Kitasato University

We aimed to examine the association between tooth count and prognosis in older patients with heart failure. In this single-center retrospective study of 287 patients aged ≥65 years with heart failure (median age 81 years; 52.8% male), natural and functional tooth counts at discharge were assessed. In Cox regression analyses, higher natural tooth count (hazard ratio 0.951; 95% confidence interval 0.917-0.985; P=0.006) and higher functional tooth count (hazard ratio 0.924; 95% confidence interval 0.882-0.968; P<0.001) were associated with lower 1-year mortality. Higher natural and functional tooth counts were associated with a better prognosis.

Supersulfides, sulfur species containing catenated sulfur atoms, are potent reducing agents produced by diverse organisms. Although their intracellular functions are increasingly recognized, the ecological and physiological importance of gut microbial supersulfides remains poorly understood. In this study, we explored two complementary aspects of gut microbiota-derived supersulfide. First, by assessing the reducing activity, we found that bacterial supersulfides contribute to the enhancement of the extracellular reducing capacity. In particular, Dorea longicatena and Enterocloster bolteae exhibit strong cystine-dependent supersulfide production, which is associated with protection against oxidative stress. Second, beyond their ecological roles, supersulfides influence protein supersulfidation, which is a reversible post-translational modification. Supersulfidated proteins have been detected across multiple commensal taxa with species-specific profiles. This modification is redox-sensitive and modulated by extracellular supersulfides. Members of the Lactobacillaceae family are particularly susceptible to exogenous supersulfides. Supersulfidation involves proteins linked to core microbial processes, including bile acid metabolism, suggesting their potential role in tuning bacterial functions. Together, these findings suggest that microbial supersulfides act as dual regulators: (i) contributing to a protective reducing milieu and (ii) modulating bacterial protein function through supersulfidation. By highlighting post-translational control in gut bacteria and their sensitivity to the local redox environment, this work broadens the current models of microbial redox biology and provides a basis for linking bacterial sulfur metabolism with gut ecosystem stability and host-microbe interactions.

Carbapenem-resistant Acinetobacter baumannii (CRAb) is designated by the World Health Organization as a critical priority pathogen, and most clinical CRAb isolates are multidrug-resistant (MDRA). However, an in vivo mouse imaging model of infection using clinical MDRA isolates has not been curated. Using antibiotic resistance genes as plasmid selection markers is incompatible with antimicrobial drug evaluation and prevents their application to MDRA isolates. To overcome this limitation, we constructed a firefly luciferase plasmid using tellurite resistance genes as non-antibiotic selection markers, enabling luminescence in multiple clinical MDRA isolates without altering susceptibility. Using a mouse pneumonia model and near-infrared luciferin derivative (TokeOni), we achieved noninvasive visualization of lung colonization by clinical MDRA isolates. Luminescence dynamics during treatment mirrored the in vitro minimum inhibitory concentration and survival outcomes, providing a therapeutic response readout. This platform overcomes a major bottleneck in MDR pathogen imaging and supports the evaluation of infection dynamics and drug efficacy.

Organ morphogenesis is essential for not only integrated organ functions in the body but also the determination of adult-tissue stem cells and their niche. Only hair follicle organs can cyclically regenerate in the variable bulbous germinative region as a form of programmed organ regeneration in adults. Here, we identified a cell population, hair follicle organ-intrinsic mesenchymal cells, with PDGFRα+/Sca1+/CD34high+ mesenchymal cells, from the boundary zone of the epithelial stem cell niche by using the organ germ method, which plays essential roles in entering and promoting the downgrowth phase of the hair cycle. The bioengineered hair follicle germ reconstituted from bulge region-derived epithelial stem cells, dermal papillae and mesenchymal cells has full functions, including downgrowth, full-size hair follicle regeneration and the hair cycle, both in in vitro artificial skin and after intracutaneous skin transplantation. This study provides significant contributions to the basic and medical science of adult organ-inductive potential stem cells and their niches in organ morphogenesis and the adult hair cycle.

Nonclinical studies in animal models have often treated male animals as the default, based on the assumption that estrous-cycle hormonal variation in females increases variability and complicates interpretation. This convention is a structural limitation in study design, particularly in therapeutic areas where sex differences in pharmacokinetics (PK), pharmacodynamics (PD), and toxicity are substantial and clinically relevant. Clinical experience shows higher adverse drug reaction rates in women and recurring examples of sex-biased toxicities, underscoring the translational cost of limited sex consideration early in development. Sex differences in nonclinical PK and toxicity arise from defined mechanisms, including sex-dependent growth hormone secretion patterns that shape hepatic and renal enzyme/transporter expression, as well as sex-specific determinants of gastrointestinal absorption and cardiac electrophysiology. Omics analyses further show that sex effects are embedded in system-wide molecular networks across immune, metabolic, cardiovascular, renal, and neural systems, supporting a shift from descriptive to predictive and stratified animal study designs. Sex bias is also an animal welfare concern: male-only strategies can generate surpluses of unused females in breeding colonies, challenging the 3Rs-particularly Reduction-when evaluated at the project or facility level. Regulatory expectations are converging through International Council for Harmonization (ICH) principles, the National Institutes of Health (NIH) sex-as-a-biological-variable (SABV) policy, and reporting frameworks such as Sex and Gender Equity in Research (SAGER), with increasing emphasis on transparent sex reporting and analysis across nonclinical evidence streams. This review integrates scientific, welfare, and regulatory perspectives to provide a practical framework for sex-aware nonclinical study design, enhancing translational validity and ethical rigor.

ABSTRACT Aim Schizonepeta spike, the dried spikes of Schizonepeta tenuifolia , are traditionally evaluated based on floret density. However, the chemical basis for this criterion remains unclear. This study aimed to provide scientific insight into this traditional quality evaluation by clarifying the association between floret density (floret‐to‐spike ratio) and pulegone content in whole spikes, and the localization of compounds between florets and rachises. Methods Two accessions of S. tenuifolia were cultivated at six sites in Japan and analyzed by LC‐Q‐TOF‐MS. Correlation analysis was performed between the floret‐to‐spike ratio and pulegone content in whole spikes. Additionally, principal component analysis (PCA) was performed to characterize the localization of compounds between florets and rachises, and the relative abundances of major compounds were compared between them. Results In whole spikes, pulegone content tended to increase with a higher floret‐to‐spike ratio. The PCA based on the comprehensive compounds showed that florets and rachises separated into distinct groups, regardless of cultivation site or accession. Florets showed higher levels of bioactive compounds, including pulegone, luteoloside, and apigetrin, whereas rachises showed higher hesperidin levels than other parts. Conclusion Floret density of Schizonepeta spikes, as described in traditional quality evaluation, was found to be related to pulegone content, which tends to increase as the floret density becomes higher. Moreover, florets were characterized by higher levels of bioactive compounds, including luteoloside and apigetrin, and this localization suggests that the accumulation of these compounds increases in spikes with dense florets. These findings provide chemical insights into the traditional quality evaluation of Schizonepeta spikes.