Hepatic innate immune function plays an important role in the pathogenesis of many diseases. Importantly, a growing body of literature has firmly established the spatial heterogeneity of hepatocyte metabolic function; however, whether innate immune function is zonated remains unknown. To test this question, we exposed adult C57BL/6 mice to endotoxemia, and hepatic tissue was assessed for the acute phase response (APR). The zone-specific APR was evaluated in periportal and pericentral/centrilobular hepatocytes isolated using digitonin perfusion and on hepatic tissue using RNAscope and immunohistochemistry. Western blot, EMSA, chromatin immunoprecipitation, and immunohistochemistry were used to determine the role of the transcription factor NF-κB in mediating hepatic C-reactive protein (CRP) expression. Finally, the ability of mice lacking the NF-κB subunit p50 (p50−/−) to raise a hepatic APR was evaluated. We found that endotoxemia induces a hepatocyte transcriptional APR in both male and female mice, with Crp, Apcs, Fga, Hp, and Lbp expression being enriched in pericentral/centrilobular hepatocytes. Focusing our work on CRP expression, we determined that NF-κB transcription factor subunit p50 binds to consensus sequence elements present in the murine CRP promoter. Furthermore, pericentral/centrilobular hepatocyte p50 nuclear translocation is temporally associated with zone-specific APR during endotoxemia. Lastly, the APR and CRP expression is blunted in endotoxemic p50−/− mice. These results demonstrate that the murine hepatocyte innate immune response to endotoxemia includes zone-specific activation of transcription factors and target gene expression. These results support further study of zone-specific hepatocyte innate immunity and its role in the development of various disease states.

Chemotherapy-induced peripheral neuropathy (CIPN) is a disabling, often irreversible toxicity that affects millions of patients, limits life-saving cancer therapy, and lacks proven treatment. In this work, we show that as little as two doses of psilocybin before chemotherapy durably prevented the onset of CIPN across platinum- and taxane-based models, including repeated chemotherapy cycles, without impairing antitumor efficacy. Peripherally, psilocybin maintained tactile sensitivity and intraepidermal nerve fiber endings through axonal mitochondrial trafficking and distribution preservation, through the TrkB-Akt-PAK5-MAP2-KIF5B pathway and remobilization of syntaphilin-anchored mitochondria. Centrally, it normalized medial prefrontal cortical synaptic activity and cortical alpha and beta electroencephalography power. This stabilization of peripheral axonal energy balance establishes psilocybin as a first-in-class prophylactic agent for CIPN while also preserving central neural function. Given psilocybin’s established safety, these discoveries support clinical evaluation as a strategy to prevent CIPN.

Background: Urogenital schistosomiasis is a major cause of preventable morbidity, primarily in rural, resource-limited regions. After decades of mass drug administration, changing epidemiologic landscapes, and ongoing resource limitations, test-and-treat models may be necessary to meet elimination goals. However, diagnostic capacity remains centralized and laboratory-dependent, and community-led, contextually adapted implementation strategies remain poorly defined. This study describes the accuracy and feasibility of a low-cost diagnostic toolkit and explores community-integrated implementation models. Methodology/Principal Findings: This mixed-methods study enrolled 418 participants from five endemic sites near Oyan River Dam, Ogun State, Nigeria in July 2025. Urine samples underwent parallel analysis by community health extension workers utilizing the toolkit and by laboratory technicians using standard microscopy. The toolkit consisted of a reusable urine filtration device paired with a under-$2 paper microscope. Semi-structured interviews with community health extension workers and key informants were analyzed using the Consolidated Framework for Implementation Research. Prevalence was 27.5% (115/418). Community health extension workers demonstrated progressive improvement in diagnostic accuracy across five sequential communities (n=237), rising from 52.5% (95% CI 37.5–67.1) to 92.1% (79.2–97.3) over eight study days (Cochran-Armitage Z=3.08, p=0.002). Specificity improved from 53.6% to 96.3% (Z=3.00, p=0.003), final sensitivity reached 81.8% (52.3–94.9), and final Cohen's kappa reached 0.803. In the hands of laboratory scientists, Foldscope microscopy achieved 91.0% sensitivity and 99.3% specificity. Conclusions/Significance: Community-led diagnostic task-shifting for urogenital schistosomiasis control is accurate, feasible, and implementation-ready. Consolidated Framework for Implementation Research-guided analysis demonstrated strong end-user acceptability, with local ownership, collaboration, and trust-building as key implementation facilitators. This approach addresses diagnostic gaps in resource-limited endemic settings with relevance to other community health worker-led strategies