Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nao Honda Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takato Hasegawa Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Chika Araga Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroyuki Imanaka Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Naoyuki Ishida Department of Chemical Engineering and Material Sciences, Faculty of Science and Engineering, Doshisha University Koreyoshi Imamura Division of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University This study investigates the characteristics of amorphous solid dispersions (ASDs) formed using an amphiphilic carrier polymer, focusing on the effects of source solution conditions on flavor retention. Cinnamaldehyde and polyvinylpyrrolidone (PVP) were dissolved as flavor and carrier components in methanol or ethanol under different conditions and subsequently spray-dried into fine powders. The amount of cinnamaldehyde retained in the spray-dried ASDs was quantified to assess the impact of solution conditions. The results indicate that cinnamaldehyde molecules were physically entrapped within the entangled PVP chains during the spray-drying process. The flavor encapsulation capacity of PVP reached a maximum of approximately 4 mmol/g-PVP under specific conditions. This maximum capacity implies that each cinnamaldehyde molecule is associated with approximately two PVP monomer units, which is higher than those reported for selected cyclodextrin-based systems in comparable contexts of cinnamaldehyde encapsulation. Additionally, the dissipation of cinnamaldehyde from the ASD samples during storage under vacuum was examined. No potential conflict of interest relevant to this article was reported.

SAGE Publications Acta Medica Okayama 1758-8359 17 2025 Clinical impact of hypomagnesemia induced by necitumumab plus cisplatin and gemcitabine treatment in patients with advanced lung squamous cell carcinoma: a subanalysis of the NINJA study 1 16 EN Shigeru Tanzawa Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Hiroshige Yoshioka Department of Thoracic Oncology, Kansai Medical University Hospital Toshihiro Misumi Department of Data Science, National Cancer Center Hospital East Eisaku Miyauchi Department of Respiratory Medicine, Tohoku University Hospital Kiichiro Ninomiya Center for Comprehensive Genomic Medicine, Okayama University Hospital Yasunori Murata Department of Respiratory Medicine, Ichinomiya Nishi Hospital Masafumi Takeshita Department of Respiratory Medicine, Ichinomiya Nishi Hospital Fumihiko Kinoshita Department of Thoracic Oncology, NHO Kyushu Cancer Center Takatoshi Fujishita Department of Thoracic Oncology, NHO Kyushu Cancer Center Shunichi Sugawara Department of Pulmonary Medicine, Sendai Kousei Hospital Yosuke Kawashima Department of Pulmonary Medicine, Sendai Kousei Hospital Kazuki Hashimoto Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Masahide Mori Department of Thoracic Oncology, NHO Osaka Toneyama Medical Center Akihiko Miyanaga Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Anna Hayashi Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School Hisashi Tanaka Department of Respiratory Medicine, Hirosaki University Graduate School of Medicine Ryoichi Honda Department of Respiratory Medicine, Asahi General Hospital Masafumi Nojiri Department of Respiratory Medicine, Kanazawa Medical University Yuki Sato Department of Respiratory Medicine, Kobe City Medical Center General Hospital Akito Hata Division of Thoracic Oncology, Kobe Minimally Invasive Cancer Center Nobuhisa Ishikawa Department of Respiratory Medicine, Hiroshima Prefectural Hospital Toshiyuki Kozuki Department of Thoracic Oncology and Medicine, NHO Shikoku Cancer Center Takahisa Kawamura Department of Thoracic Oncology, Osaka International Cancer Institute Go Saito Department of Respirology, Graduate School of Medicine, Chiba University Teppei Yamaguchi Department of Thoracic Oncology, Aichi Cancer Center Hospital Kazuhiro Asada Department of Respiratory Medicine, Shizuoka General Hospital Satoshi Tetsumoto Department of Respiratory Medicine and Clinical Immunology, Suita Municipal Hospital Hiroshi Tanaka Department of Internal Medicine, Niigata Cancer Center Hospital Satoshi Watanabe Department of Respiratory Medicine and Infectious Diseases, Niigata University Graduate School of Medical and Dental Sciences Yukihiro Umeda Department of Respiratory Medicine, Faculty of Medical Sciences, University of Fukui Kakuhiro Yamaguchi Department of Respiratory Medicine, Hiroshima University Hospital Kazuya Nishii Department of Respiratory Medicine, NHO Iwakuni Clinical Center, Iwakuni, Yamaguchi, Japan Kosuke Tsuruno Department of Respiratory Medicine, Iizuka Hospital Yuki Misumi Department of Respiratory Medicine, Yokohama Municipal Citizen�fs Hospital Hiroshi Kuraishi Department of Pulmonary Medicine, Nagano Red Cross Hospital Ken Yoshihara Department of Internal Medicine, Division of Medical Oncology and Respiratory Medicine, Shimane University Faculty of Medicine Akira Nakao Department of Respiratory Medicine, Fukuoka University Hospital Akihito Kubo Department of Respiratory Medicine and Allergology, Aichi Medical University Toshihiko Yokoyama Department of Respiratory Medicine, Japanese Red Cross Aichi Medical Center Nagoya Daiichi Hospital Kana Watanabe Department of Respiratory Medicine, Miyagi Cancer Center Nobuhiko Seki Division of Medical Oncology, Department of Internal Medicine, Teikyo University School of Medicine Background: The clinical impact of hypomagnesemia induced by necitumumab plus gemcitabine and cisplatin (GCN) as a second-line or later therapy is unclear.<br> Objective: We aimed to evaluate the clinical characteristics and survival impact of hypomagnesemia induced by this therapy.<br> Design: This was a sub-analysis of the retrospective multicenter NINJA study.<br> Methods: Among the 93 patients enrolled in the NINJA study, this subanalysis included 75 patients with baseline serum magnesium concentrations.<br> Results: The incidence of grade ⩾2 hypomagnesemia was 18.0% in the patients with normal baseline serum magnesium concentrations and 42.8% in those with low concentrations (p = 0.073). The discontinuation rates of GCN treatment owing to hypomagnesemia in each group were 0% and 7.1%, respectively (p = 0.187). The number of necitumumab doses and severity of hypomagnesemia were positively correlated (r = 0.389, p < 0.001). Patients who developed hypomagnesemia in fewer than 21 days after the first dose of GCN (n = 12) had significantly poorer progression-free survival (PFS) than those without the condition (n = 63; median: 4.1 vs 4.4 months, p = 0.048). A similar trend was observed for OS (median: 9.7 vs 15.7 months, p = 0.062). These results were maintained after multivariate analyses (PFS: hazard ratio (HR) 2.46, p = 0.014; OS: HR 2.78, p = 0.021).<br> Conclusion: GCN as a second-line or later therapy may be tolerable regardless of the patient�fs baseline serum magnesium concentration. On the other hand, early serum magnesium reduction with this therapy is associated with a poor prognosis. However, caution should be needed because our results lacked sufficient information for confounding variables other than those analyzed here that may influence the correlation between hypomagnesemia and survival. No potential conflict of interest relevant to this article was reported.

BMJ Acta Medica Okayama 2044-6055 16 8 2026 Study protocol for a phase II clinical trial evaluating the safety and efficacy of favipiravir injection combined with oseltamivir in influenza treatment e106715 EN Sayaka Hikida Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Hidetoshi Nomoto Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Yukari Uemura Laboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health Security Tadaki Suzuki Department of Infectious Disease Pathology, National Institute of Infectious Diseases, Japan Institute for Health Security Koichi Izumikawa Department of Infectious Diseases, Nagasaki University Graduate School of Biomedical Sciences Hiroki Ohge Project Research Center for Nosocomial Infectious Diseases, Hiroshima University Masaya Yamato Infectious Diseases Center, Rinku General Medical Center Yasuyuki Kato Department of Infectious Diseases, International University of Health and Welfare Narita Hospital Ryota Hase Department of Infectious Diseases, Japanese Red Cross Narita Hospital Tetsuji Aoyagi Department of Clinical Microbiology and Infection, Tohoku University Graduate School of Medicine Hideharu Hagiya Department of Infectious Diseases, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoko Nukui Department of Infection Control & Laboratory Medicine, Kyoto Prefectural University of Medicine Kazuko Yamamoto First Department of Internal Medicine, Division of Infectious, Respiratory, and Digestive Medicine, University of the Ryukyus Graduate School of Medicine Yoshio Takesue Chita Peninsula General Medical Organization, Rinku Hospital Kota Sawada Laboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health Security Yosuke Shimizu Laboratory of Biostatistics, Department of Data Science, Center for Clinical Sciences, Japan Institute for Health Security Sho Miyamoto Department of Infectious Disease Pathology, National Institute of Infectious Diseases, Japan Institute for Health Security Namiko Tamura Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Kozue Takahashi Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Sho Saito Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Kazuki Miyazaki Center for Clinical Sciences, Japan Institute for Health Security Eriko Morino Center for Clinical Sciences, Japan Institute for Health Security Daisuke Tokita Center for Clinical Sciences, Japan Institute for Health Security Norio Ohmagari Disease Control and Prevention Center, National Center for Global Health and Medicine, Japan Institute for Health Security Introduction Older adults are at an increased risk of influenza-related hospitalisation and mortality due to a combination of risk factors. Severe influenza and excess mortality in this population remain major public health concerns, underscoring the need for novel treatment strategies.<br> Methods and analysis This multicentre, investigator-initiated, randomised, double-blind clinical trial evaluated the efficacy and safety of the investigational drug favipiravir injection (T-705IV) in combination with oseltamivir phosphate, compared with oseltamivir monotherapy in hospitalised patients with influenza aged ≥65 years. Both T-705IV and oseltamivir phosphate will be administered for 5 days. The primary endpoint is time from randomisation to recovery within 15 days. Recovery is defined as either actual hospital discharge or sustained clinical status permitting discharge for 3 consecutive days. Clinical status will be assessed using a 7-point ordinal scale based on hospitalisation status and oxygen requirement. The primary analysis employs a Bayesian Cox proportional hazards model with a non-informative prior to estimate the posterior probability that the HR exceeds 1.0. The secondary endpoints include the distribution of 7-point scale scores over a 29-day period; rates of clinical worsening at days 15 and 29; duration of fever; all-cause mortality; intensive care unit admission within 29 days; pneumonia complication rate at 15 days; and changes in viral titre and viral RNA load on days 1, 2, 3 and 7. Safety will be assessed through the collection of adverse events (AEs) up to day 29. Pharmacokinetic evaluation will include measurement of plasma favipiravir concentrations on day 3. The planned sample size is 80 patients (40 per group).<br> Ethics and dissemination Written informed consent will be obtained from all participants. This study was approved by the Center Hospital of the National Center for Global Health and Medicine Institutional Review Board (approval number: NCGM-I-022-24a) and registered in the Japan Registry of Clinical Trials. Study findings will be disseminated through peer-reviewed publications and/or presentations at academic conferences.<br> Trial registration number jRCT2031240586, No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2328-8957 12 3 2025 Effects of Amikacin Liposome Inhalation Suspension and Amikacin Resistance Development in Patients With Refractory Mycobacterium avium Complex Pulmonary Disease ofaf118 EN Yu Kurahara Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center Shiomi Yoshida Clinical Research Center, NHO Kinki Chuo Chest Medical Center , Osaka , Asami Osugi Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association Yuya Tanaka Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center Takehiko Kobayashi Clinical Research Center, NHO Kinki Chuo Chest Medical Center Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Yohei Kawasaki Department of Biostatistics, Graduate School of Medicine, Saitama Medical University Satoshi Mitarai Department of Mycobacterium Reference and Research, Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association Kazunari Tsuyuguchi Department of Internal Medicine, NHO Kinki Chuo Chest Medical Center Background. Amikacin liposome inhalation suspension (ALIS) is key for treating refractory Mycobacterium avium complex pulmonary disease (MAC-PD). However, microbiological efficacy by subtype remains unknown. The frequency and mechanism of amikacin (AMK) resistance during ALIS administration are also unclear.<br> Methods. We retrospectively analyzed data from refractory MAC-PD patients who received ALIS for at least 6 months as an adjunct to guideline-based therapy at the NHO Kinki Chuo Chest Medical Center. We investigated the efficacy of ALIS and analyzed gene expression and the frequency of AMK resistance.<br> Results. We enrolled 44 patients (median age, 72.0 years): 19 (43.2%) with the noncavitary nodular bronchiectatic (NC-NB) subtype and 25 (56.8%) with the cavitary subtype. Overall, sputum culture conversion was 56.8% (25/44): 84.2% (16/19) in the NC-NB subtype and 36.0% (9/25) in the cavitary subtype (P = .001). During intermittent dosing, conversion occurred in 50.0% (9/18). In patients with C-reactive protein (CRP) ≥1 mg/dL, cavitary subtype, and clarithromycin (CLM) resistance, the risk ratio for persistently positive cultures was 10.81 (95% CI, 1.66–70.40) compared with those with CRP <1 mg/dL, NC-NB subtype, and CLM susceptibility. Of all participants, 15.9% (7/44) had isolates with AMK resistance (minimum inhibitory concentration ≥128 µg/mL), and of these 71.4% (5/7) had rrs mutations.<br> Conclusions. Regimens that included ALIS achieved higher culture conversion in NC-NB than cavitary MAC-PD cases. High CRP levels, cavitary disease, and CLM resistance predicted persistent culture positivity. AMK resistance acquired during ALIS administration may limit treatment options for refractory MAC-PD. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0969-806X 251 2027 A rule-based calculation approach to derive bone-suppressed chest X-ray images using photon-counting techniques 114493 EN Natsumi Kimoto Department of Radiological Science, Faculty of Health Sciences, Junshin Gakuen University Rina Nishigami Graduate School of Medical Sciences, Kanazawa University Takashi Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Mana Mitani Division of Radiology, Medical Support Department, Okayama University Hospital Daiki Kobayashi Graduate School of Medical Sciences, Kanazawa University Noriaki Akagi Division of Radiology, Medical Support Department, Okayama University Hospital Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Takao Hiraki Department of Radiology, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroaki Hayashi College of Transdisciplinary Sciences for Innovation, Kanazawa University Improving the visibility of lung nodules, which are often hidden by bone shadows and difficult to identify, remains a challenge in chest radiography. This study aims to develop an algorithm for generating novel bone-suppressed images using photon-counting techniques. The core idea of our algorithm is to fit photon interaction cross-sections to X-ray attenuation data measured with photon-counting detectors. Based on further calculations using the derived fitting coefficients, both density (��) and amount-of-substance concentration (mol) were determined. The product of these values produced a �ρ~mol image exhibiting a clear bone-suppression effect. We conducted a virtual chest imaging simulation using 10 patient datasets acquired via clinical photon-counting computed tomography (PC-CT). The CT images were converted into �ρ~mol images following the proposed processing procedure, and two-dimensional chest images were generated through projection. Quantitative evaluations confirmed that the proposed images achieved sufficient bone suppression. Furthermore, commercial software provided by a vendor was used to generate bone-suppressed images from conventional images projected from CT data. A comparable bone-suppression effect on the ribs was observed between the vendor-generated images and our proposed images, while lesion visibility (e.g., lung nodules) was preserved. Additionally, bone-suppression effects in our images were observed in the vertebrae and clavicles located outside the lung fields. Our research demonstrates the value of constructing general X-ray imaging systems using photon-counting detectors. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0739-7240 98 2027 Transcriptional remodeling of local thyroid hormone metabolism is associated with feather growth termination in chicken wing feathers 107057 EN Masamichi Shinohara Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yuri Nozawa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hibiki Fukuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Yu Takeuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sayaka Aizawa Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Sakae Takeuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Feather elongation is sustained by continuous cell proliferation within the feather follicle; however, the molecular mechanisms responsible for feather growth termination remain poorly understood. In this study, we investigated molecular changes associated with feather growth termination by comparing two chicken wing feather types with contrasting growth characteristics: primary wing feathers and primary coverts. Histological and bromodeoxyuridine incorporation analyses demonstrated that primary wing feathers remained in an active growth phase, whereas primary coverts exhibited pulp regression, reduced cell proliferation, and characteristics of growth termination. Gene expression analyses showed that primary coverts exhibited reduced expression of prolactin receptor (PRLR), type 2 iodothyronine deiodinase (DIO2), and insulin-like growth factor 2 (IGF2), together with marked induction of the thyroid hormone (TH)-inactivating enzyme type 3 iodothyronine deiodinase (DIO3). In contrast, primary wing feathers exhibited relatively higher expression of PRLR, DIO2, and IGF2 than primary coverts, while maintaining consistently low DIO3 expression. Reporter assays showed increased IGF2 promoter activity following triiodothyronine (T3) treatment in all three independent experiments, although the increase did not reach statistical significance. Thus, the reporter assay provides only tentative support for T3 responsiveness of the IGF2 promoter, consistent with our previous in vivo and primary-culture findings showing T3-dependent increases in IGF2 expression. These coordinated transcriptional changes are consistent with remodeling of local TH metabolism during the transition from active feather growth to growth termination. While local TH concentrations and direct deiodinase activities remain to be quantified, and the causal relationship between PRL/PRLR signaling and DIO3 induction remains unresolved, this study provides a molecular framework for understanding how local endocrine regulation translates systemic hormonal signals into feather type-specific growth responses during avian feather development. Graphical abstract No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0016-7037 430 2026 Pervasive and rapid enrichment of nitrogen in newly erupted oceanic basalt 249 262 EN Juan Felipe Bustos-Moreno Department of Earth and Environmental Sciences, Lehigh University Tobias B. Weisenberger Geology and Sustainable Mining Institute, University Mohammed VI Polytechnic Ryoji Tanaka The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Hiroshi Kitagawa The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Gray E. Bebout Department of Earth and Environmental Sciences, Lehigh University The alteration of oceanic crust by seawater is a critical sink in the global nitrogen (N) cycle, yet the mechanisms and timescales of N enrichment remain poorly constrained. We present N concentrations and isotope compositions from a 192-meter drill core (SE-02b) retrieved from the then 50-year-old Surtsey Island in Iceland, a pristine analog for rapid alteration of young oceanic basalt. The altered basaltic tuffs show significant N enrichment (average 11 �} 8 ��g/g), relative to unaltered Icelandic basalt glasses (0.028 �} 0.026 ��g/g) and MORB (∼1.1 to 1.5 ��g/g), matching the global average for altered oceanic crust (11 ��g/g; ranging in ages from 5 to 170 Ma). Nitrogen isotope compositions (��15Nair = �|1.7 �} 4.6��) are primarily consistent with incorporation of seawater- and meteoric-derived ammonium (NH4+), more likely into secondary K-minerals, palagonitized glass and smectites throughout the core. To a lesser extent, N could be incorporated into Na/Ca-minerals such as analcime in the meteoric water altered zone and sulphates such as anhydrite and gypsum when present. Incorporation of NH4+ into secondary phases occurs with little isotope fractionation consistent with equilibrium fractionation between clay and aqueous NH4+. We demonstrate that seawater-rock interaction alone can produce the ubiquitous background N enrichment of the oceanic crust without the addition of remobilized N from sedimentary sources. Such magnitude of enrichment is also observed via meteoric water alteration. Localized high enrichments in N in areas of enhanced fluid flow at core SE-02b with exceptionally low ��15N values (as low as �|20.1��), are attributed to abiotic reduction of dissolved N2 under anoxic conditions and/or microbial activity. We propose that N incorporation into the oceanic crust can occur rapidly in days to decades rather than at a constant rate over geologic time. This has major implications for N transfer in subduction zones, N exchange between the oceanic crust, seawater and the atmosphere and for planetary habitability. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0376-7388 757 2026 Multi-criteria evaluation of graphene oxide nanofiltration membranes for decaffeination 125992 EN Yihan Tian School of Materials Science and Engineering, University of New South Wales Tongxi Lin School of Materials Science and Engineering, University of New South Wales Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Xiaojun Ren School of Materials Science and Engineering, University of New South Wales Rakesh Joshi School of Materials Science and Engineering, University of New South Wales Nanofiltration (NF) offers a promising low-energy approach for producing decaffeinated instant coffee, while requires membranes that balance caffeine removal, water permeance, and retention of key coffee matrix compounds. Here, graphene oxide membranes (GOMs) were modified by sodium alginate (SA) intercalation, Ca2+ crosslinking, and their combined strategy to tune nanochannel structure and separation performance. The results show that membrane modification does not follow a simple monotonic trend; instead, small structural and chemical changes generate competing effects on permeance and selectivity through coupled transport, adsorption, and confinement mechanisms. To identify the most suitable membrane, a multi-criteria evaluation framework (MCEF) combining entropy weighting and TOPSIS was established using five key performance indicators: caffeine removal, flavour-related marker retention index, choline retention, water permeance, and concentration increase. This framework identified CGSM-1 as the best-performing flat membrane, which also showed promising performance in hollow-fibre form. In coffee filtration tests, CGSM-1 reduced caffeine concentration from 24.64 to 12.95 ��g/mg, corresponding to a 47.4% reduction, while retaining measurable levels of HMF, trigonelline, NMP, and choline. These findings demonstrate the potential of engineered GOMs for selective caffeine reduction in coffee liquor and provide a practical evaluation strategy for membrane-based decaffeination. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1880-6546 76 3 2026 Effects of serotonin transporters on myocardial cell injury during ischemia/reperfusion in rats 100085 EN Yoshimasa Kishi Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Shuji Shimizu Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Yosuke Kuroko Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Yasuhiro Kotani Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Tsuyoshi Akiyama Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Shingo Kasahara Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Serotonin (5-HT) reuptake in the heart is mediated by the platelet serotonin reuptake transporter (SERT) and the cardiomyocyte plasma membrane monoamine transporter (PMAT). However, the specific roles of these transporters in myocardial cell injury during ischemia/reperfusion remain unclear. Sprague-Dawley rats underwent left coronary artery occlusion followed by reperfusion. Using cardiac microdialysis technique, fluoxetine (SERT inhibitor, 900 ��M) or decynium 22 (PMAT inhibitor, 100 ��M) was administered locally to the ischemic region. Myoglobin concentrations in the dialysate were measured during ischemia followed by reperfusion. In the fluoxetine-treated group, peak myoglobin concentration (14,889 �} 1364 ng/mL) during 0–15 min of reperfusion was significantly higher compared to both the control group (9800 �} 1627 ng/mL) and the decynium 22-treated group (8172 �} 877 ng/mL) (P < 0.01 for both). Local SERT inhibition exacerbated myocardial cell injury during ischemia/reperfusion. However, co-inhibition of PMAT reduced myocardial cell injury under SERT inhibition to the control level. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1660-3397 24 9 2026 A Marine Brevibacillus-Derived Membrane-Lytic Peptide: Molecular Insight and Biophysical Characterization of a Novel AMP, FNL62-AMP 309 EN Namfa Sermkaew School of Pharmacy, Walailak University Apichart Atipairin School of Pharmacy, Walailak University Sucheewin Krobthong Center of Excellence in Natural Products Chemistry (CENP), Department of Chemistry, Faculty of Science, Chulalongkorn University Chanat Aonbangkhen Center of Excellence in Natural Products Chemistry (CENP), Department of Chemistry, Faculty of Science, Chulalongkorn University Yodying Yingchutrakul National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency Jumpei Uchiyama Department of Infectious Diseases, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nuttapon Songnaka School of Pharmacy, Walailak University This study characterizes the genomic identity, functional efficacy, and computational biophysics of FNL62-AMP, a novel antimicrobial peptide isolated from a phylogenomically distinct, newly identified Brevibacillus species. Production kinetics revealed a late-exponential phase onset of antibacterial activity with sustained potency against methicillin-resistant Staphylococcus aureus (MRSA). LC-MS/MS analysis identified the peptide sequence as NH2-LLLLFR-COOH. FNL62-AMP demonstrated excellent formulation resilience, retaining full anti-MRSA activity under high thermal stress (80 ��C for 6 h) and showing robust resistance to generic trypsin and proteinase K proteolysis. Formulative co-incubation assays demonstrated charge-dependent compatibility, where nonionic Triton X-100 preserved baseline efficacy while ionic surfactants induced antagonism. In vitro time-kill kinetics, scanning electron microscopy, and SYTOX Green assays confirmed rapid, concentration-dependent bactericidal action driven by immediate membrane permeabilization. Molecular dynamics simulations successfully captured the spontaneous self-assembly of 64 FNL62-AMP monomers into a stable macro-aggregate. This consolidation process was quantitatively characterized by a simultaneous contraction in the radius of gyration (Rg), a sharp drop in solvent-accessible surface area (SASA), and a transitional plateau in mean squared displacement (MSD). Ultimately, the high thermal stability, structural resilience, and predictable surfactant compatibility of FNL62-AMP propose ways to be developed for lead optimization and druggability. No potential conflict of interest relevant to this article was reported.

Ceramic Society of Japan Acta Medica Okayama 1348-6535 134 9 2026 Preparation of chitosan/apatite composite particles with core–shell structure 676 681 EN Takuya Kataoka Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Ryo Ikeda Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Eiji Fujii Industrial Technology Center of Okayama Prefecture Tomohiko Yoshioka Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Satoshi Hayakawa Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University In this study, a novel sequential preparation process of core–shell particles with chitosan (CS) cores and hydroxyapatite (HAp) shells is presented. This process involved the formation of phosphorylated CS particles, followed by HAp precipitation. Importantly, the precipitation of HAp on the surface of phosphorylated CS was confirmed. Different CaCl2 concentrations during the HAp precipitation step resulted in different HAp contents in the particles. To confirm the formation of the core–shell structure, the particles were immersed in hydrochloric acid (pH 2) for 5, 10, and 30 min. Notably, samples with higher HAp content (59 wt % and 84 wt %) retained their core morphology after 30 min of immersion, whereas samples with lower HAp content (28 wt %) rapidly lost their morphology. These results indicate that higher HAp content contributes to improved morphological stability under acidic conditions, leading to the formation of more stable core–shell particles. Overall, these findings clarify the role of phosphorylated CS in inducing HAp precipitation and show that the proposed preparation process leads to the formation of CS/HAp core–shell structures. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2212-8778 112 2026 Adaptive oligodendrogenesis regulates blood-hypothalamus barrier permeability, hypothalamic glucose sensing and systemic glucose homeostasis in male mice 102428 EN Sophie Buller Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Emily O. Staricoff Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Christine Riches Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Anthony Tsang Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Giada Giavara Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Masa Josipovic Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Kentaro Ikemura Department of Medical Technology, Graduate School of Health Sciences, Okayama University Gabriel Opoku Department of Medical Technology, Graduate School of Health Sciences, Okayama University Ikumi Sato Department of Medical Technology, Graduate School of Health Sciences, Okayama University Satoshi Hirohata Department of Medical Technology, Graduate School of Health Sciences, Okayama University Saskia Stenzel Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Stuart G. Nayar Wolfson Institute for Biomedical Research, University College London Marta Ramos Vega GUBRA Jacob Hecksher-Sørensen GUBRA Sebastian Timmler Cambridge Stem Cell Institute, University of Cambridge Georgina K.C. Dowsett Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Brian Y.H. Lam Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Giles S.H. Yeo Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Kimberly M. Alonge Diabetes Institute, University of Washington Huiliang Li Wolfson Institute for Biomedical Research, University College London William D. Richardson Wolfson Institute for Biomedical Research, University College London Mark L. Evans Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Clemence Blouet Institute of Metabolic Science Metabolic Research Laboratories, University of Cambridge Objective: Brain glucose sensing is critical for survival during hypoglycaemia, yet how glucose-sensing neurons access circulating glucose concentrations to maintain glucose homeostasis remains poorly understood. Here we tested the hypothesis that adult oligodendrogenesis in the median eminence (ME) is responsive to changes in blood glucose levels and contributes to hypothalamic glucose sensing through regulation of the blood-hypothalamus barrier.<br> Methods: We used glycemic challenges and hypoinsulinaemic clamp studies to identify the effect of systemic changes in glycaemia on hypothalamic oligodendrocyte lineage cells. We used conditional knockout mouse models to dissect the respective contributions of adult oligodendrogenesis and new myelin formation to glucose homeostasis in adult male mice. Analyses combined immunofluorescence, serial electron microscopy, whole-brain tissue clearing, and transcriptomic analyses.<br> Results: We found that adult oligodendrogenesis in the median eminence (ME) is modulated by changes in circulating glucose levels and rapidly upregulated by hypoglycaemia. Genetic blockade of new oligodendrocyte production in adult male mice impairs the regulation of glucose homeostasis, the integrity of the ME blood-hypothalamus barrier, and hypothalamic glucose sensing. Unexpectedly, functional integrity of adult-formed myelin is not required for the maintenance of glucose homeostasis. Instead, we show that blockade of adult oligodendrogenesis disrupts hypothalamic expression of A disintegrin and metallopeptidase with thrombospondin motifs 4 (ADAMTS4), a metallopeptidase whose brain expression is restricted to the oligodendrocyte lineage and whose ME expression requires ongoing adult oligodendrogenesis. We show that ADAMTS4 regulates hypothalamic perineuronal net deposition, vascular permeability and glucose sensing. Finally, we show that ME ADAMTS4 expression is regulated by changes in peripheral glycaemia and is dysregulated in diabetes, providing a mechanism by which ME oligodendrocytes contribute to the regulation of glucose homeostasis. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1939-8425 19 1 2026 GWAS and Candidate Gene Prediction of Elemental Accumulation Traits in Rice Using a Multiparental Population 44 EN Qian Zhang Institute of Plant Science and Resources, Okayama University Tomoyuki Furuta Institute of Plant Science and Resources, Okayama University Kazunari Kashihara Institute of Plant Science and Resources, Okayama University Daisuke Ogawa Institute of Crop Science, National Agriculture and Food Research Organization Junichi Yonemaru Research Center for Agricultural Information Technology, National Agriculture and Food Research Organization Jian Feng Ma Institute of Plant Science and Resources, Okayama University Toshio Yamamoto Institute of Plant Science and Resources, Okayama University Rice plants accumulate essential elements to sustain physiological processes during growth and development and to ensure the nutritional quality of the grain as a food source. However, the genetic basis of elemental accumulation and the interrelationships among elemental concentrations across different tissues remain poorly understood. To conduct breeding aimed at improving the absorption characteristics of multiple interrelated elements, genetic analysis using experimental populations that retain diversity while sharing the genetic background of cultivated varieties is effective. Here we show genetic variations in the concentrations of 13 elements (P, K, Ca, Mg, As, Cd, Cr, Cu, Fe, Mo, Mn, Ni, and Zn) in rice straw at the flowering stage and grain at the mature stage using a multi-parent advanced generation inter-cross (MAGIC) population that derived from eight cultivars including both Japonica and Indica. Comprehensive evaluation of the correlation coefficients revealed divergences in the association between grain and straw for several combinations of elements. Haplotype-based genome-wide association studies (GWAS) identified 51 and 53 quantitative trait loci (QTLs) in straw and grain, respectively. In total, the 104 QTLs were grouped into 19 clusters and 60 independent QTLs. By leveraging the haplotype information from the MAGIC population, 52 candidate genes associated with the accumulation of Ca, Mg, Cd, Cu, Fe, and Mo were efficiently predicted from these QTLs, including both previously reported and novel genes. Among them, OsMOT1;1 encoding a molybdenum transporter, was predicted to be within a QTL associated with Mo accumulation in grain on chromosome 8. OsACA9, a homolog of autoinhibited Ca²⁺-ATPases, was predicted within a QTL related to Ca accumulation in straw on chromosome 2. In addition, an unidentified gene, OsCML6, which is presumed to be involved in calcium signaling, was predicted to be a candidate for a Ca-accumulation QTL on chromosome 11. These findings offer insights into haplotypes and putative genes associated with element accumulation and trait interrelationships, providing valuable information for optimizing plant growth and enhancing grain nutritional quality in rice breeding programs. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1759-9954 17 29 2026 Effect of graphene oxide sheet size on pickering miniemulsion polymerization of styrene 3226 3236 EN Yue Zhang Cluster for Advanced Macromolecular Design, School of Chemical Engineering, The University of New South Wales Yasemin Fadil Cluster for Advanced Macromolecular Design, School of Chemical Engineering, The University of New South Wales Yuta Nishina Research Core for Interdisciplinary Sciences, Okayama University Vipul Agarwal Cluster for Advanced Macromolecular Design, School of Chemical Engineering, The University of New South Wales Per B. Zetterlund Cluster for Advanced Macromolecular Design, School of Chemical Engineering, The University of New South Wales The effect of graphene oxide (GO) sheet size on the progression of Pickering miniemulsion polymerization of styrene was systematically investigated using two GO samples with lateral dimensions (∼500 nm and 5–10 µm). Key parameters, including the presence of the conventional surfactant sodium dodecyl sulfate (SDS), GO loading, and initiator concentration, were investigated individually. Miniemulsion polymerization with GO was successfully conducted both in the absence and presence of SDS, with the addition of SDS leading to a significant rate enhancement attributed to SDS-induced secondary nucleation. In the presence of SDS, GO sheet size influenced polymerization behavior, and its effect on polymerization rate and monomer conversion exhibited opposite trends at different GO loadings. Small GO (∼500 nm) led to higher conversion and faster rates at high GO loading (5 wt%), whereas large GO (5–10 µm) resulted in higher conversion and faster rates at low GO loading (0.5 wt%). This size-dependent effect became more pronounced at lower initiator concentration. Overall, while GO sheet size exhibited a measurable influence on polymerization behavior, the overall kinetics were primarily governed by SDS-induced secondary nucleation. These findings provide new insights into the role of GO lateral dimensions in miniemulsion polymerization and offer guidance for the design and synthesis of polymer/graphene (oxide) nanocomposites with tunable properties. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1939-5981 2026 Micro-segregation of Primary Si in ADC14 (Al–17Si–4Cu) Alloy Produced by Unidirectional Continuous Casting EN Shuhei Takeuchi Graduate School of Environment, Life, Natural Science and Technology, Okayama University Shota Nakagawa UACJ Corporation Yoshifumi Shinzato UACJ Corporation Tadashi Minoda UACJ Corporation Naotaka Ohtsuka UACJ Corporation Mitsuhiro Okayasu Department of Mechanical and Systems Engineering, Okayama University An upgrading approach for hypereutectic Al–Si alloys was investigated through controlled segregation of Si using a unidirectional casting process. The precipitation behavior and spatial distribution of primary Si in the hypereutectic ADC14 (Al–17Si–4Cu) alloy were systematically examined at different casting speeds (0.06, 1.9, and 10 mm/s). Microstructural observations revealed that high casting speed suppresses primary Si formation due to rapid solidification, whereas intermediate speed leads to a relatively uniform distribution of primary Si. In contrast, low casting speed combined with a holding period for 2 min promotes pronounced segregation and coarsening of primary Si in localized regions. Energy-dispersive X-ray spectroscopy analysis confirmed significant fluctuations in Si concentration along the casting direction, particularly after process interruption. Based on these results, a preliminary upgrading process was proposed, involving the selective removal of Si-enriched regions followed by remelting. This approach resulted in a reduction of Si content to approximately 13.9 wt.%, corresponding to a decrease of about 3%. The results demonstrate that controlling solidification behavior to induce phase separation provides a promising and energy-efficient strategy for upgrading recycled Al–Si alloys. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2304-6767 14 8 2026 Oral Supplementation of Bacillus subtilis Attenuated Alveolar Bone Loss in a Mouse Model of Ligature-Induced Periodontitis 494 EN Yixuan Zhang Department of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Naoki Toyama Dental School, Okayama University Mohammad Nurhamim Department of Preventive Dentistry, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Momoko Nakahara Department of Preventive Dentistry, Academic Field of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daiki Fukuhara Dental School, Okayama University Takayuki Maruyama Department of Preventive Dentistry, Academic Field of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Ekuni Department of Preventive Dentistry, Academic Field of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: This study aimed to investigate the effects of oral Bacillus subtilis (BS) on alveolar bone loss, intestinal morphology, and gut microbiota in a mouse model of ligature-induced periodontitis. Methods: A total of 24 male C57BL/6J mice (6 weeks old) were allocated to control, periodontitis (P), BS, and BS+P groups. Periodontitis was induced by bilateral ligation of maxillary second molars, and BS was orally administered for 18 consecutive days. Gut microbiota composition was analyzed by 16S rDNA sequencing, alveolar bone loss and gut morphology were evaluated using ImageJ version 1.54g, and ELISA-detectable serum vitamin D metabolite concentrations were measured using an enzyme-linked immunosorbent assay. Results: Compared with the P group, the BS+P group showed reduced bone loss. Serum vitamin D metabolite concentrations, small-intestine villus height, and villus height-to-crypt depth ratios were higher in the BS+P group. In gut microbiota, alpha diversity differed significantly among groups based on the Shannon index. Bray–Curtis-based beta diversity differed significantly among groups. Conclusions: Oral supplementation of BS attenuated the progression of ligature-induced periodontitis in a mouse model, and changes in gut microbiota may be associated with this effect. No potential conflict of interest relevant to this article was reported.

Public Library of Science (PLoS) Acta Medica Okayama 1932-6203 21 8 2026 Study protocol: Effect of inulin supplementation on gut microbiota in patients with oral lichen planus �\ A double-blind, randomised, placebo-controlled parallel-group trial e0356180 EN Koki Nambu Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Naoki Kaneko Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Shiho Yokomizo Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Hu Chen Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Lijing Yan Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Wang Shiyao Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Ryusei Shizuma Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Eiji Iwata Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yukiko Ohyama Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Shohei Akagawa Department of Pediatrics, Kansai Medical University Soichiro Ibaragi Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shintaro Kawano Section of Oral and Maxillofacial Oncology, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Masafumi Moriyama Section of Oral and Maxillofacial Surgery, Division of Maxillofacial Diagnostic and Surgical Sciences, Faculty of Dental Science, Kyushu University Oral lichen planus is a chronic inflammatory disease of the oral mucosa characterised by immune dysregulation, but its pathogenesis remains incompletely understood and no curative treatment has been established. Our previous work showed that patients with oral lichen planus exhibit gut dysbiosis, including reduced microbial diversity and depletion of butyrate-producing bacteria. Because butyrate promotes regulatory T-cell differentiation and supports immune homeostasis, targeting this dysbiosis may represent a microbiota-directed approach for immune modulation in oral lichen planus. This study aims to investigate the effects of inulin supplementation on the gut microbiota and related immune markers in patients with oral lichen planus. This multicentre, double-blind, randomised, placebo-controlled parallel-group trial will enrol 80 patients with oral lichen planus. Participants will be randomly assigned in a 1:1 ratio to receive either inulin (8 g/day) or a maltose placebo for 4 weeks, in addition to standard care. The primary outcome is the change in the relative abundance of prespecified butyrate-producing gut bacteria from baseline to the end of intervention at Week 6. Secondary outcomes include changes in gut microbiota diversity, salivary microbiota composition, faecal short-chain fatty acid concentrations, peripheral blood regulatory T-cell counts, blood test parameters, and clinical symptoms of oral lichen planus. Analyses will follow the intention-to-treat principle, and between-group differences will be assessed using appropriate statistical methods. This trial is designed to evaluate, in a randomised placebo-controlled setting, whether a microbiota-directed intervention can modify gut microbial profiles and related immune markers in patients with oral lichen planus. The findings are expected to clarify whether inulin supplementation can modify gut microbial profiles and related immunological markers in patients with oral lichen planus. Trial registration: UMIN Clinical Trials Registry (UMIN-CTR), UMIN000060840, registered on 1 April 2026 (https://rctportal.mhlw.go.jp/detail/um?trial_id=UMIN000060840#). No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0449-3060 67 4 2026 Enhancement of antioxidant function in various organs in mice using combined thermal and radon inhalation treatment 538 549 EN Shogo Miyanaga Graduate School of Health Sciences, Okayama University Ayumi Tanaka Graduate School of Health Sciences, Okayama University Reiju Takenaka Graduate School of Health Sciences, Okayama University Shota Naoe Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Shuna Goto Graduate School of Health Sciences, Okayama University Mitsuki Nagano Graduate School of Health Sciences, Okayama University Kotaro Tano Graduate School of Health Sciences, Okayama University Norie Kanzaki Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Akihiro Sakoda Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Kiyonori Yamaoka Faculty of Health Sciences, Okayama University Takahiro Kataoka Faculty of Health Sciences, Okayama University Enhancing antioxidant function is a key strategy for preventing and treating oxidative stress-related diseases. Radon inhalation and thermal treatment (TT) increase the levels of antioxidant enzymes, such as superoxide dismutase (SOD). The positive effects of this combination on pain-related diseases have been reported; however, few studies have elucidated the underlying mechanisms. In this study, we examined the enhancement of antioxidant function in various organs of mice subjected to combined TT and radon inhalation. The mice were placed in an incubator once daily for 40 min at 38.5 �} 0.5��C and treated for 1, 3 and 7 days. The mice then inhaled radon at a concentration of 2000 Bq/m3 for 24 h. The characteristic changes in antioxidant function following combined TT and radon inhalation could be categorized into four groups: (i) increased antioxidant function in the brain and colon; (ii) increased or decreased antioxidant function, as observed in the kidney; (iii) decreased antioxidant function, such as in the lungs and (iv) no changes, such as in the small intestine, spleen, pancreas, heart, liver and stomach. Additionally, SOD may be the antioxidant enzyme most sensitive to combined TT and radon treatment. Collectively, the combined treatment may be the most effective in activating antioxidative functions in the brain and colon. This study provides new insights into the effects of combined TT and radon inhalation. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0021-9258 302 8 2026 Proton pump rhodopsins for optogenetic manipulation of biological activities and beyond 113318 EN Keiichi Kojima Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Miyu Inokuchi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuki Sudo Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Water (H2O), the principal component of living organisms including humans, dissociates into H+ and OH- in aqueous environments, and the resulting H+ concentration determines both cellular pH and the proton motive force (PMF) across cellular membranes. These physicochemical parameters are fundamental regulators of a wide range of biological processes. Optogenetics enables the manipulation of biological and cellular functions using light, typically through the ectopic expression of microbial rhodopsins as photoreceptive proteins in target cells or organs. This review provides a comprehensive overview of optogenetic studies employing H+ pump rhodopsins in diverse biological systems and highlights their growing relevance to neuroscience, cell biology, bioengineering, and therapeutic research. Notably, optical control of H+ concentration allows the precise modulation of neural and non-neural activities in animals and bacteria, highlighting the broad applicability and significant potential of H+ pump rhodopsins for optogenetics. Based on previous and current studies, we discuss how further expansion of the molecular toolkit of H+ pump rhodopsins could enable increasingly fine-tuned manipulation of intracellular pH dynamics and PMF for probing cellular physiology and designing next-generation therapeutic strategies and consider emerging directions that extend beyond classical optogenetics toward the optical control of bioenergetic and chemical processes. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1473-0502 65 5 2026 Association of initial interface formation time with CD34+ collection efficiency in continuous mononuclear cell collection: A retrospective study 104504 EN Hiroyuki Murakami Department of Hematology, Okayama University Hospital Keiko Fujii Department of Hematology, Okayama University Hospital Wataru Kitamura Department of Hematology, Okayama University Hospital Kazuhiro Ikeuchi Department of Hematology, Okayama University Hospital Joji Shimono Department of Hematology, Okayama University Hospital Fumio Otsuka Division of Clinical Laboratory, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Okayama University Hospital Nobuharu Fujii Department of Hematology, Okayama University Hospital Background: Factors influencing CD34+ cell collection efficiency (CE) during peripheral blood stem cell harvesting have been investigated; however, the impact of procedural management remains unclear. In continuous mononuclear cell (CMNC) collection, a stable cell–plasma interface (IF) is formed through channel priming, initial IF establishment, and mononuclear cell (MNC) collection. Although IF instability is known to impair CE, the adequacy of initial IF formation has not been examined as an independent factor. Therefore, we focused on the time required for initial IF formation and its association with CE.<br> Methods: We retrospectively analyzed 291 Spectra Optia CMNC procedures (52 autologous and 239 allogeneic) performed between 2016 and 2025. Initial interface formation time (IFT) was defined as the interval from the start of the procedure to transition to MNC collection. CE2 was defined as the ratio of collected CD34+ cells to the product of pre-apheresis peripheral blood CD34+ cell concentration and processed blood volume. Results: CE2 was lower in autologous than in allogeneic collections (41.3% vs. 59.2%) and was associated with longer IFT (median, 18 vs. 15 min). CE2 correlated with white blood cell count (r = �|0.24), hematocrit (r = 0.36), and IFT (r = �|0.23; all p < 0.001). In multivariable analysis, these factors remained independently associated with CE2, and IFT was inversely correlated with hematocrit (r = �|0.44, p < 0.001).<br> Conclusion: IFT is independently associated with CE2 and provides insight into the early dynamics of IF formation during leukapheresis, highlighting an underexplored procedural aspect of CE. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-2607 14 7 2026 Upregulation of the Outer Membrane Protein OmpV and Its Role in Polymyxin B Stress Adaptation in Vibrio mimicus 1527 EN Shin-ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yuta Onodera Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shunki Annoi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Basilua Andre Muzembo Research Center for Intestinal Health Science, Okayama University Daisuke Imamura Research Institute of Nursing Care for People and Community, University of Hyogo OmpV is an outer membrane protein found in a variety of Gram-negative bacteria. In this study, we demonstrated that V. mimicus strain CS-66, isolated from a patient with diarrhea, was resistant to polymyxin B (PL-B) and colistin (CL) but susceptible to chloramphenicol and ciprofloxacin. When strain CS-66 was cultured in Luria–Bertani broth containing a sub-minimal inhibitory concentration of each antibiotic used for the susceptibility tests, ompV expression as assayed by reverse transcription-qPCR, significantly increased regardless of the antibiotic tested. In contrast, cell aggregation during the early log phase was observed only when the strain was grown in the broth supplemented with PL-B or CL. A space-filling model of V. mimicus OmpV was generated. The model showed that, although OmpV adopted a ��-barrel conformation, it had closed top and bottom ends and possessed a lateral cavity. Structural analysis further indicated that the interior of this lateral cavity was negatively charged and sufficiently large to accommodate PL-B. These results suggest that V. mimicus may adapt to PL-B stress through physical sequestration within the negatively charged cavity of OmpV. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0170-0839 83 10 2026 Osmotic pressure, correlation lengths and viscosity of aqueous pullulan solutions beyond the overlap concentration 565 EN Lingzi Meng Department of Materials Science and Engineering, The Pennsylvania State University Rene Iwato Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Takaichi Watanabe Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Carlos G. Lopez Department of Materials Science and Engineering, The Pennsylvania State University We investigate the thermodynamic, scattering, and flow properties of pullulan, a flexible non-ionic polysaccharide in aqueous solution, focusing on semidilute and concentrated solutions. We review dilute solution data for the intrinsic viscosity and radius of gyration and hydrodynamic radius of aqueous pullulan and find the Kuhn length and thermal blob size, below which the polymer chain is nearly ideal, to be 3 nm and 20 nm, respectively. We establish the scaling laws for static correlation length, specific viscosity, osmotic pressure, and osmotic compressibility across dilute, semidilute, and concentrated regions, finding that the scaling exponents align well with theoretical predictions but the crossover concentrations obtained from different methods are not consistent. The ratio between the osmotic and Ornstein–Zernike correlation lengths �̃�/��OZ is approximately 2.5 for aqueous solutions, similar to that observed in polystyrene in a theta solvent. This similarity may arise because the crossover concentration between the semidilute and concentrated regions c∗∗ is close to the overlap concentration c∗. No potential conflict of interest relevant to this article was reported.

American Society for Horticultural Science Acta Medica Okayama 1063-0198 36 5 2026 Effects of Transplanting Date and Photoperiod on Flowering of Everbearing Strawberries 789 797 EN Minori Hikawa-Endo Okayama University, Graduate School of Environmental, Life, Natural Science and Technology Ryosuke Yamanaka Western Region Agricultural Research Center, NARO Takayoshi Yano Western Region Agricultural Research Center, NARO Everbearing strawberries have the potential to produce fruit year-round if transplanted early. However, temperature and plant physiological status limit the continuous flowering. Herein, we aimed to investigate whether promoting flowering through long-day phototreatment enables earlier transplanting. The interaction between transplanting date and photoperiod in two everbearing strawberry cultivars was examined. In the 04 cultivar, which exhibited strong everbearing characteristics, rapid and continuous flowering occurred largely independent of long-day treatment, and early transplanting alone increased inflorescence number and early yield. However, excessive flowering was associated with reduced average fruit weight, soluble solid concentration, and firmness. Conversely, in Yotsuboshi, a cultivar with weak everbearing characteristics, earlier transplanting combined with extended photoperiods advanced the emergence of the first and second inflorescences. However, gains in total early yield were small, and the average fruit weight decreased compared with that in the control, indicating physiological stress. Across the cultivars, earlier inflorescence emergence was negatively correlated with days to flowering and positively associated with cumulative yield. For practical applications, cultivars with strong everbearing characteristics can be managed with early transplanting and minimal long-day supplementation to ensure early production. In contrast, cultivars with weak everbearing characteristics require extended photoperiods following early transplanting along with stress-mitigation strategies to maintain fruit size and quality. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0022-1759 541 2025 Development of a novel histidine-rich glycoprotein measurement system as a biomarker for sepsis 113868 EN Takaoki Uchiumi Diagnostic Drug Office, Shionogi & Co., Ltd. Masahiro Nishibori Department of Translational Research and Drug Development, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoko Inoue Diagnostic Drug Office, Shionogi & Co., Ltd. Hiroshi Nishi Diagnostic Drug Office, Shionogi & Co., Ltd. Norio Ota Diagnostic Drug Office, Shionogi & Co., Ltd. The plasma histidine-rich glycoprotein concentration is a marker of sepsis severity. In this study, we generated selective and specific monoclonal antibodies against histidine-rich glycoprotein for use in a prototype enzyme-linked immunosorbent assay-based in vitro diagnostic system. First, we investigated the properties of monoclonal antibodies produced by 21 hybridomas that we developed using immunized mice, and we identified monoclonal antibodies 69-1A and 75-2D to be the most suitable combination for use in the sandwich enzyme-linked immunosorbent assay. Wild-type histidine-rich glycoprotein (Form-1, 75 kDa) with a proline residue at amino acid position 204 is the most common isoform of the protein in humans, followed by its variant (Form-2, 77 kDa), which has a serine residue at position 204.<br> The epitope mapping was examined for the HRG amino acid sequence with 69-1A and 75-2D mAbs to achieve the identification of respective specific binding domains, though the other kinds of mAbs showed considerably complex domains. The identified epitopes recognized by 69-1A and 75-2D monoclonal antibodies did not span position 204. Furthermore, immunoprecipitation-immunoblotting analysis showed that the 69-1A and 75-2D monoclonal antibodies could bind to both Form-1 and Form-2 in human plasma samples. Thus, these two new antibodies can be used to clearly detect both forms of histidine-rich glycoproteins in human plasma samples. In our analysis of clinical samples by enzyme-linked immunosorbent assays using various combinations of our newly synthesized antibodies, we found that the histidine-rich glycoprotein concentration was significantly lower in plasma samples from septic patients than in those from healthy volunteers (p < 0.01). Thus, our novel analysis system using the new antibodies is expected to be a useful tool for sepsis research, and it may be adapted as an in vitro diagnostic tool for many other kinds of diseases in the future. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1078-8174 32 6 2026 Students�f perceptions of an electronic one-minute paper in a radiography training programme: An exploratory cross-sectional questionnaire study 103486 EN Y. Komatsu Division of Radiological Technology, Graduate School of Health Sciences, Okayama University S. Abe Department of Radiological Technology, Faculty of Health Care Sciences, Jikei University of Health Care Sciences S. Tsudou Department of Radiological Technology, Faculty of Health Care Sciences, Jikei University of Health Care Sciences Y. Yamamoto Division of Radiological Technology, Graduate School of Health Sciences, Okayama University Y. Tanabe Faculty of Health Sciences, Department of Radiological Technology, Okayama University Medical School, Okayama University Introduction: Formative assessment can support health professions education; however, reports on electronic 1-min papers as classroom feedback and engagement tools in radiography programmes remain limited. This study explored radiography students�f perceptions of an electronic 1-min paper, focusing on in-class reflection, ease of asking questions, and instructor feedback.<br> Methods: An electronic 1-min paper was used in a radiotherapy course across 45 class sessions in the 2024 academic year for third-year students enrolled in a 4-year radiography programme. Each 90-min class comprised a 60-min lecture, 10-min completion of the paper, and 20-min instructor feedback. After the course, a de-identified online questionnaire was administered. Eleven 5-point Likert-scale items were analysed using descriptive statistics and Spearman's rank correlations. Free-text responses were analysed using inductive qualitative content analysis.<br> Results: Of the 77 eligible students, 74 responded (96.1%). Ease of use received the highest rating (mean, 4.76; standard deviation [SD], 0.52), followed by ease of asking questions (mean, 4.32), question resolution (mean, 4.16), and usefulness of instructor feedback (mean, 4.08). Motivation to review after class was lowest (mean, 3.04; SD, 1.16). Active participation showed a strong positive association with in-class concentration (rs = 0.815; P < 0.001). Free-text responses indicated reflection and improved understanding, anonymous sharing of questions, active listening and concentration, and suggestions for improvement.<br> Conclusion: The electronic 1-min paper was widely accepted and perceived to support in-class reflection, question expression, and immediate feedback. However, students�f perceptions of its influence on out-of-class review motivation were limited. The findings indicate perceived value and engagement rather than demonstrated educational effectiveness.<br> Implications for practice: Electronic 1-min papers may help instructors identify students�f questions and respond during class, providing a practical approach to in-class feedback. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2041-1723 17 1 2026 Atomic imaging for hydrogen and boron aggregates in boron-doped diamond by spectro-photoelectron holography 3482 EN Hiroto Tomita Graduate School of Science and Technology, Nara Institute of Science and Technology Wataru Hosoda Research Institute for Interdisciplinary Science, Okayama University Takumi Taniguchi Research Institute for Interdisciplinary Science, Okayama University Hirokazu Fujiwara Department of Advanced Materials Science, Graduate School of Frontier Sciences, The University of Tokyo Noriyuki Kataoka Research Institute for Interdisciplinary Science, Okayama University Taisuke Kageura Sensing Technology Research Institute, National Institute of Advanced Industrial Science and Technology Yoshihiko Takano Research Center for Materials Nanoarchitectonics, National Institute for Materials Science Hiroshi Kawarada Faculty of Science and Engineering, Waseda University Tamio Oguchi Center for Spintronics Research Network, The University of Osaka Takayoshi Yokoya Research Institute for Interdisciplinary Science, Okayama University Tomohiro Matsushita Graduate School of Science and Technology, Nara Institute of Science and Technology The electrical properties of diamond are modulated by impurity doping. Isolated substitutional boron atoms introduce holes; however, the fraction of electrically inactive boron atoms increases at higher doping concentrations. This has been attributed to boron aggregation and hydrogen passivation, although their structural identification based on atomic arrangement has yet to be experimentally verified. Here we show the origin of multiple chemical states in homoepitaxially grown boron-doped diamond thin films by analyzing the atomic environment of boron using spectro-photoelectron holography. Our analysis identifies boron dimers and boron-hydrogen complexes, with hydrogen occupying different atomic sites that give rise to distinct chemical shifts. These results suggest that hydrogen incorporation during growth leads to passivation of boron acceptors. We demonstrate that photoelectron holography serves as a promising tool for imaging hydrogen as well as determining the atomic sites of dopants. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Asthma-like bronchodilator responsiveness in patients with neuronal intranuclear inclusion disease 16760 EN Daisuke Tahara Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Nao Tahara Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Chisato Tamai Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Akio Akagi Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Yuichi Riku Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Hiroaki Miyahara Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Rei Kobayashi Department of Neurology, NHO Nagoya Medical Center Hisashi Okada Department of Neurology, NHO Nagoya Medical Center Michi Kawamoto Department of Neurology, Kobe City Medical Center General Hospital Junko Ishii Department of Neurology, Kobe City Medical Center General Hospital Hiroki Yamazaki Department of Neurology, Tokushima University Graduate School of Biomedical Science Takashi Kurashige Department of Neurology, NHO Kure Medical Center and Chugoku Cancer Center Atsuhiko Sugiyama Department of Neurology, Chiba University Akiko Nagaishi Department of Neurology, NHO Nagasaki Kawatana Medical Center Katsuya Nishida Department of Neurology, NHO Hyogo Chuo National Hospital Kazuma Sugie Department of Neurology, Nara Medical University Hospital Takayasu Fukudome Department of Neurology, NHO Nagasaki Kawatana Medical Center Kazuko Hasegawa Department of Neurology, NHO Sagamihara National Hospital Hiroyuki Ishiura Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haruki Koike Department of Neurology, Saga University Takashi Kasai Department of Neurology, Kyoto Prefectural University of Medicine Toshiki Mizuno Department of Neurology, Kyoto Prefectural University of Medicine Masahiro Ando Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Yujiro Higuchi Department of Neurology and Geriatrics, Kagoshima University Graduate School of Medical and Dental Sciences Fumiaki Tanaka Department of Neurology and Stroke Medicine, Yokohama City University Graduate School of Medicine Yuishin Izumi Department of Neurology, Tokushima University Graduate School of Biomedical Science Gen Sobue Aichi Medical University Yasushi Iwasaki Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Satoru Ito Division of Respiratory Medicine and Allergology, Department of Internal Medicine, School of Medicine, Aichi Medical University Jun Sone Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University Neuronal intranuclear inclusion disease (NIID) is a neurodegenerative condition characterized by the presence of intranuclear inclusions in neuronal and visceral cells. Patients with NIID can present respiratory symptoms; however, data on pulmonary functions in NIID are lacking. This study investigated the respiratory conditions in NIID patients diagnosed with histopathological and genetic studies. We conducted two spirometries before and after administrating the bronchodilator in NIID patients with asthmatic histories or symptoms. We statistically compared pre- and post-measured values including forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and peak expiratory flow (PEF). Before two spirometries, we also measured fractional concentration of exhaled nitric oxide (FeNO), if possible. Of the 51finally enrolled patients, 17 (33.3%, 95% CI 20.8% to 47.9%) patients had asthmatic histories or symptoms, and 14 patients received two spirometries. After administrating the bronchodilator, FEV1 and PEF significantly increased by 150 mL (6.01%, p = 0.002) and 260 mL/s (6.72%, p = 0.017), respectively. The median (interquartile range) of FeNO measured in nine patients was 15 (10–21) ppb. Patients with NIID have airflow reversibility like asthma. This condition appears to be less associated with airway inflammation and may be related to autonomic dysfunction. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0278-0372 46 3 2026 Estimating the distributional expansion of the invasive crayfish Procambarus clarkii (Girard, 1852) (Decapoda: Astacidea: Cambaridae) in South Korea using environmental DNA analysis ruag033 EN Seong-Nam Ham Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kaito Moriuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mayuko Hamada Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Kazuyoshi Nakata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University The red swamp crayfish Procambarus clarkii (Girard, 1852) is a globally invasive species that poses serious threats to native biodiversity and ecosystem functioning. In South Korea, established populations of P. clarkii have been documented from the Jiseokcheon River in the Yeongsangang River basin since 2018; however, information on its current nationwide distribution remains limited. We conducted environmental DNA (eDNA) surveys at 19 sites across 11 river systems in South Korea, including sites with no prior distributional records, to evaluate the current distribution and potential range expansion of P. clarkii. Water samples collected during July-August 2024 were analyzed using quantitative real-time PCR (qPCR) with two species-specific primer-probe sets targeting the mitochondrial COI gene. Procambarus clarkii eDNA was detected at three sites in the Yeongsangang River basin, whereas no eDNA was detected in the other surveyed river systems. Notably, P. clarkii eDNA was not detected at a site in the Mangyeonggang River system despite previous reports of individuals and eDNA data sampled there, indicating a possible local population decline or very low abundance. By contrast, detections within the Yeongsangang River basin, together with elevated eDNA concentrations at some sites, are consistent with localized upstream expansion and increased local abundance. The concordant results from the two primer-probe sets, together with Sterivex-based on-site filtration, support the reliability of the applied eDNA framework. These findings identify the Yeongsangang River basin as the current primary focus of the P. clarkii invasion in South Korea, with evidence consistent with localized upstream expansion and increasing abundance, and provide baseline data for early detection and long-term monitoring, as well as for developing management strategies. No potential conflict of interest relevant to this article was reported.

Pharmaceutical Society of Japan Acta Medica Okayama 0918-6158 47 12 2024 Staphylococcus aureus ��-Toxin Induces Ca2+ Influx-Independent Degranulation of Murine Cultured Mast Cells 2058 2064 EN Kang Liu Laboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University Tomoaki Katayama Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hitomi Sato Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yuho Hamaoka-Tamura Laboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University Michiko Saito Bioscience Research Center, Kyoto Pharmaceutical University Kazuyuki Furuta Division of Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Satoshi Tanaka Laboratory of Pharmacology, Division of Pathological Sciences, Kyoto Pharmaceutical University Cutaneous colonization with Staphylococcus aureus (SA) is frequently observed in patients with atopic dermatitis. SA produces a wide variety of bacterial toxins, among which ��-toxin was found to induce degranulation of mast cells. Degranulation of mast cells could enhance bacterial clearance and protection from future SA infection but lead to exacerbation of atopic dermatitis. Because it remains to be determined how ��-toxin triggers degranulation, we investigated ��-toxin-induced changes in murine bone marrow-derived cultured mast cells in this study. We found that ��-toxin-induced degranulation could be classified into two phases, an early Ca2+-independent and a late Ca2+-dependent phase. Recent studies suggest that NOD-like receptor family, pyrin domain containing 3 is involved in the degranulation of mast cells, raising a possibility that leakage of K+ induced by ��-toxin is involved in the Ca2+-independent phase. However, Ca2+-independent degranulation remains unchanged although Ca2+-influx and degranulation induced by ��-toxin were significantly suppressed in the presence of high concentrations of K+. Because actin depolymerization was reported to induce degranulation in the absence of Ca2+ in the permeabilized rat peritoneal mast cells, a slow but steady decrease in the amount of filamentous actin observed here may be involved in Ca2+-independent degranulation induced by ��-toxin. Although Mas-related G protein-coupled receptor (MRGPR) X2 in humans and Mrgprb2 in mice are regarded as the receptors responsible for immunoglobulin E-independent degranulation, ��-toxin-induced degranulation remained unchanged in Mrgprb2�|/�| mast cells. Our findings pave the way for identification of the target receptors of ��-toxin. No potential conflict of interest relevant to this article was reported.

American Society for Microbiology Acta Medica Okayama 0021-9193 206 10 2024 Overexpression of diglucosyldiacylglycerol synthase leads to daptomycin resistance in Bacillus subtilis e00307-24 EN Ryogo Yamamoto Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuya Ishikawa Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yusuke Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuyuki Furuta Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin-Ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chikara Kaito Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The lipopeptide antibiotic daptomycin exhibits bactericidal activity against Gram-positive bacteria by forming a complex with phosphatidylglycerol (PG) and lipid II in the cell membrane, causing membrane perforation. With the emergence of daptomycin-resistant bacteria, understanding the mechanisms of bacterial resistance to daptomycin has gained great importance. In this study, we aimed to identify the genetic factors contributing to daptomycin resistance in Bacillus subtilis, a model Gram-positive bacterium. Our findings demonstrated that overexpression of ugtP, which encodes diglucosyldiacylglycerol synthase, induces daptomycin resistance in B. subtilis. Specifically, overexpression of ugtP resulted in increased levels of diglucosyldiacylglycerol (Glc2DAG) and decreased levels of acidic phospholipids cardiolipin and PG, as well as the basic phospholipid lysylphosphatidylglycerol. However, ugtP overexpression did not alter the cell surface charge and the susceptibility to the cationic antimicrobial peptide nisin or the cationic surfactant hexadecyltrimethylammonium bromide. Furthermore, by serial passaging in the presence of daptomycin, we obtained daptomycin-resistant mutants carrying ugtP mutations. These mutants showed increased levels of Glc2DAG and a >4-fold increase in the minimum inhibitory concentration of daptomycin. These results suggest that increased Glc2DAG levels, driven by ugtP overexpression, modify the phospholipid composition and confer daptomycin resistance in B. subtilis without altering the cell surface charge of the bacteria. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0743-7463 40 52 2024 Formation of Nonspherical Cellulose Acetate Microparticles under Microflow 27314 27322 EN Kurumi Mori Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takaichi Watanabe Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tsutomu Ono Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nonspherical particles have gained significant interest owing to their unique shapes and large specific surface areas, making them suitable for a wide range of applications, such as drug delivery, catalysis, and adsorption. However, conventional methods for preparing nonspherical particles face certain limitations. In this study, we propose a simple method for fabricating nonspherical cellulose acetate (CA) microparticles using a microfluidic device in which droplets undergo rapid diffusion in a continuous aqueous phase. The influence of variations in the flow rate ratio and continuous phase composition on the dimensionless Péclet number (Pe) within the droplet and shape of the resultant particles is investigated. Pe is critical, because it indicates the balance between polymer diffusion and droplet shrinkage dynamics. Our findings reveal that increasing the flow rate ratio and reducing the methyl acetate concentration in the continuous phase lead to faster droplet shrinkage and an increased Pe. A high Pe (>100) suggests that the reduction of the droplet interface predominates over polymer diffusion, resulting in the formation of a viscous layer near the droplet surface, which subsequently leads to nonspherical particle shapes (such as bowl-like or biconcave structures). In situ time-lapse observations of droplets from the top and side of a microchannel reveal that the formation of a viscous layer near the droplet surface and the deformation of the droplet, influenced by the z-axis location of the droplets during particle formation, ultimately determine the final particle shape. Based on these observations, a linear correlation between the initial conditions, i.e., the Pe and z-axis location at which the viscous layer formed, is established, enabling the prediction of the particle structure. In summary, the present study enhances the understanding of shape control in microfluidic particle formation and offers a novel guideline for the fabrication of spherical and nonspherical particles. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2637-6105 8 11 2026 Solution Structure and Counterion Condensation of Carboxymethyl Cellulose in Organic Solvents 8183 8197 EN Anish Gulati Institute of Physical Chemistry, RWTH Aachen University Lingzi Meng Materials Science and Engineering Department, The Pennsylvania State University Can Hou Institute of Physical Chemistry, RWTH Aachen University Takaichi Watanabe Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Carlos G. Lopez Materials Science and Engineering Department, The Pennsylvania State University We report scattering (SANS and SAXS) and electrical conductivity data for aqueous and organic solutions of carboxymethyl cellulose with tetrabutylammonium counterions. For SANS in deuterated solvents, the contrast is heavily dominated by the hydrogen-rich counterions, while for SAXS the polymer backbone has a more significant contribution to the scattering signal. The correlation length calculated from the SAXS measurements follows a scaling law of �� �� c–1/2, while that measured by SANS displays a weaker exponent at higher concentrations for solvents of high dielectric constants. These results indicate a decoupling in the characteristic length scales of fluctuations of the polymer backbone and counterions at high polyelectrolyte concentrations. The stretching parameter calculated from the correlation length indicates a highly stretched local conformation for TBACMC in water and several high dielectric constant solvents, consistent with the semiflexible nature of the cellulose backbone. In solvents of lower dielectric permittivity, the chains display a higher degree of local coiling. Combining electrical conductivity and scattering data, we find that the fraction of monomers bearing a dissociated charge is nearly independent of concentration and approximately proportional to the reciprocal of the Bjerrum length of the solvent, as expected by the Oosawa-Manning model. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0883-2927 207 2026 Effects of secondary hydrothermal fluids on gallium distribution and coordination in hot springs silica using Ga K-edge XANES 106961 EN M.C. Rowe School of Environment, University of Auckland K.A. Campbell School of Environment, University of Auckland D.A. Stallard School of Environment, University of Auckland B. Lyon School of Environment, University of Auckland A. Langendam Australian Synchrotron Facility (Ansto) E. Kalinina The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University M. Yamanaka The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University R. Tanaka The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University T. Christopher School of Chemical Sciences, University of Auckland S.W. Ruff Arizona State University, School of Earth And Space Exploration E. Nersezova School of Environment, University of Auckland T. Ota The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University A. Hamilton School of Environment, University of Auckland Gallium (Ga), a critical element in the electronics industry, is enriched in hot spring silica deposits (sinter) at concentrations comparable to, and in some cases greater than, bauxite, coal, and sphalerite deposits from which it is currently extracted. Focusing on well characterized Holocene and Pleistocene New Zealand sinters, we utilize synchrotron-X-ray fluorescence (sXRF) and Ga K-edge X-ray absorption near edge structure (XANES) spectroscopy to examine the spatial distribution of Ga as well as its changing coordination number. Ga+3 is the only observed oxidation state in the analyzed sinters. Gallium is predominantly found in tetrahedral coordination in sinter deposited from alkali chloride fluids, with analyses best matching Ga-aluminosilicate standards. However, Ga coordination is octahedral in sinter samples that have undergone alteration by acidic fluids/gases, associated with a change in hydrology from alkali-chloride to acid-sulfate fluid conditions. High Ga concentrations are found associated with both these coordination environments, with a heterogeneous distribution. Octahedral Ga is observed both as particles and in larger regions affected by Fe-rich fluid overprinting. The combined use of sXRF and XANES demonstrates an ability to fingerprint diagenesis and alteration in these complex geothermal settings where tetrahedral and octahedral Ga co-exist. The transition from tetrahedral to octahedral Ga also appears to mimic the inferred natural process forming lateritic bauxite deposits, where remobilized tetrahedral Ga is reconcentrated and adsorbed to oxides. A similar process may occur for sinter Ga enrichment, whereby introduced Ga in acidic conditions is adsorbed to oxide phases as the Fe-rich secondary fluids infiltrate porous sinter material. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 3042-6081 2 2 2026 Interfacial Bond Strength of Resin Cement to Polyetheretherketone (PEEK) Using Experimental Primers Doping Multifunctional Methacrylate and Acrylate Monomers 12 EN Yukinori Maruo Department of Prosthodontics, Okayama University Kumiko Yoshihara Health Research Institute, National Institute of Advanced Industrial Science and Technology Masao Irie Okayama University Dental School Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Naoki Kodama Department of Prosthodontics, Okayama University Yuki Tanaka Department of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Miho Kuwahara Department of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Akiyama Department of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Polyetheretherketone (PEEK) is a high-performance thermoplastic polymer with low surface energy, chemical inertness, and a highly crystalline structure, which limit durable adhesion to resin-based materials and require improved bonding strategies. This in vitro study evaluated the effect of incorporating multifunctional methacrylate (TMPTMA) and acrylate monomers (A-TMPT and A-DPH) into an experimental primer on the 24 h shear bond strength (SBS) of resin cement to PEEK (n = 6 per group). Experimental primers were prepared by adding varying amounts (100–500 µL) of each multifunctional monomer to a UDMA/MMA-based primer, and SBS was measured after cementation with a dual-cure resin cement. TMPTMA-containing primers produced median SBS values of approximately 10–12 MPa, while acrylate-based primers showed slightly higher values, particularly at higher concentrations, reaching up to ~15.8 MPa; however, no statistically significant improvement over the control group was observed (p > 0.05). Failure modes were predominantly mixed across all conditions. These findings indicate that multifunctional monomers, despite their potential to enhance cross-link density and wetting, do not substantially overcome the intrinsic adhesion-resistant nature of polished PEEK. The results underscore that monomer modification alone is insufficient and that effective adhesion to PEEK likely requires integrated strategies combining chemical activation with mechanical surface conditioning. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 3 2026 HIP COMPASS®: A Mechanical Intraoperative Navigation Guide Associated with Improved Revision-Free Implant Survivorship after Ceramic-on-Ceramic Total Hip Arthroplasty at Minimum 10-Year Follow-up 195 202 EN Yoshiaki Tei Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Norio Imai Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences Keishi Kimura Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Yuki Hirano Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Yoji Horigome Division of Comprehensive Musculoskeletal Medicine, Niigata University Graduate School of Medical and Dental Sciences Ken Suda Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Hiroyuki Kawashima Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences Original Article 10.18926/AMO/70855 HIP COMPASS® has demonstrated improved accuracy in intraoperative support for the acetabular component insertion angle. We assessed long-term revision-free implant survivorship following total hip arthroplasty (THA) using HIP COMPASS, with ≥10 years of follow-up. We retrospectively analyzed 210 hips of 186 patients who underwent cementless THA with ceramic-on-ceramic bearing couples, with or without HIP COMPASS. The mean follow-up duration was 10.8 years in the HIp COMPASS group and 12.7 years in the control group. Overall, 86.0% and 78.2% of cups were placed within Lewinnek�fs safe zone with and without HIP COMPASS, respectively. Variability in radiographic inclination and anteversion was greater in the control group than in the HIP COMPASS group. Dislocation rates were 3.2% in the control group and 1.2% in the HIP COMPASS group, with no significant difference between groups. The control group had a significantly higher revision rate than the HIP COMPASS group (7.3% vs. 1.2%). Use of HIP COMPASS was associated with improved long-term revision-free implant survivorship over ≥ 10 years and more consistent acetabular component positioning at an appropriate insertion angle, which may contribute to stable initial fixation. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1663-9812 17 2026 Hochuekkito attenuates anxiety-like behavior associated with pulmonary inflammation induced by intratracheal lipopolysaccharides in mice 1774957 EN Yasuhisa Izushi Department of Pharmacotherapy, Graduate School of Pharmacy, Shujitsu University Soichiro Ushio Department of Pharmaceutical Sciences for Health Crisis Management, Faculty of Pharmaceutical Sciences, Fukuoka University Teppei Ueda Department of Pharmacotherapy, Graduate School of Pharmacy, Shujitsu University Yuichi Tasaka Laboratory of Clinical Pharmacy, School of Pharmacy, Shujitsu University Ikuko Miyazaki Department of Medical Neurobiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masato Asanuma Department of Medical Neurobiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshihisa Kitamura Department of Pharmacotherapy, Graduate School of Pharmacy, Shujitsu University Introduction: We have previously demonstrated that intratracheal lipopolysaccharide (LPS) injection induces significant pulmonary inflammation accompanied by hippocampal microglial activation, indicative of neuroinflammation. Hochuekkito (HET) is a traditional Japanese herbal medicine used to treat various conditions, including mental disorders and physical weakness. We have previously reported that HET ameliorates anxiety-like behaviors induced by intraperitoneal LPS injections in mice. However, its anxiolytic effects on anxiety-like behaviors due to pulmonary inflammation remain poorly understood. Therefore, in the present study, we aimed to investigate the effects of HET on anxiety-like behaviors induced by intratracheal LPS injection in mice.<br> Methods: Mice received HET (1.0 g/kg) once daily for 2 weeks through oral gavage prior to LPS treatment. The light-dark box test was conducted 24 h following LPS injection to assess anxiety-like behaviors. Diazepam, a clinically used anxiolytic, served as a positive control. The lung wet-to-dry weight ratio was determined, and the concentrations of interleukin-6 (IL-6) in the lungs and serum were assessed.<br> Results: Repeated administration of HET prevented the development of anxiety-like behaviors and reduced serum IL-6 concentrations and hippocampal Il6 mRNA expression levels in LPS-treated mice. Diazepam failed to exert significant effects in LPS-treated mice, whereas HET remained effective under inflammatory conditions. Moreover, LPS injections significantly increased the number of Iba-1-immunoreactive microglial cells in the CA1 region of the hippocampus, whereas this effect was suppressed by treatment with HET. In the bronchoalveolar lavage fluid (BALF), the LPS-induced increase in white blood cell count was significantly reduced by treatment with HET. Furthermore, HET alleviated LPS-induced pulmonary inflammation, as evidenced by decreased lung wet-to-dry weight ratios.<br> Conclusion: This study suggests that inflammation induced by intratracheal LPS injection contributes to anxiety-like behaviors in mice and that IL-6 may play a key role in linking peripheral inflammation to neuroinflammatory responses. The anxiolytic effects of HET appear to be associated, at least in part, with the suppression of IL-6 elevation in both the periphery and the hippocampus, along with attenuation of microglial activation. Our findings suggest that HET may serve as a potential therapeutic agent for anxiety-like behaviors associated with pulmonary inflammation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 1 2026 Adolescent envy-like social comparison stress induces HPA axis hypoactivity and anxiety in female mice: implications for somatic symptom disorder 15771 EN Hiroshi Ueno Department of Medical Technology, Kawasaki University of Medical Welfare Yoshihiro Tanaka Department of Psychiatry, Kawasaki Medical School Eriko Kitano Department of Psychiatry, Kawasaki Medical School Yu Takahashi Department of Psychiatry, Kawasaki Medical School Sachiko Mori Department of Psychiatry, Kawasaki Medical School Shinji Murakami Department of Psychiatry, Kawasaki Medical School Kenta Wani Department of Psychiatry, Kawasaki Medical School Yosuke Matsumoto Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Motoi Okamoto Department of Medical Technology, Graduate School of Health Sciences, Okayama University Takeshi Ishihara Department of Psychiatry, Kawasaki Medical School Adolescence is a critical developmental window marked by heightened neuroplasticity and maturation of the stress response system, conferring vulnerability to psychosocial stress. Chronic stress during this period increases the risk of anxiety and depressive disorders and may contribute to somatic symptom disorder (SSD), which is characterized by medically unexplained physical complaints and shows a striking female predominance. The impact of envy-like stress arising from social comparison, a pervasive psychosocial factor in modern society, remains poorly understood. Male and female C57BL/6N mice were exposed to chronic envy-like stress from postnatal day (P)21 to P52 by housing them adjacent to enriched cages, while control mice were housed without such exposure. From P52 onward, mice underwent behavioral testing of anxiety-like behavior, exploratory activity, social interaction, spatial working memory, motor coordination, nociception, and depression-like behavior. Serum corticosterone and adrenocorticotropic hormone (ACTH) concentrations were measured to assess hypothalamic–pituitary–adrenal (HPA) axis function. Envy-like stress induced sex-specific phenotypes. Male mice exhibited hyperactivity, reduced social interaction, and impaired spatial working memory. In contrast, female mice displayed robust increases in anxiety-like behavior, impaired motor coordination, and significant reductions in basal corticosterone and ACTH levels. Chronic envy-like stress during adolescence elicits distinct, sex-dependent behavioral and endocrine alterations. The phenotype observed in female mice�\characterized by heightened anxiety and lower basal HPA axis hormone levels�\shares some biological features with clinical observations in SSD. This model may serve as a starting point for elucidating the mechanisms linking psychosocial stress and somatic symptoms in a sex-dependent manner. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 27 6 2026 Minimal Association Between Immunoglobulin A Coating and Gut Microbiota Alterations Induced by High-Fat Diets with Distinct Fatty Acid Compositions 2645 EN Mao Teraoka Faculty of Environmental, Life, Natural Science and Technology, Okayama University Naoki Nishino Faculty of Environmental, Life, Natural Science and Technology, Okayama University Tianyang Wang Faculty of Environmental, Life, Natural Science and Technology, Okayama University Kuiyi Chen Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takeshi Tsuruta Faculty of Environmental, Life, Natural Science and Technology, Okayama University High-fat diets (HFDs) containing dietary fats with different fatty acid (FA) compositions alter gut microbiota composition in a fat-source-dependent manner. Immunoglobulin A (IgA) and unabsorbed lipids in the distal gut are potential regulators of the gut microbiota. However, their roles in mediating gut microbiota alterations induced by dietary fats with different FA compositions remain unclear. This study aims to examine the associations of these two factors with fat-source-dependent gut microbiota alterations. BALB/c mice were fed a normal diet, a high-lard diet, a high-olive oil diet, or a high-soybean oil diet for 27 weeks. Fecal samples were collected to assess microbiota composition, the IgA coating index (ICI)�\which quantifies the extent of IgA coating on gut microbiota�\and fecal fatty acid concentrations. At the phylum level, the concentration of fecal total long-chain fatty acids (LCFAs) was positively correlated with the relative abundance (RA) of Bacillota and negatively correlated with that of Bacteroidota. In addition, a trend toward a positive association between the RA and the ICI was observed for Bacillota but not for Bacteroidota. At the genus level, the RAs of 12 taxa were positively correlated with fecal LCFA concentrations, whereas those of 6 taxa were negatively correlated. Although the RAs of most taxa appeared to be influenced by unabsorbed lipids and additional factors, only four Bacillota genera exhibited a positive correlation between the RA and the ICI. Our observations suggest that IgA coating of the gut microbiota may have a minimal association with fat-source-specific alterations in gut microbiota composition during HFD intake. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2214-1804 51 2026 Highly sensitive detection of cancer cells using a voltage-tuned terahertz chemical microscope 100972 EN Xue Ding Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yuto Ohmi Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jin Wang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Hirofumi Inoue Department of Medical Support, Okayama University Hospital Toshihiko Kiwa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Terahertz chemical microscopy (TCM) is a promising label-free technique for detecting biochemical interactions by monitoring changes in terahertz (THz) wave emission from semiconductor sensing plates. However, quantitative biological detection has been hindered by large plate-to-plate variations originating from uncontrolled depletion-layer electric fields formed during fabrication. These variations shift the response curve of THz amplitude and reduce reproducibility and sensitivity. Here, we introduce a voltage-tuned sensing plate that allows direct control of the depletion-layer electric field by applying a bias voltage to the Si layer of the sensing plate. This enables deliberate adjustment of surface potential and alignment of the THz response curve to the region of highest gain. Using lung adenocarcinoma cells (PC9) captured via AE1/AE3 antibodies targeting specific cell-surface antigens, we demonstrate that voltage tuning enhances detection sensitivity by up to 50-fold and restores linearity between THz amplitude and the logarithm of cell concentration, even in plates with negligible response at 0 V. These findings establish voltage control as a simple, universally applicable strategy to stabilize TCM performance, reduce fabrication-induced variability, and improve analytical sensitivity for biosensing and materials-analysis applications. No potential conflict of interest relevant to this article was reported.

American Geophysical Union (AGU) Acta Medica Okayama 2169-9313 130 8 2025 Linking the Spin Transition of Ferric Iron in �](Al,Fe)OOH to Water Storage in the Lower Mantle e2025JB031715 EN Johannes Buchen Bayerisches Geoinstitut, Universität Bayreuth Olivia S. Pardo Seismological Laboratory, California Institute of Technology Vasilije V. Dobrosavljevic Seismological Laboratory, California Institute of Technology Wolfgang Sturhahn Seismological Laboratory, California Institute of Technology Takayuki Ishii Now at Institute for Planetary Materials, Okayama University Stella Chariton GSECARS, The University of Chicago Eran Greenberg GSECARS, The University of Chicago Thomas S. Toellner Advanced Photon Source, Argonne National Laboratory Jennifer M. Jackson Seismological Laboratory, California Institute of Technology As the most massive geochemical reservoir, the lower mantle affects the Earth's budget of volatile elements, including hydrogen or H2O. The properties of minerals in the lower mantle are further affected by changes in the electronic configurations of iron cations, that is, by spin transitions. The feedback between spin transitions and potential storage of H2O in solid hydrous phases in the lower mantle, however, remains unexplored. By combining high-pressure nuclear resonant inelastic X-ray scattering and high-pressure high-temperature X-ray diffraction experiments, we constrained the thermal equation of state of ��-(Al,Fe)OOH, a member of the phase H solid solution. Based on the derived thermal equation of state of ��-(Al,Fe)OOH and the underlying thermodynamic model, we calculate the excess Gibbs free energy that arises from the spin transition of ferric iron in this compound and evaluate the effect on phase equilibria. The results of our analysis show that the spin transition of ferric iron in phase H may significantly reduce the thermodynamic activity and hence the concentration of H2O in a coexisting hydrous melt. As a consequence, nominally anhydrous minerals of the lower mantle may become dehydrated in the presence of phase H. Our analysis further suggests that, under certain conditions, the spin transition may expand the thermal stability of Fe3+-bearing phase H and create a geochemical link between the storage of H2O in phase H and ferric iron in the lower mantle. No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 2026 The DNA integrity number and concentration are useful parameters for successful comprehensive genomic profiling test for cancer using formalin-fixed paraffin embedded tissue EN Emii MATSUOKA Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0003-6862 2026 Effect of caffeine on life-history traits on the red flour beetle, Tribolium castaneum (Coleoptera: Tenebrionidae) EN Shine Shane Naing Okayama University (Graduate School of Environmental, Life, Natural Science and Technology) Teruhisa Matsuura Okayama University (Graduate School of Environmental, Life, Natural Science and Technology) Takahisa Miyatake Okayama University (Graduate School of Environmental, Life, Natural Science and Technology) Nowadays, addressing insect pest infestation effectively requires environmentally sound and sustainable pest control methods that minimize environmental pollution. Caffeine (1, 3, 7-trimethylxanthine), a plant-derived secondary metabolite, has insecticidal, hormonal and antifeedant properties, making it a promising and more sustainable alternative for pest management. In this study, the red flour beetle Tribolium castaneum Herbst (Coleoptera: Tenebrionidae), a serious stored pest, was used to investigate the effects of different caffeine concentrations on life-history traits. We applied two delivery methods: 1) oral exposure through a caffeine–sucrose solution for adults, and 2) dietary incorporation of caffeine powder mixed with wheat flour and brewer�fs yeast for adults and their larvae. To evaluate the effect of caffeine on life-history traits, adult longevity, pupation rate, larval period, pupal weight, adult body size and food consumption were examined. Results revealed higher caffeine concentrations (> 1%) significantly reduced longevity, delayed pupation, decreased pupal number, pupal weight and adult body size in both males and females. Lower caffeine concentration (0.01%) increased pupal number but resulted in lower offspring quality, such as smaller pupal weight and adult size. The results show that caffeine has negative effects on life-history traits of T. castaneum, suggesting its potential use as a natural pesticide in caffeine-based sustainable pest-management programs and integrated pest management (IPM). No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2731-5894 2026 Comparative study of Ni–CeO2 catalysts prepared by impregnation and coprecipitation for CO2 methanation EN Nobuko Fukuda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Shuichi Imano Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nozomi Nakahara Graduate School of Environmental, Life, Natural Science and Technology, Okayama University This study explores how synthesis methods affect the structure and CO2 methanation performance of Ni–CeO2 catalysts prepared by coprecipitation and impregnation under identical conditions. Coprecipitation generated particles below 100 nm with uniform elemental distribution, together with large bulk-like particles exhibiting locally concentrated Ni species, attributed to differences in hydroxide solubility. Impregnation, by contrast, produced very large particles (> 500 nm) with smaller particles attached, while maintaining relatively homogeneous elemental distribution. Coprecipitated catalysts showed slightly higher surface area and oxygen vacancy concentration, resulting in higher apparent turnover frequencies (TOFapp) below 300 ��C due to enhanced CO2 adsorption and high Ni site density. However, at temperatures above 350 ��C, impregnated catalysts displayed higher CH4 selectivity and TOFapp, indicating reduced kinetic limitations and more efficient active-site utilization. These results provide insights for rational design of efficient CO2 methanation catalysts. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2574-0970 9 14 2026 Reversible Droplet Bridging and Tunable Viscoelasticity in Emulsions Using Biocompatible PLA-b-PEO-b-PLA Telechelic Block Copolymers: Implications for Injectable Emulsion Gels 6176 6185 EN Hinako Nakayama Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Atsushi Matsumoto Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, University of Fukui Yuya Iida Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Tsutomu Ono Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Takaichi Watanabe Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Telechelic polymers are known to form reversible networks through end-group association; however, their application as structuring agents in emulsion-based soft materials remains underexplored. Herein, we systematically investigate the biocompatible amphiphilic triblock copolymer poly(d,l-lactic acid)-block-poly(ethylene oxide)-block-poly(d,l-lactic acid)(PLA-b-PEO-b-PLA) as a rheology modifier in toluene-in-water model emulsions. Owing to the selective adsorption of PLA end blocks at the oil–water interface and the solvation of the PEO midblock in the aqueous phase, this polymer is expected to form reversible droplet-bridging networks. During the process, the polymer concentration, molecular weight of the mid and end blocks, and the dispersed phase volume fraction were adjusted, and the factors governing network formation were elucidated using oscillatory rheology and stress-relaxation measurements. The results show that anchoring of the PLA end blocks and PEO-mediated bridging predominantly control the strength and dynamic reversibility of the network. Step-strain experiments further reveal that the droplet-bridging interactions can be disrupted under large deformation and partially recover when small-strain conditions are restored, confirming the presence of reversible physical associations. These findings establish a molecular design strategy for biodegradable telechelic copolymers as effective and reprocessable structuring agents in emulsion gels. The shear-responsive, tunable, and reversible nature of the droplet-bridging network makes this material platform particularly suitable for injectable emulsion gels for advanced soft matter and biomedical engineering applications. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1868-6974 2026 Feasibility of Comprehensive Genomic Profiling for Biliary Tract Cancer Using Transpapillary Biopsy Samples: A Prospective Study EN Kazuya Miyamoto Department of Gastroenterology and Hepatology, Okayama University Hospital Kazuyuki Matsumoto Department of Endoscopy, Okayama University Hospital Toshiaki Ohara Department of Pathology and Experimental Medicine, Okayama University Hospital Masayoshi Fujisawa Department of Pathology and Experimental Medicine, Okayama University Hospital Hirohumi Inoue Department of Medical Support, Okayama University Hospital Ryosuke Sato Department of Gastroenterology and Hepatology, Okayama University Hospital Akihiro Matsumi Department of Endoscopy, Okayama University Hospital Yuki Fujii Department of Endoscopy, Okayama University Hospital Daisuke Uchida Department of Gastroenterology and Hepatology, Okayama University Hospital Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Hospital Background: Patients with biliary tract cancer (BTC) often have actionable mutations, and comprehensive genomic profiling (CGP) plays an important role. However, the feasibility of CGP using transpapillary biopsy (TPB) samples remains unclear.<br> Methods: Thirty patients with suspected BTC based on radiographic imaging were enrolled. Pre-analytical criteria for CGP suitability were based on the OncoGuide NCC Oncopanel System (NCCOP) and FoundationOne CDx (F1CDx). Each patient underwent six biopsies using an endoscopic introducer: five biopsy samples were preserved as formalin-fixed paraffin-embedded (FFPE) samples and one as a fresh frozen (FF) sample. DNA quality indicators were compared between the two groups.<br> Results: Malignancy was confirmed in 29 patients, and one had a benign biliary stricture. Suitability rate was 31% (9/29) for NCCOP and 3.4% (1/29) for F1CDx. Compared to FFPE samples, FF samples demonstrated significantly higher DNA concentration [ng/��L, interquartile range (IQR)], [0.34 (0.16–0.95) vs. 37.8 (11.6–67.6), p < 0.001] and DNA integrity number (IQR) [7.1 (6.8–7.3) vs. 8.9 (8.3–9), p = 0.021].<br> Conclusions: Introducer-assisted multipass TPB may increase the rate of obtaining adequate CGP specimens, but its suitability remains limited and strongly panel dependent. Since FF samples have better DNA quality, establishing a system detailing their use is desirable.<br> Trial Registration: ClinicalTrials.gov identifier: UMIN 000049826 No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 16 2026 Sex-related differences in blood concentrations and emergence profiles following total intravenous anesthesia with remimazolam and remifentanil 13650 EN Riko Sato Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitoshi Higuchi Department of Dental Anesthesiology, Okayama University Hospital Yukiko Nishioka Department of Dental Anesthesiology, Okayama University Hospital Saki Miyake Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Miyawaki Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Remimazolam is a novel, short-acting benzodiazepine, which is characterized by rapid onset and quick recovery. The clinical efficacy and metabolism of many intravenous anesthetics are known to be influenced by sex; however, the effects of sex on the anesthetic efficacy and metabolism of remimazolam remain unclear. This prospective observational study examined sex-related differences in pharmacokinetics and emergence profiles after total intravenous anesthesia was induced with remimazolam and remifentanil in patients undergoing oral and maxillofacial surgery. Thirty-five American Society of Anesthesiologists Physical Status 1 adults (19 females, 16 males), aged 18–49 years, received standardized dosing based on their actual body weights. Serum remimazolam concentrations were measured at the end of administration and immediately before extubation using high-performance liquid chromatography. Although the emergence time did not differ significantly between the sexes, the mean emergence time of the females was approximately 80 s shorter. Serum remimazolam concentrations were significantly lower in females at both measurement time points (p < 0.001). This may suggest that remimazolam is metabolized more rapidly in women. Although these sex-related pharmacokinetic differences did not affect the time to awakening under combined remimazolam and remifentanil anesthesia, clinicians should be aware of potential sex differences in the pharmacokinetics of remimazolam. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0449-3060 67 2 2026 Development of Linear Interpolation System for SMK Model Parameters Evaluated from Cellular-Scale Simulation (LISMEC) and its application to BNCT dosimetry 170 181 EN Takafumi Shigehira Particle Radiation Oncology Research Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University Tubasa Watanabe Particle Radiation Oncology Research Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University Minoru Suzuki Particle Radiation Oncology Research Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University Yuho Hirata Research Group for Radiation Transport Analysis, Nuclear Science and Engineering Center , Japan Atomic Energy Agency (JAEA) Tatsuhiko Ogawa Research Group for Radiation Transport Analysis, Nuclear Science and Engineering Center , Japan Atomic Energy Agency (JAEA) Atsushi Fujimura Department of Cellular Physiology, Neutron Therapy Research Center, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshinori Sakurai Particle Radiation Oncology Research Center, Institute for Integrated Radiation and Nuclear Science, Kyoto University Tatsuhiko Sato Research Group for Radiation Transport Analysis, Nuclear Science and Engineering Center , Japan Atomic Energy Agency (JAEA) Boron neutron capture therapy (BNCT) utilizes high linear energy transfer (LET) ��-particles and 7Li ions generated through the 10B(n, ��)7Li reaction. Precise dosimetry is essential for maximizing therapeutic efficacy while minimizing normal tissue adverse events, considering the microscopic distribution of 10B and cellular structures. Recently, the photon isoeffective dose (DisoE) has been proposed as a more appropriate metric for BNCT treatment planning and can be evaluated using the stochastic microdosimetric kinetic (SMK) model. However, clinical implementation of the SMK model remains challenging due to the difficulty of evaluating its input parameters, which requires computationally intensive radiation transport simulations at the cellular scale. To address this issue, we developed LISMEC (Linear Interpolation System for Stochastic Microdosimetric Kinetic model parameters Evaluated from Cellular-scale simulation), a rapid estimation framework based on precomputed cellular-scale PHITS (Particle and Heavy Ion Transport code System) simulations covering various cell geometries and boron distributions. By applying a linear interpolation algorithm, LISMEC enables the retrieval of SMK model parameters without the need for computationally intensive cellular-scale simulations. The utility of LISMEC, in conjunction with PHITS, was demonstrated through simulations of various irradiation scenarios in reactor-based BNCT. The results showed that DisoE values ranged from 7.4 to 32.7 Gy, even under a fixed macroscopic 10B concentration of 60 ppm. These findings emphasize the importance of incorporating a microscopic distribution of 10B and cellular structures into BNCT treatment planning. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0039-9140 306 2026 Instrument-free quantitative colorimetric analysis using adsorption-band length in a packed silica gel column 129728 EN Sychanh Phonxayxiong Takashi Kaneta Department of Chemistry, Okayama University A simple and instrument-free colorimetric method for quantitative analysis is reported, in which analyte concentration is determined by measuring the length of a colored adsorption band formed in a packed silica gel column. The proposed method employs a miniature silica gel column that acts as a signal transducer after it adsorbs the colored compound from a solution during its flow in the column. The length of this band increases proportionally with analyte concentration, which enables quantitative detection via simple distance measurement. A theoretical model was developed to describe the relationship between solute concentration, adsorption behavior, and band propagation along the column. The principle was validated via the detection of both iron ions and enzyme-mediated glutamic acid. For Fe2+ analysis, the o-phenanthroline complexation method shows a level of sensitivity comparable to that of conventional spectrophotometry, which enables an almost quantitative recovery of trace iron in tap water. The limit of detection (LOD) and the limit of quantification (LOQ) were estimated to be 0.20 ��M and 0.60 ��M for the proposed method and 0.23 ��M and 0.70 ��M for spectrophotometry, respectively. The approach was further extended to glutamate detection using a cascade reaction involving glutamate oxidase and horseradish peroxidase with N-benzoyl leucomethylene blue as the chromogenic substrate. The LOD and the LOQ of the proposed method were 0.08 and 0.25 ��M, and both values are superior to the 0.24 ��M and 0.73 ��M obtained using a microplate reader. By integrating preconcentration with a distance-based readout, this method provides a simple yet highly sensitive analytical platform and establishes distance as a quantitative signal for colorimetric detection. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0304-4203 276 2026 Determination of picomolar to sub-nanomolar trace metals in seawater using an alternative chelating resin 104642 EN Naoya Kanna Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hajime Obata Atmosphere and Ocean Research Institute, The University of Tokyo Yoshiko Kondo Graduate School of Fisheries and Environmental Sciences, Nagasaki University In this study, we investigated the potential use of a chelating resin that immobilizes an amine with an iminodiacetic acid group (InertSep ME-2) for trace-metal analysis in natural seawater. Seven trace metals (Mn, Fe, Co, Ni, Cu, Zn, and Pb) were quantitatively preconcentrated onto the InertSep ME-2 chelating resin, eluted with nitric acid, and analyzed using high-resolution inductively coupled plasma mass spectrometry. The blank values and detection limits obtained using our method were at the sub-nanomolar level for most trace metals. These blank values were generally comparable to, or lower than, those previously reported for other chelating resins, including NOBIAS Chelate PA-1 and Toyopearl AF-Chelate-650 M. The accuracy and precision of our method were confirmed by analyzing reference seawater samples, and the results for the open-water samples were consistent with those obtained in an independent laboratory. The established preconcentration procedure was successfully applied to determine trace metal concentrations in natural seawater collected from the northwestern Pacific Ocean. Our method, which employs the InertSep ME-2 chelating resin, is sufficiently accurate for studying trace metals in open-ocean water at picomolar- to sub-nanomolar-level concentrations. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 2 2026 Impact of Proteinuria on Postoperative Complications Following Colorectal Cancer Surgery 131 139 EN Shunsuke Nakata Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Fumiaki Takatsu Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Yoshihiro Mikuriya Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Tomokazu Kakishita Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Shinji Hato Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Koji Ohta Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Takaya Kobatake Department of Gastroenterological Surgery, National Hospital Organization Shikoku Cancer Center Original Article 10.18926/AMO/70455 Colorectal surgery is associated with a high incidence of postoperative complications regardless of the advances in surgical techniques and multidisciplinary treatment. Proteinuria is common in patients with malignancies, but few studies have investigated the association between preoperative proteinuria and patient prognoses, especially postoperative complications. We investigated the impact of proteinuria on patients undergoing colorectal surgery in a single-center, retrospective cohort study of 767 patients who underwent surgical resection for colorectal cancer between January 2016 and December 2022 at the National Hospital Organization Shikoku Cancer Center. Among them, 81 patients with preoperative proteinuria were compared with the control group of 686 patients without proteinuria. Our analyses revealed that the patients with proteinuria had malnutrition with a significantly lower prognostic nutritional index compared to the no-proteinuria control group (p<0.001). The proteinuria group had a significantly advanced tumor stage (p=0.005), experienced more bleeding during the surgery (p=0.002), and required more transfusions (p<0.001). Postoperative complications were significantly more frequent in the proteinuria group (p=0.03), thus demonstrating that proteinuria was independently associated with postoperative complications (p=0.045). Proteinuria in patients undergoing colorectal cancer surgery can therefore be considered a risk factor for postoperative complications. No potential conflict of interest relevant to this article was reported.

Pharmaceutical Society of Japan Acta Medica Okayama 0918-6158 49 2 2026 Functional Transport Properties of Human Zinc Transporter 1: Kinetics and pH-Dependency 364 370 EN Yuma Yoshioka Department of Molecular Membrane Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takaaki Miyaji Department of Molecular Membrane Biology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Intracellular zinc (Zn2+) homeostasis is essential for physiological and pathological processes and is strictly regulated by Zn2+ transporters. Zinc transporter 1 (ZnT1) is a ubiquitously expressed plasma membrane-localized Zn transporter that exports Zn2+ from the cytoplasm to the extracellular space. However, the functional transport properties regarding kinetics and driving forces of ZnT1 remain debatable. In this study, we established a cell-free proteoliposome assay system and demonstrated that ZnT1 transports Zn2+ with high affinity in pH-dependent and pH-independent manners. The Km and Vmax of pH-dependent Zn2+ transport were 0.40 ��M and 15.13 nmol/min/mg protein, and those of pH-independent Zn2+ transport were 0.52 ��M and 8.88 nmol/min/mg protein (low concentrations of Zn2+), 3.02 ��M and 17.59 nmol/min/mg protein (high concentrations of Zn2+), respectively, suggesting biphasic kinetic components of Zn2+ transport. Even without pH gradient formation, ZnT1 exhibits potent Zn2+ transport activity. In pH dependency, Zn2+ transport activity was higher at an inside pH of 6.0 than at 6.5–7.5 for proteoliposomes, despite the same ��pH of 0.5–1.5. The Zn2+ transport activity decreased at an outside pH of 8.0, despite an increase in ��pH. Although previous studies have proposed that ZnT1-mediated Zn2+ transport activity is driven by a calcium (Ca2+) gradient and not by a pH gradient, Ca2+ does not enhance Zn2+ transport activity in the presence or absence of a pH gradient. These results strongly suggest that ZnT1 protein transports Zn2+ optimally at a specific pH and exports excess intracellular Zn2+ even without ��pH. No potential conflict of interest relevant to this article was reported.

���R��w�o�ϊw�� Acta Medica Okayama 2433-4146 57 3 2026 �n��Ԃł̏��𗬂Ɋւ���l�b�g���[�N���́F�����여�挗�ł̒����ɂ�� 11 40 EN Ryohei Nakamura Natsumi Yokota 10.18926/OER/70262 �@�{�e�ł́C���R���́u�����여��A�g�����s�s���v��2014�N����J�Â���Ă���u�����여��o�ϐ����헪��c�v�ɂ�����Q����̊Ԃ̏��𗬂ɂ‚��Ẵl�b�g���[�N���͂��s�����B�����여��A�g�����s�s���i�����여�挗�j�Ƃ́C���R����������ӂɈʒu���錻�݂̐V���s�C�����s�C���Ўs�C�������C�q�~�s�C��|���C�䌴�s�C����s�C�������C�}���s��10�����̂��Q�����Ă���A�g�����s�s���ł���B�����여�挗�ɂ�����l�b�g���[�N���͂ɍۂ��ẮC��������œW�J����Ă��鎖�Ƃ��W�‚ɕ��ނ��C���ꂼ��̎��ƂɊւ���Q����̊Ԃ̏��𗬂ɂ‚��ăA���P�[�g�������s�����B�l�b�g���[�N�w�W�ɂ‚��Ă͎��Ƃ��ƂɎ������S���Ɣ}��S���̒��S���w�W���C�܂����ƕʂɖ��x�C���ڐ��C���ݐ����Z�o�����B���ƕʂɂ݂�ƁC�ό����Ƃɂ‚��Ă̏��𗬂��ł����ȃl�b�g���[�N�\�������Ă���C�l�b�g���[�N�̎��_�ł͊ό����Ƃ������여�挗���ōł����͓I�ɍs���Ă��鎖�ƂƂ�����B�܂��S���Ƃɂ����ē���̍s����̂⏤�H��c�����͂��߂Ƃ���n��o�ϒc�̓��̒��S���w�W���S�̓I�ɑ傫�Ȓl���Ƃ��Ă���C�l�b�g���[�N�ɂ����ď��𗬂̃n�u����̏W���E���U��̂Ƃ��ċ@�\���Ă��邱�Ƃ����炩�ɂȂ����B���͌��ʂ𓥂܂��C�l�b�g���[�N�̎��_���獂���여�挗�̍��x�̒n��U���ɂ‚��ĂQ�_�񌾂����B�P�‚͎��Ƃɂ���ď��𗬂̃n�u����̏W���E���U��̂���̊Ԃŕ��S���邱�Ƃɂ���āC���ׂĂ̎��ƂŖ��ȃl�b�g���[�N��z�����Ƃ�ڎw�����Ƃł���B�����P�‚͍����여�挗�̏��𗬃l�b�g���[�N�ɑS���Q�����Ă��Ȃ���̂��Ȃ������ƂŁC�S�̓I�ɖ��ȃl�b�g���[�N��ڎw�����Ƃł���B No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2076-3417 16 5 2026 Concentration-Dependent Synergistic Interfacial Interactions Between Multifunctional Acrylate and Silane Coupling Agents in an Organic–Inorganic Nanohybrid Material 2339 EN Yukinori Maruo Department of Prosthodontics, Okayama University Kumiko Yoshihara Health Research Institute, National Institute of Advanced Industrial Science and Technology Masao Irie Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Dental School, Okayama University Naoki Kodama Department of Prosthodontics, Okayama University Mai Yoshizane Department of Occlusal and Oral Functional Rehabilitation, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kentaro Akiyama Department of Occlusal and Oral Functional Rehabilitation, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Synergistic effects of a multifunctional acrylate and a long-chain silane coupling agent were investigated in an organic–inorganic nanohybrid material. We tested the bond strength of nanohybrid composites treated with experimental primers containing silane coupling agents�\3-methacryloxypropyl trimethoxysilane (��-MPTS) or 8-methacryloxyoctyl trimethoxysilane (8-MOTS)�\with or without multifunctional acrylates�\trimethylolpropane triacrylate (A-TMPT) or dipentaerythritol hexaacrylate (A-DPH). Shear bond strength was evaluated after 24 h of water storage at 37 ��C. Untreated control and silane-only groups exhibited low shear bond strengths (e.g., control: 2.4 �} 2.0 MPa) and failed exclusively at the adhesive interface. While addition of A-TMPT did not significantly improve bond strength, addition of A-DPH produced significantly higher shear bond strengths. Highest strength was achieved with 30% 8-MOTS and A-DPH (22.4 �} 6.1 MPa), followed by 20% ��-MPTS and A-DPH (19.0 �} 7.0 MPa), and A-DPH groups produced cohesive failures. Regardless of the silane used (��-MPTS or 8-MOTS), incorporating A-DPH in the primer consistently yielded superior bond strengths, indicating a promising strategy for improved adhesion for such nanohybrid systems. These findings provide new insights into optimizing resin–filler interfacial interactions and may contribute to the development of restorative materials with improved long-term clinical durability. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0732-8893 115 3 2026 Investigation of the cefazolin inoculum effect in blood culture-isolated methicillin-susceptible Staphylococcus aureus strains: A Japanese multicenter study 117345 EN Shinnosuke Fukushima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shuma Tsuji Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Sakura Ogawa Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Norihito Koyanagi Department of Clinical Laboratory, Chutoen General Medical Center Yuji Ito Department of General Internal Medicine, Chutoen General Medical Center Hiroshi Koganemaru Department of Infectious Diseases, Tokyo Metropolitan Institute for Geriatrics and Gerontology Atsushi Yoshida Department of Infectious Diseases, Tokyo Metropolitan Institute for Geriatrics and Gerontology Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Background: Cefazolin inoculum effect (CInE) is a microbiological phenomenon where the MIC of cefazolin against methicillin-susceptible Staphylococcus aureus (MSSA) strains increases with higher bacterial volumes.<br> Method: We retrospectively investigated the prevalence and characteristics of the CInE among MSSA strains isolated from blood cultures at three Japanese hospitals. The collected isolates were screened for blaZ using PCR, and the cefazolin minimum inhibitory concentration (MIC) for the blaZ-positive MSSA isolates was measured at standard and high inoculum volumes. CInE-positive MSSA strains were defined as those with a cefazolin MIC ≥16 ��g/mL at 107 CFU/mL and ≤8 ��g/mL at 105 CFU/mL. In these blaZ-positive strains, we performed blaZ typing and tested a modified nitrocefin-based rapid examination to detect the CInE.<br> Results: We collected 329 MSSA strains isolated from blood cultures. Of these, 96 (29.2%) were positive for the blaZ gene, with the following genotypes: type A (15, 15.6%), type B (3, 3.1%), type C (77, 80.2%), type D (0, 0.0%), and non-type (1, 1.0%). Among 96 blaZ-positive MSSA isolates, 11 exhibited the CInE, all of which harbored blaZ type A. The rapid nitrocefin test detected CInE positivity with high sensitivity (100%), specificity (94.1%), and diagnostic accuracy (94.8%).<br> Conclusion: This study highlighted the low prevalence of CInE-presenting MSSA isolates in Japan. When the cefazolin MIC is ≥1 ��g/mL or the penicillin G MIC is ≥0.25 ��g/mL, the rapid nitrocefin test may be useful for considering the CInE in patients with high bacterial volume MSSA infections. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1999-4923 18 1 2026 Streamlined Radiosynthesis of [18F]Fluproxadine (AF78): An Unprotected Guanidine Precursor Enables Efficient One-Step, Automation-Ready Labeling for Clinical Use 123 EN Xinyu Chen Nuclear Medicine, Faculty of Medicine, University of Augsburg Kaito Ohta Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroyuki Kimura Agency for Health, Safety and Environment, Kyoto University Yusuke Yagi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takanori Sasaki Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoko Nose Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masaru Akehi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiko Yamane Department of Molecular Imaging Research, Kobe City Medical Center General Hospital Rudolf A. Werner Department of Nuclear Medicine, LMU Hospital, and German Cancer Consortium (DKTK), Partner Site Munich, Ludwig-Maximilians-University of Munich Takahiro Higuchi Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: [18F]Fluproxadine (formerly [18F]AF78) is a PET radiotracer targeting the norepinephrine transporter (NET) with potential applications in cardiac, neurological, and oncological imaging. Its guanidine moiety, while essential for NET binding, presents major radiosynthetic challenges due to high basicity and the harsh deprotection conditions required for protected precursors. Previous methods relied on multistep procedures, strong acids, and complex purification, limiting clinical translation. This study aimed to develop a practical one-step radiosynthesis suitable for routine and automated production. Methods: A direct SN2-type nucleophilic [18F]fluorination was performed using an unprotected guanidine precursor to eliminate deprotection steps. Reaction parameters, including the base system, solvent composition, precursor concentration, and temperature, were optimized under conventional and microwave heating. Radiochemical conversion (RCC) and operational robustness were evaluated, and purification strategies were assessed for automation compatibility. Results: Direct [18F]fluorination using the unprotected precursor reduced the total synthesis time to 60–70 min. Optimal conditions employed a tert-butanol/acetonitrile (4:1) solvent system with K2CO3/Kryptofix222, affording RCC up to 33% under conventional heating. Microwave irradiation further improved efficiency, achieving RCC of up to 64% within 1.5 min at 140 ��C. The method showed broad tolerance to variations in the base molar ratio and precursor concentration and enabled isocratic HPLC purification. Conclusions: This one-step radiosynthesis overcomes longstanding challenges in [18F]fluproxadine production by eliminating harsh deprotection and enabling high-yield, automation-ready synthesis, thereby improving clinical feasibility. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2589-0042 28 9 2025 Extensive urine production in euryhaline red stingray for adaptation to hypoosmotic environments 113274 EN Naotaka Aburatani Atmosphere and Ocean Research Institute, The University of Tokyo Wataru Takagi Atmosphere and Ocean Research Institute, The University of Tokyo Marty Kwok-Shing Wong Atmosphere and Ocean Research Institute, The University of Tokyo Nobuhiro Ogawa Atmosphere and Ocean Research Institute, The University of Tokyo Shigehiro Kuraku Department of Genomics and Evolutionary Biology, National Institute of Genetics Mana Sato Department of Genomics and Evolutionary Biology, National Institute of Genetics Kazuhiro Saito Ushimado Marine Institute, Faculty of Science, Okayama University Waichiro Godo Ushimado Marine Institute, Faculty of Science, Okayama University Tatsuya Sakamoto Ushimado Marine Institute, Faculty of Science, Okayama University Susumu Hyodo Atmosphere and Ocean Research Institute, The University of Tokyo Maintaining water balance is a prerequisite for all organisms. Euryhaline elasmobranchs face the severest water-influx potential in fresh water (FW), as they retain high concentrations of urea even in hypotonic environments. To elucidate how they overcome this osmotic challenge, we assessed urine output in conscious euryhaline red stingrays (Hemitrygon akajei). Following acclimation to 5% diluted seawater, the stingrays increased urinary output by 87-fold�\the greatest change observed in vertebrates�\partly due to 6.8-fold increase in glomerular filtration rate (GFR). In the nephron, expressions of Aquaporin-1 (Aqp1), Aqp3, and Aqp15 were strongly downregulated in FW, indicating that tubular diuresis bridges the gap between GFR and final urine volume. Meanwhile, FW-acclimation upregulated Aqp1 and Aqp4 in the distinct bundle structure, which promotes urea reabsorption. Euryhaline elasmobranchs resolve the huge osmotic challenge of FW by excreting massive amounts of water and retaining osmolytes including urea through coordinated regulation of GFR and Aqp expressions. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0003-9861 779 2026 Comparison of bioavailability of quercetin and its structural analogs in mice 110775 EN Nozomi Maeda Graduate School of Environmental and Life Science, Okayama University Atsushi Hashimoto Graduate School of Environmental and Life Science, Okayama University Ryosei Morita Graduate School of Environmental and Life Science, Okayama University Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Toshiyuki Nakamura Graduate School of Environmental and Life Science, Okayama University Flavonoids are thought to provide beneficial effects on health. However, there are still uncertainties regarding their bioavailability. In this study, we investigated the bioavailability of 6 flavonoids, galangin, kaempferol, quercetin, myricetin, fisetin, and luteolin, by oral administration to mice. Analysis of plasma concentrations of free flavonoids after deconjugation by LC-MS/MS revealed that all flavonoids were rapidly absorbed after administration. Among 6 flavonoids, kaempferol and fisetin showed high absorbed amounts in blood plasma. With the LogP value of the two flavonoids as the maximum value, the amount absorbed decreased for both lower and higher LogP values. The results of the tissue distribution of galangin, kaempferol, and quercetin suggested that the order of fastest movement from the stomach to the small intestine was kaempferol > quercetin > galangin. In addition, the amount of kaempferol and quercetin distributed in the liver was greater than that of galangin. These results suggest that the bioavailability of flavonoids varies with the slight structural differences, possibly due to differences in their rapid accessibility to the small intestine that is the primary site of absorption and metabolism within the body. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 80 1 2026 Effective Treatment of Advanced Hepatocellular Carcinoma with Extensive Peritoneal Dissemination Using Lenvatinib 69 74 EN Shinya Wakatsuki Department of Obstetrics and Gynecology, Kochi Health Sciences Center Shinya Sakamoto Department of Gastroenterological Surgery, Kochi Health Sciences Center Akiko Ueno Department of Obstetrics and Gynecology, Kochi Health Sciences Center Takaomi Namba Department of Obstetrics and Gynecology, Kochi Health Sciences Center Yorito Yamamoto Department of Obstetrics and Gynecology, Kochi Health Sciences Center Manabu Matsumoto Department of Diagnostic Pathology, Kochi Health Sciences Center Jun Iwata Department of Diagnostic Pathology, Kochi Health Sciences Center Takehiro Okabayashi Department of Gastroenterological Surgery, Kochi Health Sciences Center Case Report 10.18926/AMO/70075 Patients with hepatocellular carcinoma (HCC) and extensive peritoneal dissemination generally have a poor prognosis and are often resistant to systemic therapy. We report the case of a 47-year-old woman with HCC and massive peritoneal dissemination who presented with malignant ascites requiring repeated cell-free and concentrated ascites reinfusion therapy and peritoneovenous shunt placement, as well as malignant pleural effusion requiring pleurodesis. Combined immunotherapy with durvalumab/tremelimumab was initiated;however, disease progression was observed after three treatment courses, prompting a switch to lenvatinib therapy. Two months after initiation of lenvatinib, CT imaging demonstrated complete disappearance of arterial enhancement in the primary hepatic lesion, along with reduction in the size of peritoneal dissemination nodules. Thirteen months after switching to lenvatinib (16 months after the initial diagnosis), the alpha-fetoprotein level continued to decrease, and the disease remained stable under treatment. Despite the extremely high tumor burden, lenvatinib achieved disease stabilization and symptomatic improvement. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0031-9317 178 1 2026 Reactive Carbonyl Species Mediate Isothiocyanate Signaling Pathway in Arabidopsis thaliana Guard Cells e70775 EN Sumaiya Farzana Graduate School of Environmental and Life Science, Okayama University Md. Moshiul Islam Graduate School of Environmental and Life Science, Okayama University Toshiyuki Nakamura Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University Jun'ichi Mano Science Research Center, Yamaguchi University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Our previous results demonstrated that depletion of glutathione (GSH) rather than elevation of levels of reactive oxygen species (ROS) is highly correlated with the decrease in stomatal aperture induced by isothiocyanates (ITCs), although ROS is considered a key second messenger in stomatal closure, suggesting that another signal component regulates stomatal apertures along with GSH depletion. This study, using Arabidopsis, clarified that reactive carbonyl species (RCS), especially acrolein and 4-hydroxy-(E)-2-nonenal, are determinants of stomatal aperture responses to ITCs. All tested ITCs, allyl isothiocyanate (AITC), sulforaphane (SFN), benzyl isothiocyanate (BITC), and phenethyl isothiocyanate (PEITC), significantly induced stomatal closure, which was inhibited by the RCS scavengers, carnosine and pyridoxamine. The RCS scavengers suppressed ITC-induced depletion of GSH but not elevation of ROS levels. All tested ITCs (AITC, SFN, BITC, and PEITC) increased levels of RCS and non-RCS aldehydes in the epidermal tissues. However, acrolein, 4-hydroxy-(E)-2-nonenal, crotonaldehyde, and (E)-2-pentenal induced stomatal closure at 10 and 100 ��M, whereas propionaldehyde, butyraldehyde, and n-pentanal did not at concentrations up to 100 ��M. Acrolein and 4-hydroxy-(E)-2-nonenal more effectively induced stomatal closure and GSH depletion than crotonaldehyde and (E)-2-pentenal did. The contents of RCS were more strongly correlated with GSH levels and stomatal closure than with ROS levels. These results suggest that RCS, especially acrolein and 4-hydroxy-(E)-2-nonenal, acts as key regulators of stomatal closure in guard cells in response to ITCs. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1757-4749 18 1 2026 Sodium butyrate augments the antibacterial activity of tetracycline against clinical isolates of multidrug-resistant Vibrio cholerae 9 EN Sushmita Kundu Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections Sourin Alu Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections Abhishek Singh Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections Animesh Gope Division of General Medicine, ICMR- National Institute for Research in Bacterial Infections Ranjan Kumar Nandy Division of Bacteriology, ICMR- National Institute for Research in Bacterial Infections Asish K. Mukhopadhyay Division of Bacteriology, ICMR- National Institute for Research in Bacterial Infections Shin-ichi Miyoshi Division of Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nabendu Sekhar Chatterjee Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections Sushmita Bhattacharya Division of Biochemistry, ICMR- National Institute for Research in Bacterial Infections Background Antibiotic resistance poses a major challenge in treating Vibrio cholerae infections. One promising method to counter resistance is the co-administration of antibiotics with non-antibiotic adjuvants to enhance their efficacy. This study investigated the combined action of sodium butyrate (SB) and tetracycline on tetracycline-resistant V. cholerae strains.<br> Results The combined activity of SB and antibiotics was assessed on eight V. cholerae clinical isolates using the Fractional Inhibitory Concentration Index (FICI), with SB-Tetracycline showing strong synergy (FICI: 0.09–0.5). Functional and mechanistic studies, including time-kill kinetics, live/dead staining, SEM-based morphological analysis, and fluorometric assays, demonstrated a synergistic antibacterial effect of SB and Tetracycline. This effect was associated with increased membrane permeability, disruption of membrane integrity, dissipation of the proton motive force, and suppression of efflux activity. These changes collectively led to membrane damage, enhanced intracellular accumulation of Tetracycline, decreased intracellular ATP levels, and ultimately, bacterial cell death. Moreover, GM1-CT ELISA and fluorescence microscopy revealed the synergistic anti-virulence activity of the SB- Tetracycline combination. Finally, the combination of SB and Tetracycline showed enhanced efficacy in animal models compared with monotherapy.<br> Conclusion: The observed SB-Tetracycline synergy provides a promising therapeutic approach to overcome tetracycline resistance in V. cholerae, offering a potential adjunct strategy for the management of antibiotic-resistant cholera infections. No potential conflict of interest relevant to this article was reported.

Proceedings of the National Academy of Sciences Acta Medica Okayama 0027-8424 123 6 2026 A nuclear CobW/WW-domain factor represses the CO2-concentrating mechanism in the green alga Chlamydomonas reinhardtii e2518136123 EN Daisuke Shimamura Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Junko Yasuda Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Yosuke Yamahara Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Hirobumi Nakano Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Shin-Ichiro Ozawa Institute of Plant Science and Resources, Okayama University Ryutaro Tokutsu Graduate School of Science, Division of Biological Sciences, Kyoto University Ayumi Yamagami Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Tomonao Matsushita Graduate School of Science, Division of Biological Sciences, Kyoto University Yuichiro Takahashi Research Institute for Interdisciplinary Science, Okayama University Takeshi Nakano Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Hideya Fukuzawa Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Takashi Yamano Graduate School of Biostudies, Division of Integrated Life Science, Kyoto University Microalgae induce a CO2-concentrating mechanism (CCM) to maintain photosynthesis when CO2 is limited. Because this system consumes a substantial portion of photosynthetically generated ATP, its suppression when CO2 levels rise is critical for energy balance, yet the underlying mechanism remains unclear. Here, we identify a nuclear repressor of the CCM in the green alga Chlamydomonas reinhardtii. A pull-down screen for interacting partners of the master activator CCM1/CIA5 revealed an uncharacterized protein that tightly associates with CCM1. This protein, CCM1-binding protein 1 (CBP1), combines a CobW/CobW_C GTP-binding metallochaperone module with a WW-domain characteristic of protein–protein interactions. CBP1 colocalizes and interacts with CCM1 in the nucleus regardless of CO2 conditions. Disruption of CBP1 does not affect growth or CCM induction under CO2 limitation but derepresses 27 of 41 CCM1-dependent low-CO2 inducible genes under high-CO2 conditions. These include the periplasmic and intracellular carbonic anhydrases (CAH1 and LCIB) and inorganic carbon transporters/channels (LCIA, LCI1, BST1, and BST3). Consistently, cbp1 mutants accumulate CAH1 and LCIB proteins and exhibit 40% higher inorganic carbon affinity under high-CO2 conditions; this phenotype is rescued by CBP1 complementation or by acetazolamide treatment. Crucially, cbp1 mutants exhibit significant growth delays under high-CO2 conditions, especially when light is limiting, providing direct evidence that CBP1-mediated repression is essential for energy conservation. Thus, CBP1 prevents unnecessary CCM activity when CO2 is abundant, acting upstream of both transporter/channel and carbonic anhydrase modules. Our findings suggest a regulatory mechanism potentially linking zinc-dependent protein chemistry to CCM gene repression, providing insights into energy-efficient CO2 sensing in aquatic photosynthetic organisms. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0041-1132 2026 Pediatric autologous peripheral blood stem cell collection without heparin using a highly concentrated sodium citrate anticoagulant: A retrospective comparison with standard ACD-A EN Keiko Fujii Department of Hematology, Okayama University Hospital Wataru Kitamura Department of Hematology, Okayama University Hospital Kana Washio Department of Pediatrics, Okayama University Hospital Kazuhiro Ikeuchi Department of Hematology, Okayama University Hospital Joji Shimono Department of Hematology, Okayama University Hospital Hiroyuki Murakami Department of Hematology, Okayama University Hospital Fumio Otsuka Division of Clinical Laboratory, Okayama University Hospital Yoshinobu Maeda Department of Hematology, Okayama University Hospital Nobuharu Fujii Department of Hematology, Okayama University Hospital Background: Heparin combined with sodium citrate has been used in leukocytapheresis for pediatric patients. Since 2022, we have performed leukocytapheresis using a highly concentrated sodium citrate solution (HSC, 5.32%) instead of acid citrate dextrose solution A (ACD-A). We conducted this study to determine whether HSC use reduces run time and the total amount of anticoagulant solution in children.<br> Study Design and Methods: We retrospectively analyzed data from consecutive autologous peripheral blood stem cell harvests (auto-PBSCHs) between June 2012 and May 2025, including patient characteristics, mobilization methods, protocol used, anticoagulant type, run time, total anticoagulant solution volume, and collection efficiency.<br> Results: Auto-PBSCH was performed using the mononuclear cell collection (MNC) protocol in 28 procedures and the continuous MNC protocol in 20 procedures. ACD-A was used in 35 procedures and HSC in 13. The run time was significantly shorter (204 [range, 117–302] vs. 157 min [range, 103–227], p = .02) in the HSC group and also confirmed in multivariable regression analysis (coefficient, �|55.6; 95% confidence interval, �|106.2 to �|5.04; p = .03). In a subgroup analysis of cMNC procedures, CD34+ collection efficiency showed a strong negative correlation with the proportion of run time devoted to establishing the initial interface (r = �|.73, p = .0003).<br> Conclusion: Delays in establishing the initial interface can reduce the duration of the effective MNC collection phase and may negatively affect collection efficiency. Careful attention to the initial interface phase is therefore warranted when using HSC. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1349-4147 54 1 2026 Mycobacterium mageritense-associated refractory cutaneous infection and lymphadenitis in an immunocompetent adult: insights from genomic sequencing 19 EN Shinnosuke Fukushima Department of Bacteriology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Jumpei Uchiyama Department of Bacteriology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Yoshio Kawakami Department of Dermatology, Okayama University Hospital Yoshiko Matsuura Konohana Dermatology Clinic Satoru Sugihara Department of Dermatology, Okayama University Hospital Shin Morizane Department of Dermatology, Okayama University Hospital Poowadon Muenraya Department of Bacteriology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Background Nontuberculous mycobacteria are increasingly recognized as causes of chronic and refractory skin and soft tissue infections, even in individuals without immunodeficiency. Among them, Mycobacterium mageritense is a rare, rapidly growing species that can lead to persistent lesions requiring prolonged antimicrobial therapy. Reports of M. mageritense infections involving both the skin and regional lymph nodes are limited, and this case adds new clinical and genomic insights.<br> Case presentation A 48-year-old previously healthy man presented with a slowly enlarging cutaneous lesion on his lower leg and ipsilateral inguinal lymphadenitis. Empirical antibacterial therapy with ��-lactams and macrolides was ineffective. Wound cultures subsequently grew M. mageritense, confirmed by whole-genome sequencing. Several antimicrobial regimens were attempted, and the final successful therapy consisted of oral levofloxacin and minocycline for 4 months, leading to complete clinical resolution. Genomic analysis identified resistance-related genes, including erm(40), aac(2��)-Ib, tet(V), and RbpA, although in vitro minimum inhibitory concentrations showed variable susceptibility. Phylogenetic comparison revealed that the isolate was closely related to previously reported M. mageritense strains from Japan.<br> Conclusions This case demonstrates that M. mageritense can cause cutaneous infection with secondary lymphadenitis in an immunocompetent host. Accurate species identification using molecular or genomic methods and selection of appropriate combination antibiotic therapy based on susceptibility testing are crucial for successful management of such infections. No potential conflict of interest relevant to this article was reported.

Japan Oil Chemists' Society Acta Medica Okayama 1345-8957 74 11 2025 Bioconversion and Metabolic Fate of the n-1 Polyunsaturated Fatty Acids, 6,9,12,15- Hexadecatetraenoic (C16:4 n-1) and 8,11,14,17- Octadecatetraenoic (C18:4 n-1) Acids, in HepG2 Cells 1023 1032 EN Koki Sugimoto Faculty of Food and Nutritional Sciences, Toyo University Hideto Nishiguchi Faculty of Chemistry, Materials, and Bioengineering, Kansai University Ryota Hosomi Faculty of Chemistry, Materials, and Bioengineering, Kansai University Toshifumi Tanizaki Bizen Chemical Co., Ltd. Tadahiro Tsushima Bizen Chemical Co., Ltd. Naomichi Baba Bizen Chemical Co., Ltd. Yoshihisa Misawa Bizen Chemical Co., Ltd. Ziyi Wang Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mitsuaki Ono Department of Oral Rehabilitation and Regenerative Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Murakami Department of Hygiene and Public Health, Kansai Medical University Seiji Kanda Department of Hygiene and Public Health, Kansai Medical University Kenji Fukunaga Faculty of Chemistry, Materials, and Bioengineering, Kansai University Fish oil contains not only major fatty acids with double bonds at the n-3, n-6, n-7, and n-9 positions but also those with a double bond at the n-1 position, such as 6,9,12,15-hexadecatetraenoic acid (C16:4 n-1; HDTA). However, intracellular bioconversion and metabolic fate of n-1 polyunsaturated fatty acids (PUFA) remain unclear. Therefore, in this study, we aimed to assess the intracellular bioconversion and metabolic fate of HDTA and its metabolite, 8,11,14,17- octadecatetraenoic acid (C18:4 n-1; ODTA), using HepG2 cells. Based on the results of cell viability and cytotoxicity assays for HDTA and ODTA, the concentration of each fatty acid supplemented in the experiments was set at 10 ��M. HepG2 cell culture with HDTA revealed C20:4 n-1 as a new HDTA metabolite, along with previously reported ODTA. Our findings suggest that the HDTA taken up by HepG2 cells undergoes elongation to form ODTA and C20:4 n-1. Following supplementation with HDTA, ODTA, and 5,8,11,14,17-eicosapentaenoic acid (C20:5 n-3; EPA), fatty acids disappeared from the culture medium within 24 h. Notably, the total relative level of HDTA and its metabolites, including ODTA and C20:4 n-1 in HDTA- and ODTA-supplemented cells were significantly lower than the total relative level of EPA and its metabolites, including 7,10,13,16,19-docosapentaenoic acid (C22:5 n-3), C24:6 n-3, and 4,7,10,13,16,19-docosahexaenoic acid (C22:6 n-3) in the EPA-supplemented cells. Except for a portion that was intracellularly elongated, most HDTA was taken up by HepG2 cells and may undergo rapid fatty acid ��-oxidation. However, RNA-sequencing and real-time polymerase chain reaction analysis revealed no significant changes in fatty acid ��-oxidation–related gene expression levels in HDTA-supplemented cells. Collectively, these results provide novel insights into the intracellular bioconversion mechanisms and metabolic fate of HDTA and ODTA in HepG2 cells, suggesting that the metabolic fate of n-1 PUFA is distinct from that of common PUFA. No potential conflict of interest relevant to this article was reported.

Spandidos Publications Acta Medica Okayama 2049-9450 23 5 2025 Prolonged exposure to axitinib alters the molecular profile of Caki‑2 renal cell carcinoma cells 101 EN Yuko Nakayama Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University Aya Ino Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University Kazuhiro Yamamoto Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kohji Takara Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Hyogo Medical University Axitinib, an oral second‑generation multitargeted tyrosine kinase inhibitor, is used as a second‑line treatment for metastatic renal cell carcinoma (RCC). However, patients often develop resistance after initial responsiveness, necessitating the elucidation of the underlying resistance mechanisms. Therefore, the present study aimed to investigate the mechanisms underlying axitinib resistance using the Caki‑2 human papillary RCC model cells. Cells tolerating 0.1 µM axitinib were designated as Caki/AX cells. Cell viability was assessed using the water‑soluble tetrazolium salt assay. Notably, the 50% inhibitory concentration (IC50) values of axitinib and sunitinib were significantly higher in Caki/AX cells than those in Caki‑2 cells, indicating 2.83‑ and 1.2‑fold resistance, respectively. By contrast, the IC50 values of sorafenib and erlotinib were decreased in Caki/AX cells. Moreover, Caki/AX cells showed resistance to everolimus, temsirolimus and rapamycin, and decreased sensitivity to vinblastine, vincristine, paclitaxel, doxorubicin and SN‑38 compared with Caki‑2 cells. Notably, etoposide, 5‑fluorouracil, cisplatin and carboplatin sensitivities were comparable in both cell types. Reverse transcription‑quantitative polymerase chain reaction (PCR) analysis revealed that the mRNA levels of the ATP‑binding cassette subfamily B member 1 and subfamily G member 2 were significantly higher in Caki/AX cells than those in Caki‑2 cells. A PCR array related to vascular endothelial growth factor signalling showed that the mRNA levels of FIGF (also known as vascular endothelial growth factor D) and sphingosine kinase 1 were upregulated, whereas those of Rac family small GTPase 2 were downregulated in Caki/AX cells. Overall, these findings suggested that the upregulation of the ATP‑binding cassette subfamily B member 1, FIGF and sphingosine kinase 1 mRNA levels, and downregulation of the Rac family small GTPase 2 mRNA levels may contribute to acquired resistance in Caki/AX cells. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0300-8126 2025 Hospital-acquired pneumonia caused by multidrug-resistant Streptococcus pneumoniae serotype 15A EN Hidemasa Akazawa Department of Infectious Diseases, Okayama University Hospital Shinnosuke Fukushima Department of Infectious Diseases, Okayama University Hospital Kenta Nakamoto Department of Infectious Diseases, Okayama University Hospital Kohei Oguni Department of Infectious Diseases, Okayama University Hospital Madoka Shimbe Department of Infectious Diseases, Okayama University Hospital Bin Chang Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security Yukihiro Akeda Department of Bacteriology I, National Institute of Infectious Diseases, Japan Institute for Health Security Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Background Streptococcus pneumoniae remains a common cause of community-acquired pneumonia but is an infrequent pathogen in hospital-acquired pneumonia (HAP). Non-vaccine serotypes of multidrug-resistant (MDR) S. pneumoniae strains have been emerging globally, posing an increased risk of nosocomial infection.<br> Case A 71 year-old man developed pneumonia on postoperative day 4 following spinal fusion surgery. Despite initial treatment with ampicillin/sulbactam, his condition deteriorated, requiring ICU admission and mechanical ventilation. Microbiological testing confirmed S. pneumoniae as a causative pathogen, and ceftriaxone was empirically administered based on the local antibiogram. However, antimicrobial susceptibility testing revealed resistant profiles to penicillin (minimum inhibitory concentration [MIC], 8 µg/mL), ceftriaxone (MIC, 16 µg/mL), meropenem (MIC, 1 µg/mL), macrolides, and clindamycin, while demonstrating susceptibility to levofloxacin and vancomycin. The therapeutic regimen was subsequently adjusted to levofloxacin, resulting in clinical improvement. The isolate was later identified as serotype 15A, sequence type 63 (ST63).<br> Conclusion This case highlights that MDR S. pneumoniae can cause early-onset HAP and may not be covered by standard empiric therapies, emphasizing the need for careful evaluation of treatment response. Continued surveillance of infections caused by vaccine-escape clones like MDR serotype 15A is essential, given their increasing clinical relevance. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2772-7076 16 2025 Should Japanese athletes undergo booster vaccination for pertussis? 100718 EN Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Pertussis, a highly contagious respiratory infection caused by Bordetella pertussis, has demonstrated a global resurgence in the post–COVID-19 era, with the emergence of macrolide-resistant strains. In Japan, the routine immunization schedule for pertussis remains limited compared with international standards, leaving young populations under-immunized and at elevated risk of infection. Despite international recommendations for booster vaccinations during adolescence, Japan currently provides only a four-dose primary series during infancy, without subsequent boosters. This immunization gap possibly increases the vulnerability of Japanese athletes to pertussis. Persistent cough can significantly impair athletic performance for weeks to months, posing substantial challenges to professional sports teams. To protect athletes�f health and performance capacity and prevent team-wide outbreaks, it is imperative to consider pertussis booster immunizations in Japan, especially for elite athletes. However, DTaP (diphtheria, tetanus, and acellular pertussis) (TRIBIKⓇ) is the only available vaccine in Japan, which contains higher antigen concentrations than the internationally used Tdap (tetanus, diphtheria, pertussis) vaccines (ADACEL™ and BOOSTRIXⓇ): the antigen contents of pertussis toxin, filamentous hemagglutinin, and diphtheria toxin in TRIBIKⓇ, ADACEL™, and BOOSTRIXⓇ are 23.5 µg/23.5 µg/≤15 µg, 2.5 µg/5 µg/2 µg, and 8 µg/8 µg/2.5 µg, respectively. These differences result in more severe local adverse effects in vaccinees and would complicate booster strategies in Japan. Aligning Japan�fs immunization policies with international practices represents a critical step toward ensuring individual health and public safety in increasingly globalized sports environments. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0009-2541 695 2025 Flash vaporization and migration of iodine in the oceanic plate subduction zone 123031 EN Noriyuki Suzuki Department of Earth and Planetary Sciences, Faculty of Science, Hokkaido University Jun Kameda Institute for Planetary Materials, Okayama University Miki Amo Geology and Geophysics Division, Technology Department, Japan Organization for Metals and Energy Security Crustal fluids in subduction zones, such as subsurface aquifers, submarine seeps, and gas hydrate waters, are often rich in iodine (I2) and methane (CH4). Large-scale aquifers in the Kanto subduction zone, where the Pacific Plate (PAC) and the Philippine Sea Plate (PHS) are subducting, also exhibit high concentrations of I2 and CH4. However, the origin and behavior of I2 in the subduction zone are unclear, and its coexistence with CH4 remains unresolved. To investigate this, we compiled the I2 phase diagram under high-pressure and high-temperature (P–T) conditions to predict its physicochemical properties in the subduction zone. We then applied the P–T paths of subducted PAC and PHS sediments to the I2 phase diagram. Our findings reveal that I2 can exist as a liquid in the young and hot PHS subduction zone. Transient decompressions during earthquake ruptures can cause liquid iodine to flash-vaporize and be expelled from subducted sediments. Along with I2, thermogenic CH4 and hydrogen (H2) generated in the subducted sediments are also released and transported upward, likely by slab-dehydrated fluids. Additionally, H2 may enhance microbial CH4 production through hydrogenotrophic methanogenesis. In subduction zones of young and hot oceanic plates such as the PHS, crustal fluids are enriched in I2 and coexist with CH4 owing to the simultaneous expulsion of I2, CH4, and H2 from the same subducted sediments and their migration via deep fluids. Large subsurface aquifers can act as traps and reservoirs for migrating I2 and CH4, forming large-scale I2 and CH4 deposits. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0312-5963 64 12 2025 Evaluation of Fentanyl-Emerged Adverse Events and Pharmacokinetics in Neonates: A Physiologically Based Pharmacokinetic Modeling Approach 1811 1825 EN Walaa Yousef Bassyouni Mahdy Department of Pharmacy, Kobe University Hospital Kazuhiro Yamamoto Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Risa Joji Department of Pharmacy, Kobe University Hospital Mari Hashimoto Department of Pharmacy, Kobe University Hospital Ruka Nakasone Department of Pediatrics, Graduate School of Medicine, Kobe University Kazumichi Fujioka Department of Pediatrics, Graduate School of Medicine, Kobe University Kotaro Itohara Department of Pharmacy, Kobe University Hospital Yumi Kitahiro Department of Pharmacy, Kobe University Hospital Tomohiro Omura Department of Pharmacy, Kobe University Hospital Ikuko Yano Department of Pharmacy, Kobe University Hospital Background Despite its common use for analgesia in neonatal intensive care units, the optimal dosing and safety profile of fentanyl, particularly regarding suspected fentanyl-emerged adverse events (FEAEs), such as hypotension, desaturation, and oliguria, are not well-defined.<br> Objective This study aimed to develop an optimal therapeutic monitoring and dosing strategy for fentanyl for neonates. A physiologically based pharmacokinetic (PBPK) model for predicting fentanyl pharmacokinetics across various populations, including preterm and term neonates, was developed, and the relationship between predicted fentanyl exposure and FEAE incidence in neonates was assessed.<br> Methods A PBPK model was developed and validated against the observed values in the literature. The model�fs predictive accuracy for fentanyl pharmacokinetics and association with FEAE incidence in an external retrospective cohort of Japanese neonates was evaluated using the predicted concentrations and pharmacokinetic parameters estimated by PBPK simulation.<br> Results The PBPK model exhibited reasonable predictive performance for serum fentanyl concentrations in actual neonatal patients (mean error: 9.27% [standard error: 5.06%], root mean squared error: 54.7%). The incidence of any FEAE, particularly oxygen desaturation, was associated with the fentanyl concentration-to-dose ratio, but not with some exposure parameters, such as the area under the curve and maximum concentration. The recommended reduced infusion rate allowed serum fentanyl concentrations to fall within the ranges established by the reported values and our data.<br> Conclusions Our PBPK model and proposed dosing strategy may contribute to safer and more effective fentanyl use in neonates. No potential conflict of interest relevant to this article was reported.

Ceramic Society of Japan Acta Medica Okayama 1348-6535 134 1 2026 Preparation of brookite-type titanium dioxide particle layer on titanium surfaces via hydrothermal treatment and evaluation of in vitro apatite-forming ability 24 30 EN Satoshi Hayakawa Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yushi Nakamoto Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Seiya Kojima Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Takuya Kataoka Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University Tomohiko Yoshioka Faculty of Interdisciplinary Science and Engineering in Health Systems, Okayama University In this study, we prepared a brookite-type titanium dioxide particle layer on the surface of titanium substrates via hydrothermal treatment in aqueous urea solutions containing sodium chloride (NaCl) and examined its in vitro apatite-forming ability. Increasing the urea concentration suppressed the formation of anatase-type titanium dioxide on the titanium substrate, forming a particle layer composed of pure brookite-type titanium dioxide. The size and packing density of brookite-type titanium dioxide particles formed on the titanium substrate increased with the NaCl concentration in a 7.0 mol·dm�|3 urea solution. When titanium substrates hydrothermally treated in aqueous solutions of 7.0 mol·dm�|3 urea and 2.0 mol·dm�|3 NaCl were soaked in a simulated body fluid for various periods up to 7 d, the substrate surface was densely covered with hemispherical apatite particles (5.3 µm in diameter) within 3 d, indicating that the brookite-type titanium dioxide particle layer had an excellent apatite-forming ability comparable to that of the anatase-type titanium dioxide particle layer. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0167-5273 445 2026 Cardiac characteristics of Fabry disease from baseline enrolment data in a nationwide prospective Japanese registry 134071 EN Toru Kubo Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University Yuichiro Maekawa Division of Cardiology, Internal Medicine III, Hamamatsu University School of Medicine Kenichi Hongo Division of Cardiology, Department of Internal Medicine, The Jikei University School of Medicine Saori Yamamoto Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine Yasuhiro Izumiya Department of Cardiovascular Medicine, Osaka Metropolitan University, Graduate School of Medicine Hiroyuki Yamakawa Department of Cardiology, Keio University School of Medicine Toshiyuki Yano Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine Koji Higuchi Department of Cardiovascular Medicine and Hypertension, Graduate School of Medical and Dental Sciences, Kagoshima University Yuki Kuramoto Department of Cardiovascular Medicine, The University of Osaka Graduate School of Medicine Naoki Nakagawa Division of Cardiology and Nephrology, Department of Internal Medicine, Asahikawa Medical University Masashi Amano Department of Heart Failure and Transplantation, National Cerebral and Cardiovascular Center Yu Yamada Department of Cardiology, Institute of Medicine, University of Tsukuba Masayoshi Oikawa Department of Cardiovascular Medicine, Fukushima Medical University Yuichiro Iida Department of Cardiovascular Medicine, Kitasato University School of Medicine Kenichi Tsujita Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University Yuya Matsue Department of Cardiovascular Biology and Medicine, Juntendo University Graduate School of Medicine Hideo Izawa Department of Cardiology, Fujita Health University Atsushi Suzuki Department of Cardiology, Tokyo Women's Medical University Yuji Nagatomo Department of Cardiology, National Defense Medical College Toshiyuki Nagai Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University Keisuke Kida Department of Pharmacology, St. Marianna University School of Medicine Kazuto Nakamura Department of Cardiovascular Medicine, University of Yamanashi, Faculty of Medicine Kazufumi Nakamura Center for Advanced Heart Failure, Okayama University Hospital Hiroki Ikenaga Department of Cardiovascular Medicine, Hiroshima University Graduate School of Biomedical and Health Sciences Takahiro Kanda Department of Internal Medicine, Division of Cardiology, Hamamatsu Red Cross Hospital Yoshiharu Kinugasa Department of Cardiovascular Medicine and Endocrinology and Metabolism, Faculty of Medicine, Tottori University Hiromasa Ito Department of Cardiology, Mie University Hospital Kenji Onoue Department of Cardiovascular Medicine, Nara Medical University Hiromitsu Kanamori Department of Cardiology, Gifu University Graduate School of Medicine Hiroaki Kitaoka Department of Cardiology and Geriatrics, Kochi Medical School, Kochi University Background: Fabry disease (FD) is an important disease in the cardiovascular field because a significant proportion of patients with FD die from cardiac lesions.<br> Methods: A multicenter prospective registration study of patients with FD throughout Japan was designed. The baseline clinical characteristics of 175 patients are presented here.<br> Results: The mean ages at enrolment and at diagnosis were 52 �} 16 and 43 �} 18 years, respectively, with men accounting for 38 % of the patients. In the cohort, 24 % of the patients had the classical hemizygote male type, whereas 14 % had the late-onset male type, and 62 % had the heterozygote female type. On electrocardiography data at enrolment in 92 patients with left ventricular hypertrophy (LVH) (maximum LV wall thickness > 12 mm), 12 % showed a short PQ interval (< 120 msec), and 33 % had a short PendQ interval (≤ 40 msec). The Sokolow-Lyon voltage was high (6.1 �} 13.1 mv). Regarding the distribution of LVH patterns, 77 % of the patients showed concentric diffuse LVH, 16 % of the patients had asymmetric septal hypertrophy, and 1 % of the patients had hypertrophy confined to the LV apex. With regard to implantation of cardiac devices, permanent pacemakers had been implanted in 5 % of the patients and defibrillators had been implanted in 12 patients (7 %), for primary prevention in nine patients and for secondary prevention in three patients.<br> Conclusion: As the first large-scale prospective registry of FD patients in Japan, this study has provided valuable baseline data for the cardiac features and management of FD. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0169-555X 468 2025 Surface exposure ages of middle–late Pleistocene marine and fluvial terraces along the northern and southern Sanriku coasts, Northeast Japan 109497 EN Sachi Wakasa Institute of Regional Innovation, Hirosaki University Tatsuya Ishiyama Earthquake Research Institute, University of Tokyo Daisuke Hirouchi Faculty of Education, Shinshu University Nobuhisa Matta Faculty of Education, Okayama University Natsuko Fujita Tono Geoscience center, Japan Atomic Energy Agency Tomoo Echigo Kankyo Chisitsu, Co. To estimate long-term rates of coastal uplift along the northern Pacific coast of Northeast Japan, we determined the surface exposure ages of marine and fluvial terraces based on terrestrial in situ cosmogenic radionuclide dating of exposed bedrock surfaces. Based on reinterpretation of marine and fluvial terraces, we collected samples from the northern and southern Sanriku coast. The surface exposure ages from 10Be concentrations in quartz calculated from the measured 10Be/9Be ratios commonly suggest MIS 5 and MIS 7 for the marine and fluvial terraces and averaged coastal uplift rates of ca. 0.25 �} 0.15 and 0.4 mm/yr along the northern and southern Sanriku coast at intermediate timescales. The results may demonstrate different styles of crustal strain accommodation in the northern Northeast Japan arc above the subducting Pacific plate. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0032-0889 198 1 2025 Role of polar localization of the silicon transporter OsLsi1 in metalloid uptake by rice roots kiaf196 EN Noriyuki Konishi Institute of Plant Science and Resources, Okayama University Namiki Mitani-Ueno Institute of Plant Science and Resources, Okayama University Jian Feng Ma Institute of Plant Science and Resources, Okayama University Low silicon (Si) rice 1 (OsLsi1) is a key transporter mediating Si uptake in rice (Oryza sativa). It is polarly localized at the distal side of the root exodermis and endodermis. Although OsLsi1 is also permeable to other metalloids, such as boron (B), germanium (Ge), arsenic (As), antimony (Sb), and selenium (Se), the role of its polar localization in the uptake of these metalloids remains unclear. In this study, we investigated the role of OsLsi1 polar localization in metalloid uptake by examining transgenic rice plants expressing polarly or nonpolarly localized OsLsi1 variants. Loss of OsLsi1 polar localization resulted in decreased accumulation of Ge, B, and As in shoots but increased Sb accumulation, while Se accumulation remained unaffected under normal conditions. Experiments with varying B concentrations revealed that B uptake is significantly lower at low B concentrations (0.3 to 3 ��m) but higher at high B concentrations (300 ��m) in plants expressing nonpolarly localized OsLsi1, despite the similar B permeability of both OsLsi1 variants in Xenopus oocytes and their comparable protein abundance in roots. Additionally, the loss of OsLsi1 polarity did not affect the abundance, localization, or high B-induced degradation of the borate transporter 1 (OsBOR1), an efflux transporter that cooperates with OsLsi1 for B uptake. Taken together, our findings demonstrate that the polar localization of OsLsi1 plays a critical role in regulating metalloid uptake, depending on the presence or absence of efflux transporters cooperating with OsLsi1. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 6 2025 Effects of Thoron Inhalation and Cyclosporin A Treatment on Dextran Sulfate Sodium-Induced Oxidative Damage in Mice 421 429 EN Ayumi Tanaka Graduate School of Health Sciences, Okayama University Shota Naoe Graduate School of Health Sciences, Okayama University Reiju Takenaka Graduate School of Health Sciences, Okayama University Norie Kanzaki Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Akihiro Sakoda Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Kiyonori Yamaoka Faculty of Health Sciences, Okayama University Takahiro Kataoka Faculty of Health Sciences, Okayama University Original Article 10.18926/AMO/69844 Radon (222Rn; Rn) and thoron (220Rn; Tn) inhalation have been reported to enhance antioxidant activity in various organs. However, the effects of Tn on the colon have not been investigated. This study aimed to clarify the effects of Tn inhalation, alone and in combination with cyclosporin A (CsA), on dextran sulfate sodium (DSS)-induced colitis, and the accompanying oxidative stress, in mice. Male BALB/c mice were subjected to continuous 8-day Tn inhalation (c-Tn, 533�}128 Bq/m3) or alternate-day Tn inhalation over the same period (f-Tn, 577�}63Bq/m3), followed by treatment with 3% DSS and either CsA or vehicle for 7 days. Although the disease activity index (DAI) decreased significantly by day 2 in the c-Tn group, scores remained significantly higher than those in the f-Tn group. In the c-Tn group, superoxide dismutase and catalase activity in the colon were significantly elevated compared with those in sham controls. Thus, DSS-induced damage was effectively inhibited in the earlier stages by the c-Tn mode of inhalation than by the f-Tn mode. These findings suggest that continuous Tn inhalation more effectively attenuated early colitis symptoms than alternate-day inhalation, potentially through upregulation of antioxidant defenses. Tn and CsA showed no combined effects. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2772-5022 5 2 2025 Amelioration of Cd-induced bone deterioration by orally administered calcium phosphate 101482 EN Ping-chin Sung Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ahmad Bikharudin Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masahiro Okada Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Randa Musa Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenta Uchida Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akihisa Otaka Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadaaki Matsusaka Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University Aira Matsugaki Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University Takayoshi Nakano Division of Materials and Manufacturing Science, Graduate School of Engineering, Osaka University Takuya Matsumoto Department of Biomaterials, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Cadmium (Cd) is a heavy metal that accumulates in the body, primarily through daily grain intake, and has a high affinity for bone, leading to skeletal diseases such as osteomalacia and fractures. Hydroxyapatite (HAp), a major bone mineral component, is highly pH-sensitive and is known to incorporate Cd, as observed in studies of Itai-itai disease. Based on these findings, we hypothesized that HAp could serve as an effective oral detoxification material for heavy metals. This study investigated the efficacy of orally administered HAp in inhibiting Cd-induced changes in bone physical and chemical properties, comparing its effects to those of activated charcoal (AC), a common detoxifying agent. Six-week-old male ICR mice were exposed to cadmium via drinking water containing CdCl2 and subsequently given diets containing either HAp or AC for four weeks. Three-point bending tests, micro-CT analysis, and histological observations of the femurs demonstrated that mice receiving HAp exhibited improved mechanical strength and enhanced bone quality protection compared to the control and other Cd-treated groups. Activated charcoal also contributed to bone quality improvement at low concentrations, but its effect diminished at high concentrations. These results suggest that the oral administration of HAp may be a promising therapeutic strategy for suppressing cadmium-induced osteomalacia. No potential conflict of interest relevant to this article was reported.

AIP Publishing Acta Medica Okayama 0021-9606 163 22 2025 Fourier-transform infrared spectroscopy of hydrogen fluoride dimers in solid parahydrogen 224312 EN Yuki Miyamoto Research Institute for Interdisciplinary Science, Okayama University Hiroki Ooe Graduate School of Natural Science and Technology, Okayama University Susumu Kuma Department of Physics, Rikkyo University We investigate the Fourier-transform infrared spectra of hydrogen fluoride dimers in solid parahydrogen, the detailed analysis of which has remained unexplored. We propose a plausible analysis based on concentration dependence, light polarization, annealing, and time evolution. The absorption lines exhibited multiple peaks, with intensity ratios significantly altered by annealing and by time evolution at a constant temperature. The spectral patterns and isotopic effects suggest that the dimers do not rotate freely in solid parahydrogen, while multiple peaks arise from different stable structures, including single and double substitution sites. Unlike in the gas phase and helium droplets, no tunneling splitting was observed. The broad ��1 band suggests that some dimer structures may exhibit axial rotation. Spectral changes due to annealing likely result from site conversion, while observed IR-induced changes indicate preferential dissociation of dimers in double substitution sites. These findings still remain tentative, necessitating further experimental and theoretical studies. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2574-0962 8 6 2025 Effects of Metal-Cation Doping on Photocatalytic H2 Evolution Activity of Layered Perovskite Oxynitride K2LaTa2O6N 3541 3552 EN Hideya Tsuchikado Department of Chemistry, School of Science, Institute of Science Tokyo Shuji Anabuki Graduate School of Natural Science and Technology, Okayama University Ovidiu Cretu Electron Microscopy Group, National Institute for Materials Science (NIMS) Yuki Kinoshita Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Institute of Science Tokyo Masashi Hattori Institute of Integrated Research, Institute of Science Tokyo Yuta Shiroma Department of Chemistry, School of Science, Institute of Science Tokyo Dongxiao Fan Institute of Materials Structure Science High Energy Accelerator Research Organization Megumi Okazaki Department of Chemistry, School of Science, Institute of Science Tokyo Takuto Soma Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Institute of Science Tokyo Fumitaka Ishiwari Department of Applied Chemistry, Graduate School of Engineering, Osaka University Shunsuke Nozawa Institute of Materials Structure Science High Energy Accelerator Research Organization Toshiyuki Yokoi Institute of Integrated Research, Institute of Science Tokyo Michikazu Hara Institute of Integrated Research, Institute of Science Tokyo Koji Kimoto Electron Microscopy Group, National Institute for Materials Science (NIMS) Akira Yamakata Graduate School of Natural Science and Technology, Okayama University Akinori Saeki Department of Applied Chemistry, Graduate School of Engineering, Osaka University Kazuhiko Maeda Department of Chemistry, School of Science, Institute of Science Tokyo Aliovalent cation doping into a heterogeneous photocatalyst affects several of its physicochemical properties, including its morphological characteristics, optical absorption behavior, and charge carrier dynamics, causing a drastic change in its photocatalytic activity. In the present work, we investigated the effects of aliovalent cation doping on the visible-light H2-evolution photocatalytic activity of the Ruddlesden–Popper layered perovskite oxynitride K2LaTa2O6N. The photocatalytic activity toward H2 evolution from an aqueous NaI solution was found to be enhanced by an increase in the specific surface area of the K2LaTa2O6N photocatalyst, which could be realized upon doping with lower-valence cations (e.g., Mg2+, Al3+, and Ga3+). Among the dopants examined at 1 mol % doping, Ga resulted in the highest activity. The activity of the Ga-doped specimen was further improved with increasing Ga concentration, where the maximal activity was obtained at 10 mol %, corresponding to an apparent quantum yield of 2.7 �} 0.4% at 420 nm from aqueous methanol. This number is the highest reported for a layered oxynitride photocatalyst. In the Ga-doped K2LaTa2O6N, a trade-off was observed between the Ga concentration and the photocatalytic activity. Although doping with Ga reduced the particle size of K2LaTa2O6N and suppressed undesirable charge recombination, it led to an enlarged bandgap, unsuitable for visible-light absorption. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 2352-4855 90 2025 Species-specific sensitivity of marine phytoplankton to selected herbicides and antibiotics 104413 EN Shizuka Ohara Graduate School of Integrated Science for Life, Hiroshima University Toshimitsu Onduka Hatsukaichi Field Station, Fisheries Technology Institute, Japan Fisheries Research and Education Agency Shoko Ueki Institute of Plant Science and Resources, Okayama University Shotaro Naruse Graduate School of Integrated Science for Life, Hiroshima University Kazuhiko Koike Graduate School of Integrated Science for Life, Hiroshima University The toxicity of two herbicides (diuron and bromacil) and three antibiotics (clarithromycin, azithromycin, and clindamycin) was evaluated for on four marine phytoplankton species: two diatoms, Skeletonema costatum and Chaetoceros lorenzianus, a dinoflagellate, Prorocentrum shikokuense, and a raphidophyte, Heterosigma akashiwo. The 50 % effective concentrations (EC50-��) for growth of the herbicides (approximately 2.3–24.3 ��g L�|1) were lower than those of the antibiotics, indicating their higher toxicity. The EC50-�� of diuron was close to its reported environmental concentrations. The EC50-�� values for the antibiotics substantially differed by species, ranging from 19.5 to > 1000 ��g L�|1, with diatoms showing higher sensitivity than flagellates. Herbicides inhibited the photosynthetic yield (��II) of all tested species at concentrations similar to or lower than those affecting growth, while antibiotics affected ��II at higher concentrations. Under high-light conditions, photosynthesis in S. costatum was substantially inhibited by all chemicals except clindamycin, suggesting enhanced chemical toxicity under intense light. Overall, these findings indicate that these herbicides and antibiotics can alter phytoplankton abundance and composition in coastal areas and that environmental factors, such as increased solar radiation, can potentially enhance their toxicity. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2050-6511 26 1 2025 PEGylation of liposome-encapsulated midazolam does not improve the bioavailability of midazolam when administered orally 166 EN Yukiko Nishioka Department of Dental Anesthesiology, Okayama University Hospital Yanyin Lu Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitoshi Higuchi Department of Dental Anesthesiology, Okayama University Hospital Saki Miyake Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Maki Fujimoto Department of Dental Anesthesiology, Okayama University Hospital Midori Hamaoka-Inoue Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Tanimura Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hitomi Ujita Department of Dental Anesthesiology, Okayama University Hospital Shigeru Maeda Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Miyawaki Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background Liposomes are closed vesicles made of the same phospholipid bilayer as biological membranes and are capable of containing drugs, and so they have been investigated as useful drug carriers for drug delivery. We previously developed liposome-encapsulated midazolam (LE-midazolam) for oral administration, but midazolam is metabolized in the liver, and for clinical use the encapsulation of the liposomes needed to be improved to increase the bioavailability of midazolam. The surfaces of pharmaceutical liposomes are generally coated with polyethylene glycol (PEGylation) because it prevents their capture by phagocytes and helps them to avoid the reticuloendothelial system. Therefore, we considered that PEGylation could reduce the metabolism of orally administered encapsulated midazolam in the liver.<br> Methods Midazolam solution, LE-midazolam solution, and PEGylated liposome-encapsulated midazolam (PEG-LE-midazolam) solution were prepared, and the characteristics of the liposomes in these solutions were evaluated. Furthermore, these solutions were orally administered to rabbits, and the resultant plasma midazolam concentrations were measured. The effects of the PEGylation of LE-midazolam on the plasma concentration and bioavailability of orally administered midazolam were also evaluated.<br> Results The PEG-LE-midazolam solution contained a higher percentage of larger liposomes than the LE-midazolam solution. The area under the concentration-time curve (AUC) of the LE-midazolam solution was significantly higher than that of the midazolam solution, but there was no difference between the AUC values of the PEG-LE-midazolam and midazolam solutions.<br> Conclusions These findings suggest that liposome encapsulation may reduce the first-pass effect following oral administration, but PEGylation is not expected to improve the bioavailability of orally administered midazolam. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1473-0502 64 6 2025 Novel leukocytapheresis method using highly concentrated sodium citrate solution for the manufacturing of tisagenlecleucel 104265 EN Wataru Kitamura Department of Hematology and Oncology, Okayama University Hospital Keiko Fujii Department of Hematology and Oncology, Okayama University Hospital Masaya Abe Department of Hematology and Oncology, Okayama University Hospital Kazuhiro Ikeuchi Department of Hematology and Oncology, Okayama University Hospital Kana Washio Department of Pediatrics, Okayama University Hospital Fumio Otsuka Division of Clinical Laboratory, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital For the manufacturing of tisagenlecleucel (tisa-cel) requires the non-mobilized mononuclear cell collection (MNC). CD3+ cell collection is performed using the same protocol as autologous peripheral blood stem cell harvest (auto-PBSCH), but this procedure necessitates the same target CD3+ cell yields regardless of age or body weight, which may take several days especially in pediatric and small female patients with low white blood cell counts. We previously demonstrated a novel method using highly concentration sodium citrate (HSC), which reduced the need for an anticoagulant (AC) solution and shortened the procedure time in auto-PBSCH. This novel method was expected to offer advantages for smaller patients, prompting us to investigate its application in leukocytapheresis for the manufacturing of tisa-cel. We retrospectively analyzed consecutive leukocytapheresis data obtained using Spectra Optia continuous MNC mode between November 2022 and June 2024 at our institution (n = 9). In six of nine patients, pre-leukocytapheresis CD3+ cell counts were less than 500 /��L, but all could obtain the target CD3+ cell yields in one day upon processing blood volume adjustment. When we compared patients who had received CD3+ cell collection using normal-concentration sodium citrate (NSC) as our previously reported using propensity score-matched pair analysis, the total AC solution volume was significantly lower (1168 vs. 316 mL, p < 0.001) and procedure time was significantly shorter (254 vs. 228 min, p = 0.04) in the HSC group compared to the NSC group. In conclusion, this procedure was also useful for non-mobilized MNC. Our findings warrant validation in a larger patient cohort. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0041-1132 65 9 2025 Novel method for autologous peripheral blood stem cell harvest using highly concentrated sodium citrate solution replacing acid citrate dextrose solution A 1662 1672 EN Wataru Kitamura Department of Hematology and Oncology, Okayama University Hospital Keiko Fujii Department of Hematology and Oncology, Okayama University Hospital Masaya Abe Department of Hematology and Oncology, Okayama University Hospital Kazuhiro Ikeuchi Department of Hematology and Oncology, Okayama University Hospital Joji Shimono Department of Hematology and Oncology, Okayama University Hospital Kana Washio Department of Pediatrics, Okayama University Hospital Fumio Otsuka Division of Clinical Laboratory, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Department of Hematology and Oncology, Okayama University Hospital Background: As the processed blood volume increases, a larger amount of anticoagulant (AC) is required, which leads to a serious issue of fluid dilution in large-volume leukocytapheresis (defined as ≥3-fold total blood volume). We previously reported a novel method for allogeneic peripheral blood stem cell harvest (PBSCH) using highly concentrated sodium citrate (HSC; 5.32%), which shortened the procedure time and reduced the need for an AC solution without heparin. In this study, we extended this novel method to autologous PBSCH (auto-PBSCH) and compared it with patients who received auto-PBSCH using normal concentrated sodium citrate (NSC; 2.2%).<br> Study Design and Methods: We retrospectively analyzed consecutive auto-PBSCH data obtained using the Spectra Optia continuous mononuclear cell collection mode between May 2017 and May 2025 at our institution.<br> Results: Leukocytapheresis was performed using NSC in 36 patients and HSC in 22. In the HSC group, patients tended to be younger, had significantly lower body weight, and had significantly fewer hematopoietic tumors as primary diseases compared to the NSC group. After propensity score-matched cohort adjusted for patient background, the total amount of AC solution was significantly lower (694 [range, 77–1648] vs. 298 mL [range, 64–797], p = .02), and procedure time was significantly shorter (224 [range, 117–395] vs. 181 min [range, 103–309], p = .048) in the HSC group. Furthermore, the loss rates of magnesium and potassium were lower in the HSC group.<br> Conclusion: This novel leukocytapheresis method demonstrated the efficacy and safety in auto-PBSCH, while minimizing the patient burden. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2045-2322 14 1 2024 Association between proteinuria and mineral metabolism disorders in chronic kidney disease: the Japan chronic kidney disease database extension (J-CKD-DB-Ex) 27481 EN Sho Shimamoto Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University Takako Nakahara Department of Medical Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare Shunsuke Yamada Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University Hajime Nagasu Department of Nephrology and Hypertension, Kawasaki Medical School Seiji Kishi Department of Nephrology and Hypertension, Kawasaki Medical School Naoki Nakashima Department of Medical Informatics, Graduate School of Medical Science, Kyushu University Kazuhiko Tsuruya Department of Nephrology, Nara Medical University Hirokazu Okada Department of Nephrology, Faculty of Medicine, Saitama Medical University Kouichi Tamura Department of Medical Science and Cardiorenal Medicine, Graduate School of Medicine, Yokohama City University Ichiei Narita Division of Clinical Nephrology and Rheumatology, Niigata University Graduate School of Medical and Dental Sciences Shoichi Maruyama Department of Nephrology, Nagoya University Graduate School of Medicine Yuichiro Yano Department of General Medicine, Juntendo University Faculty of Medicine Takashi Yokoo Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine Takashi Wada Department of Nephrology and Rheumatology, Kanazawa University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Eiichiro Kanda Department of Health Data Science, Kawasaki Medical School Hiromi Kataoka Department of Medical Technology, Faculty of Health Science and Technology, Kawasaki University of Medical Welfare Masaomi Nangaku Division of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine Naoki Kashihara Department of Nephrology and Hypertension, Kawasaki Medical School Toshiaki Nakano Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University Chronic kidney disease-mineral and bone disorder (CKD-MBD) are recognized as a systemic disease affecting the prognosis of patients with CKD. Proper management of CKD-MBD is important to improve the prognosis of patients with CKD. Although proteinuria is recognized as a poor prognostic factor in these patients, few reports have examined its association with CKD-MBD. We examined the association between proteinuria and CKD-MBD using data from the Japan Chronic Kidney Disease Database Extension (J-CKD-DB-Ex). Among the patients registered in the J-CKD-DB-Ex, 30,977 with CKD stages G2–G5 who had serum creatinine, albumin, calcium, and phosphate concentrations measured at least once and urinalysis performed were included. The patients were divided into four groups (negative, 1+, 2+, and 3+) according to the degree of proteinuria. The association between proteinuria and CKD-MBD was examined by a logistic regression analysis. In a model adjusted for age, sex, diabetes, and the estimated glomerular filtration rate (eGFR), the odds ratio of the 3 + group compared with the negative group significantly increased to 2.67 (95% confidence interval, 2.29–3.13) for hyperphosphatemia, 2.68 (1.94–3.71) for hypocalcemia, and 1.56 (1.24–1.98) for hypomagnesemia. Proteinuria is associated with hyperphosphatemia, hypocalcemia, and hypomagnesemia in patients with CKD independently of eGFR. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1999-4923 17 11 2025 Development of Propofol-Encapsulated Liposomes and the Effect of Intranasal Administration on Bioavailability in Rabbits 1446 EN Hitomi Ujita Department of Dental Anesthesiology, Okayama University Hospital Hitoshi Higuchi Department of Dental Anesthesiology, Okayama University Hospital Yukiko Nishioka Department of Dental Anesthesiology, Okayama University Hospital Saki Miyake Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate of Medicine, Dentistry and Pharmaceutical Sciences Riko Sato Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate of Medicine, Dentistry and Pharmaceutical Sciences Takuya Miyawaki Department of Dental Anesthesiology and Special Care Dentistry, Okayama University Graduate of Medicine, Dentistry and Pharmaceutical Sciences Background/Objectives: Propofol is frequently used as an intravenous anesthetic and is rapidly metabolized. Therefore, if it could be administered non-invasively (e.g., orally) as premedication, it might hasten emergence from anesthesia, thereby improving patient safety. However, it undergoes extensive first-pass metabolism in the liver and intestines, limiting the route for premedication. We evaluated whether intranasal delivery of a propofol-encapsulated liposome solution improves systemic exposure and bioavailability in rabbits. Methods: A propofol-encapsulated liposome solution was administered to rabbits via the intravenous, oral, and intranasal routes. Blood propofol concentrations were measured for up to 60 min after administration and the area under the concentration–time curve (AUC0–60) and bioavailability of the propofol-encapsulated liposome solution were compared with those of the non-encapsulated propofol formulation. The differences were tested by two-way analysis of variance (ANOVA) with Šidák�fs post hoc multiple-comparisons test and the Mann–Whitney test (�� = 0.05). Results: The AUC0–60 for blood propofol concentrations after intravenous administration was significantly higher with the propofol-encapsulated liposome solution than with the non-encapsulated propofol formulation (3038.8 �} 661.5 vs. 1929.8 �} 58.2 ng·min/mL; p = 0.0286). By contrast, no increase in blood propofol concentrations was observed after oral administration, whereas intranasal administration increased blood propofol concentrations and yielded significantly higher bioavailability compared with the non-encapsulated propofol formulation (16.4 �} 7.3% vs. 2.0 �} 1.2%; p = 0.0286). Conclusions: The findings of the present study suggest that intranasal liposomal propofol increased systemic availability compared with a non-encapsulated formulation, supporting further evaluation as a candidate premedication approach for propofol. No potential conflict of interest relevant to this article was reported.

S. Karger AG Acta Medica Okayama 0253-5068 2025 Current Status of Continuous Renal Replacement Therapy in Japanese Intensive Care Units: A Multicenter Retrospective Observational Study EN Hidehiko Nakano Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital Ryota Inokuchi Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital Yutaro Inoue Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital Motohiro Sekino Department of Anesthesiology and Intensive Care Medicine, Nagasaki University Graduate School of Biomedical Sciences Yasuyuki Kakihana Department of Emergency and Intensive Care Medicine, Kagoshima University Graduate School of Medical and Dental Sciences Noriyuki Hattori Department of Emergency and Critical Care Medicine, Chiba University Graduate School of Medicine Mariko Miyazaki Department of Nephrology, Tohoku University Hospital Natsuko Tokuhira Department of Intensive Care, Osaka University Hospital Shigeki Fujitani Department of Emergency and Critical Care Medicine, St. Marianna University School of Medicine Yuichiro Toda Department of Anesthesiology and Intensive Care Medicine, Kawasaki Medical School Yoshifumi Ohchi Department of Anesthesiology and Intensive Care, Oita University Faculty of Medicine Hiroshi Morimatsu Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shingo Ichiba Department of Intensive Care Medicine, Tokyo Women�fs Medical University Yoshiki Masuda Department of Intensive Care Medicine, Sapporo Medical University School of Medicine Osamu Nishida Department of Anesthesiology and Critical Care Medicine, School of Medicine, Fujita Health University Takaya Abe Department of Urology, Iwate Medical University Takeshi Moriguchi Department of Emergency and Critical Care Medicine, University of Yamanashi Graduate School of Medicine Kasumi Satoh Department of Emergency and Critical Care Medicine, Akita University Graduate School of Medicine Masafumi Idei Department of Intensive Care Medicine, Yokohama City University Hiromasa Nagata Department of Anesthesiology, Keio University School of Medicine Kent Doi Department of Emergency and Critical Care Medicine, The University of Tokyo Hospital Introduction: Continuous renal replacement therapy (CRRT) is often performed for critically ill patients in intensive care units (ICUs), but its optimal indication and settings have yet to be determined. Thus, we aimed to describe the current status of CRRT in Japan through a multicenter retrospective observational study. Methods: Adult ICU patients receiving CRRT at 18 tertiary hospitals in Japan (up to 100 patients from each hospital over the past year) were retrospectively enrolled. Patients receiving CRRT for <24 h or intermittent renal replacement therapy together with CRRT were excluded. The primary outcomes were the temporal changes in the electrolyte levels, acid-base balance, and uremia-related small solute concentrations. The secondary outcomes included potassium (K) and phosphate (P) supplementations during CRRT. Results: Altogether, 1,045 patients were enrolled. The median CRRT duration and dose were 4.4 days and 17.3 mL/kg/h, respectively. The electrolyte levels, acid-base balance, and uremia-related small solute concentrations returned to normal by day 4 of treatment. A total of 732 (70.0%) patients received K supplementation, and only a few patients had hypokalemia until day 5. Moreover, 414 (39.6%) patients received P supplementation, and approximately 30%–50% of the patients had hypophosphatemia until day 5. Conclusion: The CRRT dose in Japan was lower than that was recommended by the Kidney Disease: Improving Global Outcomes guideline. The electrolyte level abnormalities and acid-base imbalances of the studied patients were improved within 72–96 h of CRRT. Contrarily, K and P supplementations were common, indicating that the current CRRT solutions need to be modified. No potential conflict of interest relevant to this article was reported.

Japan Society on Water Environment Acta Medica Okayama 1348-2165 23 5 2025 Biochar-amended Sediment Microbial Fuel Cells for Water Quality Improvement in Intensive and Extensive Pond Drainages in Central Vietnam 234 249 EN Uyen Tu Nguyen Graduate School of Environmental and Life Science, Okayama University Morihiro Maeda Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroaki Somura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Nozomi Nakahara Department of Comprehensive Technical Solutions, Okayama University Gamamada Liyanage Erandi Priyangika Perera Graduate School of Environmental and Life Science, Okayama University Chiyu Nakano Graduate School of Environmental and Life Science, Okayama University Huu Tien Le Department of Education, Science and Technology Quang Tri Branch, Hue University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University The use of nutrient-rich feed in shrimp farming in Central Vietnam has led to high nitrogen (N) and phosphorus (P) contents in the pond sediment. The objectives of the study were to assess the effectiveness of biochar-sediment microbial fuel cells (BC-SMFCs) in suppressing P and N release from two types of sediment in intensive (Int) and extensive (Ext) pond drainages in Central Vietnam. Single chamber SMFCs were set up and operated under open or closed-circuit (no SMFC or SMFC) conditions. Coconut shell biochar (BC) was amended to sediments at 1%. For Int-sediment, total phosphorus (TP) release was reduced by no BC-SMFCs through co-precipitation with Fe. On the other hand, BC-SMFCs did not suppress TP release because P was released from BC and organic matter decomposition was enhanced in the sediment. Application of BC enhanced organic N mineralization in the sediment. Nitrification and denitrification occurred in the overlying water, reducing mineral N concentrations. For Ext-sediment, BC addition and SMFC conditions did not affect TP and total nitrogen (TN) release because of low initial organic matter content, and less reductive condition. Our study suggested that the effect of SMFCs was masked by BC which released more P from Int-sediment to the water. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0921-8831 36 10 2025 Evaluating the effects of electrolytes on the interaction forces between alumina surfaces in polyacrylic acid solutions using atomic force microscopy 105028 EN Naoto Kishimoto Graduate School of Natural Science and Technology, Okayama University Ryota Kaji Faculty of Science and Engineering, Doshisha University Katsumi Tsuchiya Faculty of Science and Engineering, Doshisha University Koreyoshi Imamura Graduate School of Natural Science and Technology, Okayama University Naoyuki Ishida Faculty of Science and Engineering, Doshisha University Evaluation and control of ceramic slurry at the microscopic level are critical to ensure consistent quality in manufactured ceramics. Notably, metal ions such as Mg2+ and Al3+ are common in ceramic slurries and significantly influence the stability of particle. This study applied atomic force microscopy to investigate the interaction forces between alumina particle surfaces in the presence of different concentrations of three metal ions and polyacrylic acid (PAA), a widely used dispersant.<br> The attractive forces observed at low PAA concentrations were attributed to polymer bridging between alumina surfaces, whereas the repulsive forces observed at high PAA concentrations were attributed to the domination of steric repulsion between adsorbed PAA molecules. The presence of multivalent metal ions, such as Mg2+ and Al3+, modulated these interactions; an increasing ion valence induced a transition from repulsive to attractive force, primarily owing to electrostatic screening, which caused conformational collapse of the PAA chains and diminished the range of steric repulsion. Similarly, increasing the concentration of these metal ions decreased the range of repulsive forces, eventually resulting in a net attraction driven by the same electrostatic and polymer conformation mechanisms. Notably, the addition of 0.1 M AlCl3 produced an anomalous long-range attraction between surfaces that could not be explained by conventional mechanisms, such as polymer bridging or electrostatic interactions between charge domains. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1876-2018 108 2025 Introduction to the �gJapanese and Western approaches to psychotrauma�h symposium 104508 EN Masanori Nagamine Division of Behavioral Science, National Defense Medical College Research Institute Tomoyo Nakao Graduate School of Humanities and Social Sciences, Okayama University Leo van Bergen Freelance Medical Historian Jun Shigemura Faculty of Health Sciences, Mejiro University Taku Saito Division of Behavioral Science, National Defense Medical College Research Institute Florentine H.S. van der Does Department of Psychiatry, Leiden University Medical Center (LUMC) Masato Kitano Division of Behavioral Science, National Defense Medical College Research Institute Erik J. Giltay Department of Psychiatry, Leiden University Medical Center (LUMC) Nic J. van der Wee Department of Psychiatry, Leiden University Medical Center (LUMC) Eric Vermetten Department of Psychiatry, Leiden University Medical Center (LUMC) Understandings of psychotrauma have changed throughout medical history, shaped by cultural and social factors. Reviewing transcultural perspectives of psychotrauma helps understand its complexities and contextual impacts. This paper summarizes the Japan–Netherlands symposium on psychotrauma held on March 1, 2024. Despite experiencing psychological trauma from World War II and numerous natural disasters, Japan did not actively research post-traumatic stress disorder (PTSD) for nearly 50 years after the war. The Great Hanshin-Awaji Earthquake and the Tokyo subway Sarin gas attack (1995) popularized the term PTSD in Japan and triggered related research. The absence of psychotrauma research in Japan may reflect a form of state-level PTSD, characterized by avoidance. Japan�fs collectivist culture, stigma against seeking psychological help, view of patience as a virtue, survivor guilt, and moral injury were potential related factors. Additionally, sociocultural factors (e.g., insufficient collective grieving and focusing on post-war reconstruction) were discussed as potential hinderances to discussing war experiences. From a European perspective, we examined how �gKonzentrationslager�h (KZ) syndrome, a trauma-related disorder, evolved independently into diverse conceptual frameworks, ultimately contributing to the acceptance of PTSD following its introduction in 1980. Beyond state compensation for concentration camp survivors, advocacy by feminist movements and veterans' groups increased awareness of psychotrauma across Europe, fostering scholarly research and public discourse. Both PTSD and KZ syndromes are diagnostic categories shaped by specific historical and cultural contexts and should not be regarded as simple, universally applicable medical conditions. They reflect how trauma is interpreted and responded to differently depending on cultural, political, and historical factors. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 5 2025 Immunoglobulin G4-related Disease Mimicking Portal Vein Tumor Thrombus 381 385 EN Atsunobu Sakurai Department of Radiology, NHO Iwakuni Clinical Center Takayuki Yabuki Department of Radiology, NHO Iwakuni Clinical Center Hideki Aoki Department of Gastroenterological Surgery, NHO Iwakuni Clinical Center Akiko Iseki Department of Pathology, NHO Iwakuni Clinical Center Case Report 10.18926/AMO/69439 We report the case of a 72-year-old Japanese man with an incidental portal vein mass that was surgically resected and diagnosed as immunoglobulin G4 (IgG4)-related disease. The mass was discovered during an atrial fibrillation examination. The patient had a history of gastric cancer and was also diagnosed with rectal cancer, raising concerns about metastasis. Due to technical challenges, a biopsy was not feasible. Imaging findings suggested portal vein tumor thrombosis, complicating the diagnosis. This case highlights a rare presentation of IgG4-related disease mimicking portal vein tumor thrombus. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1664-462X 16 2025 The response to thermospermine is fine-tuned by the balance between SAC51 and LHW family proteins in Arabidopsis thaliana EN Yao Xu Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Mitsuru Saraumi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Tomohiko Toyoshima Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Hiroyasu Motose Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Taku Takahashi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Thermospermine negatively regulates xylem formation. In Arabidopsis, SAC51 and SACL3, members of the SAC51 gene family encoding basic loop-helix-loop (bHLH) proteins play a key role in this regulation. These mRNAs contain an upstream open-reading-frame (uORF) that is highly conserved across species, and its inhibitory effect on the main ORF translation is alleviated by thermospermine. A double knockout of SAC51 and SACL3 results in thermospermine insensitivity at high concentrations that normally inhibit xylem formation and shoot growth in the wild type. Conversely, uORF mutants of SAC51, SACL3, and SACL1 suppress the excessive xylem formation and dwarf phenotype of acl5, a mutant defective in thermospermine biosynthesis. In this study, we generated genome-edited uORF mutants of SACL2 and confirmed that they partially recover the acl5 phenotype. All uORF mutants exhibited increased sensitivity to thermospermine. SACL3 represses the function of LHW, a key bHLH transcription factor required for xylem proliferation, through direct interaction. We found that the lhw mutant is also hypersensitive to thermospermine, while this sensitivity was suppressed by the sac51 sacl3 double knockout. Yeast two-hybrid assays demonstrated that all four SAC51 family members interact with LHW and its family members. These findings suggest that overaccumulation of SAC51 family proteins leads to thermospermine hypersensitivity by repressing the function of LHW family proteins, whose activity must be fine-tuned to ensure proper xylem development. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0273-1177 76 9 2025 Spatiotemporal evolution of ecosystem carbon storage under land use/land cover dynamics in the coastal region of Central Vietnam 4815 4837 EN Viet Hoang Ho Graduate School of Environmental and Life Science, Okayama University Hidenori Morita Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Thanh Ha Ho University of Agriculture and Forestry, Hue University Felix Bachofer German Aerospace Center (DLR), Earth Observation Center Ecosystem carbon storage is a cost-effective strategy for global climate change mitigation, and its fluctuation is markedly shaped by land use/land cover (LULC) dynamics. Taking Danang city as an example of Central Coastal Vietnam, this study aims to assess LULC changes and analyze the spatiotemporal evolution of carbon storage from 2023 to 2050 under four LULC change scenarios, including natural trend scenario (NTS), ecological protection scenario (EPS), economic development scenario (EDS), and cropland protection scenario (CPS), by integrating the support vector machine-cellular automata-Markov (SVM-CA-Markov) model and the InVEST model. The Optimal Parameters-based Geographical Detector (OPGD) model was subsequently employed to elucidate the impacts of driving factors on the spatial distribution of carbon storage. The results showed that, from 2007 to 2023, Danang city experienced a dramatic back-and-forth transformation between LULC types, with the predominant transitions being from natural forest to acacia tree-dominated plantation forest (6492.31 ha), and from cropland to settlements, acacia tree-dominated plantation forest, and other land (5483.05 ha, 3763.66 ha, 2762.35 ha, respectively). Between 2023 and 2050, LULC transformations in Danang city are projected to yield varying degrees of carbon storage levels across different scenarios. Specifically, carbon storage is anticipated to dwindle by 0.221 Mt, 0.223 Mt, and 0.298 Mt under NTS, EDS, and CPS, respectively, while enhancing by 0.141 Mt under EPS. Regarding the spatial distribution of carbon storage, high values will be chiefly found in the western high-elevation mountainous region, while low values will be concentrated mostly in the eastern lower-lying areas of the city. Additionally, elevation and temperature acted as the two most significant driving factors influencing the spatial distribution of carbon storage, with Q values of 0.88 and 0.86 (p-value < 0.05), respectively. For interaction detection, the combination of elevation and soil exhibited a synergistic reinforcement effect on the spatial partitioning of carbon storage, with a high Q value of 0.9566 (p-value < 0.05). Our study highlights the necessity of ecological conservation measures in Danang city in the on-track pursuit of national net-zero carbon emissions by 2050. No potential conflict of interest relevant to this article was reported.

Fuji Technology Press Ltd. Acta Medica Okayama 1883-8022 19 5 2025 Study on an Effective Coolant Supply Method in the Side Plunge Grinding Process 939 948 EN Lingxiao Gao Graduate School of Natural Science and Technology, Okayama University Taichi Fujimoto Graduate School of Natural Science and Technology, Okayama University Hiroyuki Kodama Faculty of Environmental, Life, Natural Science and Technology, Okayama University Kazuhito Ohashi Faculty of Environmental, Life, Natural Science and Technology, Okayama University Grinding is widely used for finishing components with journal and thrust surfaces, such as crankshafts. Side-plunge grinding enables the simultaneous finishing of thrust and cylindrical surfaces in a single plunge. However, compared to cylindrical grinding, it involves a larger contact area between the grinding wheel and the workpiece, leading to increased heat generation. In particular, poor coolant penetration near internal corners can degrade surface quality, potentially causing stress concentrations and cracks. To enhance coolant effectiveness in side-plunge grinding, this study installs a high-pressure nozzle that supplies coolant from the side of the grinding wheel. The effectiveness of this setup is experimentally verified. Additionally, the distribution of coolant flow within the contact area between the grinding wheel and the workpiece is measured to determine the optimal nozzle position for efficient coolant delivery. The nozzle�fs performance is evaluated by measuring the workpiece surface temperature using a wire/workpiece thermocouple, the amount of coolant discharged from the grinding wheel, and the residual stress distribution. The results show that coolant penetrates the grinding wheel and effectively reaches the grinding zone, enhancing the cooling effect. This study clarifies the relationship between effective coolant supply and the position of the side nozzle. Considering physical constraints, such as potential interference during grinding, the optimal nozzle location is as close as possible to both the edge of the grinding wheel and the workpiece. This positioning ensures maximum coolant delivery, reduces grinding temperature, and helps suppress drastic variations in residual stress. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1472-6831 25 1 2025 Phosphorylated pullulan as a local drug delivery matrix for cationic antibacterial chemicals to prevent oral biofilm 1333 EN Naoko Namba-Koide Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Yasuhiro Yoshida Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Takumi Okihara Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Yusuke Kawata Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Masahiro Ito Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Takashi Ito Center for Innovative Clinical Medicine, Okayama University Hospital Kazu Takeuchi-Hatanaka Department of Periodontics and Endodontics, Division of Dentistry, Okayama University Hospital Yuki Shinoda-Ito Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazuhiro Omori Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tadashi Yamamoto Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shogo Takashiba Department of Pathophysiology - Periodontal Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Preventing oral infections, such as oral caries and periodontal disease, helps reduce the risks of various systemic diseases. In this study, the polysaccharide pullulan produced by the black yeast Aureobasidium pullulans was modified in combination with the cationic surfactant cetylpyridinium chloride (CPC) to create a local drug delivery system, and its antibacterial potential on oral bacteria was examined in vitro.<br> Methods Pullulan was phosphorylated at the CH2OH residue of ��6 in the maltotriose structure and mixed with CPC. Bacterial attachment of cariogenic Streptococcus mutans on hydroxyapatite plates (HAPs) treated with the phosphorylated pullulan (PP) and CPC compound (0.01% PP and 0.001– 0.03% CPC, and vice versa) was assessed by observing bacteria using a field emission scanning electron microscope (FE-SEM) and quantified through 16 S rRNA amplification via real-time polymerase chain reaction (PCR). Additionally, the quartz crystal microbalance (QCM) method was employed to evaluate the sustained release of CPC.<br> Results PP-CPC compound maintained significant bactericidal activity even at 0.01%, which is one-fifth of the conventional applicable concentration of CPC. Additionally, a residual mixture was detected by the hydroxyapatite sensor of the crystal oscillator microbalance detector, suggesting an unknown molecular interaction that enables the sustained release of CPC after attachment to hydroxyapatite.<br> Conclusions The combination of PP and CPC may contribute to the low concentration and effective prevention of oral infections, such as dental caries. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0014-4800 142 2025 Cross-feeding between beneficial and pathogenic bacteria to utilize eukaryotic host cell-derived sialic acids and bacteriophages shape the pathogen-host interface milieu 104967 EN Darab Ghadimi Department of Microbiology and Biotechnology, Max Rubner-Institut Regina Fölster-Holst Clinic of Dermatology, Venerology und Allergology, University Hospital Schleswig-Holstein Sophia Blömer Clinic of Dermatology, Venerology und Allergology, University Hospital Schleswig-Holstein Michael Ebsen Städtisches MVZ Kiel GmbH (Kiel City Hospital), Department of Pathology Christoph Röcken Institute of Pathology, Kiel University, University Hospital, Schleswig-Holstein Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Shigenobu Matsuzaki Department of Medical Laboratory Science, Faculty of Health Sciences, Kochi Gakuen University Wilhelm Bockelmann Department of Microbiology and Biotechnology, Max Rubner-Institut Under an inflamed-intestinal milieu, increased free sialic acids are associated with the overgrowth of some pathogenic bacterial strains. Recently, the protective immunomodulatory activity of gut bacteriophages (phages) has also been highlighted. However, the role of phages in triple reciprocal interactions between pathogenic bacteria, beneficial bacteria, and their host cell sialic acids has not been studied so far. We established a sialidase-explicit model in which beneficial and pathogenic bacteria interact through cross-feeding and competition for free sialic acid using a human triple co-culture cell model incorporating colonocytes (T84 cells), monocytes (THP-1 cells), and hepatocytes (Huh7 cells). Triple co-cultured cells were challenged with Gram-positive Bifidobacterium bifidum (B. bifidum) and Gram-negative Pseudomonas aeruginosa PAO1 (P. a PAO1) in the absence or presence of its KPP22 phage in two different cell culture mediums: 1) standard Dulbecco's Modified Eagle Medium (DMEM) and 2) DMEM with 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (DANA). Changes in physiological, functional, and structural health markers of stimulated cocultured cells were evaluated. The concentrations of sialic acid and pro-inflammatory cytokines in the cell culture supernatants were quantified. P. a PAO1 triggered the release of interleukin 6 and 8 (IL-6 and IL-8), accompanied by increased levels of free sialic acid, reduced viability of co-cultured cells, and disrupted the integrity of the cellular monolayer. These disruptive effects were markedly attenuated by KPP22 phage and B. bifidum. In addition to well-documented differences in the structure and composition of the bacterial cell walls of Gram-negative pathogenic bacteria and bifidobacteria, two distinct factors seem to be pivotal in modulating the pathogen-host interface milieu: (i) the presence of phages and (ii) the utilization of free sialic acids secreted from host cells by bifidobacteria. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1660-3397 23 5 2025 Novel Anti-MRSA Peptide from Mangrove-Derived Virgibacillus chiguensis FN33 Supported by Genomics and Molecular Dynamics 209 EN Namfa Sermkaew School of Pharmacy, Walailak University Apichart Atipairin School of Pharmacy, Walailak University Phetcharat Boonruamkaew School of Pharmacy, Walailak University Sucheewin Krobthong Center of Excellence in Natural Products Chemistry (CENP), Department of Chemistry, Faculty of Science, Chulalongkorn University Chanat Aonbangkhen Center of Excellence in Natural Products Chemistry (CENP), Department of Chemistry, Faculty of Science, Chulalongkorn University Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yodying Yingchutrakul National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency Nuttapon Songnaka School of Pharmacy, Walailak University Antimicrobial resistance (AMR) is a global health threat, with methicillin-resistant Staphylococcus aureus (MRSA) being one of the major resistant pathogens. This study reports the isolation of a novel mangrove-derived bacterium, Virgibacillus chiguensis FN33, as identified through genome analysis and the discovery of a new anionic antimicrobial peptide (AMP) exhibiting anti-MRSA activity. The AMP was composed of 23 amino acids, which were elucidated as NH3-Glu-Gly-Gly-Cys-Gly-Val-Asp-Thr-Trp-Gly-Cys-Leu-Thr-Pro-Cys-His-Cys-Asp-Leu-Phe-Cys-Thr-Thr-COOH. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for MRSA were 8 µg/mL and 16 µg/mL, respectively. FN33 AMP induced cell membrane permeabilization, suggesting a membrane-disrupting mechanism. The AMP remained stable at 30–40 ��C but lost activity at higher temperatures and following exposure to proteases, surfactants, and extreme pH. All-atom molecular dynamics simulations showed that the AMP adopts a ��-sheet structure upon membrane interaction. These findings suggest that Virgibacillus chiguensis FN33 is a promising source of novel antibacterial agents against MRSA, supporting alternative strategies for drug-resistant infections. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2640-4567 2025 Integration of Cholesterol Oxidase�]Based Biosensors on a Smart Contact Lens for Wireless Cholesterol Monitoring from Tears 2500368 EN Yang Cui Graduate school of Information, Production and Systems, Waseda University Lin Zhuo Graduate school of Information, Production and Systems, Waseda University Yuta Nishina Graduate School of Natural Science and Technology, Okayama University Saman Azhari Graduate school of Information, Production and Systems, Waseda University Takeo Miyake Graduate school of Information, Production and Systems, Waseda University Cholesterol plays a critical role in physiological functions, but elevated levels increase the risk of cardiovascular disease. Regular cholesterol monitoring is essential for elderly or obese individuals. Current methods, such as blood tests, are invasive, inconvenient, and require a professional operator. In contrast, tears, as an accessible body fluid, offer a promising alternative for noninvasive monitoring due to their correlation with blood cholesterol levels. Herein, a noninvasive approach for monitoring cholesterol levels in tears using a biosensor integrated into a smart contact lens is reported. The biosensor employs cholesterol oxidases as the biocatalyst, coupled with an osmium-based mediator, to detect cholesterol concentrations ranging from 0.1 mM to 1.2 mM in artificial tears. A key challenge is the extremely low cholesterol concentration in tears, which is addressed using a parity-time (P-T) symmetry-based magnetic resonance coupling system. This system enables wireless signal reading and achieves high sensitivity due to its high-quality (Q) factor, which can achieve a detection limit of 0.061 mM. This portable, high-sensitivity smart contact lens demonstrates significant potential as a wearable device for continuous, noninvasive cholesterol monitoring. The findings contribute to advancing tear-based diagnostic systems and highlight the scientific importance of utilizing tear biomarkers for health monitoring. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2079-6382 13 9 2024 Unveiling a New Antimicrobial Peptide with Efficacy against P. aeruginosa and K. pneumoniae from Mangrove-Derived Paenibacillus thiaminolyticus NNS5-6 and Genomic Analysis 846 EN Namfa Sermkaew School of Pharmacy, Walailak University Apichart Atipairin School of Pharmacy, Walailak University Sucheewin Krobthong Center of Excellence in Natural Products Chemistry (CENP), Department of Chemistry, Faculty of Science, Chulalongkorn University Chanat Aonbangkhen Center of Excellence in Natural Products Chemistry (CENP), Department of Chemistry, Faculty of Science, Chulalongkorn University Yodying Yingchutrakul National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Nuttapon Songnaka School of Pharmacy, Walailak University This study focused on the discovery of the antimicrobial peptide (AMP) derived from mangrove bacteria. The most promising isolate, NNS5-6, showed the closest taxonomic relation to Paenibacillus thiaminolyticus, with the highest similarity of 74.9%. The AMP produced by Paenibacillus thiaminolyticus NNS5-6 exhibited antibacterial activity against various Gram-negative pathogens, especially Pseudomonas aeruginosa and Klebsiella pneumoniae. The peptide sequence consisted of 13 amino acids and was elucidated as Val-Lys-Gly-Asp-Gly-Gly-Pro-Gly-Thr-Val-Tyr-Thr-Met. The AMP mainly exhibited random coil and antiparallel beta-sheet structures. The stability study indicated that this AMP was tolerant of various conditions, including proteolytic enzymes, pH (1.2–14), surfactants, and temperatures up to 40 ��C for 12 h. The AMP demonstrated 4 µg/mL of MIC and 4–8 µg/mL of MBC against both pathogens. Time-kill kinetics showed that the AMP acted in a time- and concentration-dependent manner. A cell permeability assay and scanning electron microscopy revealed that the AMP exerted the mode of action by disrupting bacterial membranes. Additionally, nineteen biosynthetic gene clusters of secondary metabolites were identified in the genome. NNS5-6 was susceptible to various commonly used antibiotics supporting the primary safety requirement. The findings of this research could pave the way for new therapeutic approaches in combating antibiotic-resistant pathogens. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0016-7037 400 2025 Lithium- and oxygen-isotope compositions of a Si-rich nebular reservoir determined from chondrule constituents in the Sahara 97103 EH3 chondrite 51 71 EN Torii Douglas-Song The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University Tsutomu Ota The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University Masahiro Yamanaka The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University Hiroshi Kitagawa The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University Ryoji Tanaka The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University Christian Potiszil The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University Tak Kunihiro The Pheasant Memorial Laboratory Institute for Planetary Materials, Okayama University Here we report the in situ ion-microprobe analyses of the Li- and O-isotope compositions of enstatite, FeO-rich pyroxene, olivine, glass, and cristobalite grains from six chondrule-related objects from the Sahara 97103 EH3 chondrite. The O-isotope composition of the enstatite grains scattered around the intersection between the terrestrial fractionation and primitive chondrule minerals lines. Whereas, that of olivine varied along the primitive chondrule minerals line. Based on the mineralogy, we found cristobalite formed as a result of Si saturation, instead of the reduction of FeO-rich silicates, consistent with Si-enrichment of whole rock enstatite chondrites. Based on the mineralogy and O-isotope compositions, we infer that olivines in some chondrules are relict grains. In chondrules that contained olivine, no abundant niningerite [(Mg,Fe,Mn)S] was observed. Thus, enstatite formation can be explained by the interaction of an olivine precursor with additional SiO2 (Mg2SiO4 + SiO2 �� Mg2Si2O6), instead of sulfidation (Mg2SiO4 + S �� 1/2 Mg2Si2O6 + MgS + 1/2 O2). Using the equation Mg2SiO4 + SiO2 �� Mg2Si2O6 and the O-isotope compositions of enstatite and olivine, the O-isotope composition of the additional SiO2 was estimated. Based on the O-isotope composition, we infer that there could be a Si-rich gas with an elevated ��17O value similar to, or greater than the second trend line (��17O = 0.9 ��) suggested by Weisberg et al. (2021), during chondrule formation. The variation in the Li-isotope compositions of enstatite and olivine grains from EH3 chondrules is smaller than that for the same phases from CV3 chondrules. The variation in the Li-isotope compositions of the enstatite and olivine grains from EH3 chondrules is also smaller than that of their O-isotope compositions. During the recycling of enstatite-chondrite chondrules, both Li- and O-isotope compositions were homogenized. Although enstatite is the major carrier of Li in EH3 chondrules, the Li-isotope composition (��7Li) of enstatite is lower than that of whole rock EH3 chondrites, suggesting the existence of a phase with higher ��7Li. Meanwhile, the Li-isotope composition and concentration (��7Li, [Li]) of enstatite is higher than that of olivine. The Li-isotope composition of the Si-rich gas was estimated to be ��7Li = 1 ��, using a similar mass-balance calculation as applied for the O-isotope composition. The Li-isotope composition of the Si-rich gas from the enstatite-chondrite-chondrule forming-region, is consistent with that of whole rock EH3 chondrites, and differs significantly from that of the Si-rich gas from the carbonaceous-chondrite-chondrule forming-region (��7Li = �|11 ��) determined by a previous study. We speculate that the Si-rich gas in the carbonaceous-chondrite-chondrule forming-region maintained the Li-isotope heterogeneity inherited from light lithium synthesized by galactic cosmic-ray spallation in the interstellar medium. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 26 10 2025 Stem Cell Factors BAM1 and WOX1 Suppressing Longitudinal Cell Division of Margin Cells Evoked by Low-Concentration Auxin in Young Cotyledon of Arabidopsis 4724 EN Yuli Jiang Institute for Translational Brain Reaearch, Fudan University Jian Liang Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences Chunyan Wang Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences Li Tan Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences Yoji Kawano Institute of Plant Science and Resources, Okayama University Shingo Nagawa Center for Excellence in Molecular Plant Science, Chinese Academy of Sciences Highly differentiated tissues and organs play essential biological functions in multicellular organisms. Coordination of organ developmental process with tissue differentiation is necessary to achieve proper development of mature organs, but mechanisms for such coordination are not well understood. We used cotyledon margin cells from Arabidopsis plant as a new model system to investigate cell elongation and cell division during organ growth and found that margin cells endured a developmental phase transition from the �gelongation�h phase to the �gelongation and division�h phase at the early stage in germinating seedlings. We also discovered that the stem cell factors BARELY ANY MERISTEM 1 (BAM1) and WUSCHEL-related homeobox1 (WOX1) are involved in the regulation of margin cell developmental phase transition. Furthermore, exogenous auxin treatment (1 nanomolar,nM) promotes cell division, especially longitudinal cell division. This promotion of cell division did not occur in bam1 and wox1 mutants. Based on these findings, we hypothesized a new �gmoderate auxin concentration�h model which emphasizes that a moderate auxin concentration is the key to triggering the developmental transition of meristematic cells. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 1078-8174 31 6 2025 Impact of pre-reconstruction filtering with butterworth filter on 111In-pentetreotide SPECT image quality and quantitative accuracy: A phantom study 103121 EN D. Hasegawa Department of Radiological Technology, Graduate School of Health Sciences, Okayama University T. Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University M. Nakashima Department of Radiological Technology, Okayama University Hospital K. Yoshitomi Department of Radiological Technology, Okayama University Hospital M. Miyai Department of Radiological Technology, Graduate School of Health Sciences, Okayama University K. Kojima Department of Radiology, Okayama University Hospital T. Asahara Department of Radiological Technology, Faculty of Health Sciences, Okayama University Introduction: This study evaluates the image quality and quantitative accuracy of SPECT images with pre- and post-reconstruction smoothing filters in somatostatin receptor scintigraphy using phantom data.<br> Methods: We evaluated the spatial resolution, the contrast-to-noise ratio (CNR), and the quantitative accuracy using a NEMA IEC body phantom filled with a 111In solution. SPECT images were obtained with a Siemens Symbia T16 SPECT/CT system. Quantitative accuracy refers to the ability to accurately estimate the radioactive concentration of 111In in the phantom from the image. SPECT reconstructions were performed using three methods: post-reconstruction Gaussian filtering (post-G), pre-reconstruction Gaussian filtering (pre-G), and pre-reconstruction Butterworth filtering (pre-B). To verify each filtering method, the cut-off frequency of the Butterworth filter and the full width at half maximum (FWHM) of the Gaussian filter were each changed to eight different settings.<br> Results: FWHMs were 21.2, 19.8, and 18.0 mm for post-G, pre-G, and pre-B. CNRs (37-mm sphere) were 47.2, 63.8, and 69.5. Pre-B showed a 12.0 % error rate at 0.40 cycles/cm, while post-G and pre-G showed 20.2 % and 22.0 % at 7.2-mm FWHM. Pre-B outperformed other methods for resolution, CNR, and quantitative accuracy.<br> Conclusion: For 111In-pentetreotide SPECT images, image reconstruction with a Butterworth filter applied to the projection image before reconstruction was found to be superior to reconstruction with a Gaussian filter in terms of image quality and quantitative accuracy. This method can be easily implemented in routine clinical SPECT imaging workflows and has the potential to improve diagnostic confidence.<br> Implications for practice: The proposed method with a pre-reconstruction Butterworth filter has great potential to improve the image quality and quantitative accuracy of 111In-SPECT images. No potential conflict of interest relevant to this article was reported.

JMIR Publications Inc. Acta Medica Okayama 1929-0748 14 2025 Optimization of Preemptive Therapy for Cytomegalovirus Infections With Valganciclovir Based on Therapeutic Drug Monitoring: Protocol for a Phase II, Single-Center, Single-Arm Trial e72549 EN Naoki Tamura Department of Pharmacy, Kobe University Hospital Kotaro Itohara Department of Pharmacy, Kobe University Hospital Yo Ueda Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine Yumi Kitahiro Department of Pharmacy, Kobe University Hospital Kazuhiro Yamamoto Department of Integrated Clinical and Basic Pharmaceutical Sciences, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Omura Department of Pharmacy, Kobe University Hospital Toshiyasu Sakane Department of Pharmaceutical Technology, Kobe Pharmaceutical University Jun Saegusa Department of Rheumatology and Clinical Immunology, Kobe University Graduate School of Medicine Ikuko Yano Department of Pharmacy, Kobe University Hospital Background: Valganciclovir (VGCV) is the first-line drug for preemptive therapy of cytomegalovirus (CMV) infections. However, even when administered at the dose specified in the package insert, there is significant interindividual variability in the plasma concentrations of ganciclovir (GCV). In addition, correlations have been reported between the area under the concentration–time curve and therapeutic efficacy or adverse events. Therefore, therapeutic drug monitoring (TDM) can be used to improve the efficacy and safety of preemptive VGCV therapy.<br> Objective: This study aims to evaluate whether the dosage adjustment of VGCV based on TDM in patients undergoing preemptive therapy for CMV infections is associated with the successful completion rate of treatment without severe hematological adverse effects.<br> Methods: This phase II, single-center, single-arm trial aims to enroll 40 patients admitted at the Department of Rheumatology and Clinical Immunology, Kobe University Hospital, who will receive oral VGCV as preemptive therapy for CMV infections. Participants will begin treatment with VGCV at the dose recommended in the package insert, with subsequent dose adjustments based on weekly TDM results. The primary end point will be the proportion of patients who achieve CMV antigenemia negativity within 3 weeks without severe hematological adverse events. The secondary end points will include weekly changes in CMV antigen levels, total VGCV dose, and duration of preemptive therapy. For safety evaluation, the occurrence, type, and severity of VGCV-related adverse events will be analyzed. Additionally, this study will explore the correlations between the efficacy and safety of preemptive therapy and the pharmacokinetic parameters of GCV, CMV-polymerase chain reaction values, and nudix hydrolase 15 (NUDT15) genetic polymorphisms. The correlation between GCV plasma concentrations obtained from regular venous blood and blood concentrations will be examined using dried blood spots.<br> Results: This study began with patient recruitment in September 2024, with 5 participants enrolled as of June 16, 2025. The target enrollment is 40 participants, and the anticipated study completion is set for July 2027.<br> Conclusions: This is the first study to investigate the impact of TDM intervention in patients receiving VGCV as preemptive therapy. The findings are postulated to provide valuable evidence regarding the utility of TDM in patients receiving VGCV as preemptive therapy.<br> Trial Registration: Japan Registry of Clinical Trials jRCTs051240080; https://jrct.mhlw.go.jp/latest-detail/jRCTs051240080<br> International Registered Report Identifier (IRRID): DERR1-10.2196/72549 No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0956-5663 287 2025 A plant-insertable multi-enzyme biosensor for the real-time monitoring of stomatal sucrose uptake 117674 EN Shiqi Wu Graduate School of Information, Production and Systems, Waseda University Wakutaka Nakagawa Graduate School of Information, Production and Systems, Waseda University Yuki Mori Faculty and Graduate School of Environmental Engineering, The University of Kitakyushu Saman Azhari Graduate School of Information, Production and Systems, Waseda University Gábor Méhes Graduate School of Information, Production and Systems, Waseda University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Tomonori Kawano Faculty and Graduate School of Environmental Engineering, The University of Kitakyushu Takeo Miyake Graduate School of Information, Production and Systems, Waseda University Monitoring sucrose transport in plants is essential for understanding plant physiology and improving agricultural practices, yet effective sensors for continuous and real-time in-vivo monitoring are lacking. In this study, we developed a plant-insertable sucrose sensor capable of real-time sucrose concentration monitoring and demonstrated its application as a useful tool for plant research by monitoring the sugar-translocating path from leaves to the lower portion of plants through the stem in living plants. The biosensor consists of a bilirubin oxidase-based biocathode and a needle-type bioanode integrating glucose oxidase, invertase, and mutarotase, with the two electrodes separated by an agarose gel for ionic connection. The sensor exhibits a sensitivity of 6.22 ��A mM�|1 cm�|2, a limit of detection of 100 ��M, a detection range up to 60 mM, and a response time of 90 s at 100 ��M sucrose. Additionally, the sensor retained 86 % of its initial signal after 72 h of continuous measurement. Day-night monitoring from the biosensor inserted in strawberry guava (Psidium cattleianum) showed higher sucrose transport activity at night, following well the redistribution of photosynthetically produced sugars. In addition, by monitoring the forced translocation of sucrose dissolved in the stable isotopically labeled water, we demonstrated that a young seedling of Japanese cedar known as Sugi (Cryptomeria japonica) can absorb and transport both water and sucrose through light-dependently opened stomata, which is the recently revealed path for liquid uptake by higher plants. These findings highlight the potential of our sensor for studying dynamic plant processes and its applicability in real-time monitoring of sugar transport under diverse environmental conditions. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 1663-9812 16 2025 Histidine-rich glycoprotein inhibits TNF-��–induced tube formation in human vascular endothelial cells 1561628 EN Omer Faruk Hatipoglu Department of Pharmacology, Kindai University Faculty of Medicine Takashi Nishinaka Department of Pharmacology, Kindai University Faculty of Medicine Kursat Oguz Yaykasli Department of Internal Medicine 3�\Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen Shuji Mori Department of Pharmacology, School of Pharmacy, Shujitsu University Masahiro Watanabe Department of Pharmacology, School of Pharmacy, Shujitsu University Takao Toyomura Department of Pharmacology, School of Pharmacy, Shujitsu University Masahiro Nishibori Department of Translational Research and Dug Development, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Hirohata Department of Medical Technology, Graduate School of Health Sciences, Okayama University Hidenori Wake Department of Pharmacology, Kindai University Faculty of Medicine Hideo Takahashi Department of Pharmacology, Kindai University Faculty of Medicine Introduction: Tumor necrosis factor-�� (TNF-��)-induced angiogenesis plays a critical role in tumor progression and metastasis, making it an important therapeutic target in cancer treatment. Suppressing angiogenesis can effectively limit tumor growth and metastasis. However, despite advancements in understanding angiogenic pathways, effective strategies to inhibit TNF-��-mediated angiogenesis remain limited.<br> Methods: This study investigates the antiangiogenic effects of histidine-rich glycoprotein (HRG), a multifunctional plasma protein with potent antiangiogenic properties, on TNF-��-stimulated human endothelial cells (EA.hy926). Tube formation assays were performed to assess angiogenesis, and gene/protein expression analyses were conducted to evaluate HRG�fs effects on integrins ��V and ��8. The role of nuclear factor erythroid 2-related factor 2 (NRF2) in HRG-mediated antiangiogenic activity was also examined through nuclear translocation assays and NRF2 activation studies.<br> Results: At physiological concentrations, HRG effectively suppressed TNF-��-induced tube formation in vitro and downregulated TNF-��-induced expression of integrins ��V and ��8 at both the mRNA and protein levels. HRG treatment promoted NRF2 nuclear translocation in a time-dependent manner. Furthermore, activation of NRF2 significantly reduced TNF-��-induced tube formation and integrin expression, suggesting that NRF2 plays a key role in HRG-mediated antiangiogenic effects.<br> Discussion and Conclusion: Our findings indicate that HRG suppresses TNF-��-induced angiogenesis by promoting NRF2 nuclear translocation and transcriptional activation, which in turn inhibits integrin ��V and ��8 expression. Given the essential role of angiogenesis in tumor progression, HRG�fs ability to regulate this process presents a promising therapeutic strategy for cancer treatment. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0001-8686 343 2025 Progress in silicon-based materials for emerging solar-powered green hydrogen (H2) production 103558 EN Aminul Islam Department of Petroleum and Mining Engineering, Jashore University of Science and Technology Md. Tarekul Islam Department of Leather Engineering, Faculty of Mechanical Engineering, Khulna University of Engineering and Technology Siow Hwa Teo Industrial Chemistry Program, Faculty of Science and Natural Resources, Universiti Malaysia Sabah Hasan Mahmud Bangladesh Energy and Power Research Council (BEPRC) A.M. Swaraz Department of Genetic Engineering and Biotechnology, Jashore University of Science and Technology Ariyan Islam Rehan Department of Chemistry, School of Science, The University of Tokyo Adiba Islam Rasee Department of Chemistry, Graduate School of Science, Osaka University Khadiza Tul Kubra Department of Chemistry, Graduate School of Science, Osaka University Md. Munjur Hasan Department of Chemistry, Graduate School of Science, Osaka University Md. Shad Salman Institute for Chemical Research, Kyoto University R.M. Waliullah Institute for Chemical Research, Kyoto University Md. Nazmul Hasan Department of Chemistry, School of Science, The University of Tokyo Md. Chanmiya Sheikh Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Tetsuya Uchida Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University Mrs Eti Awual Department of Chemistry, Graduate School of Science, Osaka University Mohammed Sohrab Hossain Department of Chemistry, Graduate School of Science, Osaka University Hussein Znad Western Australian School of Mines: Minerals, Energy and Chemical Engineering, Curtin University Md. Rabiul Awual Western Australian School of Mines: Minerals, Energy and Chemical Engineering, Curtin University The imperative demand for sustainable and renewable energy solutions has precipitated profound scientific investigations into photocatalysts designed for the processes of water splitting and hydrogen fuel generation. The abundance, low toxicity, high conductivity, and cost-effectiveness of silicon-based compounds make them attractive candidates for hydrogen production, driving ongoing research and technological advancements. Developing an effective synthesis method that is simple, economically feasible, and environmentally friendly is crucial for the widespread implementation of silicon-based heterojunctions for sustainable hydrogen production. Balancing the performance benefits with the economic and environmental considerations is a key challenge in the development of these systems. The specific performance of each catalyst type can vary depending on the synthesis method, surface modifications, catalyst loading, and reaction conditions. The confluence of high crystallinity, reduced oxygen concentration, and calcination temperature within the silicon nanoparticle has significantly contributed to its noteworthy hydrogen evolution rate. This review provides an up-to-date evaluation of Si-based photocatalysts, summarizing recent developments, guiding future research directions, and identifying areas that require further investigation. By combining theoretical insights and experimental findings, this review offers a comprehensive understanding of Si-based photocatalysts for water splitting. Through a comprehensive analysis, it aims to elucidate existing knowledge gaps and inspire future research directions towards optimized photocatalytic performance and scalability, ultimately contributing to the realization of sustainable hydrogen generation. No potential conflict of interest relevant to this article was reported.

Pharmaceutical Society of Japan Acta Medica Okayama 0918-6158 48 1 2025 An Underlying Mechanism for the Altered Hypoglycemic Effects of Nateglinide in Rats with Acute Peripheral Inflammation 51 59 EN Haruka Toko Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Manami Ogino Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akane Nishiwaki Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Moeko Kojina Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tetsuya Aiba Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The hypoglycemic effects of nateglinide (NTG) were examined in rats with acute peripheral inflammation (API) induced by carrageenan treatment, and the mechanisms accounting for altered hypoglycemic effects were investigated. NTG was administered through the femoral vein in control and API rats, and its plasma concentration profile was characterized. The time courses of the changes in plasma glucose and insulin levels were also examined. Although the plasma concentration profile of NTG in API rats was marginally distinguishable from that in control rats, the hypoglycemic effect of NTG was more persistent in API rats than in control rats. In addition, NTG elevated the plasma level of insulin more intensely in API rats than in control rats. Then, the islets of Langerhans were procured by perfusing the pancreas with collagenase solution in control and API rats, and the pancreatic mRNA expression of preproinsulin (Ins1), as well as that of sulfonylurea receptor ABCC8 (Abcc8), were examined. As a result, the expression of preproinsulin and ABCC8 mRNA increased in API rats. These findings suggest that the hypoglycemic effect of NTG was potentiated in API rats due to increased insulin secretion in the pancreas, which was caused by enhanced preproinsulin synthesis and expression of the sulfonylurea receptor. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2753-670X 38 2 2024 Plasma concentrations of histidine-rich glycoprotein in primary graft dysfunction after lung transplantation ivae021 EN Toshio Shiotani Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Seiichiro Sugimoto Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Yasuaki Tomioka Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Shin Tanaka Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Ken Suzawa Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Kazuhiko Shien Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Kentaroh Miyoshi Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Hiromasa Yamamoto Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Mikio Okazaki Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital Shinichi Toyooka Department of General Thoracic Surgery and Organ Transplant Center, Okayama University Hospital OBJECTIVES: Histidine-rich glycoprotein has been reported as an anti-inflammatory glycoprotein that inhibits acute lung injury in mice with sepsis and as a prognostic biomarker in patients with sepsis. We investigated the relationship between plasma concentrations of histidine-rich glycoprotein and the risk of occurrence of primary graft dysfunction.<br> METHODS: According to the primary graft dysfunction grade at post-transplant 72 h, patients who underwent lung transplantation were divided into three groups: non-primary graft dysfunction group (grade 0–1), moderate primary graft dysfunction group (grade 2), and severe primary graft dysfunction group (grade 3). The plasma concentrations of histidine-rich glycoprotein measured daily during the first post-transplant 7 days were compared among the three groups. Appropriate cutoff values of the concentrations were set for survival analyses after lung transplantation.<br> RESULTS: A total of 68 patients were included. The plasma histidine-rich glycoprotein concentration at post-transplant 72 h was significantly lower in the severe primary graft dysfunction group (n = 7) than in the other two groups [non-primary graft dysfunction group (n = 43), P = 0.042; moderate primary graft dysfunction group (n = 18), P = 0.040]. Patients with plasma histidine-rich glycoprotein concentration ≥34.4 µg/ml at post-transplant 72 h had significantly better chronic lung allograft dysfunction-free survival (P = 0.012) and overall survival (P = 0.037) than those with the concentration <34.4 µg/ml.<br> CONCLUSIONS: Plasma histidine-rich glycoprotein concentrations at post-transplant 72 h might be associated with the risk of development of primary graft dysfunction. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 1422-0067 26 16 2025 Synergistic Antimicrobial Activity of BrSPR20-P1 Peptide and Silver Nanoparticles Against Pathogenic Bacteria 7832 EN Thanyamai Thongin School of Pharmacy, Walailak University Somchai Sawatdee School of Pharmacy, Walailak University Nuttapon Songnaka School of Pharmacy, Walailak University Jumpei Uchiyama Department of Bacteriology, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Theanchai Wiwasuku School of Science, Walailak University Teerapol Srichana Drug Delivery System Excellence Center and Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University Titpawan Nakpheng Drug Delivery System Excellence Center and Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Prince of Songkla University Apichart Atipairin School of Pharmacy, Walailak University Bacterial infection is a cause of life-threatening diseases. The emergence of antimicrobial-resistant bacteria exacerbates this situation, highlighting the need for the discovery of new antimicrobial agents. Our previous study identified a novel antimicrobial peptide, BrSPR20-P1 (P1), which showed potential activity against MRSA. Additionally, silver nanoparticles (AgNPs) exhibit broad-spectrum antibacterial activity, capable of killing multidrug-resistant bacteria. The combination of antimicrobial agents presents a novel strategy for combating these pathogens. This study aimed to evaluate the antibacterial activity of the combination of P1 and AgNPs. It revealed that the combinations showed synergy. The P1 and AgNP mixture at a concentration of 1 and 8 µg/mL (1:8) doubled the activity against S. aureus and MRSA, while that combination of 64 and 64 µg/mL (64:64) exhibited broad-spectrum activity, expanding to E. coli with a 32-fold increase. These combinations exhibited a bactericidal effect, showing the rapid killing of tested bacteria at 10�~ MIC, with killing rates during the first 3 h ranging from 4.04 �} 0.01 to 4.31 �} 0.03 h�|1. The P1 and AgNP mixtures caused a low risk of antibacterial resistance up to 30 passages. It was demonstrated that the synergistic activity of P1 and AgNPs occurred through the disruption of cell walls and membranes, leakage of intracellular materials, and cell lysis. Additionally, the mixtures appeared to interact with bacterial genomic DNA, as indicated by a gel retardation assay. These activities of the combinations were concentration-dependent. The 1:8 µg/mL mixture caused low hemolysis and cytotoxicity and did not impede the wound healing process. In contrast, although the 64:64 µg/mL mixture showed excellent antibacterial efficacy, it was toxic to erythrocytes and mammalian cells. It implies that dose optimization is required to balance its efficacy and toxicity. Therefore, the P1 and AgNP combinations exhibit synergistic antimicrobial activity and have the potential to resolve bacterial infections. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2662-4435 6 1 2025 Biogeochemical impact of nickel and urea in the great oxidation event 654 EN Dilan M. Ratnayake The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Ryoji Tanaka The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University Eizo Nakamura The Pheasant Memorial Laboratory for Geochemistry and Cosmochemistry, Institute for Planetary Materials, Okayama University The Great Oxidation Event marks the first substantial increase in atmospheric oxygen on Earth. Despite the oxygenic photosynthesis that emerged hundreds of million years before this event, the specific biogeochemical mechanisms responsible for maintaining low oxygen levels for an extended period remain elusive. Here, we show the critical role of urea as a nitrogen source for cyanobacteria, the cascading impact of nickel on abiotic urea production, and their combined effects on the proliferation of cyanobacteria leading to the great oxidation event. Urea formation was experimentally evaluated under simulated Archean conditions and cyanobacterial growth was monitored providing urea as the nitrogen source. Our findings demonstrate that urea can be produced in the Archean cyanobacterial habitats with UV-C irradiation, shedding light on the controversy regarding the evolution of nitrogen-fixing enzymes in primitive cyanobacteria. We propose that environmental conditions in the early Archean, characterized by elevated urea and nickel concentration, may have hindered cyanobacterial expansion, contributing to the delay between the evolution of oxygenic photosynthesis and the onset of the great oxidation event. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0021-8820 77 8 2024 Synthesis and biochemical characterization of naphthoquinone derivatives targeting bacterial histidine kinases 522 532 EN Teruhiko Ishikawa Graduate School of Education, Okayama University Yoko Eguchi Department of Science and Technology on Food Safety, Faculty of Biology-Oriented Science and Technology, Kindai University Masayuki Igarashi Institute of Microbial Chemistry (BIKAKEN) Toshihide Okajima SANKEN (The Institute of Scientific and Industrial Research), Osaka University Kohei Mita Graduate School of Education, Okayama University Yuri Yamasaki Graduate School of Education, Okayama University Kaho Sumikura Graduate School of Education, Okayama University Taisei Okumura Graduate School of Education, Okayama University Yuna Tabuchi Graduate School of Education, Okayama University Chigusa Hayashi Institute of Microbial Chemistry (BIKAKEN) Martina Pasqua Istituto Pasteur Italy, Department of Biology and Biotechnology, �gC. Darwin�h, Sapienza University of Rome Marco Coluccia Istituto Pasteur Italy, Department of Biology and Biotechnology, �gC. Darwin�h, Sapienza University of Rome Gianni Prosseda Istituto Pasteur Italy, Department of Biology and Biotechnology, �gC. Darwin�h, Sapienza University of Rome Bianca Colonna Istituto Pasteur Italy, Department of Biology and Biotechnology, �gC. Darwin�h, Sapienza University of Rome Chie Kohayakawa Department of Lead Exploration Units, Graduate School of Pharmaceutical Sciences, Osaka University Akiyoshi Tani Compound Library Screening Center, Graduate School of Pharmaceutical Sciences, Osaka University Jun-ichi Haruta Department of Lead Exploration Units, Graduate School of Pharmaceutical Sciences, Osaka University Ryutaro Utsumi SANKEN (The Institute of Scientific and Industrial Research), Osaka University Waldiomycin is an inhibitor of histidine kinases (HKs). Although most HK inhibitors target the ATP-binding region, waldiomycin binds to the intracellular dimerization domain (DHp domain) with its naphthoquinone moiety presumed to interact with the conserved H-box region. To further develop inhibitors targeting the H-box, various 2-aminonaphthoquinones with cyclic, aliphatic, or aromatic amino groups and naphtho [2,3-d] isoxazole-4,9-diones were synthesized. These compounds were tested for their inhibitory activity (IC50) against WalK, an essential HK for Bacillus subtilis growth, and their minimum inhibitory concentrations (MIC) against B. subtilis. As a result, 11 novel HK inhibitors were obtained as naphthoquinone derivatives (IC50: 12.6–305 µM, MIC: 0.5–128 µg ml�|1). The effect of representative compounds on the expression of WalK/WalR regulated genes in B. subtilis was investigated. Four naphthoquinone derivatives induced the expression of iseA (formerly yoeB), whose expression is negatively regulated by the WalK/WalR system. This suggests that these compounds inhibit WalK in B. subtilis cells, resulting in antibacterial activity. Affinity selection/mass spectrometry analysis was performed to identify whether these naphthoquinone derivatives interact with WalK in a manner similar to waldiomycin. Three compounds were found to competitively inhibit the binding of waldiomycin to WalK, suggesting that they bind to the H-box region conserved in HKs and inhibit HK activity. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 0022-0957 2025 Dual roles of suberin deposition at the endodermal Casparian strip in manganese uptake of rice 1 11 EN Toshiki Fujii Institute of Plant Science and Resources, Okayama University Naoki Yamaji Institute of Plant Science and Resources, Okayama University Jian Feng Ma Institute of Plant Science and Resources, Okayama University Rice roots are characterized by having two Casparian strips (CSs) at the exodermis and endodermis, where transporters for mineral nutrients are expressed. However, the exact role of the CS in expression of the transporters and subsequent nutrient uptake is poorly understood. Here, we first investigated the role of the CS in manganese (Mn) uptake by using a rice mutant (oscasp1) defective in formation of the endodermal CS. Knockout of OsCASP1 resulted in decreased Mn uptake under limited Mn conditions, but increased Mn uptake at high Mn concentration. Immunostaining revealed that knockout of OsCASP1 did not affect the cell specificity of localization of two transporters (OsNramp5 and OsMTP9) required for Mn uptake, but decreased the protein abundance of these transporters at the endodermis regardless of Mn concentrations tested. Furthermore, we found that overaccumulation of suberin at the endodermis of the mutants suppressed the expression of two transporters; the expression of the two transporters was only observed in the endodermal cells without suberin deposition, but not in the cells with suberin deposition. Taken together, our results indicate that there are two roles for the CS in Mn uptake; maintaining normal expression of the transporters at limited Mn concentration and preventing Mn diffusion to the stele at high Mn concentration. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2642-4150 2025 Electrostatically�]Driven Collapse of Polyelectrolytes: The Role of the Solvent's Dielectric Constant EN Anish Gulati Institute of Physical Chemistry, RWTH Aachen University Lingzi Meng Materials Science and Engineering Department, The Pennsylvania State University, State College Takaichi Watanabe Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science, and Technology, Okayama University Carlos G. Lopez Materials Science and Engineering Department, The Pennsylvania State University, State College We experimentally confirm a longstanding theoretical prediction of counterion-induced polyelectrolyte collapse in low dielectric media. The scattering behavior of polystyrene sulfonate in different solvents with dielectric permittivities in the range of �� ≃ 12 �| 180 is investigated. For high and intermediate �� media, typical polyelectrolyte behavior is observed: the correlation length (��) scales with concentration (c) as �� ∼ c�|1∕2, as predicted by various theories. When the dielectric constant of the solvent decreases below ≃ 22, a scaling of �� ∼ c�|1∕3, characteristic of partially collapsed polyelectrolytes, is observed. For these solvents, the correlation peak disappears at high concentrations. Interestingly, polyelectrolyte collapse is observed under both solvophilic and solvophobic conditions, supporting the existence of attractive electrostatic interactions. These results are in qualitative agreement with theoretical predictions which expect chain collapse in low dielectric media due to the influence of condensed counterions, either via dipolar attraction and/or charge-correlation-induced attractions. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0969-8051 144-145 2025 Investigating the fate of Zirconium-89 labelled antibody in cynomolgus macaques 109001 EN Takanori Sasaki Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Sadaaki Kimura Astellas Pharma Inc. Akihiro Noda Astellas Pharma Inc. Yoshihiro Murakami Astellas Pharma Inc. Sosuke Miyoshi Astellas Pharma Inc. Masaru Akehi Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Kazuhiko Ochiai School of Veterinary Nursing and Technology, Faculty of Veterinary Science, Nippon Veterinary and Life Science University Masami Watanabe Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Takahiro Higuchi Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Eiji Matsuura Faculty of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Background: Preclinical pharmacokinetic studies of therapeutic antibodies in non-human primates are desired because of the difficulty in extrapolating ADME data from animal models to humans. We evaluated the pharmacokinetics of 89Zr (Zirconium-89) -labelled anti-KLH human IgG and its metabolites to confirm their non-specific/physiological accumulation in healthy cynomolgus macaques. The anti-KLH antibody was used as a negative control, ensuring that the observed distribution reflected general IgG behavior rather than antigen-specific accumulation. This provides a valuable reference for comparing the biodistribution of targeted antibodies.<br> Methods: Selected IgG was conjugated to desferrioxamine (DFO), labelled with 89Zr, and injected into healthy cynomolgus macaques. PET/CT images at the whole-body level were acquired at different time points, and standard uptake values (SUV) in regions of interest, such as the heart, liver, spleen, kidneys, bone, and muscles, were calculated. The distribution of a shortened antibody variant, 89Zr-labelled Fab, as well as that of [89Zr]Zr-DFO and [89Zr]Zr-oxalate, the expected metabolites of 89Zr- labelled IgG, was also assessed.<br> Results: After 89Zr-labelled IgG injection, the SUV in the heart, vertebral body, and muscle decreased, in line with the 89Zr concentration decrease in the circulation, whereas radioactivity increased over time in the kidneys and liver. Autoradiography of the renal sections indicated that most of the 89Zr- labelled IgG radioactivity accumulated in the renal cortex. Relatively high accumulation in the kidneys was also observed in 89Zr- labelled Fab-injected macaques, and renal autoradiographs of these animals showed that the renal cortex was the preferred accumulation site. However, [89Zr]Zr-DFO was rapidly excreted into the urine, whereas [89Zr]Zr-oxalate was highly accumulated in the epiphysis of the long bones and vertebral body.<br> Conclusion: In the non-human primate cynomolgus macaque, 89Zr- labelled IgG accumulated in the kidneys and the liver. However, [89Zr]Zr-DFO and 89Zr did not accumulate in these organs. This preclinical pharmacokinetic study performed with human IgG in a non-human primate model using PET is of great significance as it sheds light on the basic fate and distribution of 89Zr- labelled IgG. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 2694-2496 4 4 2024 Light-Responsive and Antibacterial Graphenic Materials as a Holistic Approach to Tissue Engineering 263 272 EN Andrea Ferreras Department of Bioengineering, Universidad Carlos III de Madrid Ana Matesanz Department of Electronic Technology, Universidad Carlos III de Madrid Jabier Mendizabal Domotek ingeniería prototipado y formación S.L. Koldo Artola Domotek ingeniería prototipado y formación S.L. Yuta Nishina Graduate School of Natural Science and Technology, Okayama University Pablo Acedo Department of Electronic Technology, Universidad Carlos III de Madrid José L. Jorcano Department of Bioengineering, Universidad Carlos III de Madrid Amalia Ruiz Institute of Cancer Therapeutics, School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford Giacomo Reina Empa Swiss Federal Laboratories for Materials Science and Technology Cristina Martín Department of Bioengineering, Universidad Carlos III de Madrid While the continuous development of advanced bioprinting technologies is under fervent study, enhancing the regenerative potential of hydrogel-based constructs using external stimuli for wound dressing has yet to be tackled. Fibroblasts play a significant role in wound healing and tissue implants at different stages, including extracellular matrix production, collagen synthesis, and wound and tissue remodeling. This study explores the synergistic interplay between photothermal activity and nanomaterial-mediated cell proliferation. The use of different graphene-based materials (GBM) in the development of photoactive bioinks is investigated. In particular, we report the creation of a skin-inspired dressing for wound healing and regenerative medicine. Three distinct GBM, namely, graphene oxide (GO), reduced graphene oxide (rGO), and graphene platelets (GP), were rigorously characterized, and their photothermal capabilities were elucidated. Our investigations revealed that rGO exhibited the highest photothermal efficiency and antibacterial properties when irradiated, even at a concentration as low as 0.05 mg/mL, without compromising human fibroblast viability. Alginate-based bioinks alongside human fibroblasts were employed for the bioprinting with rGO. The scaffold did not affect the survival of fibroblasts for 3 days after bioprinting, as cell viability was not affected. Remarkably, the inclusion of rGO did not compromise the printability of the hydrogel, ensuring the successful fabrication of complex constructs. Furthermore, the presence of rGO in the final scaffold continued to provide the benefits of photothermal antimicrobial therapy without detrimentally affecting fibroblast growth. This outcome underscores the potential of rGO-enhanced hydrogels in tissue engineering and regenerative medicine applications. Our findings hold promise for developing game-changer strategies in 4D bioprinting to create smart and functional tissue constructs with high fibroblast proliferation and promising therapeutic capabilities in drug delivery and bactericidal skin-inspired dressings. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 2052-7276 11 11 2024 A low-cost dpMIG-seq method for elucidating complex inheritance in polysomic crops: a case study in tetraploid blueberry uhae248 EN Kyoka Nagasaka Graduate School of Agriculture, Kyoto University Kazusa Nishimura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Ko Motoki Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Keigo Yamagata Graduate School of Agriculture, Kyoto University Soichiro Nishiyama Graduate School of Agriculture, Kyoto University Hisayo Yamane Graduate School of Agriculture, Kyoto University Ryutaro Tao Graduate School of Agriculture, Kyoto University Ryohei Nakano Graduate School of Agriculture, Kyoto University Tetsuya Nakazaki Graduate School of Agriculture, Kyoto University Next-generation sequencing (NGS) library construction often requires high-quality DNA extraction, precise adjustment of DNA concentration, and restriction enzyme digestion to reduce genome complexity, which results in increased time and cost in sample preparation and processing. To address these challenges, a PCR-based method for rapid NGS library preparation, named dpMIG-seq, has been developed and proven effective for high-throughput genotyping. However, the application of dpMIG-seq has been limited to diploid and polyploid species with disomic inheritance. In this study, we obtained genome-wide single nucleotide polymorphism (SNP) markers for tetraploid blueberry to evaluate genotyping and downstream analysis outcomes. Comparison of genotyping qualities inferred across samples with different DNA concentrations and multiple bioinformatics approaches revealed high accuracy and reproducibility of dpMIG-seq-based genotyping, with Pearson's correlation coefficients between replicates in the range of 0.91 to 0.98. Furthermore, we demonstrated that dpMIG-seq enables accurate genotyping of samples with low DNA concentrations. Subsequently, we applied dpMIG-seq to a tetraploid F1 population to examine the inheritance probability of parental alleles. Pairing configuration analysis supported the random meiotic pairing of homologous chromosomes on a genome-wide level. On the other hand, preferential pairing was observed on chr-11, suggesting that there may be an exception to the random pairing. Genotypic data suggested quadrivalent formation within the population, although the frequency of quadrivalent formation varied by chromosome and cultivar. Collectively, the results confirmed applicability of dpMIG-seq for allele dosage genotyping and are expected to catalyze the adoption of this cost-effective and rapid genotyping technology in polyploid studies. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1422-0067 26 14 2025 Inhibitory Effects of Vandetanib on Catecholamine Synthesis in Rat Pheochromocytoma PC12 Cells 6927 EN Yoshihiko Itoh Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kenichi Inagaki Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Tomohiro Terasaka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eisaku Morimoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takahiro Ishii Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kimitomo Yamaoka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Fujisawa Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Gain-of-function gene alterations in rearranged during transfection (RET), a receptor tyrosine kinase, are observed in both sporadic and hereditary medullary thyroid cancers (MTCs) and pheochromocytomas and paragangliomas (PPGLs). Several tyrosine kinase inhibitors (TKIs) that target RET have been proven to be effective on MTCs and PCCs. Recently, TKIs, namely, sunitinib and selpercatinib, which were clinically used to target PPGLs, have been reported to decrease catecholamine levels without reducing tumor size. Our clinical case of metastatic medullary thyroid cancer, which is associated with RET mutations undergoing treatment with vandetanib, also suggests that vandetanib can decrease catecholamine levels. Therefore, we investigated the effect of vandetanib, a representative multi-targeted TKI for RET-related MTC, on cell proliferation and catecholamine synthesis in rat pheochromocytoma PC12 cells. Vandetanib reduced viable cells in a concentration-dependent manner. The dopamine and noradrenaline levels of the cell lysate were reduced in a concentration-dependent manner. They also decreased more prominently at lower concentrations of vandetanib compared to the inhibition of cell proliferation. The RNA knockdown study of Ret revealed that this inhibitory effect on catecholamine synthesis is mainly mediated by the suppression of RET signaling. Next, we focused on two signaling pathways downstream of RET, namely, ERK and AKT signaling. Treatment with vandetanib reduced both ERK and AKT phosphorylation in PC12 cells. Moreover, both an MEK inhibitor U0126 and a PI3K/AKT inhibitor LY294002 suppressed catecholamine synthesis without decreasing viable cells. This study in rat pheochromocytoma PC12 cells reveals the direct inhibitory effects of vandetanib on catecholamine synthesis via the suppression of RET-ERK and RET-AKT signaling. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 2050-7488 13 23 2025 A meta-linked isomer of ITIC: influence of aggregation patterns on open-circuit voltage in organic solar cells 17720 EN Kai Wang The Institute of Scientific and Industrial Research (SANKEN), The University of Osaka Seihou Jinnai The Institute of Scientific and Industrial Research (SANKEN), The University of Osaka Kaito Uesaka Graduate School of Natural Science & Technology, Okayama University Akira Yamakata Graduate School of Natural Science & Technology, Okayama University Yutaka Ie The Institute of Scientific and Industrial Research (SANKEN), The University of Osaka Improving the open-circuit voltage (VOC) of organic solar cells (OSCs) remains an important challenge. While it is known that the energy levels at the donor/acceptor (D/A) interface affect the VOC, the impact of aggregation patterns on the energy levels at the D/A interface has not been fully elucidated. Herein, we focus on ITIC, a widely used acceptor in OSCs, and designed a meta-linked isomer of ITIC (referred to as im-ITIC) to alter molecular symmetry and modify substitution arrangements. Concentration-dependent 1H NMR spectra revealed that im-ITIC shows stronger aggregation behavior in solution. Single-crystal X-ray analysis showed that im-ITIC forms both tail-to-tail (J-aggregation) and face-to-face (H-aggregation) stacking modes, whereas ITIC exclusively forms tail-to-tail stacking. OSCs based on PBDB-T:im-ITIC showed a high VOC value of 1.02 V, which is 0.12 V higher than that of those based on PBDB-T:ITIC. Time-resolved infrared measurements revealed the lifetime of free electrons for the pristine and blend films. The energy levels of the charge transfer state (ECT) for PBDB-T:im-ITIC- and PBDB-T:ITIC OSCs were determined to be 1.57 and 1.39 eV, respectively, correlating with the VOC values. Theoretical calculations indicated that pronounced H-aggregation in im-ITIC increases the ECT compared with J-aggregation, contributing to the improved VOC. This study underscores the critical impact of molecular aggregation patterns on energy alignment and VOC enhancement, offering insights into molecular design for achieving high VOC in OSCs. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0033-183X 262 2 2024 Analysis of the effect of permeant solutes on the hydraulic resistance of the plasma membrane in cells of Chara corallina 385 395 EN Masashi Tazawa Yoshida Biological Laboratory Randy Wayne Laboratory of Natural Philosophy, Plant Biology Section, Cornell University Maki Katsuhara Institute of Plant Science and Resources (IPSR), Okayama University In the cells of Chara corallina, permeant monohydric alcohols including methanol, ethanol and 1-propanol increased the hydraulic resistance of the membrane (Lpm�|1). We found that the relative value of the hydraulic resistance (rLpm�|1) was linearly dependent on the concentration (Cs) of the alcohol. The relationship is expressed in the equation: rLpm�|1 = ��mCs + 1, where ��m is the hydraulic resistance modifier coefficient of the membrane. Ye et al. (2004) showed that membrane-permeant glycol ethers also increased Lp�|1. We used their data to estimate Lpm�|1 and rLpm�|1. The values of rLpm�|1 fit the above relation we found for alcohols. When we plotted the ��m values of all the permeant alcohols and glycol ethers against their molecular weights (MW), we obtained a linear curve with a slope of 0.014 M�|1/MW and with a correlation coefficient of 0.99. We analyzed the influence of the permeant solutes on the relative hydraulic resistance of the membrane (rLpm�|1) as a function of the external (��0) and internal (��i) osmotic pressures. The analysis showed that the hydraulic resistance modifier coefficients (��m) were linearly related to the MW of the permeant solutes with a slope of 0.012 M�|1/MW and with a correlation coefficient of 0.84. The linear relationship between the effects of permeating solutes on the hydraulic resistance modifier coefficient (��m) and the MW can be explained in terms of the effect of the effective osmotic pressure on the hydraulic conductivity of water channels. The result of the analysis suggests that the osmotic pressure and not the size of the permeant solute as proposed by (Ye et al., J Exp Bot 55:449–461, 2004) is the decisive factor in a solute�fs influence on hydraulic conductivity. Thus, characean water channels (aquaporins) respond to permeant solutes with essentially the same mechanism as to impermeant solutes. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0031-9317 177 4 2025 CNGC2 Negatively Regulates Stomatal Closure and Is Not Required for flg22- and H2O2-Induced Guard Cell [Ca2+]cyt Elevation in Arabidopsis thaliana e70396 EN Rojina Akter Graduate School of Environmental and Life Science, Okayama University Yasuhiro Inoue Graduate School of Environmental and Life Science, Okayama University Saori Masumoto Faculty of Agriculture, Okayama University Yoshiharu Mimata Graduate School of Environmental and Life Science, Okayama University Takakazu Matsuura Institute of Plant Science and Resources, Okayama University Izumi C. Mori Toshiyuki Nakamura Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University In guard cells, cytosolic Ca2+ acts as a second messenger that mediates abscisic acid (ABA)- and pathogen-associated molecular pattern (PAMP)-induced stomatal closure. It was reported that Arabidopsis cyclic nucleotide-gated ion channel 2 (CNGC2) functions as hydrogen peroxide (H2O2)- and PAMP-activated Ca2+-permeable channels at the plasma membrane of mesophyll cells and mediates Ca2+-dependent PAMP-triggered immunity. In this study, we examined the role of CNGC2 in the regulation of stomatal movement because CNGC2 is also expressed in guard cells. We found that stomata of the CNGC2 disruption mutant cngc2-3 are constitutively closed even in the absence of ABA or the flagellar-derived PAMP, flg22. Consistently, leaf temperatures of the cngc2-3 mutant were higher than those of wild-type (WT) plants. The stomatal phenotype of the cngc2-3 mutant was restored by complementation with wild-type CNGC2 under the control of the guard cell preferential promoter, pGC1. Elevation of cytosolic free Ca2+ concentration in guard cells induced by flg22 and H2O2 remained intact in the cngc2-3 mutant. The introduction of the ost1-3 mutation into the cngc2-3 background did not alter the stomatal phenotype. However, the stomatal phenotype of the cngc2-3 mutant was successfully rescued in the double disruption mutant cngc2-3aba2-2. Taken together, these results suggest that CNGC2 negatively regulates stomatal closure response and does not function as flg22– and H2O2-activated Ca2+ channels in guard cells. Though CNGC2 is responsive for H2O2- and flg22-induced [Ca2+]cyt elevation in mesophyll cells, the involvement of CNGC2 in the response to H2O2 and flg22 in guard cells is questionable. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0039-9140 297 2026 Microfluidic paper-based analytical devices for antioxidant vitamins C and E in foods 128540 EN Mana Kawahara Department of Chemistry, Okayama University Kaewta Danchana Department of Chemistry, Okayama University Takashi Kaneta Department of Chemistry, Okayama University In this study, we developed microfluidic paper-based analytical devices (��PADs) for the determination of antioxidant vitamins. The proposed ��PADs utilize the reduction of metal ions by hydrophilic and hydrophobic antioxidant vitamins, which is followed by colorimetric reactions with chelating reagents. Hydrophilic vitamin C reduces Fe(III) to Fe(II) and forms a stable Fe(II)-bathophenanthroline complex in an aqueous solution. By contrast, this complex is unstable in organic solvents, and hydrophobic vitamin E requires Fe(III) and bathophenanthroline to be replaced with Cu(II) and bathocuproine. In these results, the relationship between the logarithm of a vitamin's concentration and its color intensity was linear and ranged from 4.4 to 35 mg L�|1 for ascorbic acid and 50–200 mg L�|1 for ��-tocopherol. The limits of detection, estimated from the standard deviation of blank samples, were 3.1 mg L�|1 for ascorbic acid and either 27 mg L�|1 (in hexane) or 48 mg L�|1 (in ethanol) for ��-tocopherol. The proposed method was used to quantify vitamin C in bell peppers, mandarin oranges, kiwifruit, and lemons, as well as vitamin E in almonds, almond milk, and dietary supplements. The results demonstrate the effectiveness of these ��PADs for the practical analysis of antioxidant vitamins in food samples. No potential conflict of interest relevant to this article was reported.

���{�G�A���]���w�� Acta Medica Okayama 0912-2834 40 2 2025 ���n�������q�ܗL�X�����[�t�H�����ߒ��̕]�� 99 108 EN Koichi Nakaso Faculty of Environmental, Life, Natural Science and Technology, Okayama University Daichi Yamashita Graduate School of Natural Science and Technology, Okayama University Yutaro Aoyama Graduate School of Natural Science and Technology, Okayama University Yasushi Mino Faculty of Environmental, Life, Natural Science and Technology, Okayama University Kuniaki Gotoh Faculty of Environmental, Life, Natural Science and Technology, Okayama University The granulation process of a slurry droplet containing a water-soluble polymer in a spray dryer is investigated. Although there have been many studies on the drying behavior of a single-component slurry droplet, there have been few reports for a multicomponent slurry droplet. This is due to the complexity and difficulty in evaluating the drying behavior of a multicomponent slurry droplet. Therefore, for the production of granules from multicomponent materials by a spray dryer, its operating conditions are usually determined by trial and error. To optimize the practical granule production process, the drying behavior of multicomponent slurry droplets should be studied. In this study, the drying behavior of a silica slurry droplet containing polyvinyl alcohol (PVA) is investigated. The drying behavior of a droplet suspended on the tip of a needle was observed. The effect of the volume fraction of PVA on the drying behavior and the morphology of a dried granule is studied. The effect of drying condition on the granule formation process is also investigated. As a result, the structure of dried granules was strongly influenced by PVA concentration. Segregation of PVA in the dried granules was observed. Based on the results, the drying process diagram is presented. No potential conflict of interest relevant to this article was reported.

MDPI AG Acta Medica Okayama 2072-6643 17 10 2025 Clinical Characteristics of Vitamin D Deficiency Detected in Long COVID Patients During the Omicron Phase 1692 EN Yui Matsuda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasue Sakurada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiaki Soejima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuya Yokota Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryosuke Takase Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Daisuke Omura Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: To characterize the clinical significance of vitamin D deficiency (VDD) detected in long COVID, a retrospective observational study was performed for outpatients who visited our clinic during the period from May 2024 to November 2024. Methods: Clinical trends in long COVID patients diagnosed with VDD who showed serum concentrations of 25-hydroxyvitamin D (25-OHD) lower than 20 ng/mL were compared with those in long COVID patients in a non-deficient vitamin D (NDD) group. Results: Of 126 patients with long COVID, 97 patients (female: 50) who had been infected during the Omicron phase were included. Sixty-six patients (68%) were classified in the VDD group. The median serum concentrations of 25-OHD were 14.8 ng/mL in the VDD group and 22.9 ng/mL in the NDD group. There were no significant differences between the two groups in terms of age, gender, BMI, severity of COVID-19, period after infection and vaccination history. Although the levels of serum calcium and phosphate were not significantly different between the two groups, the percentages of patients in the VDD group who complained of dizziness, memory impairment, palpitation and appetite loss were larger than those in the NDD group. Of note, the patients who complained of palpitation showed significantly lower concentrations of serum 25-OHD than those in the patients without palpitation (median: 11.9 vs. 17.3 ng/mL). Moreover, patients in the VDD group had significantly higher scores for physical and mental fatigue as well as higher scores for depressive symptoms. Conclusions: Collectively, VDD is involved in clinical manifestations of long COVID, particularly symptoms of palpitation, fatigue and depression. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0743-7463 41 21 2025 Unraveling the Molecular Mechanism of Transient Multilamellar Formation in Ethanol-Modified Vesicle Solutions 13372 13380 EN Kana Shibata Department of Materials Chemistry, Nagoya University Masatoshi Maeki Division of Applied Chemistry, Faculty of Engineering, Hokkaido University Manabu Tokeshi Division of Applied Chemistry, Faculty of Engineering, Hokkaido University Wataru Shinoda Research Institute for Interdisciplinary Science, Okayama University A recent microfluidic-based small-angle X-ray scattering (SAXS) measurement intriguingly suggested the transient formation of multilamellar structures during the mixing of unilamellar vesicles with ethanol in an aqueous solution. This study explores a possible molecular mechanism underlying this phenomenon, primarily through coarse-grained molecular dynamics (CG-MD) simulations. We first examined lipid aggregate morphology as a function of ethanol concentration in an aqueous solution. Even though vesicles were observed in pure aqueous solution, increasing ethanol concentrations led to more frequent pore formation in vesicular membranes. At ethanol concentrations above 52%, vesicles destabilized and transformed into worm-like micelles. We hypothesized that the transient multilamellar structures might arise from vesicle stacking due to variations in the effective interactions between vesicles. However, a series of potential of mean force (PMF) calculations consistently showed repulsive interactions between vesicles, regardless of ethanol concentration, ruling out this possibility. In contrast, once lipid aggregates transformed into worm-like micelles, the PMF barrier between them dropped (∼5kBT), promoting fusion. Our CG-MD simulations further demonstrated that lipid aggregates (micelles) readily fused and grew in high ethanol concentrations. Upon subsequent exposure to lower ethanol levels, these enlarged aggregates reorganized into vesicles with internal lamellar structure��multilamellar vesicles. These findings suggest that the heterogeneous mixing of unilamellar vesicular solutions with ethanol in a microfluidic device plays a key role in the emergence of transient multilamellar structures. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 2197-4284 12 1 2025 Stability and water solubility of calcium ferrite-type aluminum-rich phase: implications for deep water cycle caused by subducting basaltic crusts 32 EN Xinyue Zhang Deep Space Exploration Laboratory/School of Earth and Space Sciences, University of Science and Technology of China Izumi Mashino Institute for Planetary Materials, Okayama University Takayuki Ishii Institute for Planetary Materials, Okayama University The subducting crustal materials serve as a crucial channel for transporting water to the lower mantle. Recent experimental studies suggest that crustal materials such as basaltic crust can be a main water carrier and reservoir playing an important role on water cycling in the lower mantle. Despite being a primary mineral in crustal materials, the water solubility of calcium ferrite-type (CF) phase and its stability are unclear yet. A recent phase relation study of hydrous basalts showed Na-depletion in lower-mantle minerals, suggesting the presence of fluid possibly with high Na concentration and the absence of CF phase along the low-temperature slab geotherms, where Al-rich hydrous phase H and ferropericlase appear instead. These phases could consequently produce Na-depleted CF phase when reaching the dehydration temperature of Al-rich hydrous phase H. In this study, we investigated the stability and water solubility of CF-type MgAl2O4, which is a main CF component in a hydrous basalt, in water-bearing systems at 26–32 GPa and 1200–1900 ��C using a Kawai-type multi-anvil press. Our results indicate that the stability of the CF phase is strongly influenced by water content in the system. Water contents of recovered CF phases estimated by Fourier-transform infrared spectroscopy show a limited variation between 73 and 87 ppm wt at a pressure of 26 GPa and temperatures of 1500–1900 ��C. We suggest that CF phase could not be a primary water carrier at lower mantle depths. This emphasizes contributions of hydrous aluminous silica minerals to Earth�fs deep water cycling and heterogeneous structures in the lower mantle due to the strong water partitioning to this phase compared with other constituent minerals. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0039-9140 295 2025 Using a microfluidic paper-based analytical device and solid-phase extraction to determine phosphate concentration 128303 EN Kaewta Danchana Department of Chemistry, Okayama University Haruka Namba Department of Chemistry, Okayama University Takashi Kaneta Department of Chemistry, Okayama University Phosphate is an essential nutrient, but in high concentrations it contributes to water pollution. Traditional methods for phosphate measurement, such as absorption spectrophotometry and ion chromatography, require expensive equipment and skilled operators. This study introduces a microfluidic paper-based analytical device (��PAD) that is designed to accomplish field-based, low-concentration phosphate measurements. This ��PAD utilizes colorimetric detection based on the molybdenum blue method. Herein, we describe how the conditions were optimized in terms of design and sensitivity by adjusting reagent concentrations, paper thickness, and the time frames for sample introduction, and reaction. The operation consists of simply dipping the ��PAD into a sample, capturing images in a home-made photo studio box, and processing the images with ImageJ software to measure RGB intensity. An additional preconcentration step involves solid-phase extraction with an anion exchange resin that achieves a 10-fold enrichment, which enables detection that ranges from 0.05 to 1 mg L�|1 with a detection limit of 0.089 mg L�|1 and a quantification limit of 0.269 mg L�|1. The replicated measurements showed good reproducibility both intraday and interday (five different days) as 4.7 % and 3.0 % of relative standard deviations, respectively. After storage in a refrigerator for as long as 26 days, this ��PAD delivered stable and accurate results for real-world samples of natural water, soil, and toothpaste. The results produced using this system correlate well with those produced via spectrophotometry. This ��PAD-based method is a cost-effective, portable, rapid, and simple approach that allows relatively unskilled operators to monitor phosphate concentrations in field applications. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0041-1132 2025 Novel method of leukocytapheresis using a highly concentrated sodium citrate solution alternative to acid citrate dextrose solution A EN Masaya Abe Division of Transfusion and Cell Therapy, Okayama University Hospital Keiko Fujii Division of Clinical Laboratory, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Wataru Kitamura Division of Transfusion and Cell Therapy, Okayama University Hospital Kazuhiro Ikeuchi Division of Transfusion and Cell Therapy, Okayama University Hospital Takuya Fukumi Division of Transfusion and Cell Therapy, Okayama University Hospital Kana Washio Department of Pediatric Hematology and Oncology, Okayama University Hospital Fumio Otsuka Division of Clinical Laboratory, Okayama University Hospital Yoshinobu Maeda Department of Hematology and Oncology, Okayama University Hospital Nobuharu Fujii Division of Transfusion and Cell Therapy, Okayama University Hospital Background: Large-volume leukocytapheresis is time consuming. The upper limit of the inlet flow rate is determined by the inlet: anticoagulant (AC) ratio and can be changed by combining the AC with heparin. Here, we devised a protocol to increase the AC ratio using a highly concentrated sodium citrate solution without heparin.<br> Study Design and Methods: We collected data from 40 consecutive apheresis procedures performed using the Spectra Optia system on 40 donors for allogeneic peripheral blood stem cells between June 2022 and June 2023. We used AC containing 2.2% sodium citrate (normal concentrated sodium citrate [NSC]) and 5.32% sodium citrate (highly concentrated sodium citrate [HSC]). The AC ratios were set to 12:1 and 24:1 for the NSC and HSC, respectively.<br> Results: The processed volume was not different; the maximum inlet flow rate increased, the total processing time was reduced, the AC solution used was reduced, and the product volume was reduced in the HSC group, compared to the NSC group. Although the CD34+ cell CE2 was reduced in the HSC group, no difference was observed in the number of collected CD34+ cells. The incidences of citrate-related reactions were similar.<br> Discussion: We propose a novel leukocytapheresis method using HSC that shortens the procedure time and reduces the amount of AC solution used compared to the conventional method No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1996-1944 18 9 2025 Initial Bonding Performance to CAD/CAM Restorative Materials: The Impact of Stepwise Concentration Variation in 8-Methacryloxyoctyl Trimethoxy Silane and 3-Methacryloxypropyl Trimethoxy Silane on Feldspathic Ceramic, Lithium Disilicate Glass-Ceramic, and Polymer-Infiltrated Ceramic 1983 EN Yukinori Maruo Department of Prosthodontics, Okayama University Miho Kuwahara Department of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kumiko Yoshihara Health Research Institute, National Institute of Advanced Industrial Science and Technology Masao Irie Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Sciences, Okayama University Dental School Mai Yoshizane Department of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Matsumoto Department of Biomaterials, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kentaro Akiyama Department of Occlusal and Oral Functional Rehabilitation, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences This study investigated the effects of varying concentrations of two distinct silane agents, 8-methacryloxyoctyl trimethoxy silane (8-MOTS) and 3-methacryloxypropyl trimethoxy silane (��-MPTS), on their initial bonding efficacy to feldspathic ceramic (FC), lithium disilicate glass-ceramic (LD) and polymer-infiltrated ceramic (PIC) specimens, in 10% increments for concentrations ranging from 10% to 40%. Shear bond strengths between the ceramic substrates and the luting material were assessed following 24 h incubation in distilled water. For FC, the median value of shear bond strength peaked at 20% of ��-MPTS (7.4 MPa), while 8-MOTS exhibited a concentration-dependent increase, reaching its highest value at 40% (13.1 MPa). For LD, ��-MPTS above 10% yielded similar strength median values (10.2 MPa), whereas 8-MOTS at 30% (15.8 MPa) and 40% (13.4 MPa) yielded higher strength values than at 10% (2.9 MPa) and 20% (4.1 MPa), with the highest median value exhibited at 30%. For PIC, both ��-MPTS and 8-MOTS demonstrated similarly low bond strength values which were not significantly different from the non-silane-treated specimens. When applied on silica-based FC and LD, silane revealed a concentration-dependent bonding effect, with 8-MOTS exhibiting superior bond strength to ��-MPTS. However, PIC, characterized by a high inorganic filler content, demonstrated limited bondability with both silanes. No potential conflict of interest relevant to this article was reported.

Informa UK Limited Acta Medica Okayama 0737-3937 43 6 2025 Spray-drying of polymer solutions across a broad concentration range and the subsequent formation of a few micro- ∼nano-meter sized fibers 1108 1116 EN Chika Araga Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University Kaito Fukushima Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University Haruna Sato Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University Nao Honda Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University Takato Hasegawa Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University Koichi Nakaso Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University Naoyuki Ishida Department of Chemical Engineering and Material Sciences, Faculty of Science and Engineering, Doshisha University Koreyoshi Imamura Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology, Okayama University Spray drying is a widely utilized technique for the concentration and fine particulation of dried products. This study demonstrated that a versatile spray dryer, equipped with a two-fluid nozzle atomizer, can convert polymer solutions into nanoscale fibers by manipulating the conditions of the polymer solutions. The polymers employed in this research included polyvinylpyrrolidones (Mw 24.5 k to 60 kDa), dextrans (70 k to 450–650 kDa), pullulan, gum Arabic, Eudragit and agar, with methanol and water serving as solvents. Various combinations of polymers and solvents were subjected to spray drying at polymer concentrations ranging from 5 to 1000 g/L. Scanning electron microscopy analyses of the spray-dried samples indicated that the products transitioned from micrometer-sized particles to sub-micrometer fibers in several instances when the polymer concentrations exceeded specific threshold levels. The investigation also explored the relationship between these threshold concentrations and the surface tension and viscosity of the polymer solutions. No potential conflict of interest relevant to this article was reported.

Japanese Society for Pediatric Endocrinology Acta Medica Okayama 0918-5739 34 2 2025 Effect of calcium supplementation on bone deformity and histopathological findings of skin papules in a pediatric patient with vitamin D–dependent rickets type 2A: A case report 131 136 EN Kosei Hasegawa Department of Pediatrics, Okayama University Hospital Tomoko Miyake Department of Dermatology, Okayama University Hospital Mina Kobashi Department of Dermatology, Okayama University Hospital Tomonori Tetsunaga Department of Dermatology, Okayama University Hospital Yuko Ago Department of Pediatrics, Okayama University Hospital Natsuko Futagawa Department of Pediatrics, Okayama University Hospital Hiroyuki Miyahara Department of Pediatrics, Okayama University Hospital Yousuke Higuchi Department of Pediatrics, Okayama University Hospital Shin Morizane Department of Dermatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hirokazu Tsukahara Department of Pediatrics, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Vitamin D–dependent rickets type 2A (VDDR2A) is an autosomal recessive disease caused by pathogenic variants of the vitamin D receptor (VDR) gene. VDDR2A rickets are usually resistant to native or active vitamin D treatment because of impaired active calcium absorption against the calcium concentration gradient, which is a ligand-dependent VDR action in the small intestine. Alopecia due to an impaired skin follicular cycle is occasionally observed in patients with VDDR2A. Among the pathogenic VDR variants, most in the DNA-binding domain and some in the ligand-binding domain, which affect the dimerization of VDR with the retinoic X receptor, are associated with alopecia. Herein, we report a case of VDDR2A caused by compound heterozygous pathogenic variants of the DNA-binding domain of VDR. Active vitamin D treatment did not ameliorate genu varum, rachitic changes in the roentgenogram, or abnormal laboratory findings. However, oral administration of calcium lactate dramatically improved these findings. The patient also experienced hair loss at two months of age and multiple papules on the skin at two yr of age, which did not improve with vitamin D or calcium supplementation. We also report the histopathological findings of skin papules in this patient. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9032 13 6 2025 Effects of Trehalose on Halitosis: A Randomized Cross-Over Clinical Trial 619 EN Hisataka Miyai Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takaaki Tomofuji Department of Community Oral Health, School of Dentistry, Asahi University Hirofumi Mizuno Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Manabu Morita Department of Oral Health Sciences, Faculty of Health Care Sciences, Takarazuka University of Medical and Health Care Momoko Nakahara Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital Kota Kataoka Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital Ichiro Sumita Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital Yurika Uchida Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital Naoki Toyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aya Yokoi Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Reiko Yamanaka-Kohno Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital Noriko Takeuchi Department of Preventive Dentistry, Division of Dentistry, Okayama University Hospital Takayuki Maruyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: Halitosis is a condition characterized by an unpleasant malodor. Intra-oral halitosis is caused by volatile sulfur compounds (VSCs) and can be associated with oral dryness. Trehalose is one of the materials used to relieve oral dryness. The aim of the present study was to investigate the effect of trehalose on halitosis. Methods: This prospective, double-blinded, placebo-controlled, cross-over study enrolled volunteers from Okayama University Hospital. The participants were randomly divided into two groups, with one group receiving trehalose (a 10% trehalose solution) and the other receiving a placebo (distilled water) in a 1:1 allocation. The primary study outcome was the subjective organoleptic test. The secondary outcomes were the concentrations of the VSCs, which were measured using a portable gas chromatography device, and the oral moisture status, which was measured using an oral moisture meter. The planned sample size was 10 participants based on the previous study. Results: The final intention-to-treat analysis was performed using the data from 9 participants. After applying 10% trehalose as an oral spray, the organoleptic score decreased in a time-dependent manner. However, no significant differences were seen between the trehalose and placebo groups. In terms of secondary outcomes, the oral moisture levels increased immediately after the trehalose spray application, and significant differences in the amount of change from the baseline were seen between the trehalose and placebo groups (p = 0.047). No significant differences were seen in any of the other variables (p > 0.05). Conclusions: We could not identify any positive effects on halitosis from a one-time 10% trehalose application as an oral spray in this prospective, double-blinded, placebo-controlled, cross-over study. However, the trehalose application immediately improved the oral moisture levels and was useful for treating oral dryness. No potential conflict of interest relevant to this article was reported.

���R��w���t����J���Z���^�[ Acta Medica Okayama 2186-1323 15 2025 �������񊳎��ɑ΂��鋳��I�x���Ƃ��̌������� 341 355 EN Yiwen CHEN Graduate School of Education Doctoral Programs, Hyogo University of Teacher Education Munehisa YOSHITOSHI Graduate School of Education, Okayama University 10.18926/CTED/68503 �@�{�����́A�������񊳎��̋���I�x���Ɋւ��錤���̓����𖾂炩�ɂ��A����̉ۑ�Ƃ��̉�������N���邱�Ƃ�ړI�Ƃ����B�u�w�K�v�A�u���ȊǗ��v�A�u�ΐl�v�A�u�S���v�A�u�A�g�v��5�‚̎��_���番�͂��s�����B�w�K�x���ɂ‚��āA���Âɔ����w�K�̒x���W���͂̒ቺ�ɑ΂��A�•ʂ̋���x���v���̌��I�Ȋw�K�A����щ��u����̎��{�Ɋ��҂���Ă����B���ȊǗ��x���ł́A���������g�̕a��⎡�Âɂ�镛��p�𗝉����A�����I�ɊǗ��ł���\�͂��琬���邱�Ƃ����߂��Ă����B�ΐl�x���ɂ‚��āA�����̒������@�ɂ��A�F�l�֌W�̍\�z������ɂȂ�A���@���╜�w��̃R�~���j�P�[�V�����̎x�����d�v�ł��邱�Ƃ��m�F���ꂽ�B�S���x���ɂ����ẮA���͂ւ̌��ʓI�Ȃ��񋳈���w���{�����e�B�A�ɂ��x�����A�����̐S���I����𑣂����Ƃ������ꂽ�B�Ō�ɁA�w�Z�ƈ�Ë@�ցA�ی�҂̘A�g�s�����w�E����Ă���A�A�g�c�[���̊J�������߂��Ă���B No potential conflict of interest relevant to this article was reported.

���R��w�o�ϊw�� Acta Medica Okayama 2433-4146 56 3 2025 �n���n����P���ɂ����鐻�����Ə��̑����C�����C���� 15 33 EN Ryohei Nakamura 10.18926/OER/68444 �@�n���Ɉʒu���鑽���̎����̂ɂ����ẮC�]�����炠�鎖�Ə��̊�������V�K���Ə��̒a���ɉ����āC�����H��̗U�v�͒n��U���ɂƂ��Ă��܂��d�v�Ȑ���ƂȂ��Ă���B�����C���x�o�ϐ������ɂ�����d������^�̎Y�Ƃ̗U�v�Ƃ͈قȂ�C�n��D�ʐ����ł��邾�����p������ƗU�v�̌X���ɂȂ��Ă���B�ٗp�n�o���ʂ͐̂ɔ�ׂď������Ȃ��Ă���Ƃ͂����C�����Ƃ̑����ɂ����āC�n��̊�ՎY�ƂƂ��Ă̈ʒu�Â��͎c���Ă���B��1���̒n���n���̊��ԂŁC�ǂ̂悤�Ȓn��ɂ����āC�ǂ̂悤�Ȑ����H�ꂪ�����C�P�ނ�o���C�������Ă���̂������ʂ��C�����̗v���𕪐͂���B<br> �@2014�N��2019�N�̎��Ə��̔�r�ɂ����āC�t�����l���Y���̕��ςƕ��z�������2014�N�C2019�N�Ƃ��ɑ��݂��鎖�Ə��̘J�����Y�����ł������B�����ō����̂�2019�N�ɑ��݂��鎖�Ə��ŁC�ł��Ⴉ�����̂�2014�N�ɂ͑��݂�����2019�N�ɂ͑��݂��Ă��Ȃ����Ə��ł������B�܂����W�b�g���͂̌��ʂ���C���Y�����������Ə��K�͂��傫���Ə��ł��Ȃ��X��������C�܂��s�s���̒��x�������Ə��ŌX���ɂ��邱�Ƃ����肳�ꂽ�B�����C���������������Ə��ɂ‚��āC�Y�ƕʂɓ��Ǝ�W�ςƐl���K�͂ő������s�s�W�ς�����ϐ��Ƃ����s�����P�ʂ̉�A���͂���͐��̌��ʂ������ꂽ�B No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9032 13 5 2025 Efficacy of Oral Intake of Hydrogen-Rich Jelly Intake on Gingival Inflammation: A Double-Blind, Placebo-Controlled and Exploratory Randomized Clinical Trial 577 EN Takayuki Maruyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Eiji Takayama Department of Oral Biochemistry, Asahi University School of Dentistry Shinichi Tokuno Graduate School of Health Innovation, Kanagawa University of Human Services Manabu Morita Department of Oral Health, Takarazuka University of Medical and Health Care Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background/Objectives: Initiation and progression of periodontal disease include oxidative stress. Systemic application of antioxidants may provide clinical benefits against periodontal disease including gingivitis. Recently, a jelly containing a high concentration of hydrogen (40 ppm) was developed. We hypothesized that oral intake of this hydrogen-rich jelly may be safe and effective on gingivitis. This clinical trial was designed to investigate the safety and efficacy of oral intake of hydrogen-rich jelly against gingival inflammation. Methods: Participants with gingivitis were instructed to orally ingest 30 g of hydrogen-rich jelly (experimental group) or placebo jelly (control group) three times a day for 14 consecutive days. The primary outcome of this trial was the percentage of bleeding on probing (BOP) sites. Secondary outcomes were oral parameters, serum reactive oxygen metabolites, antioxidant capacity, oxidative index, concentrations of cytokine (interleukin [IL]-1��, IL-6, IL-10, IL-17, and tumor necrosis factor-alpha) in gingival crevicular fluid, and adverse events. For all parameters, Mann–Whitney U test was used for comparison between experimental and control groups. Analysis of covariance, controlling for baseline periodontal inflamed surface area, was performed to evaluate the association between the effect of the hydrogen-rich jelly and gingival inflammation. Results: In the experiment and control groups, the percentage of sites with BOP and PISA significantly decreased at the end of the experiment compared to the baseline. However, no significant differences were found between groups (p > 0.05). Conclusions: Administration of hydrogen-rich jelly for 14 days decreased gingival inflammation. However, no significant differences were identified compared to the control group. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0026-265X 210 2025 A microfluidic paper-based analytical device that uses gelatin film to assay protease activity via time readout 112952 EN Jianchao Ren Department of Chemistry, Okayama University Kaewta Danchana Department of Chemistry, Okayama University Takashi Kaneta Department of Chemistry, Okayama University Food processing, detergents, and pharmaceuticals frequently employ proteases, which are enzymes that break the chemical bonds of both proteins and peptides. In this work, we developed a microfluidic paper-based analytical device (µPAD) for protease activity assays via time readout. To accomplish this, we folded the µPAD to form layers, then inserted a water-insoluble gelatin film between the layers of paper to form the device. Lamination helps to maintain the gelatin film between the introduction zone, which is the upper layer, and the detection channel, which is the lower layer. Proteases decompose the gelatin film when it enters the introduction zone, which then allows it to flow into the detection channel. The protease activity in the sample solution determines the time required to dissolve the gelatin film, which leads to a linear relationship between the logarithm of the protease concentration and the time required to flow the solution a specific distance on the detection channel. The µPAD was used to measure proteases in concentrations that ranged from 0.25 to 1 mg L�|1 for bromelain, 2.5 to 10 mg L�|1 for papain, and 1 to 8 mg L�|1 for trypsin. The limits of quantification for bromelain, papain, and trypsin were 0.41, 2.7, and 9.2 mg mL�|1, respectively. The relative standard deviations for bromelain were smaller than 2 % for concentrations ranging from 0.5 to 1.0 mg L�|1. We compared the µPAD to a commercially available protease activity assay kit, which relies on quenching fluorescein isothiocyanate-labeled casein. Both methods demonstrated the same order of activity: bromelain > papain > trypsin. The proposed device allowed the assay of bromelain in both pineapple pulp and juice, which were stored at room temperature. When first using the proposed device, the bromelain in the pulp gradually lost its activity, while the activity of the bromelain in the juice showed no significant change for five days. The µPAD requires no analytical instruments for quality control and monitoring of the protease activity in food. No potential conflict of interest relevant to this article was reported.

Japan Society of Hydrology and Water Resources Acta Medica Okayama 1882-3416 19 1 2025 Evaluation of the temporal behavior of fulvic acid iron in Asahi River, Okayama, Japan 36 43 EN Rohdof Lactem Yengeh Graduate School of Environmental and Life Science, Okayama University Hiroaki Somura Graduate School of Environmental and Life Science, Okayama University Toshitsugu Moroizumi Graduate School of Environmental and Life Science, Okayama University Yasushi Mori Graduate School of Environmental and Life Science, Okayama University Morihiro Maeda Graduate School of Environmental and Life Science, Okayama University Iron is essential for biogeochemical processes in aquatic ecosystems, but its riverine concentration can be affected by environmental conditions. This study assessed weekly fulvic acid iron (FAFe) concentration at a single sampling site in Asahi River from 2022–2023 to explore the differences in the temporal scales. The objectives of this study were to evaluate the effects of physicochemical properties of the river on the concentration of FAFe, analyze the concentration of FAFe in spring, summer, autumn and winter, and assess the relationship between FAFe concentration and land use types of the watershed. The results indicated that physicochemical parameters, such as pH and surface water temperature (SWT) seemed to influence FAFe concentration (p < 0.05). Hydrological dynamics influenced FAFe concentration and transport, revealing an increasing trend during spring (p < 0.001) and summer (p = 0.05), with non-significant trends during autumn and winter (p > 0.05). FAFe exhibited a strong positive correlation with total organic carbon (TOC) (p < 0.001). Upland fields significantly influenced FAFe concentration (p < 0.01) through runoff with abundant NO3– and PO43– into the river. Thus, FAFe concentration in Asahi River was influenced by pH, SWT, TOC, hydrological regime, and agricultural runoff. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 15 1 2025 Microfluidic fabrication of rattle shaped biopolymer microcapsules via sequential phase separation in oil droplets 6666 EN Takaichi Watanabe Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology Yuko Sakai Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology Kurumi Mori Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology Tsutomu Ono Department of Applied Chemistry, Graduate School of Environmental, Life, Natural Science and Technology Multilayer microcapsules containing a small particle within a larger capsule have recently attracted considerable attention owing to their potential applications in diverse fields, including drug delivery, active ingredient storage, and chemical reactions. These complex capsules have been fabricated using interfacial polymerization or seeded emulsion polymerization. However, these methods often require complex and lengthy polymerization processes, limiting their utility, particularly in biopolymer systems. This study introduces a simple and efficient approach for preparing rattle-shaped cellulose acetate (CA) microcapsules through sequential phase separation in droplets. We systematically examine the effects of various preparation parameters, including the amount of co-solvent, initial droplet size, and flow rates, and reveal that the incorporation of a co-solvent-ethyl acetate (EA)- in the dispersed phase significantly impacts the microcapsule morphology. Our findings demonstrate a transition from a core-shell to a rattle-shaped structure as the EA concentration increases. Furthermore, the initial droplet diameter and flow rates influence microcapsule formation-larger droplets and reduced continuous-phase flow rates favor the development of multi-layered structures. These results indicate that the formation mechanism of these rattle-shaped microcapsules arises from the establishment of a radial solvent concentration gradient and subsequent phase separation within the droplets, driven by kinetic rather than thermodynamic factors. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1612-1872 2025 Antifouling Activity of Xylemin, Its Structural Analogs, and Related Polyamines e202403213 EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takefumi Yorisue Institute of Natural and Environmental Sciences, University of Hyogo Kenta Tanaka Research Institute for Interdisciplinary Science, Okayama University Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Biofouling, which is the accumulation of organisms on undersea structures, poses significant global, social, and economic issues. Although organotin compounds were effective antifoulants since the 1960s, they were banned in 2008 due to their toxicity to marine life. Although tin-free alternatives have been developed, they also raise environmental concerns. This underscores the need for effective, nontoxic antifouling agents. We previously synthesized N-(4-aminobutyl)propylamine (xylemin) and its structural analogs. In this study, we assayed the antifouling activity and toxicity of xylemin, its structural analogs, and related polyamines toward cypris larvae of the barnacle Amphibalanus amphitrite. Xylemin and its Boc-protected analog exhibited antifouling activities with 50% effective concentrations (EC50) of 4.25 and 6.11 µg/mL, respectively. Four xylemin analogs did not show a settlement-inhibitory effect at a concentration of 50 µg/mL. Putrescine, spermidine, spermine, and thermospermine, which are xylemin-related polyamines, did not display antifoulant effects (EC50 > 50 µg/mL). All evaluated compounds were nontoxic at a concentration of 50 µg/mL. These findings indicate that the size and structure of the N-alkyl group are essential for the antifouling activity of xylemin. Therefore, xylemin and its analogs hold promise as nontoxic, eco-friendly antifouling agents, offering a sustainable solution to biofouling in marine environments. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0278-6915 197 2025 Fraglide-1 from traditional Chinese aromatic vinegar: A natural AhR antagonist for atopic dermatitis 115301 EN Kosuke Kato Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Miki Akamatsu Graduate School of Environmental and Life Science, Okayama University Saya Kakimaru Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mayuko Koreishi Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Masahiro Takagi School of Materials Science, Japan Advanced Institute of Science and Technology Masahiro Miyashita Graduate School of Agriculture, Kyoto University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Ayano Satoh Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yoshio Tsujino Graduate School of Science, Technology and Innovation, Kobe University Traditional Chinese Zhenjiang aromatic vinegar (Kozu) contains Fraglide-1 (FG1), a bioactive lactone with demonstrated peroxisome proliferator-activated receptor gamma (PPAR��) agonist and antioxidant activities. This study explored FG1's novel ability to antagonize the aryl hydrocarbon receptor (AhR) signaling pathway, which regulates artemin expression and contributes to itching and inflammation in atopic dermatitis. Through molecular docking simulations and cell-based assays in human keratinocytes, we demonstrated FG1's potent antagonistic activity against AhR signaling. FG1 effectively suppressed FICZ-induced inflammatory responses, including artemin expression, with potency (half maximal inhibitory concentration, IC50 = 5.1 ��M) comparable to the synthetic antagonist StemRegenin 1 (SR1) while demonstrating a superior safety profile (median lethal concentration, LC50 > 100 ��M vs. 27.5 ��M for SR1). These findings expand our understanding of bioactive compounds from traditional fermented foods and their regulatory effects on AhR signaling, providing a foundation for future studies on FG1's role in modulating skin inflammation. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 0003-6862 2025 Effects of caffeine on the longevity and locomotion activity of the common green bottle fly, Lucilia sericata (Diptera: Calliphoridae) EN Shine Shane Naing Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Haruna Fujioka Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Teruhisa Matsuura Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Takahisa Miyatake Graduate School of Environmental, Life, Natural Science and Technology, Okayama University The common green bottle fly, Lucilia sericata (Meigen) (Diptera: Calliphoridae), is a promising and useful managed pollinator for greenhouse agricultural crops. The fly can pollinate at lower and higher temperatures than European honeybee. However, management of the longevity of pollinators is important for growers using greenhouses. Previous studies using other insects showed that caffeine affects insect longevity and behaviors. For instance, European honeybee live longer and have increased memory after caffeine consumption. How caffeine affects the longevity and behavior of pollinators is worth investigating because it can affect pollinator�fs behavior, extend longevity, or be an insecticide against pollinators. In the present study, therefore, the longevity and locomotion of L. sericata were investigated when they were given different caffeine concentrations. First, the longevity of L. sericata with five different caffeine concentrations was compared to the control. The results showed that higher concentrations of caffeine (2%, 1%, and 0.5%) significantly decreased the life span compared to lower concentrations (0.05% and 0.01%). Second, the locomotion activities of L. sericata were examined at those two caffeine concentrations with treated and control male and female flies utilizing a Drosophila Activity Monitor (DAM). Treatment with 0.05% caffeine dramatically reduced locomotion, but treatment of 0.01% caffeine did not. We also compared lipid concentrations of flies: flies treated with 0.05% caffeine had a lower lipid concentration compared to flies treated with 0% and 0.01% caffeine. These results indicate that caffeine had negative effects on the longevity and locomotion activities of the pollinator L. sericata in laboratory conditions. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 79 1 2025 Photoinitiators Induce Histamine Production in Human Mast Cells 51 58 EN Taro Miura Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoichi Kawasaki Laboratory of Clinical Pharmacology and Therapeutics, Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University Hirofumi Hamano Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshito Zamami Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toshiaki Sendo Department of Clinical Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/68362 Photoinitiators are used in the manufacture of many daily products, and may produce harmful effects due to their cytotoxicity. They have also been detected in human serum. Here, we investigated the histamine-producing effects in HMC-1 cells and the inflammatory cytokine release effects in RAW264 cells for four photoinitiators: 1-hydroxycyclohexyl phenyl ketone; 2-isopropylthioxanthone; methyl 2-benzoylbenzoate; and 2-methyl-4�L-(methylthio)-2-morpholinopropiophenone. All four promoted histamine production in HMC-1 cells; however, they did not significantly affect the release of inflammatory cytokines in RAW264 cells. These findings suggest that these four photoinitiators induce inflammatory cytokine-independent histamine production, potentially contributing to histamine-mediated chronic inflammation in vitro. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2079-6374 15 1 2025 Mapping Surface Potential in DNA Aptamer-Neurochemical and Membrane-Ion Interactions on the SOS Substrate Using Terahertz Microscopy 46 EN Kosei Morita Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Yuta Mitsuda Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Sota Yoshida Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Toshihiko Kiwa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jin Wang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University In this study, we utilized a terahertz chemical microscope (TCM) to map surface potential changes induced by molecular interactions on silicon-on-sapphire (SOS) substrates. By functionalizing the SOS substrate with DNA aptamers and an ion-selective membrane, we successfully detected and visualized aptamer-neurochemical complexes through the terahertz amplitude. Additionally, comparative studies of DNA aptamers in PBS buffer and artificial cerebrospinal fluid (aCSF) were performed by computational structure modeling and terahertz measurements. Beyond neurochemicals, we also investigated calcium ions, measuring their concentrations in PDMS-fabricated micro-wells using minimal sample volumes. Our results highlight the capability of TCM as a powerful, label-free, and sensitive platform for the probing and mapping of surface potential arising from molecular interactions, with broad implications for biomedical diagnostics and research. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0008-6223 234 2025 Reversible chemical modifications of graphene oxide for enhanced viral capture and release in water 120015 EN Pilar Ferré-Pujol Research Institute for Interdisciplinary Science, Okayama University Seiji Obata Research Institute for Interdisciplinary Science, Okayama University Jésus Raya Institut de Chimie, UMR 7177 CNRS, Université de Strasbourg Alberto Bianco Research Institute for Interdisciplinary Science, Okayama University Hiroyuki Katayama Department of Urban Engineering, School of Engineering, The University of Tokyo Takashi Kato Research Center for Water Environment Technology, School of Engineering, The University of Tokyo Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University Detecting low concentrations of viruses in sewage water is crucial for monitoring the spread of emerging viral diseases. However, current detection methods, which involve concentrating viruses using traditional materials such as gauze or cotton, have limitations in effectively accomplishing this task. This study demonstrates that graphene oxide (GO), a two-dimensional carbon material, possesses strong viral adsorption capabilities. However, it lacks efficiency for effective viral release. Therefore, we designed a series of new GO-based materials, which exhibited a viral adsorption similar to pristine GO, while significantly enhancing their release performance by attaching alkyl chains and hydrophilic functional groups. Among the synthesized materials, 1,8-aminooctanol grafted to GO (GO-NH2C8OH) has emerged as the most promising candidate, achieving a viral release rate higher than 50 %. This superior performance can be attributed to the synergistic effect of the alkyl chain and the terminal OH group, which enhances both its affinity for viruses and water dispersibility. Furthermore, we have successfully applied GO-NH2C8OH in a new protocol for concentrating viruses from sewage wastewater. This approach has demonstrated a 200-fold increase in virus concentration, allowing PCR detection of this type of pathogens present in wastewater below the detection limit by direct analysis, underscoring its significant potential for virus surveillance. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1756-4646 125 2025 Resveratrol, a food-derived polyphenol, promotes Melanosomal degradation in skin fibroblasts through coordinated activation of autophagy, lysosomal, and antioxidant pathways 106672 EN Saki Okamoto Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Saya Kakimaru Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mayuko Koreishi Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mika Sakamoto National Institute of Genetics, ROIS Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Hideya Ando Department of Applied Chemistry and Biotechnology, Okayama University of Science Yoshio Tsujino Graduate School of Science, Technology, and Innovation, Kobe University Ayano Satoh Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Resveratrol, a polyphenol found in grapes and peanuts, is known for diverse biological activities, yet its effects on dermal hyperpigmentation (so-called dark spots) remain unexplored. We investigated resveratrol's ability to enhance melanosomal degradation in human dermal fibroblasts. At concentrations of 25-50 mu M, resveratrol increased autophagy as measured by microtubule-associated protein 1A/1B-light chain 3 (LC3)-II/LC3-I ratio and enhanced lysosomal activity as assessed by a lysosomal activity reporter system. RNA sequencing revealed upregulation of lysosomal and autophagy-related genes, including cathepsins. Furthermore, reporter assays showed resveratrol's activation of antioxidant response via nuclear factor erythroid 2-related factor 2 (NRF2)mediated, leading to upregulation of transcription factor EB/transcription factor E3 (TFEB/TFE3), master regulators of lysosomal function. In fibroblasts pre-loaded with melanosomes, resveratrol reduced melanosome content compared to control by day 3. The findings reveal the activation of interconnected autophagy, lysosomal, and antioxidant pathways by resveratrol, suggesting potential applications in functional foods targeting dermal hyperpigmentation. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1520-6106 129 2 2024 Hydronium Ions Are Less Excluded from Hydrophobic Polymer–Water Interfaces than Hydroxide Ions 726 735 EN Ryan L. Myers Department of Chemistry, The Pennsylvania State University, University Park Aoi Taira Department of Chemistry, Okayama University Chuanyu Yan Department of Chemistry, The Pennsylvania State University, University Park Seung-Yi Lee Department of Chemistry, The Pennsylvania State University, University Park Lauren K. Welsh Department of Chemistry, The Pennsylvania State University, University Park Patrick R. Ianiro Department of Chemistry, University of Pittsburgh at Bradford Tinglu Yang Department of Chemistry, The Pennsylvania State University, University Park Kenichiro Koga Department of Chemistry, Okayama University Paul S. Cremer Department of Chemistry, The Pennsylvania State University, University Park The cloud point temperatures of aqueous poly(N-isopropylacrylamide) (PNIPAM) and poly(ethylene) oxide (PEO) solutions were measured from pH 1.0 to pH 13.0 at a constant ionic strength of 100 mM. This ionic strength was reached by mixing the appropriate concentration of NaCl with either HCl or NaOH. The phase transition temperature of both polymers was nearly constant between pH 2.0 and 12.0. However, the introduction of 100 mM HCl (pH 1.0) led to an increase in the cloud point temperature, although this value was still lower than the cloud point temperature in the absence of salt. By contrast, the introduction of 100 mM NaOH (pH 13.0) caused a decrease in the cloud point temperature, both relative to adding 100 mM NaCl and adding no salt. Nuclear magnetic resonance (NMR) studies of these systems were performed below the cloud point temperature, and the chemical shifts closely tracked the corresponding changes in the phase transition temperature. Specifically, the introduction of 100 mM HCl caused the 1H chemical shift to move downfield for the CH resonances from both PNIPAM and PEO, while 100 mM NaOH caused the same resonances to move upfield. Virtually no change in the chemical shift was seen between pH 2.0 and 12.0. These results are consistent with the idea that a sufficient concentration of H3O+ led to polymer swelling compared to Na+, while substituting Cl– with OH– reduced swelling. Finally, classical all-atom molecular dynamics (MD) simulations were performed with a monomer and 5-mer corresponding to PNIPAM. The results correlated closely with the thermodynamic and spectroscopic data. The simulation showed that H3O+ ions more readily accumulated around the amide oxygen moiety on PNIPAM compared with Na+. On the other hand, OH– was more excluded from the polymer surface than Cl–. Taken together, the thermodynamic, spectroscopic, and MD simulation data revealed that H3O+ was less depleted from hydrophobic polymer/water interfaces than any of the monovalent Hofmeister metal cations or even Ca2+ and Mg2+. As such, it should be placed on the far-right side of the cationic Hofmeister series. On the other hand, OH– was excluded from the interface and could be positioned in the anionic Hofmeister series between H2PO4– and SO42–. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0013-9351 222 2023 Environmental water in Kolkata is suitable for the survival of Vibrio cholerae O1 115374 EN Eizo Takahashi Collaborative Research Center of Okayama University for Infectious Diseases in India Kei Kitahara Collaborative Research Center of Okayama University for Infectious Diseases in India Shin-ichi Miyoshi Graduate School of Medicine, Dentistry and Pharmaceutical Sciences of Okayama University Goutam Chowdhury National Institute of Cholera and Enteric Diseases Asish K. Mukhopadhyay National Institute of Cholera and Enteric Diseases Shanta Dutta National Institute of Cholera and Enteric Diseases Sadayuki Ochi Department of Health Pharmacy, Yokohama University of Pharmacy Keinosuke Okamoto Graduate School of Medicine, Dentistry and Pharmaceutical Sciences of Okayama University Many patients with cholera emerge in Kolkata, India throughout the year. Such emergency indicates that cholera toxin-producing Vibrio cholerae O1 (toxigenic V. cholerae O1) are widespread in Kolkata. This suggests that the suitable conditions for replication of toxigenic V. cholerae O1 is provided in Kolkata. In previous studies, we found that the replication rate of toxigenic V. cholerae O1 is low in the low ionic aqueous solution. Then we measured the ion concentration in the environmental water of Kolkata. As a control, we measured them in Japanese environmental water. The ion concentration in the environmental water of Kolkata was significantly high. Then, we examined the survival of toxigenic V. cholerae O1 in groundwater from Kolkata and found that V. cholerae O1 survive for long time in the solution but not in the solution diluted with Milli Q water. In addition, we found that V. cholerae O1 proliferated in environmental water of Kolkata to which a small amount of nutrient was added, but did not grow in the environmental water diluted with water to which the same amount of nutrient was added. These results indicate that the environmental water from Kolkata is suitable for survival of V. cholerae O1. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1341-321X 31 2 2024 Clinical and microbiological characteristics of high-level daptomycin-resistant Corynebacterium species: A systematic scoping review 102575 EN Shinnosuke Fukushima Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Kazuyoshi Gotoh Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Shuma Tsuji Department of Medical Laboratory Science, Okayama University Graduate School of Health Sciences Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Hidemasa Akazawa Department of Infectious Diseases, Okayama University Hospital Osamu Matsushita Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of Infectious Diseases, Okayama University Hospital Introduction: Corynebacterium species potentially develop high-level daptomycin resistance (HLDR) shortly after daptomycin (DAP) administration. We aimed to investigate the clinical and microbiological characteristics of HLDR Corynebacterium infections.<br> Methods: We first presented a clinical case accompanied by the results of a comprehensive genetic analysis of the isolate, and then performed a systematic scoping review. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, we searched for articles with related keywords, including �gCorynebacterium�h, �gDaptomycin", and "Resistance�h, in the MEDLINE and Web of Science databases from the database inception to October 25, 2024. Clinical case reports and research articles documenting the isolation of HLDR Corynebacterium species, defined by a minimum inhibitory concentration of DAP at ≥256 ��g/mL, were deemed eligible for this review.<br> Results: Of 80 articles screened, seven case reports detailing eight cases of HLDR Corynebacterium infections, as well as five research articles, were included. C. striatum was the most common species (7/9 cases, 77.8 %), and prosthetic device-associated infections accounted for 66.7 % of the cases. Duration of DAP administration before the emergence of HLDR isolates ranged from 5 days to 3 months; three-quarters of the cases developed within 17 days. Three HLDR isolates were genetically confirmed to have an alteration in pgsA2. The majority of the patients were treated with either glycopeptides or linezolid, with favorable outcomes. In vitro experiments confirmed that C. striatum strains acquire the HLDR phenotype at higher rates (71 %–100 %) within 24 h of incubation, compared to other Corynebacterium strains.<br> Conclusion: DAP monotherapy, especially for prosthetic device-associated infections, can result in the development of HLDR Corynebacterium. Additional research is warranted to investigate the clinical implications of this potentially proliferating antimicrobial resistant pathogen. No potential conflict of interest relevant to this article was reported.

Informa UK Limited Acta Medica Okayama 0038-0768 71 2 2024 Effects of aged microplastics on paddy soil properties and greenhouse gas emissions under laboratory aerobic conditions 215 224 EN Tian Zhang Graduate School of Environmental and Life Science, Okayama University Hiroaki Somura Graduate School of Environmental and Life Science, Okayama University Satoshi Akao Faculty of Science and Engineering, Doshisha University Nozomi Nakahara Environmental Management Center, Okayama University Gamamada Liyanage Erandi Priyangika Perera Graduate School of Environmental and Life Science, Okayama University Chiyu Nakano Graduate School of Natural Science and Technology, Okayama University Morihiro Maeda Graduate School of Environmental and Life Science, Okayama University Microplastics (MPs) formed after changes in chemical or physical properties may alter soil properties, which in turn may affect microbial activities and greenhouse gas (GHG) emissions. However, few studies have focused on the effects of aged MPs changes on soil properties and greenhouse gas emissions. Therefore, we aimed to investigate the impact of MPs with different aging times on soil GHG emissions and dissolved organic carbon (DOC). Low-density polyethylene (PE) and polylactic acid (PLA) were treated with ultraviolet (UV) irradiation for 0–2 weeks. Soil was incubated with PE or PLA 1% (w/w) concentration at 60% water holding capacity (WHC) for 35 days. Emissions of nitrous oxide (N2O) and carbon dioxide (CO2) were measured on days 0, 1, 3, 5, 7, 14, 21, 28, and 35. Results showed that CO2 and N2O emissions were higher (p < 0.05) in MPs-amended treatments than those without MPs and increased with MPs age. The addition of virgin PE did not affect soil DOC content, whereas aged PE and all PLA additions significantly increased soil DOC content on day 0, probably because UV irradiation caused the degradation of MPs to smaller molecules. In addition, aged MPs addition altered DOC spectral characteristics on day 7, possibly because aged PE and PLA promote microbial decomposition of organic matter by altering soil properties. Changes in soil DOC content and specific ultraviolet absorbance (SUVA) by aged PE and PLA probably promoted the emissions of CO2 and N2O compared to virgin MPs or soil only. Our study revealed that aged PE and PLA promote GHG emissions from soil by changing DOC contents and qualities. No potential conflict of interest relevant to this article was reported.

Public Library of Science Acta Medica Okayama 1932-6203 19 12 2024 Phase-dependent trends in the prevalence of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) related to long COVID: A criteria-based retrospective study in Japan e0315385 EN Satoru Morita Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naruhiko Sunada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasue Sakurada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yui Matsuda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiaki Soejima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keigo Ueda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background <br> The characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) related to COVID-19 have remained uncertain. To elucidate the clinical trend of ME/CFS induced by long COVID, we examined data for patients who visited our outpatient clinic established in a university hospital during the period from Feb 2021 to July 2023.<br> <br> Methods <br> Long COVID patients were classified into two groups, an ME/CFS group and a non-ME/CFS group, based on three diagnostic criteria.<br> <br> Results <br> The prevalence of ME/CFS in the long COVID patients was 8.4% (62 of 739 cases; female: 51.6%) and factors related to ME/CFS were severe illness, smoking and alcohol drinking habits, and fewer vaccinations. The frequency of ME/CFS decreased from 23.9% in the Preceding period to 13.7% in the Delta-dominant period and to 3.3% in the Omicron-dominant period. Fatigue and headache were commonly frequent complaints in the ME/CFS group, and the frequency of poor concentration in the ME/CFS group was higher in the Omicron period. Serum ferritin levels were significantly higher in female patients in the ME/CFS group infected in the Preceding period. In the ME/CFS group, the proportion of patients complaining of brain fog significantly increased from 22.2% in the Preceding period to 47.9% in the Delta period and to 81.3% in the Omicron period. The percentage of patients who had received vaccination was lower in the ME/CFS group than the non-ME/CFS group over the study period, whereas there were no differences in the vaccination rate between the groups in each period.<br> <br> Conclusion <br> The proportion of long COVID patients who developed ME/CFS strictly diagnosed by three criteria was lower among patients infected in the Omicron phase than among patients infected in the other phases, while the proportion of patients with brain fog inversely increased. Attention should be paid to the variant-dependent trends of ME/CFS triggered by long COVID (300 words). No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 6 2024 Risk Factors for Gangrenous Cholecystitis and the Outcomes of Early Cholecystectomy: A Retrospective Study of a Single-Center City General Hospital 439 447 EN Mampei Yamashita Department of Surgery, Sasebo City General Hospital Takayuki Tanaka Department of Surgery, Sasebo City General Hospital Yorihisa Sumida Department of Surgery, Sasebo City General Hospital Shoto Yamazaki Department of Surgery, Sasebo City General Hospital Yuki Hara Department of Surgery, Sasebo City General Hospital Akiko Fukuda Department of Surgery, Sasebo City General Hospital Makoto Hisanaga Department of Surgery, Sasebo City General Hospital Koki Wakata Department of Surgery, Sasebo City General Hospital Masato Araki Department of Surgery, Sasebo City General Hospital Susumu Eguchi Department of Surgery, Nagasaki University Graduate School of Biomedical Science Original Article 10.18926/AMO/67869 Gangrenous cholecystitis (GC) is classified as moderate acute cholecystitis according to the Tokyo Guidelines from 2018 (TG18). We evaluated the risk factors for GC and the outcomes of early cholecystectomy. A total of 136 patients who underwent emergency cholecystectomy for acute cholecystitis were retrospectively analyzed; 58 of these patients (42.6%) were diagnosed with GC (GC group) based on our retrospective pathologic diagnosis. We comparatively evaluated the patient backgrounds and surgical outcomes between the GC group and non-GC group. The GC group was significantly older and included more hypertensive patients than the non-GC group. The GC group was prescribed more antibiotics as initial treatment than the non-GC group, and they had more days between onset and surgery. The preoperative white blood cell count and C-reactive protein values were significantly higher in the GC group than in the non-GC group, and these values were predictive factors for GC. Cholecystectomy required a longer operation time and caused greater blood loss in the GC group. The GC group also had longer hospitalization times than the non-GC group; however, no significant differences were observed in terms of postoperative complications. In conclusion, gangrenous changes should be assessed when diagnosing cholecystitis, and appropriate treatment, such as surgery or drainage, should be undertaken. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1424-8220 24 22 2024 Microdetection of Nucleocapsid Proteins via Terahertz Chemical Microscope Using Aptamers 7382 EN Xue Ding Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Mana Murakami Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Jin Wang Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University Hirofumi Inoue Graduate School of Medicine Dentistry and Pharmaceutical Sciences, Okayama University Hospital Toshihiko Kiwa Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University In the detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), several methods have been employed, including the detection of viral ribonucleic acid (RNA), nucleocapsid (N) proteins, spike proteins, and antibodies. RNA detection, primarily through polymerase chain reaction tests, targets the viral genetic material, whereas antigen tests detect N and spike proteins to identify active infections. In addition, antibody tests are performed to measure the immune response, indicating previous exposure or vaccination. Here, we used the developed terahertz chemical microscope (TCM) to detect different concentrations of N protein in solution by immobilizing aptamers on a semiconductor substrate (sensing plate) and demonstrated that the terahertz amplitude varies as the concentration of N proteins increases, exhibiting a highly linear relationship with a coefficient of determination (R2 = 0.9881), indicating that a quantitative measurement of N proteins is achieved. By optimizing the reaction conditions, we confirmed that the amplitude of the terahertz wave was independent of the solution volume. Consequently, trace amounts (0.5 ��L) of the N protein were successfully detected, and the detection process only took 10 min. Therefore, this study is expected to develop a rapid and sensitive method for the detection and observation of the SARS-CoV-2 virus at a microdetection level. It is anticipated that this research will significantly contribute to reducing the spread of novel infectious diseases in the future. No potential conflict of interest relevant to this article was reported.

Korean Society for Parasitology Acta Medica Okayama 2982-5164 61 3 2023 Evaluating the activity of N-89 as an oral antimalarial drug 282 291 EN Nagwa S. M. Aly Department of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hiroaki Matsumori Department of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Thi Quyen Dinh Department of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akira Sato Department of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shin-ichi Miyoshi Department of Sanitary Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kyung-Soo Chang Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan Hak Sun Yu Department of Parasitology and Tropical Medicine, School of Medicine, Pusan National University Takaaki Kubota Department of Natural Products Chemistry, Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University Yuji Kurosaki Department of Pharmaceutical Formulation Design, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Duc Tuan Cao Department of Pharmaceutical Chemistry and Quality Control, Faculty of Pharmacy, Hai Phong University of Medicine and Pharmacy Gehan A. Rashed Department of Parasitology, Benha Faculty of Medicine, Benha University Hye-Sook Kim Department of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Despite the recent progress in public health measures, malaria remains a troublesome disease that needs to be eradicated. It is essential to develop new antimalarial medications that are reliable and secure. This report evaluated the pharmacokinetics and antimalarial activity of 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) using the rodent malaria parasite Plasmodium berghei in vivo. After a single oral dose (75 mg/kg) of N-89, its pharmacokinetic parameters were measured, and t1/2 was 0.97 h, Tmax was 0.75 h, and bioavailability was 7.01%. A plasma concentration of 8.1 ng/ml of N-89 was maintained for 8 h but could not be detected at 10 h. The dose inhibiting 50% of parasite growth (ED50) and ED90 values of oral N-89 obtained following a 4-day suppressive test were 20 and 40 mg/kg, respectively. Based on the plasma concentration of N-89, we evaluated the antimalarial activity and cure effects of oral N-89 at a dose of 75 mg/kg 3 times daily for 3 consecutive days in mice harboring more than 0.5% parasitemia. In all the N-89- treated groups, the parasites were eliminated on day 5 post-treatment, and all mice recovered without a parasite recurrence for 30 days. Additionally, administering oral N-89 at a low dose of 50 mg/kg was sufficient to cure mice from day 6 without parasite recurrence. This work was the first to investigate the pharmacokinetic characteristics and antimalarial activity of N-89 as an oral drug. In the future, the following steps should be focused on developing N-89 for malaria treatments; its administration schedule and metabolic pathways should be investigated. No potential conflict of interest relevant to this article was reported.

���R��w�o�ϊw�� Acta Medica Okayama 2433-4146 56 2 2024 �G�[�W�F���g�x�[�X���f���ɂ�鎩�ȑg�D���I�W�ς̍Č��F���ʋ�ɂ�����ICT ���Ə� 41 71 EN Ryohei Nakamura Takeshi Nagamune Syusei Hayashi 10.18926/OER/67707 �@As a preliminary step to conducting a self-organizing simulation of the agglomeration and dispersion of the information and communications industry, we quantify the spatial agglomeration of the information and communications industry in Japan�fs major cities. Using the town and district data from the Economic Census for Economic Activity, we attempted a spatial analysis of the information and communications industry in the Tokyo Special Wards as well as in Sapporo, Sendai, Hiroshima, and Fukuoka, which have regional central functions. As a result of detecting spatial autocorrelation in small areas within each city, hotspots indicating the agglomeration of information and communications industry offi ces were found in the city center of each city. At the same time, we were able to confi rm the impact of agglomeration economies, which are the premise of the self-organizing model, and confi rmed that the information and communications industry is an industry suitable for simulation of the self-organizing model. �@Krugman�i1996�jwas the fi rst to model the self-organizing model in cities and clarifi ed the emergence principle of peripheral cities, but this was limited to numerical simulations. Later, Kumar et al.�i2007�jused actual data to show that Krugman�fs self-organizing model could be applied to predict corporate agglomeration and dispersion. In this paper, we use an agent-based model to examine whether a self-organizing model is also effective in reproducing and predicting the concentration and dispersion of the information and communications industry in Japanese cities. No potential conflict of interest relevant to this article was reported.

Nature Portfolio Acta Medica Okayama 2045-2322 14 1 2024 Effects of dapagliflozin on myoglobin efflux from cardiomyocyte during myocardial ischemia/reperfusion in anesthetized rats 16337 EN Tomohiro Hayashida Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yosuke Kuroko Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Shuji Shimizu Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tsuyoshi Akiyama Department of Cardiac Physiology, National Cerebral and Cardiovascular Center Takanori Suezawa Department of Cardiovascular Surgery, Fukuyama City Hospital Yukio Kioka Department of Cardiovascular Surgery, Fukuyama City Hospital Yasuhiro Kotani Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital Toshiaki Shishido Department of Research Promotion and Management, National Cerebral and Cardiovascular Center Shingo Kasahara Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and Okayama University Hospital It has been suggested that sodium-glucose cotransporter 2 (SGLT2) inhibitors have cardioprotective effects during myocardial ischemia/reperfusion (I/R) independent of glucose-lowering action. However, the effects of SGLT2 inhibitors on structural damage to cardiomyocytes in the ischemic region during I/R remain unknown. We applied a microdialysis technique to the heart of anesthetized rats and investigated the effects of an SGLT2 inhibitor, dapagliflozin, on myocardial interstitial myoglobin levels in the ischemic region during coronary occlusion followed by reperfusion. Dapagliflozin was administered systemically (40 mu g/body iv) or locally via a dialysis probe (100 mu M and 1 mM) 30 min before coronary occlusion. In the vehicle group, coronary occlusion increased the dialysate myoglobin concentration in the ischemic region. Reperfusion further increased the dialysate myoglobin concentration. Intravenous administration of dapagliflozin reduced dialysate myoglobin concentration during ischemia and at 0-15 min after reperfusion, but local administration (100 mu M and 1 mM) did not. Therefore, acute systemic administration of dapagliflozin prior to ischemia has cardioprotective effects on structural damage during I/R. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 5 2024 Effect of Radon Inhalation on Murine Brain Proteins: Investigation Using Proteomic and Multivariate Analyses 387 399 EN Shota Naoe Graduate School of Health Sciences, Okayama University Ayumi Tanaka Graduate School of Health Sciences, Okayama University Norie Kanzaki Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Reiju Takenaka Graduate School of Health Sciences, Okayama University Akihiro Sakoda Ningyo-toge Environmental Engineering Center, Japan Atomic Energy Agency Takaaki Miyaji Advanced Science Research Center, Okayama University Kiyonori Yamaoka Faculty of Health Sciences, Okayama University Takahiro Kataoka Faculty of Health Sciences, Okayama University Original Article 10.18926/AMO/67663 Radon is a known risk factor for lung cancer; however, it can be used beneficially, such as in radon therapy. We have previously reported the enhancement of antioxidant effects associated with trace amounts of oxidative stress as one of the positive biological effects of radon inhalation. However, the biological effects of radon inhalation are incompletely understood, and more detailed and comprehensive studies are required. Although several studies have used proteomics to investigate the effects of radon inhalation on body proteins, none has focused on brain proteins. In this study, we evaluated the expression status of proteins in murine brains using proteomic and multivariate analyses to identify those whose expressions changed following two days of radon inhalation at a concentration of 1,500 Bq/m3. We found associations of radon inhalation with the expressions of seven proteins related to neurotransmission and heat shock. These proteins may be proposed as biomarkers indicative of radon inhalation. Although further studies are required to obtain the detailed biological significance of these protein alterations, this study contributes to the elucidation of the biological effects of radon inhalation as a low-dose radiation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 5 2024 Phenotypic and Genetic Characteristics of Carbapenemase-Producing Enterobacterales Isolates at Okayama University Hospital 371 376 EN Kazuyoshi Gotoh Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Makoto Miyoshi Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University I Putu Bayu Mayura Department of Clinical Microbiology, Faculty of Medicine, Udayana University Shuma Tsuji Department of Medical Laboratory Science, Graduate School of Health Sciences, Okayama University Koji Iio Microbiology Division, Clinical Laboratory, Okayama University Hospital Shinnosuke Fukushima Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Osamu Matsushita Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Original Article 10.18926/AMO/67657 Spread of carbapenemase-producing Enterobacterales (CPE) is an ongoing public health issue worldwide, including in Japan. In this study, we investigated the phenotypic and genetic characteristics of CPE isolates at Okayama University Hospital over the 5 years (2013-2018) prior to the outbreak of the 2019 coronavirus pandemic. Of 24 carbapenem-resistant Enterobacterales isolated during the study period, we identified 8 CPE isolates harboring blaIMP-1 (5 isolates) and blaIMP-6 genes (3 isolates). Bacterial species and carbapenem susceptibility patterns exhibited diversity. Minimum inhibitory concentrations (MICs) of meropenem were generally higher than those of imipenem and biapenem. Results of pulsed-field gel electrophoresis demonstrated that neither clonal nor plasmid-mediated outbreaks of blaIMP-harboring CPE isolates have developed at our hospital. One Klebsiella oxytoca isolate showed a high MIC (128 ��g/mL) of meropenem, which could be explained by the high plasmid copy number. Subsequent analysis of this isolate may elucidate the intricacies of carbapenem resistance profiles among CPE isolates. Collectively, our findings underscore the necessity for ongoing genetic surveillance of CPE, complemented by tailored approaches for infection prevention and control. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1996-1944 17 17 2024 Antibacterial Dental Adhesive Containing Cetylpyridinium Chloride Montmorillonite 4368 EN Yohei Okazaki Department of Oral Health Sciences, BIOMAT, KU Leuven Kiichi Nakamori Department of Advanced Prosthodontics, Graduate School of Biomedical and Health Sciences, Hiroshima University Chenmin Yao Department of Oral Health Sciences, BIOMAT, KU Leuven Mohammed H. Ahmed Department of Oral Health Sciences, BIOMAT, KU Leuven Benjamin Mercelis Department of Oral Health Sciences, BIOMAT, KU Leuven Noriyuki Nagaoka Advanced Research Center for Oral and Craniofacial Science, Okayama University Dental School Yukinori Maruo Department of Prosthodontics, Okayama University Yasuhiro Yoshida Department of Biomaterials and Bioengineering, Faculty of Dental Medicine, Hokkaido University Yasuhiko Abe Department of Advanced Prosthodontics, Graduate School of Biomedical and Health Sciences, Hiroshima University Meerbeek, Bart Van Meerbeek Department of Oral Health Sciences, BIOMAT, KU Leuven Kumiko Yoshihara Department of Pathology & Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Oral bacteria cause tooth caries and periodontal disease. Much research is being conducted to prevent both major oral diseases by rendering dental materials' antimicrobial potential. However, such antimicrobial materials are regarded as 'combination' products and face high hurdles for regulatory approval. We loaded inorganic montmorillonite with the antimicrobial agent cetylpyridinium chloride, referred to below as 'CPC-Mont'. CPC-Mont particles in a 1, 3 and 5 wt% concentration were added to the considered gold-standard self-etch adhesive Clearfil SE Bond 2 ('CSE2'; Kuraray Noritake) to render its antibacterial potential (CSE2 without CPC-Mont served as control). Besides measuring (immediate) bonding effectiveness and (aged) bond durability to dentin, the antibacterial activity against S. mutans and the polymerization-conversion rate was assessed. Immediate and aged bond strength was not affected by 1 and 3 wt% CPC-Mont addition, while 5 wt% CPC-Mont significantly lowered bond strength and bond durability. The higher the concentration of the antimicrobial material added, the stronger the antimicrobial activity. Polymerization conversion was not affected by the CPC-Mont addition in any of the three concentrations. Hence, adding 3 wt% CPC-Mont to the two-step self-etch adhesive rendered additional antimicrobial potential on top of its primary bonding function. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9059 12 8 2024 Surface Pre-Reacted Glass-Ionomer Eluate Suppresses Osteoclastogenesis through Downregulation of the MAPK Signaling Pathway 1835 EN Janaki Chandra Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Shin Nakamura Department of Pathophysiology-Periodontal Science, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoru Shindo Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Elizabeth Leon Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Maria Castellon Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Maria Rita Pastore Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Alireza Heidari Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Lukasz Witek Biomaterials Division, NYU Dentistry Paulo G. Coelho Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami Toshiyuki Nakatsuka R&D Department, Shofu Inc. Toshihisa Kawai Department of Oral Science and Translational Research, College of Dental Medicine, Nova Southeastern University Surface pre-reacted glass-ionomer (S-PRG) is a new bioactive filler utilized for the restoration of decayed teeth by its ability to release six bioactive ions that prevent the adhesion of dental plaque to the tooth surface. Since ionic liquids are reported to facilitate transepithelial penetration, we reasoned that S-PRG applied to root caries could impact the osteoclasts (OCs) in the proximal alveolar bone. Therefore, this study aimed to investigate the effect of S-PRG eluate solution on RANKL-induced OC-genesis and mineral dissolution in vitro. Using RAW264.7 cells as OC precursor cells (OPCs), TRAP staining and pit formation assays were conducted to monitor OC-genesis and mineral dissolution, respectively, while OC-genesis-associated gene expression was measured using quantitative real-time PCR (qPCR). Expression of NFATc1, a master regulator of OC differentiation, and the phosphorylation of MAPK signaling molecules were measured using Western blotting. S-PRG eluate dilutions at 1/200 and 1/400 showed no cytotoxicity to RAW264.7 cells but did significantly suppress both OC-genesis and mineral dissolution. The same concentrations of S-PRG eluate downregulated the RANKL-mediated induction of OCSTAMP and CATK mRNAs, as well as the expression of NFATc1 protein and the phosphorylation of ERK, JNK, and p38. These results demonstrate that S-PRG eluate can downregulate RANKL-induced OC-genesis and mineral dissolution, suggesting that its application to root caries might prevent alveolar bone resorption. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0016-6480 357 2024 Revisiting the hormonal control of sexual dimorphism in chicken feathers 114601 EN Li You Graduate School of Natural Science and Technology, Okayama University Kaori Nishio Graduate School of Natural Science and Technology, Okayama University Kinue Kowata Graduate School of Natural Science and Technology, Okayama University Minaru Horikawa Department of Biology, Faculty of Science, Okayama University Hibiki Fukuchi Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Maho Ogoshi Graduate School of Natural Science and Technology, Okayama University Sayaka Aizawa Graduate School of Natural Science and Technology, Okayama University Sakae Takeuchi Graduate School of Natural Science and Technology, Okayama University Sexual dimorphism in plumage is widespread among avian species. In chickens, adult females exhibit countershading, characterized by dull-colored round feathers lacking fringe on the saddle, while adult males display vibrant plumage with deeply fringed bright feathers. This dimorphism is estrogen-dependent, and administering estrogen to males transforms their showy plumage into cryptic female-like plumage. Extensive studies have shown that estrogen�fs role in female plumage formation requires thyroid hormone; however, the precise mechanisms of their interaction remain unclear. In this study, we investigated the roles of estrogen and thyroid hormone in creating sexual dimorphism in the structure and coloration of saddle feathers by administering each hormone to adult males and observing the resulting changes in regenerated feathers induced by plucking. RT-PCR analysis revealed that the expression of type 3 deiodinase (DIO3), responsible for thyroid hormone inactivation, correlates with fringing. Estrogen suppressed DIO3 and agouti signaling protein (ASIP) expression while stimulating BlSK1, a marker of barbule cells, resulting in female-like feathers with mottled patterns and lacking fringes. Administration of thyroxine (T4) stimulated BlSK1 and proopiomelanocortin (POMC) expression, with no effect on ASIP, leading to the formation of solid black feathers lacking fringes. Triiodothyronine (T3) significantly increased POMC expression in pulp cells in culture. Taken together, these findings suggest that estrogen promotes the formation of solid vanes by suppressing DIO3 expression, while also inducing the formation of mottled patterns through inhibition of ASIP expression and indirect stimulation of melanocortin expression via changes in local T3 concentration. This is the first report describing molecular mechanism underlying hormonal crosstalk in creating sexual dimorphism in feathers. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1860-8965 38 2 2020 The neurotoxicity of psychoactive phenethylamines �g2C series�h in cultured monoaminergic neuronal cell lines 394 408 EN Masato Asanuma Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ikuko Miyazaki Department of Medical Neurobiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masahiko Funada Division of Drug Dependence, National Institute of Mental Health, National Center of Neurology and Psychiatry Purpose The aim of this study was to evaluate the neurotoxicity of psychoactive abused 2,5-dimethoxy-substituted phenethylamines �g2C series�h in monoaminergic neurons.<br> Methods After the exposure to �g2C series�h, 2,5-dimethoxy-4-propylthiophenethylamine (2C-T-7), 2,5-dimethoxy-4-isopropylthiophenethylamine (2C-T-4), 2,5-dimethoxy-4-ethylthiophenthylamine (2C-T-2), 2,5-dimethoxy-4-iodophenethylamine (2C-I) or 2,5-dimethoxy-4-chlorophenethylamine (2C-C), we examined their neurotoxicity, morphological changes, and effects of concomitant exposure to 3,4-methylenedioxymethamphetamine (MDMA) or methamphetamine (METH), using cultured neuronal dopaminergic CATH.a cells and serotonin-containing B65 cells.<br> Results Single dose exposure to �g2C series�h for 24 h showed significant cytotoxicity as increase in lactate dehydrogenase (LDH) release from both monoaminergic neurons: 2C-T-7, 2C-C (EC50; 100 µM) > 2C-T-2 (150 µM), 2C-T-4 (200 µM) > 2C-I (250 µM) in CATH.a cells and 2C-T-7, 2C-I (150 µM) > 2C-T-2 (250 µM) > 2C-C, 2C-T-4 (300 µM) in B65 cells. The �g2C series�h-induced neurotoxicity in both cells was higher than that of MDMA or METH (EC50: ≥ 1–2 mM). In addition, apoptotic morphological changes were observed at relatively lower concentrations of �g2C series�h. The concomitant exposure to non-toxic dose of MDMA or METH synergistically enhanced 2C series drugs-induced LDH release and apoptotic changes in B65 cells, but to a lesser extent in CATH.a cells. In addition, the lower dose of 2C-T-7, 2C-T-2 or 2C-I promoted reactive oxygen species production in the mitochondria of B65 cells, even at the early stages (3 h) without apparent morphological changes.<br> Conclusion The 2,5-dimethoxy-substitution of �g2C series�h induced severe neurotoxicity in both dopaminergic and serotonin-containing neurons. The non-toxic dose of MDMA or METH synergistically enhanced its neurotoxicity in serotonergic neurons. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 2666-8319 10 2024 Reduction with zinc - Impact on the determination of nitrite and nitrate ions using microfluidic paper-based analytical devices 100347 EN Mika I. Umeda Okayama University Kaewta Danchana Okayama University Takatoshi Fujii National Institute of Technology, Yonago College Eiichi Hino National Institute of Technology, Yonago College Yusuke Date National Institute of Technology, Yonago College Kaoru Aoki National Institute of Technology, Yonago College Takashi Kaneta Okayama University We used a microfluidic paper-based analytical device (mu PAD) to investigate the influence that zinc reduction exerts on the determination of nitrite and nitrate ions in natural water samples. The mu PAD consists of layered channels for the reduction of nitrate to nitrite with zinc powder and the subsequent detection of nitrite with Griess reagent. The amount of zinc, number of layers, and reaction time for the reduction were optimized to obtain an intense signal for nitrate. Initially, the sensitivity to nitrate corresponded to 55% that of nitrite, which implied an incomplete reduction. We found, however, that zinc decreased the sensitivity to nitrite in both the mu PAD and spectrophotometry. The sensitivity to nitrite was decreased by 48% in spectrophotometry and 68% in the mu PAD following the reaction with zinc. One of the reasons for the decreased sensitivity is attributed to the production of ammonia, as we elucidated that both nitrite and nitrate produced ammonia via the reaction with zinc. The results suggest that the total concentration of nitrite and nitrate must be corrected by constructing a calibration curve for nitrite with zinc, in addition to developing curves for nitrate with zinc and for nitrite without zinc. Using these calibration curves, the absorbance at different concentration ratios of nitrite and nitrate ions could be reproduced via calculation using the calibration curves with zinc for nitrite and nitrate. Eventually, the developed mu PAD was applied to the determination of nitrite and nitrate ions in natural water samples, and the results were compared with those using a conventional spectrophotometric method. The results of the mu PAD are in good agreement with those of conventional spectrophotometry, which suggests that the mu PAD is reliable for the measurement of nitrite and nitrate ions in natural water samples. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1347-6947 88 10 2024 Cytosolic acidification and oxidation are the toxic mechanisms of SO2 in Arabidopsis guard cells 1164 1171 EN Mahdi Mozhgani Institute of Plant Science and Resources, Okayama University Lia Ooi Institute of Plant Science and Resources, Okayama University Christelle Espagne Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC) Sophie Filleur Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC) Izumi C Mori Institute of Plant Science and Resources, Okayama University SO2/H2SO3 can damage plants. However, its toxic mechanism has still been controversial. Two models have been proposed, cytosolic acidification model and cellular oxidation model. Here, we assessed the toxic mechanism of H2SO3 in three cell types of Arabidopsis thaliana, mesophyll cells, guard cells (GCs), and petal cells. The sensitivity of GCs of Chloride channel a (CLCa)-knockout mutants to H2SO3 was significantly lower than those of wildtype plants. Expression of other CLC genes in mesophyll cells and petal cells were different from GCs. Treatment with antioxidant, disodium 4,5-dihydroxy-1,3-benzenedisulfonate (tiron), increased the median lethal concentration (LC50) of H2SO3 in GCs indicating the involvement of cellular oxidation, while the effect was negligible in mesophyll cells and petal cells. These results indicate that there are two toxic mechanisms of SO2 to Arabidopsis cells: cytosolic acidification and cellular oxidation, and the toxic mechanism may vary among cell types. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 13 15 2024 Impact of Serum Indoxyl Sulfate on One-Year Adverse Events in Chronic Kidney Disease Patients with Heart Failure 4384 EN Keiichiro Iwasaki Department of Cardiovascular Medicine, Okayama University Institute of Academic and Research, Medicine, Dentistry and Pharmaceutical Sciences Toru Miyoshi Department of Cardiovascular Medicine, Okayama University Institute of Academic and Research, Medicine, Dentistry and Pharmaceutical Sciences Chikara Urabe Department of Cardiovascular Medicine, Okayama University Institute of Academic and Research, Medicine, Dentistry and Pharmaceutical Sciences Satoru Sakuragi Department of Cardiovascular Medicine, Iwakuni Clinical Center Yusuke Kawai Department of Cardiovascular Medicine, Okayama City Hospital Soichiro Fuke Department of Cardiovascular Medicine, Japanese Red Cross Okayama Hospital Masayuki Doi Department of Cardiology, Kagawa Prefectural Central Hospital Atsushi Takaishi Department of Cardiology, Mitoyo General Hospital Takefumi Oka Department of Cardiology, Tsuyama Chuo Hospital Naoto Tokunaga Department of Cardiology, Ibara City Hospital Hiroshi Ito Department of General Internal Medicine 3, Kawasaki Medical School Background/Objectives: Indoxyl sulfate, a uremic toxin, is associated with mortality and cardiovascular events in patients with chronic kidney disease (CKD). This study aimed to evaluate the prognostic implications of serum indoxyl sulfate levels in patients with heart failure and CKD. Methods and Results: This was a prospective multicenter observational study. Overall, 300 patients with chronic heart failure with a previous history of hospitalization and an estimated glomerular filtration rate (eGFR) of 45 mL/min/1.73 m2 or less (CKD stage G3b to G5) without dialysis were analyzed. The primary outcome assessed in a time-to-event analysis from the measurement of indoxyl sulfate was a composite of all-cause death, hospitalization for heart failure, nonfatal myocardial infarction, and nonfatal stroke. Clinical events were followed-up to one year after indoxyl sulfate measurement. The median patient age was 75 years, and 57% of the patients were men. We divided the cohort into low and high indoxyl sulfate categories according to a median value of 9.63 mg/mL. The primary outcome occurred in 27 of 150 patients (18.0%) in the low indoxyl sulfate group and 27 of 150 patients (18.0%) in the high indoxyl sulfate group (hazard ratio, 1.00; 95% confidence interval, 0.58 to 1.70, p = 0.99). In the post hoc exploratory analyses, the results were consistent across age, sex, body mass index, left ventricular ejection fraction, eGFR, and N-terminal pro b-type natriuretic peptide. Conclusions: Among heart failure patients with CKD stages G3b to 5G, serum indoxyl sulfate concentrations were not significantly associated with the subsequent occurrence of cardiovascular events. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2077-0383 13 14 2024 New Delhi Metallo-Beta-Lactamase Inhibitors: A Systematic Scoping Review 4199 EN Lutfun Nahar Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Kazuyoshi Gotoh Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Md Asaduzzaman Department of Bacteriology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background/Objectives: Among various carbapenemases, New Delhi metallo-beta-lactamases (NDMs) are recognized as the most powerful type capable of hydrolyzing all beta-lactam antibiotics, often conferring multi-drug resistance to the microorganism. The objective of this review is to synthesize current scientific data on NDM inhibitors to facilitate the development of future therapeutics for challenging-to-treat pathogens. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews, we conducted a MEDLINE search for articles with relevant keywords from the beginning of 2009 to December 2022. We employed various generic terms to encompass all the literature ever published on potential NDM inhibitors. Results: Out of the 1760 articles identified through the database search, 91 met the eligibility criteria and were included in our analysis. The fractional inhibitory concentration index was assessed using the checkerboard assay for 47 compounds in 37 articles, which included 8 compounds already approved by the Food and Drug Administration (FDA) of the United States. Time-killing curve assays (14 studies, 25%), kinetic assays (15 studies, 40.5%), molecular investigations (25 studies, 67.6%), in vivo studies (14 studies, 37.8%), and toxicity assays (13 studies, 35.1%) were also conducted to strengthen the laboratory-level evidence of the potential inhibitors. None of them appeared to have been applied to human infections. Conclusions: Ongoing research efforts have identified several potential NDM inhibitors; however, there are currently no clinically applicable drugs. To address this, we must foster interdisciplinary and multifaceted collaborations by broadening our own horizons. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry Acta Medica Okayama 2046-2069 14 32 2024 Lead-free iron-doped Cs3Bi2Br9 perovskite with tunable properties 23177 23183 EN Thiri Htun Graduate School of Natural Science and Technology, Okayama University Amr Elattar Department of Chemistry, Faculty of Science, Ain Shams University Hytham Elbohy Physics Department, Faculty of Science, Damietta University Kosei Tsutsumi Graduate School of Natural Science and Technology, Okayama University Kazumasa Horigane Research Institute for Interdisciplinary Science, Okayama University Chiyu Nakano Advanced Science Research Center, Okayama University Xiaoyu Gu Guangdong University Key Laboratory for Advanced Quantum Dot Displays and Lighting and Department of Electronic & Electrical Engineering, Southern University of Science and Technology Hiroo Suzuki Graduate School of Natural Science and Technology, Okayama University Takeshi Nishikawa Graduate School of Natural Science and Technology, Okayama University Aung Ko Ko Kyaw Guangdong University Key Laboratory for Advanced Quantum Dot Displays and Lighting and Department of Electronic & Electrical Engineering, Southern University of Science and Technology Yasuhiko Hayashi Graduate School of Natural Science and Technology, Okayama University Perovskite based on cesium bismuth bromide offers a compelling, non-toxic alternative to lead-containing counterparts in optoelectronic applications. However, its widespread usage is hindered by its wide bandgap. This study investigates a significant bandgap tunability achieved by introducing Fe doping into the inorganic, lead-free, non-toxic, and stable Cs3Bi2Br9 perovskite at varying concentrations. The materials were synthesized using a facile method, with the aim of tuning the optoelectronic properties of the perovskite materials. Characterization through techniques such as X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, energy dispersive spectroscopy (EDS), and UV-vis spectroscopy was conducted to elucidate the transformation mechanism of the doping materials. The substitution process results in a significant change in the bandgap energy, transforming from the pristine Cs3Bi2Br9 with a bandgap of 2.54 eV to 1.78 eV upon 70% Fe doping. The addition of 50% Fe in Cs3Bi2Br9 leads to the formation of the orthorhombic structure in Cs2(Bi,Fe)Br5 perovskite, while complete Fe alloying at 100% results in the phase formation of CsFeBr4 perovskite. Our findings on regulation of bandgap energy and crystal structure through B site substitution hold significant promise for applications in optoelectronics. No potential conflict of interest relevant to this article was reported.

IOS Press Acta Medica Okayama 1387-2877 100 1 2024 A Novel Peptidome Technology for the Diagnosis of Mild Cognitive Impairment and Alzheimer�fs Disease by Selected Reaction Monitoring 219 228 EN Yusuke Fukui Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koh Tadokoro Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Minaki Hamada Protosera, Inc. Kyoichi Asada Protosera, Inc. Lyang-Ja Lee Protosera, Inc. Hidehisa Tachiki Protosera, Inc. Ryuta Morihara Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koji Abe Department of Neurology, National Center of Neurology and Psychiatry Toru Yamashita Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background:With the aging of populations worldwide, Alzheimer�fs disease (AD) has become a concern due to its high prevalence and the continued lack of established treatments. Early diagnosis is required as a preventive intervention to modify the disease�fs progression. In our previous study, we performed peptidomic analysis of serum samples obtained from AD patients and age-matched healthy subjects to seek peptide biomarker candidates for AD by using BLOTCHIP-MS analysis, and identified four peptides as AD biomarker candidates. <br> Objective:The objective was to validate the serum biomarker peptides to distinguish mild cognitive impairment (MCI) and AD in comparison to cognitively healthy controls using a new peptidome technology, the Dementia Risk Test. <br> Methods:We enrolled 195 subjects with normal cognitive function (NC; n = 70), MCI (n = 55), and AD (n = 70), The concentrations of cognitive impairment marker peptides (Fibrinogen �� chain (FAC), Fibrinogen �� chain (FBC), Plasma protease C1 inhibitor (PPC1I), ��2-HS-glycoprotein (AHSG)) were quantified by using a selected reaction monitoring assay based on liquid chromatography-MS/MS. <br> Results:The present study confirmed that three peptides, FAC, FBC, and PPC1I, were significantly upregulated during the onset of AD. This three-peptide set was both highly sensitive in determining AD (sensitivity: 85.7%, specificity: 95.7%, AUC: 0.900) and useful in distinguishing MCI (sensitivity: 61.8%, specificity: 98.6%, AUC: 0.824) from NC. <br> Conclusions:In this validation study, we confirmed the high diagnostic potential of the three peptides identified in our previous study as candidate serum biomarkers for AD. The Dementia Risk Test may be a powerful tool for detecting AD-related pathological changes. No potential conflict of interest relevant to this article was reported.

AIP Publishing Acta Medica Okayama 0003-6951 125 2 2024 Enhanced thermal conductivity of fluids by percolating high-concentration few-layer graphene 023104 EN Keiko Ishii College of Science and Engineering, Chuo University Takahiro Ogiyama College of Science and Engineering, Aoyama Gakuin University Koji Fumoto College of Science and Engineering, Aoyama Gakuin University Yuta Nishina Research Institute for Interdisciplinary Science, Okayama University High-performance and small-sized heat exchangers have been demanded due to the miniaturization and higher output of electronic devices, lasers, and energy harvesting/storage systems. Graphene nanosheet suspension has attracted attention as a next-generation nanofluid because of its high thermal conductivity and low pressure drop, while being dispersed stably without any additives. Graphene-based nanofluids have been mostly investigated using graphene oxide, and there are a few studies on pure graphene because of the limitation in mass production and stabilization at high concentrations of graphene. In this study, we prepared a 10 wt. % high-concentration few-layer graphene suspension by pulverizing graphite particles. Scanning electron microscopy, atomic force microscopy, and Raman spectra confirmed the few-layer graphene is formed in the suspension. The thermal conductivity of the suspension increased with concentration and suddenly jumped at a specific concentration. Furthermore, a significant improvement in thermal conductivity of >40% compared to base liquid was confirmed at 10 wt. % graphene content. A similar trend was observed for electrical resistance; 10 wt. % graphene suspension showed 62% lower resistance than that of 1 wt. %. These results suggest the percolation of graphene in a liquid, which has not been observed for graphene-based materials in previous research. No potential conflict of interest relevant to this article was reported.

Japan Society of Mechanical Engineers Acta Medica Okayama 2187-9745 11 6 2024 Effect of artificial defect on tensile properties of thin titanium alloy wire 24-00129 EN Junji SAKAMOTO Okayama University Naoya TADA Okayama University Takeshi UEMORI Okayama University Koyo OISHI Okayama University This study investigated the effects of artificial defects, introduced via focused ion beam (FIB) processing, on the tensile properties of thin titanium alloy wires (Ti-6Al-4V). Results indicated that the defective wires fractured when the net-section nominal stress reached the ultimate tensile strength of the smooth wires, probably because of localized stress concentrations relaxing due to plastic deformation around the defects. The effect of defects on tensile properties was classified into three regions based on the size of the defect area. In the case of small defects, wires fractured at the smooth area away from the defects where the cross-sectional strength was lower. In this case, the defects minimally affected the tensile properties. This is attributable to variations in the cross-sectional strength of the wire, which resulted in some sections with lower strength as compared with the defect area. In the case of medium-sized defects, the fracture strain decreased gradually as the defect area increased. Finally, in the case of large defects, the fracture strain was extremely small. The boundary between the medium-sized and large defects indicates the transition from plastic deformation to no plastic deformation in the smooth area. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1613-4125 68 15 2024 Unabsorbed Fecal Fat Content Correlates with a Reduction of Immunoglobulin a Coating of Gut Bacteria in High�]Lard Diet�]Fed Mice 2400078 EN Emiko Katsumata Graduate School of Environmental and Life Science, Okayama University Takeshi Tsuruta Graduate School of Environmental and Life Science, Okayama University Kei Sonoyama Research Faculty of Agriculture, Hokkaido University Takashi Yoshida TAIYO YUSHI Corporation Mio Sasaki TAIYO YUSHI Corporation Mao Teraoka Graduate School of Environmental and Life Science, Okayama University Tianyang Wang Graduate School of Environmental and Life Science, Okayama University Naoki Nishino Graduate School of Environmental and Life Science, Okayama University Scope: Immunoglobulin A (IgA) selectively coats gut bacteria and contributes to regulatory functions in gastrointestinal inflammation and glucose metabolism. Excess intake of lard leads to decrease in the IgA coating of gut bacteria, although the underlying mechanisms remain unknown. This study validates how unabsorbed fat derived from a high-lard diet in the gut affects the IgA coating of bacteria, as assessed in mouse models using three types of dietary fat (lard, medium-, and long-chain triglycerides [MLCTs], and medium-chain triglycerides [MCTs]) exhibiting different digestibilities.<br> Methods and results: C57BL/6J mice are maintained on diets containing lard, MLCTs, or MCTs at 7% or 30% w/w for 10 weeks (n = 6 per group). The fecal fatty acid concentration is measured to quantify unabsorbed fat content. The ratio of IgA-coated bacteria to total bacteria (IgA coating ratio) in the feces is measured by flow cytometry. Compared to lard-fed mice, MLCT- and MCT-fed mice exhibit lower fecal concentrations of palmitic acid, stearic acid, and oleic acid and higher IgA coating ratios at both 7% and 30% dietary fat, and these parameters exhibit significant negative correlations.<br> Conclusion: Unabsorbed fat content in the gut may result in attenuated IgA coating of bacteria in high-lard diet-fed mice.<br> No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2072-6643 16 12 2024 Prognostic Implications of Insulin Resistance in Heart Failure in Japan 1888 EN Keiichiro Iwasaki Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Kazufumi Nakamura Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Akagi Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoichi Takaya Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hironobu Toda Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toru Miyoshi Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shinsuke Yuasa Department of Cardiovascular Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Diabetes mellitus (DM) is a major risk and prognostic factor for heart failure (HF). Insulin resistance (IR) is an important component of DM, but the relationship between IR and HF prognosis has not yet been established across a wide variety of HF populations. We retrospectively evaluated the relationship between IR and clinical outcomes of HF patients at our hospital between 2017 and 2021. IR was defined as a homeostatic model assessment of IR (HOMA-IR) index >= 2.5, calculated from fasting blood glucose and insulin concentrations. The primary outcome was a composite of all-cause death and hospitalisation for HF (HHF). Among 682 patients included in the analyses, 337 (49.4%) had IR. The median age was 70 [interquartile range (IQR): 59-77] years old, and 66% of the patients were men. Among the patients, 41% had a left ventricular ejection fraction below 40%, and 32% had DM. The median follow-up period was 16.5 [IQR: 4.4-37.3] months. IR was independently associated with the primary outcome (HR: 1.91, 95% CI: 1.39-2.62, p < 0.0001), death (hazard ratio [HR]: 1.86, 95% confidence interval [CI]: 1.28-2.83, p < 0.01), and HHF (HR: 1.91, 95% CI: 1.28-2.83, p < 0.01). HOMA-IR is an independent prognostic factor of HF in a wide variety of HF populations. No potential conflict of interest relevant to this article was reported.

Japan Concrete Institute Acta Medica Okayama 1346-8014 22 5 2024 Freeze-thaw Resistance of Concrete using Ground Granulated Blast-furnace Slag and Blast-furnace Slag Sand in Salt Water 253 266 EN Toshiki Ayano Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takashi Fujii Faculty of Environmental, Life, Natural Science and Technology, Okayama University Kanako Okazaki Division of Social Engineering and Environmental Management, Graduate School of Environmental and Life Science, Okayama University The freeze-thaw resistance of concrete is significantly lower in salt water than in fresh water. Concrete deteriorates through repeated freezing and thawing, but in salt water, freezing alone leads to destruction. This paper investigated the effect of calcium hydroxide in concrete on the failure of concrete under such low temperatures. Calcium hydroxide precipitates at the transition zone between aggregate and cement paste due to the hydration of cement. The lower the temperature and the higher the concentration of salt water, the more calcium hydroxide dissolves. From concrete, more calcium hydroxide is eluted in salt water than in fresh water. This accelerates the deterioration of mortar and concrete due to freeze-thaw action. Mortar and concrete using ground granulated blast-furnace slag produces less calcium hydroxide. In mortar and concrete using blast-furnace slag sand, calcium hydroxide precipitated around the aggregate reacts with cement paste and blast-furnace slag sand to modify the transition zone. From these results, it was clarified that concrete using blast-furnace slag exhibits high freeze-thaw resistance even in salt water.<br> This paper is the English translation of the authors�f previous work [Ayano, T., Fujii, T. and Okazaki, K., (2023). �gFreeze-thaw resistance of concrete using ground granulated blast-furnace and blast-furnace slag sand in salt water.�h Japanese Journal of JSCE, 79(12), 23-00042. (in Japanese)]. No potential conflict of interest relevant to this article was reported.

Zoological Society of Japan Acta Medica Okayama 0289-0003 41 3 2024 Volume X-Ray Micro-Computed Tomography Analysis of the Early Cephalized Central Nervous System in a Marine Flatworm, Stylochoplana pusilla 281 289 EN Takanori Ikenaga Graduate School of Science and Engineering, Kagoshima University Aoshi Kobayashi Ushimado Marine Institute (UMI), Faculty of Environmental, Life, Natural Science and Technology, Okayama University Akihisa Takeuchi Japan Synchrotron Radiation Research Institute/SPring-8 Kentaro Uesugi Japan Synchrotron Radiation Research Institute/SPring-8 Takanobu Maezawa Department of Integrated Science and Technology, National Institute of Technology, Tsuyama College Norito Shibata Department of Integrated Science and Technology, National Institute of Technology, Tsuyama College Tatsuya Sakamoto Ushimado Marine Institute (UMI), Faculty of Environmental, Life, Natural Science and Technology, Okayama University Hirotaka Sakamoto Ushimado Marine Institute (UMI), Faculty of Environmental, Life, Natural Science and Technology, Okayama University Platyhelminthes are a phylum of simple bilaterian invertebrates with prototypic body systems. Compared with non-bilaterians such as cnidarians, the bilaterians are likely to exhibit integrated free-moving behaviors, which require a concentrated nervous system �gbrain�h rather than the distributed nervous system of radiatans. Marine flatworms have an early cephalized �ecentral�f nervous system compared not only with non-bilaterians but also with parasitic flatworms or freshwater planarians. In this study, we used the marine flatworm Stylochoplana pusilla as an excellent model organism in Platyhelminthes because of the early cephalized central nervous system. Here, we investigated the three-dimensional structures of the flatworm central nervous system by the use of X-ray micro-computed tomography (micro-CT) in a synchrotron radiation facility. We found that the obtained tomographic images were sufficient to discriminate some characteristic structures of the nervous system, including nerve cords around the cephalic ganglion, mushroom body-like structures, and putative optic nerves forming an optic commissure-like structure. Through the micro-CT imaging, we could obtain undistorted serial section images, permitting us to visualize precise spatial relationships of neuronal subpopulations and nerve tracts. 3-D micro-CT is very effective in the volume analysis of the nervous system at the cellular level; the methodology is straightforward and could be applied to many other non-model organisms. No potential conflict of interest relevant to this article was reported.

Hindawi Acta Medica Okayama 2090-8113 2024 2024 Circadian Rhythms Fluctuate the Treatment Effects of Intravesical Treatments on Rat Urinary Frequency Models 6505595 EN Tomofumi Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takuya Sadahira Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yusuke Tominaga Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Maruyama Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naoya Nagasaki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takanori Sekito Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Edamura Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Toyohiko Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Motoo Araki Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masami Watanabe Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Objectives. It is still not clear how the intravesical instillation of drugs affects rat urinary frequency. This study aimed to examine the dynamics of intravesical treatments' treatment effect on rat urinary frequency models by real-time and extended monitoring using a novel continuous urination monitoring system. Methods. Nine eleven-week-old female Wistar rats were divided into three groups to receive intravesical instillation of 0.1% acetic acid (AA), 1.0% AA, or phosphate-buffered saline (PBS). Thirty minutes later, these drugs were voided, and rats were moved to a continuous urination monitoring system, UM-100. UM-100 monitored rat urination quantitatively and continuously for 24 hours. Rats were then euthanized, and histopathologic examinations using a damage score validated the severity of bladder inflammation. We used nine additional rats to determine the treatment effect of various drugs against the urinary frequency. These rats were also treated with 1.0% AA in the same way and divided into three groups (n = 3 each) to receive intravesical instillation of lidocaine, silver nitrate (AgNO3), or dimethyl sulfoxide (DMSO), respectively. Thirty minutes later, rats were catheterized again and moved to the UM-100, and their voiding was monitored for 24 hours. Results. Intravesical instillation of AA increased the urinary frequency and decreased the mean voided volume (VV) in a concentration-dependent manner, with statistical significance at a concentration of 1.0% (urinary frequency; p = 0.0007 , mean VV; p = 0.0032 , respectively) compared with PBS. Histopathological analysis of these models demonstrated a significantly higher damage score of bladder mucosa in both 0.1% AA and 1.0% AA compared with PBS, with the severity in concordance with the clinical severity of urinary frequency (0.1% AA: p < 0.0001 , 1.0% AA: p < 0.0001 ). Moreover, intravesical instillation of lidocaine, AgNO3, and DMSO decreased the urinary frequency. Continuous monitoring with UM-100 also demonstrated that the treatment effect of these intravesically instilled drugs occurred only at night. Conclusions. The extended monitoring of rat urination by UM-100 revealed a significant fluctuation in the treatment effect of intravesically instilled drugs between day and night. These findings may help establish novel therapies for urinary frequency. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 3 2024 The Role of the Lipid Profile and Oxidative Stress in Fatigue, Sleep Disorders and Cognitive Impairment in Patients with Multiple Sclerosis 259 270 EN Gonul Vural Department of Neurology, Faculty of Medicine, Ankara Yildirim Beyazit University Esra Demir Department of Neurology, Ankara City Hospital Sadiye Gumusyayla Department of Neurology, Faculty of Medicine, Ankara Yildirim Beyazit University Funda Eren Department of Clinical Biochemistry, Ankara City Hospital Serdar Barakli Department of Neurology, Ankara City Hospital Salim Neselioglu Department of Clinical Biochemistry, Ankara City Hospital Ozcan Erel Department of Clinical Biochemistry, Ankara City Hospital Original Article 10.18926/AMO/67201 The aim of this study is to investigate the relationship of the lipid profile, dysfunctional high-density lipoprotein, ischaemia-modified albumin and thiol–disulfide homeostasis with cognitive impairment, fatigue and sleep disorders in patients with multiple sclerosis. The cognitive functions of patients were evaluated with the Brief International Cognitive Assessment for Multiple Sclerosis battery. Fatigue was evaluated with the Fatigue Severity Scale and the Fatigue Impact Scale. The Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale were used to assess patients�f sleep disturbance. Peripheral blood samples were collected, and lipid levels and myeloperoxidase and paraoxonase activity were measured. The myeloperoxidase/paraoxonase ratio, which indicates dysfunctional high-density lipoprotein, was calculated. Thiol–disulfide homeostasis and ischaemia-modified albumin were measured.<br> We did not identify any relationship between dysfunctional high-density lipoprotein and the physical disability, cognitive decline, fatigue and sleep problems of multiple sclerosis. Thiol–disulfide homeostasis was associated with cognitive scores. The shift of the balance towards disulfide was accompanied by a decrease in cognitive scores. On the other hand, we did not detect any relationship between fatigue and sleep disorders and thiol–disulfide homeostasis. Our findings revealed a possible correlation between cognitive dysfunction and thiol–disulfide homeostasis in multiple sclerosis patients. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2227-9032 12 10 2024 Effect of Antimicrobial Photodynamic Therapy on the Tongue Dorsum on Reducing Halitosis and the Duration of the Effect: A Randomized Clinical Trial 980 EN Takayuki Maruyama Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Daisuke Ekuni Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aya Yokoi Department of Preventive Dentistry, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Junichiro Nagasaki Okayama University Dental School Nanami Sawada Department of Preventive Dentistry, Okayama University Hospital Manabu Morita Department of Oral Health Sciences, Takarazuka University of Medical and Health Care Antimicrobial photodynamic therapy (PDT) is a treatment that is gaining popularity in modern clinical medicine. However, little is known about the effect of PDT alone on reducing oral halitosis and the duration of the effect. This trial examined the effect of PDT on the tongue dorsum on reducing oral halitosis and the duration of the effect. This study was approved by the Ethics Committee of Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, and Okayama University Hospital (CRB20-015), and it was registered in the Japan Registry of Clinical Trials (jRCTs061200060). Twenty-two participants were randomly assigned to two groups: an intervention group and control group. PDT was performed in the intervention group using red laser emission and methylene blue gel on the middle and posterior area of the tongue dorsum. The concentration of volatile sulfur compounds, bacterial count on the tongue dorsum, probing pocket depth, bleeding on probing, and simplified oral debris index score were determined before and 1 week after PDT. The Mann-Whitney U test was used to assess the significance of the differences in each parameter between the two groups. We found that the hydrogen sulfide concentration and bacterial count on the tongue dorsum were decreased in the intervention group, but there was no statistically significant difference between the two groups. These results indicated that performing only PDT on the tongue dorsum may not contribute to reducing halitosis. No potential conflict of interest relevant to this article was reported.

Informa UK Limited Acta Medica Okayama 1071-5762 58 2 2024 Enhancing effect of the coexisting alpha-tocopherol on quercetin absorption and metabolism 88 97 EN Rikito Mitsuzane Graduate School of Environmental and Life Science, Okayama University Reiko Okubo Graduate School of Environmental and Life Science, Okayama University Miyu Nishikawa Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University Shinichi Ikushiro Department of Biotechnology, Faculty of Engineering, Toyama Prefectural University Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Toshiyuki Nakamura Graduate School of Environmental and Life Science, Okayama University The aim of this study is to investigate the modulating effect of coexisting food components on the absorption and metabolism of quercetin and blood plasma antioxidant potentials. The combination of quercetin with ��-tocopherol (��T), cellulose, or a commercially available vegetable beverage containing ��T and dietary fiber was orally administered to mice. Compared to the single administration of quercetin aglycone, the coadministration of ��T with quercetin significantly increased the plasma quercetin concentration at 0.5 h, whereas the combination of quercetin and cellulose decreased it. Interestingly, the administration of quercetin mixed with the vegetable beverage showed no significant change in the quercetin concentration in the mice plasma. The treatment of the cells with the blood plasma after the coadministration of ��T with quercetin significantly upregulated the gene expression of the antioxidant enzyme (heme oxygenase-1), whereas the quercetin and cellulose combination did not. In the plasma of the quercetin-administered mice, eight types of quercetin metabolites were detected, and their quantities were affected by the combination with ��T. The potentials of the heme oxygenase-1 gene expression by these metabolites were very limited, although several metabolites showed radical scavenging activities comparable to aglycone in the in vitro assays. These results suggested that the combination of ��T potentiates the quercetin absorption and metabolism and thus the plasma antioxidant potentials, at least in part, by the quantitative changes in the quercetin metabolites. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1932-7447 127 25 2023 Li-Ion Transport and Solution Structure in Sulfolane-Based Localized High-Concentration Electrolytes 12295 12303 EN Taku Sudoh Taku Sudoh Department of Chemistry and Life Science, Yokohama National University Shuhei Ikeda Department of Materials Chemistry, Nagoya University Keisuke Shigenobu Department of Chemistry and Life Science, Yokohama National University Seiji Tsuzuki Advanced Chemical Energy Research Centre (ACERC), Institute of Advanced Sciences, Yokohama National University Kaoru Dokko Department of Chemistry and Life Science, Yokohama National University Masayoshi Watanabe Advanced Chemical Energy Research Centre (ACERC), Institute of Advanced Sciences, Yokohama National University Wataru Shinoda Research Institute for Interdisciplinary Science and Department of Chemistry, Okayama University Kazuhide Ueno Department of Chemistry and Life Science, Yokohama National University Localized high-concentration electrolytes (LHCEs), which are mixtures of highly concentrated electrolytes (HCEs) and non-coordinating diluents, have attracted significant interest as promising liquid electrolytes for next-generation Li secondary batteries, owing to their various beneficial properties both in the bulk and at the electrode/electrolyte interface. We previously reported that the large Li+-ion transference number in sulfolane (SL)-based HCEs, attributed to the unique exchange/hopping-like Li+-ion conduction, decreased upon dilution with the non-coordinating hydrofluoroether (HFE) despite the retention of the local Li+-ion coordination structure. Therefore, in this study, we investigated the effects of HFE dilution on the Li+ transference number and the solution structure of SL-based LHCEs via the analysis of dynamic ion correlations and molecular dynamics simulations. The addition of HFE caused nano-segregation in the SL-based LHCEs to afford polar and nonpolar domains and fragmentation of the polar ion-conducting pathway into smaller clusters with increasing HFE content. Analysis of the dynamic ion correlations revealed that the anti-correlated Li+–Li+ motions were more pronounced upon HFE addition, suggesting that the Li+ exchange/hopping conduction is obstructed by the non-ion-conducting HFE-rich domains. Thus, the HFE addition affects the entire solution structure and ion transport without significantly affecting the local Li+-ion coordination structure. Further studies on ion transport in LHCEs would help obtain a design principle for liquid electrolytes with high ionic conductivity and large Li+-ion transference numbers. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0961-8368 32 10 2023 Molecular mechanism of the common and opposing cosolvent effects of fluorinated alcohol and urea on a coiled coil protein e4763 EN Noa Nakata Department of Chemistry, Faculty of Science, Okayama University Ryuichi Okamoto Graduate School of Information Science, University of Hyogo Tomonari Sumi Department of Chemistry, Faculty of Science, Okayama University Kenichiro Koga Department of Chemistry, Faculty of Science, Okayama University Takeshi Morita Department of Chemistry, Graduate School of Science, Chiba University Hiroshi Imamura Department of Bio-Science, Nagahama Institute of Bio-Science and Technology Alcohols and urea are widely used as effective protein denaturants. Among monohydric alcohols, 2,2,2-trifluoroethanol (TFE) has large cosolvent effects as a helix stabilizer in proteins. In contrast, urea efficiently denatures ordered native structures, including helices, into coils. These opposing cosolvent effects of TFE and urea are well known, even though both preferentially bind to proteins; however, the underlying molecular mechanism remains controversial. Cosolvent-dependent relative stability between native and denatured states is rigorously related to the difference in preferential binding parameters (PBPs) between these states. In this study, GCN4-p1 with two-stranded coiled coil helices was employed as a model protein, and molecular dynamics simulations for the helix dimer and isolated coil were conducted in aqueous solutions with 2 M TFE and urea. As 2 M cosolvent aqueous solutions did not exhibit clustering of cosolvent molecules, we were able to directly investigate the molecular origin of the excess PBP without considering the enhancement effect of PBPs arising from the concentration fluctuations. The calculated excess PBPs of TFE for the helices and those of urea for the coils were consistent with experimentally observed stabilization of helix by TFE and that of coil by urea. The former was caused by electrostatic interactions between TFE and side chains of the helices, while the latter was attributed to both electrostatic and dispersion interactions between urea and the main chains. Unexpectedly, reverse-micelle-like orientations of TFE molecules strengthened the electrostatic interactions between TFE and the side chains, resulting in strengthening of TFE solvation. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1471-230X 24 1 2024 Endoscopic manifestation of intestinal transplant-associated microangiopathy after stem cell transplantation 140 EN Masaya Iwamuro Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Daisuke Ennishi Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Nobuharu Fujii Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Ken-Ichi Matsuoka Department of Hematology and Oncology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toshihiro Inokuchi Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Sakiko Hiraoka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Motoyuki Otsuka Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Background Endoscopic features of intestinal transplant-associated microangiopathy (iTAM) have not been comprehensively investigated. This study aimed to examine the endoscopic characteristics of patients diagnosed with iTAM.<br> Methods This retrospective analysis included 14 patients pathologically diagnosed with iTAM after stem cell transplantation for hematolymphoid neoplasms (n = 13) or thalassemia (n = 1). The sex, age at diagnosis, endoscopic features, and prognosis of each patient were assessed. Serological markers for diagnosing transplant-associated thrombotic microangiopathy were also evaluated.<br> Results The mean age at the time of iTAM diagnosis was 40.2 years. Patients diagnosed based on the pathognomonic pathological changes of iTAM presented with diverse symptoms at the times of endoscopic examinations, including diarrhea (n = 10), abdominal pain (n = 5), nausea (n = 4), appetite loss (n = 2), bloody stools (n = 2), abdominal discomfort (n = 1), and vomiting (n = 1). At the final follow-up, six patients survived, while eight patients succumbed, with a median time of 100.5 days (range: 52-247) post-diagnosis. Endoscopic manifestations included erythematous mucosa (n = 14), erosions (n = 13), ulcers (n = 9), mucosal edema (n = 9), granular mucosa (n = 9), and villous atrophy (n = 4). Erosions and/or ulcers were primarily observed in the colon (10/14, 71%), followed by the ileum (9/13, 69%), stomach (4/10, 40%), cecum (5/14, 36%), duodenum (3/10, 30%), rectum (4/14, 29%), and esophagus (1/10, 10%). Cytomegalovirus infection (n = 4) and graft-versus-host disease (n = 2) coexisted within the gastrointestinal tract. Patients had de novo prolonged or progressive thrombocytopenia (6/14, 43%), decreased hemoglobin concentration (4/14, 29%), reduced serum haptoglobin level (3/14, 21%), and a sudden and persistent increase in lactate dehydrogenase level (2/14, 14%). Peripheral blood samples from 12 patients were evaluated for schistocytes, with none exceeding 4%.<br> Conclusions This study provides a comprehensive exploration of the endoscopic characteristics of iTAM. Notably, all patients exhibited erythematous mucosa throughout the gastrointestinal tract, accompanied by prevalent manifestations, such as erosions (93%), ulcers (64%), mucosal edema (64%), granular mucosa (64%), and villous atrophy (29%). Because of the low positivity for serological markers of transplant-associated thrombotic microangiopathy in patients with iTAM, endoscopic evaluation and biopsy of these lesions are crucial, even in the absence of these serological features. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 78 2 2024 Photon-Counting Detector CT: Potential for 75% Reduction in Contrast Medium Amount: A Phantom Study 135 142 EN Fumiyo Higaki Department of Radiology, Okayama University Hospital Yusuke Morimitsu Department of Radiological Technology, Okayama University Hospital Toshihiro Iguchi Department of Radiological Technology, Faculty of Health Sciences, Okayama University Hayato Saito Department of Radiological Technology, Okayama University Medical School Haruhiko Takaki Department of Radiological Technology, Okayama University Medical School Ayako Nakagoshi Department of Radiological Technology, Okayama University Medical School Maki Wada Department of Radiological Technology, Okayama University Medical School Mayu Uka Department of Radiology, Okayama University Hospital Noriaki Akagi Department of Radiological Technology, Okayama University Hospital Toshiharu Mitsuhashi Center for Innovative Clinical Medicine, Okayama University Hospital Yusuke Matsui Department of Radiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Takao Hiraki Department of Radiology, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Original Article 10.18926/AMO/66916 This study aimed to evaluate the potential reduction in contrast medium utilization using photon-counting detector computed tomography (PCD-CT). One PCD-CT scan (CT1) and three conventional (non-PCD-CT) CT scans (CT2-CT4) were performed using a multi-energy CT phantom that contained eight rods with different iodine concentrations (0.2, 0.5, 1, 2, 5, 10, 15, and 20 mg/ml). The CT values of the seven groups (CT1 for 40, 50, 60, and 70 keV; and CT2-4) were measured. Noise and contrast-to-noise ratio (CNR) were assessed for the eight rods at various iodine concentrations. CT2 and CT1 (40 keV) respectively required 20 mg/ml and 5 mg/ml of iodine, indicating that a comparable contrast effect could be obtained with approximately one-fourth of the contrast medium amount. The standard deviation values increased at lower energy levels irrespective of the iodine concentration. The CNR exhibited a decreasing trend with lower iodine concentrations, while it remained relatively stable across all iodine levels (40-70 keV). This study demonstrated that virtual monochromatic 40 keV images offer a similar contrast effect with a reduced contrast medium amount when compared to conventional CT systems at 120 kV. No potential conflict of interest relevant to this article was reported.

The Royal Society Acta Medica Okayama 0962-8452 290 2000 2023 Diacamma ants adjust liquid foraging strategies in response to biophysical constraints 20230549 EN Haruna Fujioka Faculty of Environmental and Life Science, Okayama University Manon Marchand Department of Physics, University of Fribourg Adria C. LeBoeuf Department of Biology, University of Fribourg Ant foragers provide food to the rest of the colony, often requiring transport over long distances. Foraging for liquid is challenging because it is difficult to transport and share. Many social insects store liquids inside the crop to transport them to the nest, and then regurgitate to distribute to nest-mates through a behaviour called trophallaxis. Some ants instead transport fluids with a riskier behaviour called pseudotrophallaxis�\holding a drop of liquid between the mandibles through surface tension. Ants share this droplet with nest-mates without ingestion or regurgitation. We hypothesised that ants optimize their liquid-collection approach depending on viscosity. Using an ant that employs both trophallaxis and pseudotrophallaxis, we investigated the conditions where each liquid-collection behaviour is favoured by measuring biophysical properties, collection time and reaction to food quality for typical and viscosity-altered sucrose solutions. We found that ants collected more liquid per unit time by mandibular grabbing than by drinking. At high viscosities ants switched liquid collection method to mandibular grabbing in response to viscosity and not to sweetness. Our results demonstrate that ants change transport and sharing methods according to viscosity–a natural proxy for sugar concentration–thus increasing the mass of sugar returned to the nest per trip. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0925-9635 143 2024 First-principles molecular dynamics simulations for the properties of boron-doped tetrahedral amorphous carbon 110894 EN Qiang Yue Graduate School of Natural Science and Technology, Okayama University Takayoshi Yokoya Research Institute for Interdisciplinary Science, Okayama University Yuji Muraoka Research Institute for Interdisciplinary Science, Okayama University Based on first-principles molecular dynamics (FPMD) simulations combined with a liquid quenching method, we study the effects of boron doping at 0 %, 2 %, 4 %, 6 % on the properties of tetrahedral amorphous carbon (ta-C) with an initial density of 3.0 g/cm3. The results of bond structures and internal stress show the promotion of graphitization with increase in the concentration of boron doping. In addition, simulation of electronic states reveals that the Fermi level shifts to valence band and the intensity of density of electronic states near Fermi level increases with the boron concentration increasing. A covalent bond formation between carbon and boron atoms is also shown by analyzing projected densities of electronic states (PDOS) and electron density distribution. The results of electronic state and bond formation strongly indicate that the boron-doped ta-C is like a p-type semiconductor. The present simulation results provide useful information for deeper understanding on the physical properties of boron-doped ta-C. No potential conflict of interest relevant to this article was reported.

Ovid Technologies (Wolters Kluwer Health) Acta Medica Okayama 2641-7650 5 2 2023 Inhibition of Amino Acids Influx into Proximal Tubular Cells Improves Lysosome Function in Diabetes 182 194 EN Yuzuki Kano Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Satoshi Yamaguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Koki Mise Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Chieko Kawakita Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yasuhiro Onishi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Naoko Kurooka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ryosuke Sugawara Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Haya Hamed Hassan Albuayjan Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Atsuko Nakatsuka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Eguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Background Inhibition of glucose influx into proximal tubular cells (PTCs) by sodium–glucose cotransporter 2 inhibitors revealed prominent therapeutic effects on diabetic kidney disease. Collectrin (CLTRN) serves as a chaperone for the trafficking of neutral amino acid (AA) transporters in the apical membranes of PTCs. We investigated the beneficial effects of reduced influx of AAs into PTCs in diabetes and obesity model of Cltrn�|/y mice.<br> Methods Cltrn+/y and Cltrn�|/y mice at age 5 weeks were assigned to standard diet and streptozotocin and high-fat diet (STZ-HFD)–treated groups.<br> Results At age 22–23 weeks, body weight and HbA1c levels significantly increased in STZ-HFD-Cltrn+/y compared with standard diet-Cltrn+/y; however, they were not altered in STZ-HFD-Cltrn�|/y compared with STZ-HFD-Cltrn+/y. At age 20 weeks, urinary albumin creatinine ratio was significantly reduced in STZ-HFD-Cltrn�|/y compared with STZ-HFD-Cltrn+/y. Under the treatments with STZ and HFD, the Cltrn gene deficiency caused significant increase in urinary concentration of AAs such as Gln, His, Gly, Thr, Tyr, Val, Trp, Phe, Ile, Leu, and Pro. In PTCs in STZ-HFD-Cltrn+/y, the enlarged lysosomes with diameter of 10 ��m or more were associated with reduced autolysosomes, and the formation of giant lysosomes was prominently suppressed in STZ-HFD-Cltrn�|/y. Phospho-mTOR and inactive form of phospho-transcription factor EB were reduced in STZ-HFD-Cltrn�|/y compared with STZ-HFD-Cltrn+/y.<br> Conclusions The reduction of AAs influx into PTCs inactivated mTOR, activated transcription factor EB, improved lysosome function, and ameliorated vacuolar formation of PTCs in STZ-HFD-Cltrn�|/y mice. No potential conflict of interest relevant to this article was reported.

Oxford University Press (OUP) Acta Medica Okayama 1347-6947 87 11 2023 The effect of exogenous dihydroxyacetone and methylglyoxal on growth, anthocyanin accumulation, and the glyoxalase system in Arabidopsis 1323 1331 EN Maoxiang Zhao Graduate School of Environmental and Life Science, Okayama University Toshiyuki Nakamura Graduate School of Environmental and Life Science, Okayama University Yoshimasa Nakamura Graduate School of Environmental and Life Science, Okayama University Shintaro Munemasa Graduate School of Environmental and Life Science, Okayama University Izumi C Mori Institute of Plant Science and Resources, Okayama University Yoshiyuki Murata Graduate School of Environmental and Life Science, Okayama University Dihydroxyacetone (DHA) occurs in wide-ranging organisms, including plants, and can undergo spontaneous conversion to methylglyoxal (MG). While the toxicity of MG to plants is well-known, the toxicity of DHA to plants remains to be elucidated. We investigated the effects of DHA and MG on Arabidopsis. Exogenous DHA at up to 10 mM did not affect the radicle emergence, the expansion of green cotyledons, the seedling growth, or the activity of glyoxalase II, while DHA at 10 mM inhibited the root elongation and increased the activity of glyoxalase I. Exogenous MG at 1.0 mM inhibited these physiological responses and increased both activities. Dihydroxyacetone at 10 mM increased the MG content in the roots. These results indicate that DHA is not so toxic as MG in Arabidopsis seeds and seedlings and suggest that the toxic effect of DHA at high concentrations is attributed to MG accumulation by the conversion to MG. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 25 3 2024 Inhibitory Effect of a Tankyrase Inhibitor on Mechanical Stress-Induced Protease Expression in Human Articular Chondrocytes 1443 EN Yoshifumi Hotta Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Keiichiro Nishida Locomotive Pain Center, Okayama University Hospital Aki Yoshida Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshihisa Nasu Department of Orthopaedic Surgery, Okayama University Hospital Ryuichi Nakahara Department of Orthopaedic Surgery, Okayama University Hospital Shuichi Naniwa Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Noriyuki Shimizu Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chinatsu Ichikawa Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Deting Lin Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Tomohiro Fujiwara Department of Orthopaedic Surgery, Okayama University Hospital Toshifumi Ozaki Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences We investigated the effects of a Tankyrase (TNKS-1/2) inhibitor on mechanical stress-induced gene expression in human chondrocytes and examined TNKS-1/2 expression in human osteoarthritis (OA) cartilage. Cells were seeded onto stretch chambers and incubated with or without a TNKS-1/2 inhibitor (XAV939) for 12 h. Uni-axial cyclic tensile strain (CTS) (0.5 Hz, 8% elongation, 30 min) was applied and the gene expression of type II collagen a1 chain (COL2A1), aggrecan (ACAN), SRY-box9 (SOX9), TNKS-1/2, a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), and matrix metalloproteinase-13 (MMP-13) were examined by real-time PCR. The expression of ADAMTS-5, MMP-13, nuclear translocation of nuclear factor-��B (NF-��B), and ��-catenin were examined by immunocytochemistry and Western blotting. The concentration of IL-1�� in the supernatant was examined by enzyme-linked immunosorbent assay (ELISA). TNKS-1/2 expression was assessed by immunohistochemistry in human OA cartilage obtained at the total knee arthroplasty. TNKS-1/2 expression was increased after CTS. The expression of anabolic factors were decreased by CTS, however, these declines were abrogated by XAV939. XAV939 suppressed the CTS-induced expression of catabolic factors, the release of IL-1��, as well as the nuclear translocation of NF-��B and ��-catenin. TNKS-1/2 expression increased in mild and moderate OA cartilage. Our results demonstrated that XAV939 suppressed mechanical stress-induced expression of catabolic proteases by the inhibition of NF-��B and activation of ��-catenin, indicating that TNKS-1/2 expression might be associated with OA pathogenesis. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 1661-6596 25 3 2024 Mutual Effects of Orexin and Bone Morphogenetic Proteins on Catecholamine Regulation Using Adrenomedullary Cells 1585 EN Yoshiaki Soejima Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nahoko Iwata Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Koichiro Yamamoto Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuhito Suyama Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Orexins are neuronal peptides that play a prominent role in sleep behavior and feeding behavior in the central nervous system, though their receptors also exist in peripheral organs, including the adrenal gland. In this study, the effects of orexins on catecholamine synthesis in the rat adrenomedullary cell line PC12 were investigated by focusing on their interaction with the adrenomedullary bone morphogenetic protein (BMP)-4. Orexin A treatment reduced the mRNA levels of key enzymes for catecholamine synthesis, including tyrosine hydroxylase (Th), 3,4-dihydroxyphenylalanie decarboxylase (Ddc) and dopamine beta-hydroxylase (Dbh), in a concentration-dependent manner. On the other hand, treatment with BMP-4 suppressed the expression of Th and Ddc but enhanced that of Dbh with or without co-treatment with orexin A. Of note, orexin A augmented BMP-receptor signaling detected by the phosphorylation of Smad1/5/9 through the suppression of inhibitory Smad6/7 and the upregulation of BMP type-II receptor (BMPRII). Furthermore, treatment with BMP-4 upregulated the mRNA levels of OX1R in PC12 cells. Collectively, the results indicate that orexin and BMP-4 suppress adrenomedullary catecholamine synthesis by mutually upregulating the pathway of each other in adrenomedullary cells. No potential conflict of interest relevant to this article was reported.

���R��w�_�w�� Acta Medica Okayama 2186-7755 113 2024 ����NERICA�i��̔_�ƌ`���Ɋւ����`�I�v�� 11 16 EN Asami Tomita Course of Applied Plant Science Yui Akimoto Course of Applied Plant Science Genetic factors of yield related traits in lowland New Rice for Africa variety (NERICA) using different nitrogen condition and QTL to increase rice yield in lowland NERICAs were clarified. Indica Group rice variety (Oryza sativa L.) IR64 increased panicle number, culm weight and panicle weight, according to nitrogen concentration. The tendency is especially remarkable under low nitrogen concentration. NERICA‒L‒19, which is derived from a cross between IR64 and TOG5681 (Oryza glaberrima S.), showed similar values for panicle weight and culm weight, and it showed higher plant height, panicle weight and culm weight and lower harvest index than those of IR64 under all the concentrations. QTL analysis for the agronomic traits were performed using hybrid population derived from a cross between IR64 and NERICA‒L‒19. A total of 22 QTLs were detected on chromosomes (chrs.) 1 (3 QTLs), 2 (2), 4 (2), 5 (5), 6 (1), 7 (1), 8 (6) and 10 (2). Among them, 4 regions at 34.1‒36.6Mbp of chr. 1, at 23.8‒27.8Mbp of chr. 5 and at 4.8Mbp and 20.3‒28.4Mbp of chr. 8 showed several QTLs�f peaks overlapped. The regions of chr. 5 and 4.8Mbp of chr. 8 increased panicle weight by IR64 allele. Those of chr. 1 and 20.3-28.4Mbp of chr. 8 increased plant height and harvest index, respectively, by NERICA‒L‒19 allele. These results indicated that the larger panicle type of lowland NERICA is suitable under low nitrogen condition. Also, the plant type was controlled by the combination of 4 QTLs�f regions on chr. 1 and short arm of chr. 8 originated from O. glaberrima, and those of chr. 5 and long arm of chr. 8 from O. sativa Indica Group. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 1549-9596 64 2 2023 pSPICA Force Field Extended for Proteins and Peptides 532 542 EN Yusuke Miyazaki Research Institute for Interdisciplinary Science, Okayama University Wataru Shinoda Research Institute for Interdisciplinary Science, Okayama University Many coarse-grained (CG) molecular dynamics (MD) studies have been performed to investigate biological processes involving proteins and lipids. CG force fields (FFs) in these MD studies often use implicit or nonpolar water models to reduce computational costs. CG-MD using water models cannot properly describe electrostatic screening effects owing to the hydration of ionic segments and thus cannot appropriately describe molecular events involving water channels and pores through lipid membranes. To overcome this issue, we developed a protein model in the pSPICA FF, in which a polar CG water model showing the proper dielectric response was adopted. The developed CG model greatly improved the transfer free energy profiles of charged side chain analogues across the lipid membrane. Application studies on melittin-induced membrane pores and mechanosensitive channels in lipid membranes demonstrated that CG-MDs using the pSPICA FF correctly reproduced the structure and stability of the pores and channels. Furthermore, the adsorption behavior of the highly charged nona-arginine peptides on lipid membranes changed with salt concentration, indicating the pSPICA FF is also useful for simulating protein adsorption on membrane surfaces. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1350-6307 153 2023 Prediction of slip activity of crystal grains around semi-circular and semi-elliptical notches in thin-sheet specimens of pure titanium using formulated macroscopic stress distribution and crystal orientation 107623 EN Naoya Tada Faculty of Environmental, Life, Natural Science and Technology, Okayama University Takeshi Uemori Faculty of Environmental, Life, Natural Science and Technology, Okayama University Junji Sakamoto Faculty of Environmental, Life, Natural Science and Technology, Okayama University Thin metal sheets and wires are important materials for various devices used in electrical, mechanical, and medical fields. With the downsizing of these devices, demand for thinner sheets and wires has increased. Amongst the many metals available, pure titanium has been attracting much attention for use in medical and dental devices because of its good biocompatibility in addition to its light weight and high corrosion resistance. However, thin metal sheets and wires are usually polycrystalline materials and, with the downsizing of materials, there is a loss of homogeneity during deformations. Inhomogeneous deformation becomes significant in thin sheets and wires, owing to the different crystal orientations and geometries of crystal grains. Furthermore, the shapes of such devices are not uniform, unlike, say, a simple rod. Therefore, macroscopic stress and strain concentrations should be taken into consideration when designing these devices as they affect the localization of deformation and the resultant fracture. In this study, semi-circular and semi-elliptical notched specimens made of thin-sheet polycrystalline pure titanium are subjected to tensile testing. Inhomogeneous deformation caused by crystallographic slip is observed near the notch root. Analysis of the crystal orientation and observation of the slip line show that the slip initiation in crystal grains is affected by the macroscopic stress distribution and can be predicted from the slip activity calculated from both the critical resolved shear stress on the slip systems and the resolved shear stress acting on prospective slip planes obtained from the macroscopic multiaxial stress distribution. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1341-321X 30 3 2024 Relevance of complement immunity with brain fog in patients with long COVID 236 241 EN Hideharu Hagiya Department of Infectious Diseases, Okayama University Hospital Kazuki Tokumasu Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Naruhiko Sunada Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yasuhiro Nakano Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroyuki Honda Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masanori Furukawa Clinical Laboratory, Okayama University Hospital Fumio Otsuka Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Introduction<br> This study aimed to elucidate the prevalence and clinical characteristics of patients with long COVID (coronavirus disease 2019), especially focusing on 50% hemolytic complement activity (CH50).<br> <br> Methods<br> This retrospective observational study focused on patients who visited Okayama University Hospital (Japan) for the treatment of long COVID between February 2021 and March 2023. CH50 levels were measured using liposome immunometric assay (Autokit CH50 Assay, FUJIFILM Wako Pure Chemical Corporation, Japan); high CH50 was defined as ≥59 U/mL. Univariate analyses assessed differences in the clinical background, long COVID symptoms, inflammatory markers, and clinical scores of patients with normal and high CH50. Logistic regression model investigated the association between high CH50 levels and these factors.<br> <br> Results<br> Of 659 patients who visited our hospital, 478 patients were included. Of these, 284 (59.4%) patients had high CH50 levels. Poor concentration was significantly more frequent in the high CH50 group (7.2% vs. 13.7%), whereas no differences were observed in other subjective symptoms (fatigue, headache, insomnia, dyspnea, tiredness, and brain fog). Multivariate analysis was performed on factors that could be associated with poor concentration, suggesting a significant relationship to high CH50 levels (adjusted odds ratio [aOR], 2.70; 95% confidence interval [CI], 1.33–5.49). Also, high CH50 was significantly associated with brain fog (aOR, 1.66; 95% CI, 1.04–2.66).<br> <br> Conclusions<br> High CH50 levels were frequently reported in individuals with long COVID, indicating a relationship with brain fog. Future in-depth research should examine the pathological role and causal link between complement immunity and the development of long COVID. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 0531-5565 180 2023 Attenuation of pulmonary damage in aged lipopolysaccharide-induced inflammation mice through continuous 2 % hydrogen gas inhalation: A potential therapeutic strategy for geriatric inflammation and survival 112270 EN Toshiyuki Aokage Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Masumi Iketani Biological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology Mizuki Seya Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ying Meng Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kohei Ageta Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiromichi Naito Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsunori Nakao Department of Emergency, Critical Care and Disaster Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ikuroh Ohsawa Biological Process of Aging, Tokyo Metropolitan Institute for Geriatrics and Gerontology Introduction: With the global population aging, there is an increased prevalence of sepsis among the elderly, a demographic particularly susceptible to inflammation. This study aimed to evaluate the therapeutic potential of hydrogen gas, known for its anti-inflammatory and antioxidant properties, in attenuating inflammation specifically in the lungs and liver, and age-associated molecular markers in aged mice.<br> Methods: Male mice aged 21 to 23 months, representative of the human elderly population, were subjected to inflammation via intraperitoneal injection of lipopolysaccharide (LPS). The mice were allocated into eight groups to examine the effects of varying durations and concentrations of hydrogen gas inhalation: control, saline without hydrogen, saline with 24-hour 2 % hydrogen, LPS without hydrogen, LPS with 24-hour 2 % hydrogen, LPS with 6-hour 2 % hydrogen, LPS with 1-hour 2 % hydrogen, and LPS with 24-hour 1 % hydrogen. Parameters assessed included survival rate, activity level, inflammatory biomarkers, and organ injury.<br> Results: Extended administration of hydrogen gas specifically at a 2 % concentration for 24 h led to a favorable prognosis in the aged mice by reducing mRNA expression of inflammatory biomarkers in lung and liver tissue, mitigating lung injury, and diminishing the expression of the senescence-associated protein p21. Moreover, hydrogen gas inhalation selectively ameliorated senescence-related markers in lung tissue, including C-X-C motif chemokine 2, metalloproteinase-3, and arginase-1. Notably, hydrogen gas did not alleviate LPS-induced liver injury under the conditions tested.<br> Conclusion: The study highlights that continuous inhalation of hydrogen gas at a 2 % concentration for 24 h can be a potent intervention in the geriatric population for improving survival and physical activity by mitigating pulmonary inflammation and modulating senescence-related markers in aged mice with LPS-induced inflammation. This finding paves the way for future research into hydrogen gas as a therapeutic strategy to alleviate severe inflammation that can lead to organ damage in the elderly. No potential conflict of interest relevant to this article was reported.

Elsevier Acta Medica Okayama 1751-7311 17 7 2023 Effects of liquefied sake lees on growth performance and faecal and blood characteristics in Japanese Black calves 100873 EN S. Katsumata Graduate School of Environmental, Life, Natural Science and Technology, Okayama University Y. Hayashi Shiga Prefectural Livestock Production Technology Promotion Center K. Oishi Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University T. Tsukahara Kyoto Institute of Nutrition and Pathology R. Inoue Department of Applied Biological Sciences, Faculty of Agriculture, Setsunan University A. Obata Shiga Prefectural Livestock Production Technology Promotion Center H. Hirooka Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University H. Kumagai Department of Applied Biosciences, Graduate School of Agriculture, Kyoto University Liquefied sake lees, a by-product of Japanese sake, is rich in Saccharomyces cerevisiae, proteins, and prebiotics derived from rice and yeast. Previous studies have reported that Saccharomyces cerevisiae fermentation products improved the health, growth, and faecal characteristics of preweaning calves. This study investigated the effects of adding liquefied sake lees to milk replacer on the growth performance, faecal characteristics, and blood metabolites of preweaning Japanese Black calves from 6 to 90 days of age. Twenty-four Japanese Black calves at 6 days of age were randomly assigned to one of three treatments: No liquefied sake lees (C, n = 8), 100 g/d (on a fresh matter basis) liquefied sake lees mixed with milk replacer (LS, n = 8), and 200 g/d (on a fresh matter basis) liquefied sake lees mixed with milk replacer (HS, n = 8). The intake of milk replacer and calf starter, as well as, the average daily gain did not differ between the treatments. The number of days counted with faecal score 1 in LS was higher than in HS (P < 0.05), while the number of days with diarrhoea medication in LS and C was lower than HS (P < 0.05). The faecal n-butyric acid concentration tended to be higher in LS compared to C (P = 0.060). The alpha diversity index (Chao1) was higher in HS than in C and LS at 90 days of age (P < 0.05). The principal coordinate analysis (PCoA) using weighted UniFrac distance showed that the bacterial community structures in faeces among the treatments at 90 days of age were significantly different (P < 0.05). The plasma ��-hydroxybutyric acid concentration, an indicator of rumen development, was higher for LS than in C throughout the experiment (P < 0.05). These results suggested that adding liquefied sake lees up to 100 g/d (on a fresh matter basis) might promote rumen development in preweaning Japanese Black calves. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 Effects of Nutritional Support Combined with Neuromuscular Electrical Stimulation on Muscle Strength and Thickness: A Randomized Controlled Trial in Healthy Young Adult Males 635 645 EN Tomohiro Ikeda Department of Rehabilitation Medicine, Okayama University Hospital Kazunori Okamura Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Masaki Hasegawa Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Satoshi Tanaka Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Shusaku Kanai Department of Physical Therapy, Faculty of Health and Welfare, Prefectural University of Hiroshima Original Article 10.18926/AMO/66156 In the management of post-injury patients with activity limitations, methods to prevent musculoskeletal disorders and hasten recovery are important. This randomized controlled, single-blinded study was a preliminary investigation of the combined effect of nutritional support with neuromuscular electrical stimulation (NMES) on muscle strength and thickness. Healthy young adult males (median age, 21 years) were enrolled; each of their hands was randomly assigned to one of the following four groups: Placebo, Nutrition, NMES, and Nutrition + NMES. All participants received whey protein or placebo (3x/week for 6 weeks) and NMES training (3x/week for 6 weeks) on the abductor digiti minimi (ADM) muscle of either the left or right hand. ADM muscle strength and thickness were analyzed at baseline and at week 7. We analyzed 38 hands (9 Placebo, 10 Nutrition, 9 NMES, 10 Nutrition + NMES). There was significantly greater muscle strengthening in the Nutrition + NMES group compared to the Placebo group or the NMES group, but no significant difference in gain of muscle thickness. The combined intervention may be effective in improving muscle strength. Future clinical trials targeting various muscles after sports-related injuries are warranted. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 77 6 2023 Concomitant Use of Multiple Nephrotoxins including Renal Hypoperfusion Medications Causes Vancomycin-Associated Nephrotoxicity: Combined Retrospective Analyses of Two Real-World Databases 595 605 EN Takashi Bando Department of Pharmacy, Tokushima University Hospital Masayuki Chuma Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Hirofumi Hamano Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Takahiro Niimura Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Naoto Okada Department of Pharmacy, Tokushima University Hospital Masateru Kondo Department of Pharmacy, Tokushima University Hospital Yuki Izumi Department of Pharmacy, Tokushima University Hospital Shunsuke Ishida Department of Pharmacy, Tokushima University Hospital Toshihiko Yoshioka Department of Pharmacy, Tokushima University Hospital Mizuho Asada Department of Medical Molecular Informatics, Meiji Pharmaceutical University Yoshito Zamami Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Kenshi Takechi Department of Drug Information Analysis, College of Pharmaceutical Sciences, Matsuyama University Mitsuhiro Goda Department of Pharmacy, Tokushima University Hospital Koji Miyata Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences Kenta Yagi Clinical Research Center for Developmental Therapeutics, Tokushima University Hospital Yuki Izawa-Ishizawa Department of Pharmacology, Tokushima University Graduate School of Biomedical Sciences Momoyo Azuma Department of Infection Control and Prevention, Tokushima University Hospital Hiroaki Yanagawa Department of Nursing, Faculty of Health and Welfare, Tokushima Bunri University Yoshikazu Tasaki Department of Hospital Pharmacy and Pharmacology, Asahikawa Medical University Keisuke Ishizawa Department of Pharmacy, Tokushima University Hospital Original Article 10.18926/AMO/66151 There is a growing concern about the relationship between vancomycin-associated nephrotoxicity (VAN) and concomitant use of nephrotoxins. We examined this relationship by combined retrospective analyses of two real-world databases. Initially, the FDA Adverse Event Reporting System (FAERS) was analyzed for the effects of concomitant use of one or more nephrotoxins on VAN and the types of combinations of nephrotoxins that exacerbate VAN. Next, electronic medical records (EMRs) of patients who received vancomycin (VCM) at Tokushima University Hospital between January 2006 and March 2019 were examined to confirm the FAERS analysis. An elevated reporting odds ratio (ROR) was observed with increases in the number of nephrotoxins administered (VCM + one nephrotoxin, adjusted ROR (95% confidence interval [CI]) 1.67 [1.51-1.85]; VCM + ≥2 nephrotoxins, adjusted ROR [95% CI] 1.54 [1.37-1.73]) in FAERS. EMRs analysis showed that the number of nephrotoxins was associated with higher incidences of VAN [odds ratio: 1.99; 95% CI: 1.42-2.78]. Overall, concomitant use of nephrotoxins was associated with an increased incidence of VAN, especially when at least one of those nephrotoxins was a renal hypoperfusion medication (furosemide, non-steroidal anti-inflammatory drugs, and vasopressors). The concomitant use of multiple nephrotoxins, especially including renal hypoperfusion medication, should be avoided to prevent VAN. No potential conflict of interest relevant to this article was reported.

American Chemical Society (ACS) Acta Medica Okayama 0743-7463 39 44 2023 Analysis of Evaporation of Droplet Pairs by a Quasi-Steady-State Diffusion Model Coupled with the Evaporative Cooling Effect 15587 15596 EN Yutaka Yamada Faculty of Environmental, Life, Natural Science and Technology, Okayama University Kazuma Isobe Faculty of Environmental, Life, Natural Science and Technology, Okayama University Akihiko Horibe Faculty of Environmental, Life, Natural Science and Technology, Okayama University Multidroplet evaporation is a common phase-change phenomenon not only in nature but also in many industrial applications, including inkjet printing and spray cooling. The evaporation behavior of these droplets is strongly affected by the distance between neighboring droplets, and in particular, evaporation suppression occurs as the distance decreases. However, further quantitative information, such as the temperature and local evaporation flux, is limited because the analytical models of multidroplet evaporation only treat vapor diffusion, and the effect of the latent heat transfer through the liquid–vapor phase change is ignored. Here, we perform a numerical analysis of evaporating droplet pairs that linked vapor diffusion from the droplet surface and evaporative cooling. Heat transfer through the liquid and gas phases is also considered because the saturation pressure depends on the temperature. The results show an increase in the vapor concentration in the region between the two droplets. Consequently, the local evaporation flux in the proximate region significantly decreases with decreasing separation distance. This means that the latent heat transfer through the phase change is diminished, and an asymmetrical temperature distribution occurs in the liquid and gas phases. These numerical results provide quantitative information about the temperature and local evaporation flux of evaporating droplet pairs, and they will guide further investigation of multiple droplet evaporation. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0006-3495 121 17 2022 High hydrostatic pressure induces slow contraction in mouse cardiomyocytes 3286 3294 EN Yohei Yamaguchi Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masayoshi Nishiyama Department of Physics, Faculty of Science and Engineering, Kindai University Hiroaki Kai Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Toshiyuki Kaneko Department of Physiology, Asahikawa Medical University Keiko Kaihara Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Gentaro Iribe Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Akira Takai Department of Physiology, Asahikawa Medical University Keiji Naruse Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Masatoshi Morimatsu Department of Cardiovascular Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Cardiomyocytes are contractile cells that regulate heart contraction. Ca2+ flux via Ca2+ channels activates actomyosin interactions, leading to cardiomyocyte contraction, which is modulated by physical factors (e.g., stretch, shear stress, and hydrostatic pressure). We evaluated the mechanism triggering slow contractions using a high-pressure microscope to characterize changes in cell morphology and intracellular Ca2+ concentration ([Ca2+]i) in mouse cardiomyocytes exposed to high hydrostatic pressures. We found that cardiomyocytes contracted slowly without an acute transient increase in [Ca2+]i, while a myosin ATPase inhibitor interrupted pressure-induced slow contractions. Furthermore, transmission electron microscopy showed that, although the sarcomere length was shortened upon the application of 20 MPa, this pressure did not collapse cellular structures such as the sarcolemma and sarcomeres. Our results suggest that pressure-induced slow contractions in cardiomyocytes are driven by the activation of actomyosin interactions without an acute transient increase in [Ca2+]i. No potential conflict of interest relevant to this article was reported.

BMC Acta Medica Okayama 1880-6546 73 1 2023 Connective tissue mast cells store and release noradrenaline 24 EN Yusuke Otani Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Soichiro Yoshikawa Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kei Nagao Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Takehiro Tanaka Department of Pathology and Oncology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinichi Toyooka Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsushi Fujimura Department of Cellular Physiology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mast cells are present in mucosal and connective tissues throughout the body. They synthesize and release a wide variety of bioactive molecules, such as histamine, proteases, and cytokines. In this study, we found that a population of connective tissue mast cells (CTMCs) stores and releases noradrenaline, originating from sympathetic nerves. Noradrenaline-storing cells, not neuronal fibers, were predominantly identified in the connective tissues of the skin, mammary gland, gastrointestinal tract, bronchus, thymus, and pancreas in wild-type mice but were absent in mast cell-deficient W-sash c-kit mutant KitW-sh/W-sh mice. In vitro studies using bone marrow-derived mast cells revealed that extracellular noradrenaline was taken up but not synthesized. Upon ionomycin stimulation, noradrenaline was released. Electron microscopy analyses further suggested that noradrenaline is stored in and released from the secretory granules of mast cells. Finally, we found that noradrenaline-storing CTMCs express organic cation transporter 3 (Oct3), which is also known as an extraneuronal monoamine transporter, SLC22A3. Our findings indicate that mast cells may play a role in regulating noradrenaline concentration by storing and releasing it in somatic tissues. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0003-9969 155 2023 Ruxolitinib altered IFN-�� induced necroptosis of human dental pulp stem cells during osteoblast differentiation 105797 EN Atsuko Tanaka Department of Orthodontics, Okayama University Hospital Satoru Hayano Department of Orthodontics, Okayama University Hospital Masayo Nagata Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Takahiro Kosami Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Ziyi Wang Department of Molecular Biology and Biochemistry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hiroshi Kamioka Department of Orthodontics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Objective: This study aimed to evaluate the role of ruxolitinib in the interferon beta (IFN-��) mediated osteoblast differentiation using human dental pulp stem cells (hDPSCs).<br> Design: hDPSCs from five deciduous teeth of healthy patients were stimulated by adding human recombinant IFN-�� protein (1 or 2 ng/ml) to the osteogenic differentiation induction medium. Substrate formation was determined using Alizarin Red staining, calcium concentration, and osteoblast marker expression levels. Ruxolitinib was used to inhibit the Janus kinase/signal transducers and activators of transcription (JAK-STAT) pathway. Apoptosis was detected using terminal deoxynucleotidyl nick-end labeling (TUNEL) staining, and necroptosis was detected using propidium iodide staining and phosphorylated mixed lineage kinase domain-like protein (pMLKL) expression.<br> Results: In the IFN-��-treated group, substrate formation was inhibited by a reduction in alkaline phosphatase (ALP) expression in a concentration-dependent manner. Although the proliferation potency was unchanged between the IFN-��-treated and control groups, the cell number was significantly reduced in the experimental group. TUNEL-positive cell number was not significantly different; however, the protein level of necroptosis markers, interleukin-6 (IL-6) and pMLKL were significantly increased in the substrate formation. Cell number and ALP expression level were improved in the group administered ruxolitinib, a JAK-STAT inhibitor. Additionally, ruxolitinib significantly suppressed IL-6 and pMLKL levels.<br> Conclusion: Ruxolitinib interfered with the IFN-��-mediated necroptosis and osteogenic differentiation via the JAK-STAT pathway. No potential conflict of interest relevant to this article was reported.

Royal Society of Chemistry (RSC) Acta Medica Okayama 1477-0520 2023 Relative stereochemical determination of the C61–C83 fragment of symbiodinolide using a stereodivergent synthetic approach EN Hiroyoshi Takamura Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Kosuke Hattori Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Takumi Ohashi Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Taichi Otsu Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Isao Kadota Department of Chemistry, Graduate School of Natural Science and Technology, Okayama University Structural determination is required in the use of marine natural products to create novel drugs and drug leads in medicinal chemistry. Symbiodinolide, which is a polyol marine natural product with a molecular weight of 2860, increases the intracellular Ca2+ concentration and exhibits inhibitory activity against cyclooxygenase-1. Seventy percent of the structure of symbiodinolide has been stereochemically clarified. Herein, we report the elucidation of the relative configuration of the C61–C83 fragment, which is among the remaining thirty percent, using a stereodivergent synthetic strategy. We first assigned the relative configuration of the C61–C74 fragment. Two candidate diastereomers of the C61–C74 fragment were synthesized, and their NMR data were compared with those of the natural product, revealing the relative stereochemistry of this component. We then narrowed down the candidate compounds for the C69–C83 fragment from 16 possible diastereomers by analyzing the NMR data of the natural product, and we thus selected eight candidate diastereomers. Stereodivergent synthesis of the candidates for this fragment and comparison of the NMR data of the natural product and the eight synthetic products resulted in the relative stereostructural clarification of the C69–C83 fragment. These individually determined relative stereochemistries of the C61–C74 and C69–C83 fragments were connected via the common C69–C73 tetrahydropyran moiety of the fragments. Finally, the relative configuration of the C61–C83 fragment of symbiodinolide was determined. The stereodivergent synthetic approach used in this study can be extended to the stereochemical determination of other fragments of symbiodinolide. No potential conflict of interest relevant to this article was reported.

���R��w�� Acta Medica Okayama 0030-1558 135 2 2023 �ߘa�S�N�x���R��w��܁@�]�_�o��������܁i�V���܁j 61 62 EN Yuji Yada Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 0028-646X 236 3 2022 A tonoplast�]localized magnesium transporter is crucial for stomatal opening in Arabidopsis under high Mg2+ conditions 864 877 EN Shin�]ichiro Inoue Division of Biological Science, Graduate School of Science, Nagoya University Maki Hayashi Division of Biological Science, Graduate School of Science, Nagoya University Sheng Huang Institute of Plant Science and Resources, Okayama University Kengo Yokosho Institute of Plant Science and Resources, Okayama University Eiji Gotoh Department of Forest Environmental Sciences, Faculty of Agriculture, Kyushu University Shuka Ikematsu Institute of Transformative Bio-Molecules (WPI-ITbM), Nagoya University Masaki Okumura Division of Biological Science, Graduate School of Science, Nagoya University Takamasa Suzuki Department of Biological Chemistry, College of Bioscience and Biotechnology, Chubu University Takumi Kamura Division of Biological Science, Graduate School of Science, Nagoya University Toshinori Kinoshita Division of Biological Science, Graduate School of Science, Nagoya University Jian Feng Ma Institute of Plant Science and Resources, Okayama University Plant stomata play an important role in CO2 uptake for photosynthesis and transpiration, but the mechanisms underlying stomatal opening and closing under changing environmental conditions are still not completely understood.<br> Through large-scale genetic screening, we isolated an Arabidopsis mutant (closed stomata2 (cst2)) that is defective in stomatal opening. We cloned the causal gene (MGR1/CST2) and functionally characterized this gene.<br> The mutant phenotype was caused by a mutation in a gene encoding an unknown protein with similarities to the human magnesium (Mg2+) efflux transporter ACDP/CNNM. MGR1/CST2 was localized to the tonoplast and showed transport activity for Mg2+. This protein was constitutively and highly expressed in guard cells. Knockout of this gene resulted in stomatal closing, decreased photosynthesis and growth retardation, especially under high Mg2+ conditions, while overexpression of this gene increased stomatal opening and tolerance to high Mg2+ concentrations. Furthermore, guard cell-specific expression of MGR1/CST2 in the mutant partially restored its stomatal opening.<br> Our results indicate that MGR1/CST2 expression in the leaf guard cells plays an important role in maintaining cytosolic Mg2+ concentrations through sequestering Mg2+ into vacuoles, which is required for stomatal opening, especially under high Mg2+ conditions. No potential conflict of interest relevant to this article was reported.