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Background: The growth of parotid glands is inhibited by liquid diet intake during growing period, while that of submandibular glands is not affected. This study examined how liquid diet intake affects nerve growth in the parotid and submandibular glands of growing rats, because nerves are closely involved in the maintenance of salivary gland structure. Materials and methods: Male Wistar rats were weaned at 21 days of age. Then, rats were fed a pellet diet and a liquid diet in the control group and experimental group, respectively. At 0, 2, 4, or 8 weeks, they were euthanised by isoflurane overdose, and parotid and submandibular glands were removed. The frozen sections were made and immuno-stained with anti-protein gene product 9.5 (PGP 9.5) antibody (general nerve marker), anti-tyrosine hydroxylase (TH) antibody (sympathetic nerve marker), or anti-neuronal nitric oxide synthase (nNOS) antibody (parasympathetic nerve marker). Results: In control parotid glands, scattered punctate or short linear patterns of PGP 9.5-positive sites were observed at week 0. After 2 weeks, PGP 9.5-positive sites, some of which were arranged in long linear patterns, increased in number. There were some TH-positive sites at week 0. After 2 weeks, there were increasing numbers of TH-positive sites, often in long linear patterns. At week 0, there were very few nNOS-positive sites, and nNOS immunoreactivity increased over time. After week 4, they demonstrated linear patterns. In the experimental parotid glands, there were fewer PGP 9.5- and nNOS-positive sites than in control parotid glands at each time point, although TH immunoreactivity was similar between two groups at each time point. In control submandibular glands, few punctate exhibited PGP 9.5-positive site were observed at week 0. At week 4, PGP 9.5 immunoreaction increased and showed linear patterns. TH-positive sites demonstrated punctate or short linear patterns at week 0, and thereafter TH immunoreactivity increased and were arranged in long linear patterns. There were few nNOS-positive sites at week 0, and they gradually increased after week 4. The immunoreactivities of all antibodies in the experimental submandibular glands were similar to those in the control at each time point. Conclusions: Parasympathetic nerve growth in rat parotid glands was inhibited by liquid diet intake during the growth period, while liquid diet intake did not affect parasympathetic nerve growth nor sympathetic nerve growth in rat submandibular glands. [ABSTRACT FROM AUTHOR]

Background The number of patients living with depression continues to increase in Japan. The economic effects of depression include loss of productivity due to both absenteeism and presenteeism. Gender differences have been reported in prevalence, onset pathways and subjective symptoms of depression. Aims To understand how workers with major depressive disorder (MDD) perceive problems in the workplace and examine gender differences in their self-perceived levels of functioning at work, noticed during the initial stages of depression. Methods This is a cross-sectional study of Japanese workers with MDD. Participants' self-perceived changes in the level of functioning at work were surveyed after the diagnosis during the first visit. The relationship between gender and changes in the level of functioning at work as initially perceived by the participants themselves was analysed using the chi-square test, supplemented by a residual analysis. Results We administered the survey to 147 workers with MDD. In terms of gender differences in initial self-perceived changes in the level of functioning at work, the proportion of men reporting reduced work efficiency was significantly higher than that of women, while the proportion of women reporting deterioration in relationships with colleagues and superiors was significantly higher than that of men. Conclusions The findings suggest that greater attention to reduced work efficiency by men and to deterioration in work relationships by women with MDD should be essential components of self-care. Managers need to pay attention to the level of functioning and provide adequate social support for employees. [ABSTRACT FROM AUTHOR]

The Raman spectra of hydrogen-bonded molecular solid H2S have been measured up to 23 GPa at 300 K in a gasketed diamond-anvil cell. In the orientationally disordered phase I between 0.47 and 11 GPa, the symmetric stretching mode ν1 shows a red-shift in frequency (dν1/dP=-10.1 cm-1/GPa ) and a dramatic broadening with pressure. At about 11 GPa, the antisymmetric stretching band ν3 appears at the higher-frequency side of ν1. Near this same pressure five low-frequency vibrational modes also appear and show pressure-sensitive features. These results indicate a pressure-induced phase transition near 11 GPa. This new solid phase, which persists to at least 23 GPa at 300 K, seems to be the same phase as previously found above 3.3 GPa at 25 K. [ABSTRACT FROM AUTHOR]

It is now viable to use coarse-grained molecular dynamics (CGMD) to model interacting clay particles in simulations of soil mechanics element tests. In CGMD, particle interactions are described by the Gay-Berne (GB) potential, which can approximate the potential energy between clay particles as a function of their separation and relative orientations; however, a previous study identified a significant shortcoming of the GB potential, which is that it lacks a local maximum called the “energy barrier” that the true interaction possesses at very close range. In this study, we propose a modified GB potential which can capture the energy barrier at and we use this new potential function to simulate the clay mineral kaolinite under isotropic compression. Our simulations show that the energy barrier is a crucial ingredient required to reproduce the elastoplastic behaviour observed in laboratory tests upon unloading from an isotropic normally consolidated state. Our data show that the difference in mechanical behaviour between normally consolidated clay and overconsolidated clay can be explained by the fact that, during the initial loading, some pairs of interacting particles surmount the energy barrier so that they then experience a large attractive force. Effectively, these particles become bounded and do not separate when the stress applied to the sample is released. The response of overconsolidated clay to applied stress is stiffer than that of normally consolidated clay because a larger proportion of the clay particle interactions exist in this bonded state.

Neurologic pupil index - the pupil contraction percentage measured by a pupillometer, is useful in evaluating the condition that arises from ingesting high levels of organic phosphorus. Learning points for physiciansDyscoria is a common symptom of organic phosphorus poisoning. [Extracted from the article]

Odontoclasts and cementoclasts are considered to play major roles in the internal resorption of dentin and the external resorption of tooth roots. In this study, we evaluated the osteoclast-inducing ability of human dental pulp and periodontal ligament cells, which are mesenchymal cells in dental tissues.These cells expressed RANKL and OPG mRNA constitutively. As osteoclast precursors, CD14+ monocytes derived from human peripheral blood were isolated, and incubated together with human dental pulp or periodontal ligament cells. Both cell types spontaneously induced the differentiation of CD14+ monocytes into osteoclasts without osteotropic factors. These results suggest that dental pulp and periodontal ligament cells are involved in regulating the differentiation and function of osteoclasts. [ABSTRACT FROM AUTHOR]

Sulfonylurea and glinide drugs, commonly used for antidiabetes therapies, are known to stimulate insulin release from pancreatic beta-cells by closing ATP-sensitive K+ channels. However, the specific actions of these drugs on insulin granule motion are largely unknown. Here, we used total internal reflection fluorescence (TIRF) microscopy to analyze the docking and fusion of single insulin granules in live beta-cells exposed to either the sulfonylurea drug glibenclamide or the glinide drug mitiglinide. TIRF images showed that both agents caused rapid fusion of newcomer insulin granules with the cell membrane in both control and diabetic Goto-Kakizaki (GK) rat pancreatic beta-cells. However, in the context of beta-cells from sulfonylurea receptor 1 (SUR1) knockout mice, TIRF images showed that only mitiglinide, but not glibenclamide, caused fusion of newcomer insulin granules. Compositely, our data indicate that 1) the mechanism by which both sulfonylurea and glinide drugs promote insulin release entails the preferential fusion of newcomer, rather than previously docked, insulin granules, and that 2) mitiglinide can induce insulin release by a mechanism independent of mitiglinide binding to SUR1. [ABSTRACT FROM AUTHOR]

The physiological role of soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) proteins in insulin exocytosis has been reported in pancreatic beta-cells. To determine whether the beta-cells of GK rats, a nonobese rodent model of type 2 diabetes, exhibit abnormalities in their SNARE proteins, we studied the expression and function of target (t)-SNAREs, syntaxin 1A, and synaptosomal-associated protein of 25 kDa (SNAP-25) in GK rat islets. Although insulin release and insulin content of islets isolated from 12-week-old GK rats were reduced, the proinsulin biosynthetic rate was about twofold higher than that in control rat islets, and no change in the preproinsulin mRNA level was observed. Pulse-chase experiments suggested the increased degradation of insulin in GK rat islets. Immunoblot analysis revealed that protein levels of syntaxin 1A and SNAP-25 in GK rat islets decreased to approximately 60% of the levels in control rat islets. We then examined whether the restoration of the decreased expression of t-SNAREs to the normal level in GK rat islets affected insulin secretion. Restoration was achieved by the overexpression of syntaxin 1A and SNAP-25 via the recombinant adenovirus-mediated gene transduction system, which recovered levels of these proteins to almost control levels. Glucose-stimulated insulin release from AdexlCA syntaxin 1A and Adex1CA SNAP-25-infected GK rat islets increased up to approximately 135 and 200%, respectively, of those from uninfected GK rat islets, although no difference in basal (2.2 mmol/l glucose) insulin release was evident between them. We conclude that decreased expression of t-SNAREs in GK rat islets is in part the defect responsible for impaired insulin secretion. [ABSTRACT FROM AUTHOR]

Examines an experiment which investigated water-tree characteristics for polyethlene of low-density. Details on the experimental procedures; Results of the experiment; Discussion and conclusions on the experiment.

This study investigates the association between parity and type 2 diabetes mellitus (T2DM) in Japanese women, considering the clinical history of gestational diabetes mellitus (GDM) and menopausal status, which are known risk factors for T2DM. Overall, 30,116 Japanese women (6,588 premenopausal and 23,528 postmenopausal) were included in this cross-sectional study. They were divided into two groups according to menopausal status (premenopausal and postmenopausal women), and the association between parity and T2DM was evaluated using a multiple logistic regression model with possible confounders, including a clinical history of GDM. The association between parity and T2DM was not statistically significant in premenopausal women. In contrast, a linear graded association between parity and T2DM was found in postmenopausal women. Furthermore, the association between parity and T2DM in postmenopausal women was attenuated after adjusting for body weight gain after the age of 20 years. A clinical history of GDM was significantly associated with a high risk for T2DM, regardless of adjustment for body weight gain after the age of 20 years in both premenopausal and postmenopausal women. Parity is associated with an increased risk of T2DM in postmenopausal women but not in premenopausal women. Maintaining appropriate body weight would be beneficial in attenuating the risk of T2DM in postmenopausal women. A clinical history of GDM is a risk factor for T2DM in both pre- and postmenopausal women; therefore, women with a clinical history of GDM require continuous medical care to survey for T2DM., Competing Interests: Declarations. Ethical Statement: Approval of the research protocol: This study was approved by the Institutional Review Board of Tohoku University School of Medicine (approval numbers:2021–1-608, 2022–1-069, 2022–1-216, and 2022–1-825). Written informed consent was obtained from all the participants. Conflict of Interest: This study was supported by research funding from Women’s Health Care Medical Science at Tohoku University Graduate School of Medicine. Noriyuki Iwama, Nobuo Yaegashi, and Masatoshi Saito belong to Women’s Health Care Medical Science at Tohoku University Graduate School of Medicine. Both You Nakamichi and Keiichi Yuwaki are employed by Dai-ichi Life Insurance Company, Limited, which had no role in the statistical analysis, interpretation of results, manuscript drafting, or decision to submit the manuscript for publication. The other authors declare no conflicts of interest., (© 2024. The Author(s).)

Bone remodeling is regulated by the interaction between receptor activator of nuclear factor kappa-B ligand (RANKL) and its receptor RANK on osteoblasts and osteoclasts, respectively. Osteoprotegerin (OPG) is secreted from osteoblasts and inhibits osteoclast differentiation by acting as a decoy receptor for RANKL. Despite its importance, the mechanism underlying the secretion of OPG remains poorly understood. Here, we applied a method of video-rate bioluminescence imaging using a fusion protein with Gaussia luciferase (GLase) and visualized the secretion of OPG from living mouse osteoblastic MC3T3-E1 cells. The bioluminescence imaging revealed that the secretion of OPG fused to GLase (OPG-GLase) occurred frequently and widely across the cell surface. Notably, co-expression of RANKL significantly reduced the secretion of OPG-GLase, indicating an inhibitory role of RANKL on OPG secretion within cells. Further imaging and biochemical analyses using deletion mutants of OPG and RANKL, as well as RANKL mutants that cause autosomal recessive osteopetrosis, demonstrated the essential role of protein-protein interaction between OPG and RANKL in the inhibition of OPG secretion. Treatment with proteasome inhibitors resulted in increased levels of OPG in both culture medium and cell lysates. However, the fold-increase of OPG was similar regardless of the presence or absence of RANKL, suggesting that the regulation of OPG secretion by RANKL is independent of proteasome activity. This report visualized the secretion of OPG from living cells and provided evidence for a novel intracellular inhibitory effect of RANKL on OPG secretion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Coenzyme F 420 is recognized as a crucial electron carrier in methane-generating metabolism but, beyond this, has garnered significant attention for its role in diverse microbial physiologies and relevance in industrial, medical, and environmental applications. However, one limitation of current application of F 420 is the necessity of chemical electron donors for its reduction. In this study, an electrochemical reaction system was designed to facilitate electron transfer between the electrode and F 420 using F 420 -dependent sulfite reductase (Fsr) as the catalyst and benzyl viologen (BV) as the redox mediator. Photometric analysis and cyclic potential scanning demonstrated that the occurrence of bidirectional (reversible) electrochemical oxidation and reduction of F 420 in this system depended on the electrode potential. The formal redox potential of F 420 in this system was -540 mV vs. Ag|AgCl|sat. KCl, which aligned with values previously determined using biochemical assays., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Competing Interests: Conflict of interestThe authors declare no conflict of interest.

Background: Acute kidney injury (AKI) is a prevalent complication in critically ill patients that affects the timing of renal replacement therapy (RRT) initiation. This study aimed to develop and validate the SACrA score for predicting non-emergent initiations (BUN ≥112 mg/dL or oliguria for >72 h) of RRT in critically ill patients., Methods: We conducted a retrospective cohort study using data from two cohorts. The derivation cohort included patients admitted to the ICU between November 2021 and December 2023, whereas the validation cohort included patients admitted between September 2019 and October 2021. The primary outcome was non-emergent RRT initiation. The multivariate logistic regression with stepwise selection based on the Akaike information criterion finalized the model, including the variables, such as sex, albumin (Alb), creatinine (Cr), and APACHE II score (SACrA)., Results: The derivation and validation cohorts comprised 470 and 476 patients, respectively. The SACrA score showed a strong predictive performance for non-emergent RRT initiation in both the cohorts. Cohort 1 had an ROC-AUC of 0.971, with a calibration slope of 0.982 and an intercept of 0.009, whereas cohort 2 had an ROC-AUC of 0.918, with a calibration slope of 0.988 and an intercept of 0.004., Conclusions: The SACrA score is a robust tool for predicting non-emergent RRT initiation in critically ill patients using readily available clinical variables. Though additional data are needed to validate the SACrA score, our analysis suggests the tool may help clinicians make informed decisions, reduce unnecessary RRT, and thereby improve patient outcomes.

d-Allulose is a low-calorie sweetener with multiple nutritional functions that can be produced through d-fructose isomerization by ketose 3-epimerase (KEase). l-Ribulose 3-epimerase from Arthrobacterglobiformis (AgLRE) is one of the most important enzymes that produce d-allulose; however, its substrate recognition mechanism is unknown. In this study, the crystal structures of AgLRE and its complex with d-allulose and d-fructose were determined. Upon substrate binding, the hydrophobic residues around the active-site entrance move toward the bound substrate. A comparison of AgLRE and other KEase structures revealed that the substrate-binding residues are not the main factors responsible for its marked specificity for d-allulose and d-fructose, but the hydrophobicity of the active site pocket influences substrate recognition. Particularly, the two hydrophobic regions at the active site entrance are the regulatory elements that modulate substrate recognition by AgLRE. This study provides useful information for designing AgLRE to increase its affinity for d-allulose and d-fructose., (Copyright © 2024 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)

Objective Adult-onset Still's disease (AOSD) is a rare orphan disease, the diagnosis of which remains challenging. This study aimed to identify additional clues for establishing early diagnosis beyond the existing criteria. Methods A retrospective longitudinal cohort study was conducted at two community hospitals in Japan between March 2012 and December 2022. The clinical characteristics and medical histories of patients with AOSD were extracted from the clinical records. The primary outcome was to identify the key manifestations of AOSD for an early diagnosis beyond the existing criteria. Results Twenty-one patients (mean age, 58 years) were included in the study. Fever was the first symptom in 13 out of 21 patients (62%). Six out of 21 patients (29%) presented with a pruritic rash only, while two out of 21 (10%) initially presented with a sore throat. All patients visited more than one medical institution. The median time to reach a correct diagnosis was 41 days (IQR 19-138). Nineteen out of 20 patients (95%) exhibited a pruritic rash, identified as persistent pruritic linear streaks, with a median duration of 21 days (IQR 12-64) before the diagnosis of AOSD as a cutaneous manifestation. Conclusions Persistent pruritic linear streaks were a key feature in the context of an early diagnosis of AOSD, offering an option for reconsidering and revising the existing classification criteria., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethics Committees of Tokyo Bay Urayasu Ichikawa Medical Center and Nerima Hikarigaoka Hospital issued approval 861 and 23110901, respectively. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Iwanami et al.)

Objectives: To ascertain whether a mobile patient lift facilitates early mobilization in ventilated ICU patients., Design: A single-center, open-label, randomized controlled trial., Setting: An academic ICU in Tokyo., Patients: Eighty patients were admitted to ICU and expected ventilation for at least 48 hours., Interventions: In the intervention group, in addition to the rehabilitation protocol received by the control group, patients were assisted in sitting, standing, transfers, and walking using the mobile patient lift., Measurements and Main Results: The intervention group predominantly stood faster than the control group (1.0 vs. 3.0 d, p < 0.01). The Intervention group also had significantly higher Functional Status Score-ICU scores at ICU discharge. However, the Medical Research Council score and Barthel index at discharge, length of ICU stay, and number of ventilator-free days did not differ between the two groups., Conclusions: The use of mobile patient lifts facilitates the earlier standing of patients on ventilators. This may contribute to patients improved physical function in the ICU., Trial Registration: The study protocol was registered with the University Hospital Medical Information Network (UMIN) under the registration number UMIN000044965. Registered July 30, 2021., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Background: Recent studies have indicated the importance of muscle quality in addition to muscle quantity in sarcopenia pathophysiology. Intramuscular adipose tissue (IMAT), which originates from mesenchymal progenitors (MPs) in adult skeletal muscle, is a key factor affecting muscle quality in older adults, suggesting that controlling IMAT formation is a promising therapeutic strategy for sarcopenia. However, the molecular mechanism underlying IMAT formation in older adults has not been clarified. We recently found that the vitamin D receptor (VDR) is highly expressed in MPs in comparison to myotubes (P = 0.028, N = 3), indicating a potential role of vitamin D signalling in MPs. In this study, we aimed to clarify the role of vitamin D signalling in MP kinetics, with a focus on adipogenesis., Methods: MPs isolated from mouse skeletal muscles were subjected to adipogenic differentiation conditions with or without vitamin D (1α,25(OH)2D3, 100 nM) for 7 days, and adipogenicity was evaluated based on adipogenic marker expression. For in vivo analysis, tamoxifen-inducible MP-specific VDR-deficient (Vdr MPcKO ) mice were newly developed to investigate whether lack of vitamin D signalling in MPs is involved in IMAT formation. To induce muscle atrophy, Vdr MPcKO male mice were subjected to tenotomy of the gastrocnemius muscle, and then muscle weight, myofibre cross-sectional area, adipogenic marker expression, and fatty infiltration into the muscle were evaluated at 3 weeks after operation (N = 3-4). In addition, a vitamin D-deficient diet was provided to wild-type male mice (3 and 20 months of age, N = 5) for 3 months to investigate whether vitamin D deficiency causes IMAT formation., Results: Vitamin D treatment nearly completely inhibited adipogenesis of MPs through Runx1-mediated transcriptional modifications of early adipogenic factors such as PPARγ (P = 0.0031) and C/EBPα (P = 0.0027), whereas VDR-deficient MPs derived from Vdr MPcKO mice differentiated into adipocytes even in the presence of vitamin D (P = 0.0044, Oil-Red O + area). In consistency with in-vitro findings, Vdr MPcKO mice and mice fed a vitamin D-deficient diet exhibited fat deposition in atrophied (P = 0.0311) and aged (P = 0.0216) skeletal muscle, respectively., Conclusions: Vitamin D signalling is important to prevent fate decision of MPs towards the adipogenic lineage. As vitamin D levels decline with age, our data indicate that decreased vitamin D levels may be one of the causes of IMAT formation in older adults, and vitamin D signalling may be a novel therapeutic target for sarcopenia., (© 2024 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: Global studies exploring the relationship between parity and chronic kidney disease (CKD) are scarce. Furthermore, no study has examined the relationship between parity and CKD in Japan. Therefore, this study aimed to examine the relationship between parity and the prevalence of CKD in a Japanese population, considering the clinical history of hypertensive disorders of pregnancy (HDP) and current body mass index (BMI) based on menopausal status., Methods: This cross-sectional study included 26,945 Japanese multiparous women (5,006 premenopausal and 21,939 postmenopausal women) and 3,247 nulliparous women (1,599 premenopausal and 1,648 postmenopausal women). Participants were divided into two groups based on their menopausal status (premenopausal and postmenopausal women). The relationship between parity and the prevalence of CKD was evaluated using a multiple logistic regression model adjusted for several covariates, including a clinical history of HDP and current BMI., Results: The relationship between parity and the prevalence of CKD was not statistically significant in either premenopausal or postmenopausal multiparous women. A clinical history of HDP was significantly associated with an increased risk of CKD in premenopausal and postmenopausal multiparous women. However, the relationship between a clinical history of HDP and CKD in premenopausal women was weakened after adjusting for current BMI. Furthermore, the current BMI was significantly associated with an increased risk of CKD in both premenopausal and postmenopausal women., Conclusions: Parity is not significantly associated with the prevalence of CKD in premenopausal and postmenopausal multiparous women. A clinical history of HDP is a risk factor for CKD in both premenopausal and postmenopausal women. Current BMI is also associated with an increased risk of CKD in premenopausal and postmenopausal women. Therefore, continuous surveillance and preventive measures against CKD should be provided to women with a clinical history of HDP. In addition, maintaining an appropriate body weight is beneficial in reducing the risk of CKD., (© 2024. The Author(s).)

Acetogens are among the key microorganisms involved in the bioproduction of commodity chemicals from diverse carbon resources, such as biomass and waste gas. Thermophilic acetogens are particularly attractive because fermentation at higher temperatures offers multiple advantages. However, the main target product is acetic acid. Therefore, it is necessary to reshape metabolism using genetic engineering to produce the desired chemicals with varied carbon lengths. Although such metabolic engineering has been hampered by the difficulty involved in genetic modification, a model thermophilic acetogen, M. thermoacetica ATCC 39073, is the case with a few successful cases of C2 and C3 compound production, other than acetate. This brief report attempts to expand the product spectrum to include C4 compounds by using strain Y72 of Moorella thermoacetica . Strain Y72 is a strain related to the type strain ATCC 39073 and has been reported to have a less stringent restriction-modification system, which could alleviate the cumbersome transformation process. A simplified procedure successfully introduced a key enzyme for acetoin (a C4 chemical) production, and the resulting strains produced acetoin from sugars and gaseous substrates. The culture profile revealed varied acetoin yields depending on the type of substrate and culture conditions, implying the need for further engineering in the future. Thus, the use of a user-friendly chassis could benefit the genetic engineering of M. thermoacetica ., Competing Interests: This work has been included in a patent application by Hiroshima University and AIST., (Copyright © 2024 Kato, Fujii, Kato, Wada, Watanabe, Nakamichi, Aoi, Morita, Murakami and Nakashimada.)

Background: Xylobiose, a non-digestible disaccharide, largely contributes to the beneficial physiological effects of xylooligosaccharides. However, there is insufficient evidence to assess the direct effect of xylobiose on intestinal barrier function. Here, we investigated the intestinal barrier function in human intestinal Caco-2 cells treated with xylobiose., Results: In total, 283 genes were upregulated and 256 genes were downregulated in xylobiose-treated Caco-2 cells relative to the controls. We focused on genes related to intestinal barrier function, such as tight junction (TJ) and heat shock protein (HSP). Xylobiose decreased the expression of the TJ gene Claudin 2 (CLDN2) and increased the expression of the cytoprotective HSP genes HSPB1 and HSPA1A, which encode HSP27 and HSP70, respectively. Immunoblot analysis confirmed that xylobiose suppressed CLDN2 expression and enhanced HSP27 and HSP70 expression. A quantitative reverse transcription-PCR and promoter assays indicated that xylobiose post-transcriptionally regulated CLDN2 and HSPB1 levels. Additionally, selective inhibition of phosphatidyl-3-inositol kinase (PI3K) inhibited xylobiose-mediated CLDN2 expression, whereas HSP27 expression induced by xylobiose was sensitive to the inhibition of PI3K, mitogen-activated protein kinase kinase and Src., Conclusion: The results of the present study reveal that xylobiose suppresses CLDN2 and increases HSP27 expression in intestinal Caco-2 cells via post-transcriptional regulation, potentially strengthening intestinal barrier integrity; however, these effects seem to occur via different signaling pathways. Our findings may help to assess the physiological role of xylobiose. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Mitochondrial dysfunction in pancreatic β-cells leads to impaired glucose-stimulated insulin secretion (GSIS) and type 2 diabetes (T2D), highlighting the importance of autophagic elimination of dysfunctional mitochondria (mitophagy) in mitochondrial quality control (mQC). Imeglimin, a new oral anti-diabetic drug that improves hyperglycemia and GSIS, may enhance mitochondrial activity. However, chronic imeglimin treatment's effects on mQC in diabetic β-cells are unknown. Here, we compared imeglimin, structurally similar anti-diabetic drug metformin, and insulin for their effects on clearance of dysfunctional mitochondria through mitophagy in pancreatic β-cells from diabetic model db/db mice and mitophagy reporter (CMMR) mice. Pancreatic islets from db/db mice showed aberrant accumulation of dysfunctional mitochondria and excessive production of reactive oxygen species (ROS) along with markedly elevated mitophagy, suggesting that the generation of dysfunctional mitochondria overwhelmed the mitophagic capacity in db/db β-cells. Treatment with imeglimin or insulin, but not metformin, reduced ROS production and the numbers of dysfunctional mitochondria, and normalized mitophagic activity in db/db β-cells. Concomitantly, imeglimin and insulin, but not metformin, restored the secreted insulin level and reduced β-cell apoptosis in db/db mice. In conclusion, imeglimin mitigated accumulation of dysfunctional mitochondria through mitophagy in diabetic mice, and may contribute to preserving β-cell function and effective glycemic control in T2D., (© 2024. The Author(s).)

The coronavirus disease 2019 (COVID-19) pandemic and government regulations have affected the daily lives and mental health of individuals worldwide. This study aimed to determine how much the change in time spent on exercise (exercise time), outdoor activities ("going-out" time), and screen usage (screen time) before and after the COVID-19 pandemic has affected mental health (depression, anxiety, and insomnia). In June 2021, during the third wave of the COVID-19 pandemic, a web-based, cross-sectional survey was conducted in Japan through an online research company. A total of 824 workers participated in this study. Depression, anxiety, and insomnia were assessed using the Patient Health Questionnaire-9, General Anxiety Disorder-7, and Insomnia Severity Index, respectively. The symptoms of depression were associated with age and decreased exercise time. Symptoms of anxiety were associated with not decreased going-out time. Symptoms of insomnia were associated with reduced exercise time. The results indicated that during the COVID-19 pandemic, an increase in exercise time could have prevented depression and insomnia. Similarly, a decrease in going-out time could have prevented anxiety. Furthermore, in the event of future outbreaks of unpredictable infections, such as COVID-19, decreased going out and increased exercise may help maintain mental health., (© 2023 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

This study investigated the association of parity with hypertension prevalence in Japanese women while considering a clinical history of hypertensive disorders of pregnancy (HDP) and menopausal status. This cross-sectional study included 30,530 Japanese women (6700 premenopausal; 23 830 postmenopausal). The association between parity and the prevalence of hypertension was evaluated using a multiple logistic regression model with possible confounders. In premenopausal women, no statistically significant association between parity and hypertension prevalence was found. When not adjusted for current body mass index (BMI), a linear graded association was observed between parity and the prevalence of hypertension in postmenopausal women. However, the association between parity and hypertension prevalence in postmenopausal women was attenuated after adjustment for current BMI. Both current BMI and a clinical history of HDP were significantly associated with a high risk of hypertension in both premenopausal and postmenopausal women. Our results also suggest that continuous surveillance and preventive measures for hypertension should be provided for women with HDP and high parity., (© 2023 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Background: Isopropanol (IPA) is a commodity chemical used as a solvent or raw material for polymeric products, such as plastics. Currently, IPA production depends largely on high-CO 2 -emission petrochemical methods that are not sustainable. Therefore, alternative low-CO 2 emission methods are required. IPA bioproduction using biomass or waste gas is a promising method., Results: Moorella thermoacetica, a thermophilic acetogenic microorganism, was genetically engineered to produce IPA. A metabolic pathway related to acetone reduction was selected, and acetone conversion to IPA was achieved via the heterologous expression of secondary alcohol dehydrogenase (sadh) in the thermophilic bacterium. sadh-expressing strains were combined with acetone-producing strains, to obtain an IPA-producing strain. The strain produced IPA as a major product using hexose and pentose sugars as substrates (81% mol-IPA/mol-sugar). Furthermore, IPA was produced from CO, whereas acetate was an abundant byproduct. Fermentation using syngas containing both CO and H 2 resulted in higher IPA production at the specific rate of 0.03 h -1 . The supply of reducing power for acetone conversion from the gaseous substrates was examined by supplementing acetone to the culture, and the continuous and rapid conversion of acetone to IPA showed a sufficient supply of NADPH for Sadh., Conclusions: The successful engineering of M. thermoacetica resulted in high IPA production from sugars. M. thermoacetica metabolism showed a high capacity for acetone conversion to IPA in the gaseous substrates, indicating acetone production as the bottleneck in IPA production for further improving the strain. This study provides a platform for IPA production via the metabolic engineering of thermophilic acetogens., (© 2024. The Author(s).)

Background: Although the resuscitation rate for out-of-hospital cardiac arrest (OHCA) patients in Japan is increasing due to the widespread use of automated external defibrillators, the proportion of patients who can return to society remains low at approximately 7%. Many patients have poor neurological outcomes and cannot return to society because of post-resuscitation hypoxic-ischemic encephalopathy. While the resumption of cardiac rhythm is important for patients with OHCA, improving neurological outcomes and returning to society are also important., Objectives: To investigate whether perampanel, an antiepileptic drug that provides neurological protection against stroke and head injury, could improve neurological outcomes in patients resuscitated after OHCA., Methods: The participants included 33 patients with OHCA admitted to our hospital from January 2021 to June 2022 and 33 patients admitted before that time. Perampanel was administered to the patients in the intervention group immediately after resuscitation. We defined a  Cerebral Performance Category (CPC) score  of 1.2 as a good neurological outcome., Results: There was no significant difference in neurological outcomes at intensive care unit discharge between the intervention and non-intervention groups (number of CPC 1.2: 16/33 vs. 9/33); however, neurological outcomes at hospital discharge were significantly better in the intervention group (number of CPC 1.2: 19/33 vs. 9/33 P = 0.01)., Conclusion: The α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor inhibitory and neuronal protective effects of perampanel may have inhibited the progression of hypoxic-ischemic encephalopathy, which develops after the resumption of cardiac rhythm, and suppressed neuronal damage. Early administration of perampanel after resuscitation of patients with OHCA may improve neurological outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Nakamichi et al.)

α-Xylosidase releases xylopyranosyl side chains from xyloglucan oligosaccharides and is vital for xyloglucan degradation. Previously, we identified and characterized two α-xylosidases, intracellular AxyA and extracellular AxyB, in Aspergillus oryzae . In this study, we identified a third α-xylosidase, termed AxyC, in A. oryzae . These three A. oryzae α-xylosidases belong to the glycoside hydrolase family 31, but there are clear differences in substrate specificity. Both AxyA and AxyB showed much higher hydrolytic activity toward isoprimeverose (α-D-xylopyranosyl-1,6-glucose) than p -nitrophenyl α-D-xylopyranoside. In contrast, the specific activity of AxyC toward the p -nitrophenyl substrate was approximately 950-fold higher than that toward isoprimeverose. Our study revealed that there are multiple α-xylosidases with different substrate specificities in A. oryzae ., Competing Interests: The authors declare no conflict of interest., (2023 by The Japanese Society of Applied Glycoscience.)

Mannosylerythritol lipids (MELs) are extracellular glycolipids produced by the basidiomycetous yeast strains. MELs consist of the disaccharide mannosylerythritol, which is acylated with fatty acids and acetylated at the mannose moiety. In the MEL biosynthesis pathway, an acyltransferase from Pseudozyma tsukubaensis , PtMAC2p, a known excellent MEL producer, has been identified to catalyze the acyl-transfer of fatty acid to the C3'-hydroxyl group of mono-acylated MEL; however, its structure remains unclear. Here, we performed X-ray crystallography of recombinant PtMAC2p produced in Escherichia coli and homogeneously purified it with catalytic activity in vitro . The crystal structure of PtMAC2p was determined by single-wavelength anomalous dispersion using iodide ions. The crystal structure shows that PtMAC2p possesses a large putative catalytic tunnel at the center of the molecule. The structural comparison demonstrated that PtMAC2p is homologous to BAHD acyltransferases, although its amino acid-sequence identity was low (<15%). Interestingly, the HXXXD motif, which is a conserved catalytic motif in the BAHD acyltransferase superfamily, is partially conserved as His158-Thr159-Leu160-Asn161-Gly162 in PtMAC2p, i.e. , D in the HXXXD motif is replaced by G in PtMAC2p. Site-directed mutagenesis of His158 to Ala resulted in more than 1,000-fold decrease in the catalytic activity of PtMAC2p. These findings suggested that His158 in PtMAC2p is the catalytic residue. Moreover, in the putative catalytic tunnel, hydrophobic amino acid residues are concentrated near His158, suggesting that this region is a binding site for the fatty acid side chain of MEL (acyl acceptor) and/or acyl-coenzyme A (acyl donor). To our knowledge, this is the first study to provide structural insight into the catalytic activity of an enzyme involved in MEL biosynthesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nakamichi, Saika, Watanabe, Fujii and Morita.)

4-Amino-4-deoxychorismate synthase (ADCS), a chorismate-utilizing enzyme, is composed of two subunits: PabA and PabB. PabA is a glutamine amidotransferase that hydrolyzes glutamine into glutamate and ammonia. PabB is an aminodeoxychorismate synthase that converts chorismate to 4-amino-4-deoxychorismate (ADC) using the ammonia produced by PabA. ADCS functions under allosteric regulation between PabA and PabB. However, the allosteric mechanism remains unresolved because the structure of the PabA-PabB complex has not been determined. Here, the crystal structure and characterization of PapA from Streptomyces venezuelae (SvPapA), a bifunctional enzyme comprising the PabA and PabB domains, is reported. SvPapA forms a unique dimer in which PabA and PabB domains from different monomers complement each other and form an active structure. The chorismate-bound structure revealed that recognition of the C1 carboxyl group by Thr501 and Gly502 of the 498-PIKTG-502 motif in the PabB domain is essential for the catalytic Lys500 to reach the C2 atom, a reaction-initiation site. SvPapA demonstrated ADCS activity in the presence of Mg 2+ when glutamate or NH + 4 was used as the amino donor. The crystal structure indicated that the Mg 2+ -binding position changed depending on the binding of chorismate. In addition, significant structural changes were observed in the PabA domain depending on the presence or absence of chorismate. This study provides insights into the structural factors that are involved in the allosteric regulation of ADCS.

TcXyn30A from Talaromyces cellulolyticus, which belongs to subfamily 7 of the glycoside hydrolase family 30 (GH30-7), releases xylose from the reducing end of xylan and xylooligosaccharides (XOSs), the so-called reducing-end xylose-releasing exoxylanase (ReX). In this study, the crystal structures of TcXyn30A with and without xylose at subsite +1 (the binding site of the xylose residue at the reducing end) were determined. This is the first report on the structure of ReX in the family GH30-7. TcXyn30A forms a dimer. The complex structure of TcXyn30A with xylose revealed that subsite +1 is located at the dimer interface. TcXyn30A recognizes xylose at subsite +1 composed of amino acid residues from each monomer and blocks substrate binding to subsite +2 by dimer formation. Thus, the dimeric conformation is responsible for ReX activity. The structural comparison between TcXyn30A and the homologous enzyme indicated that subsite -2 is composed of assembled three stacked Trp residues, Trp49, Trp333, and Trp334, allowing TcXyn30A to accommodate xylan and any branched XOSs decorated with a substitution such as α-1,2-linked 4-O-methyl-d-glucuronic acid or α-1,2- and/or -1,3-linked L-arabinofuranose. These findings provide an insight into the structural determinants for ReX activity of TcXyn30A., (© 2023 Wiley Periodicals LLC.)

The vitamin D receptor (VDR) is expressed most abundantly in osteoblasts and osteocytes (osteoblastic cells) in bone tissues and regulates bone resorption and calcium (Ca) and phosphate (P) homeostasis in association with parathyroid hormone (PTH). We previously reported that near-physiological doses of vitamin D compounds suppressed bone resorption through VDR in osteoblastic cells. We also found that supra-physiological doses of 1α,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] induced bone resorption and hypercalcemia via VDR in osteoblastic cells. Here, we report that the latter, a proresorptive dose of 1,25(OH) 2 D 3 , causes soft tissue calcification through VDR in osteoblastic cells. High concentrations of vitamin D affect multiple organs and cause soft tissue calcification, with increases in bone resorption and serum Ca levels. Such a variety of symptoms is known as hypervitaminosis D, which is caused by not only high doses of vitamin D but also impaired vitamin D metabolism and diseases that produce 1,25(OH) 2 D 3 ectopically. To clarify the biological process hierarchy in hypervitaminosis D, a proresorptive dose of 1,25(OH) 2 D 3 was administered to wild-type mice in which bone resorption had been suppressed by neutralizing anti-receptor activator of NF-κB ligand (RANKL) antibody. 1,25(OH) 2 D 3 upregulated the serum Ca x P product, concomitantly induced calcification of the aorta, lungs, and kidneys, and downregulated serum PTH levels in control IgG-pretreated wild-type mice. Pretreatment of wild-type mice with anti-RANKL antibody did not affect the down-regulation of PTH levels by 1,25(OH) 2 D 3 , but inhibited the increase of the serum Ca x P product and soft tissue calcification induced by 1,25(OH) 2 D 3 . Consistent with the effects of anti-RANKL antibody, VDR ablation in osteoblastic cells also did not affect the down-regulation of PTH levels by 1,25(OH) 2 D 3 , but suppressed the 1,25(OH) 2 D 3 -induced increase of the serum Ca x P product and calcification of soft tissues. Taken together with our previous results, these findings suggest that bone resorption induced by VDR signaling in osteoblastic cells is critical for the pathogenesis of hypervitaminosis D, but PTH is not involved in hypervitaminosis D., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Although feeding with a liquid diet does not affect the growth of rat submandibular glands, it inhibits the growth of rat parotid glands during growth periods. In these growth-inhibited parotid glands, the growth of parasympathetic nerves is also suppressed. Meanwhile, the mature parotid glands of animals maintained on a liquid diet become morphologically and functionally atrophic, however, there is no effect of a liquid diet on mature submandibular glands. The objective of the present study was to clarify whether the nerve distribution in the mature salivary glands of rats was affected by a liquid diet., Materials and Methods: Seven-week-old male Wistar rats were used in this study. Half of the rats were kept on a pellet diet, and half were kept on a liquid diet, for 3, 7, 14, or 21 days. All rats were euthanised by isoflurane at each endpoint. Then, the parotid and submandibular glands were removed, frozen in liquid nitrogen, cryosectioned, and stained with antibodies against protein gene product 9.5 (PGP 9.5; general nerve marker), tyrosine hydroxylase (TH; sympathetic nerve marker), or neuronal nitric oxide synthase (nNOS; parasympathetic nerve marker)., Results: In parotid and submandibular glands of the pellet diet group, PGP 9.5- and TH-like immunoreactivity were seen around acini and ducts, and nNOS-like immunoreactivity was lower than PGP 9.5- and TH-like immunoreactivity. In the parotid glands of the liquid diet group, similar immunoreactivities were seen throughout the experimental period. The distribution of antibody labelling in the submandibular glands of the liquid diet group was similar to that of the pellet diet group and remained unchanged during the experimental period., Conclusions: The present study demonstrated no regressive effects of a liquid diet on the distribution of sympathetic or parasympathetic nerves in mature parotid glands and submandibular glands. This differed from inhibitory effects on the growth of parotid glands seen during growth periods.

N-linked oligosaccharides in the fission yeast Schizosaccharomyces pombe contain large amounts of d-galactose (Gal), which mainly comprises α1,2- and α1,3-linked Gal except for pyruvylated β1,3-linked Gal (PvGalβ) at the non-reducing end. The PvGalβ unit of N-glycans is important for regulating nonsexual flocculation and invasive growth, but the mechanistic basis for β-galactosylation in fission yeast is poorly understood. To gain insight into this mechanism, we have characterized three genes previously identified to be involved in PvGalβ biosynthesis (pvg2, pvg3, and pvg5), with a focus on pvg3, which is predicted to contain a domain conserved in galactosyltransferase family 31 (GT31) proteins. Fluorescent microscopy revealed that Pvg3 is stably localized at the Golgi membrane, regardless of the presence of pvg2 + or pvg5 + , suggesting that Pvg2 and Pvg5 are essential for the function of Pvg3 as a β1,3-galactosyltransferase, and not for its localization to the Golgi. Mutation of the GT31 family DXD motif and GT-A fold in Pvg3 resulted in loss of catalytic activity in vivo, supporting the idea that Pvg3 is a GT-A type β1,3-galactosyltransferase. Docking simulations further indicated that Pvg3 can recognize donor and acceptor substrates suitable for β-(1→3) bond formation. Yeast two-hybrid assay showed that Pvg5 physically interacts with Pvg3 and the pyruvyltransferase Pvg1. Collectively, these results provide insight into β-galactosylation catalyzed by Pvg3 and the supporting role of Pvg5 in PvGalβ biosynthesis., (Copyright © 2023 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.)