A miR-99a-TGF-β1 feedback circuit drives miR-99a upregulation.

Whether the number and quality of births have been changed after the COVID-19 pandemic remains unclear. We aimed to examine whether the number of births, gestation weeks, and birth weight changed after COVID-19 in Chongqing, the largest municipality by area in China. Birth registration data of Chongqing from January 2015 to July 2022 were used to compare the quantity and quality (gestation week, preterm birth rate, birth weight, low birth weight rate) of births before and after the pandemic by interrupted time series analysis by autoregressive average moving models (ARIMA) and linear models of interrupted time series analysis (ITSA). October 2020, which was nine months after the onset of the first-wase of COVID-19 pandemic, was designated as the cut point to account for the gestation duration. Data from the Chongqing Preconception Reproductive Health and Birth Outcome Cohort were then utilized to analyze the temporal changes in pre-pregnancy body mass index (BMI) among reproductive-age women before (January 2019 to January 2020) and after the pandemic (March 2020 to March 2023). There were 2,099,898 birth records included. Before the pandemic, there were monthly declining trends in the number of births (β=-100.44, 95

Circadian disruption has been linked to impaired male fecundity, but its association with semen molecular phenotypes and circadian genes remains unclear. We analyzed 441 men from the Male Reproductive Health in Chongqing College Students cohort to assess whether social jetlag, an indicator of circadian disruption, was associated with whole-semen mitochondrial DNA copy number (mtDNAcn), an emerging biomarker of male fecundity. Core circadian genes related to mtDNAcn were screened using genetic polymorphism data. A light-cycle phase-shifting mouse model, Cry1-knockout mice, and testicular Cry1 re-expression models were used for experimental validation, with histology, transcriptomics, single-cell data, and proteomics analyses used to explore mechanisms. Social jetlag was associated with higher mtDNAcn in men (1.29-fold, p = 0.026), with a concordant increase in circadian-disrupted mice (1.33-fold, p = 0.010). Among core circadian genes, CRY1 showed the strongest association with mtDNAcn (p = 0.048). Cry1 knockout elevated mtDNAcn (2.18-fold, p < 0.001), whereas testicular Cry1 re-expression reduced it toward wild-type levels. Circadian disruption and Cry1 deficiency were accompanied by seminiferous epithelial disorganization, spermatogenesis-related transcriptomic changes, and altered mitochondrial pathway signatures. To our knowledge, this study is the first to identify whole-semen mtDNAcn as a circadian-disruption-associated molecular phenotype and supports CRY1 as a candidate regulator.

EV-miR-99a targets NLRP2 and activates NF-kB signaling in fibroblasts.

Background:Osteoporosis is a common skeletal disorder among older adults, characterized by reduced bone density and increased susceptibility to fractures, particularly in individuals with autoimmune diseases. Adequate knowledge of osteoporosis and active engagement in bone-protective behaviors may help prevent its onset; however, research examining this hypothesis within autoimmune populations remains limited. This study aimed to evaluate osteoporosis knowledge levels in patients with autoimmune diseases and to investigate the relationship between osteoporosis knowledge scores and bone mineral density (BMD). Methods:This hospital-based cross-sectional study enrolled 562 participants aged 18 years and older who underwent complete dual-energy X-ray absorptiometry (DXA) scans with autoimmune diseases between March 2023 and September 2024. Latent class analysis (LCA) was applied to the four dimensions of the Chinese version of the Osteoporosis Prevention and Awareness Tool (OPAAT-C), namely symptoms, diagnostic methods, preventive measures and risk factors, to classify participants into high, moderate and low knowledge groups, and bone mass was compared across these groups. Results:This study included 562 adults with autoimmune diseases who completed the OPAAT-C (48.2% male; mean age 45.9 years). The average osteoporosis knowledge score was 12.67 ± 5.63 (57.6% of 22 points). Among 253 patients (45.0%) with low BMD, 78 (30.8%) were in the low knowledge score group based on LCA. Higher osteoporosis knowledge was significantly associated with greater lumbar spine BMD and lower osteoporosis risk. In multivariate linear regression adjusted for all covariates, higher osteoporosis knowledge scores derived from LCA were positively associated with lumbar spine BMD (β = 0.051; 95% CI: 0.013 to 0.088; p = 0.008). In multivariate logistic regression, participants in the highest knowledge quartile (Q4) had a 51.7% lower risk of low BMD compared with those in the lowest quartile (Q1) (OR = 0.481; 95% CI, 0.240 to 0.956; p = 0.038). Mediation analysis showed a significant indirect effect via the action score (β = -0.015; 95% CI: -0.031 to -0.003; p = 0.041), and subgroup analysis revealed a significant interaction between knowledge quartile and sex on lumbar BMD (p = 0.027). Conclusion:Patients with autoimmune diseases and limited osteoporosis knowledge had significantly lower bone mineral density and an increased risk of osteoporosis. Increasing physical activity and adopting healthy lifestyle behaviors can reduce this risk.

Synthetic phenolic antioxidants (SPAs) and their transformation products (TPs) are widespread environmental contaminants with endocrine-disrupting potential, yet their distribution across the maternal–fetal interface and relevance to maternal metabolic health remain unclear. Leveraging 222 paired maternal and umbilical cord plasma samples (51 cases of gestational diabetes mellitus [GDM] and 171 normoglycemic controls) from the Chongqing Preconception Reproductive Health and Birth Outcome Cohort (PREBIC), we quantified eight SPAs (AO246, DTBSBP, DtAP, AO2246, 4-tOP, BHA, 2,4-DtBP, and BHT) and five BHT-derived TPs (BHT-OH, BHT-CHO, BHT-COOH, BHT-quinol, and BHT-Q) using UPLC-MS/MS and performed targeted metabolomic profiling of 446 maternal plasma metabolites. In maternal plasma, 2,4-DtBP and BHT were the predominant compounds, whereas BHT-derived TPs, particularly BHT-Q and BHT-quinol, predominated in umbilical cord plasma. The transplacental transfer efficiency of BHT-quinol was significantly lower in GDM pregnancies. Maternal plasma concentrations of BHT-quinol and total TPs were higher in women with GDM. Each one-unit increase in ln-transformed BHT-quinol and total TP concentrations was associated with higher odds of GDM (adjusted odds ratio [OR], 1.83; 95% CI: 1.34–2.59; adjusted OR, 1.49; 95% CI: 1.08–2.11, respectively). Bayesian kernel machine regression identified BHT-quinol as the dominant contributor to the observed positive mixture-GDM association. Integrative metabolomic analyses identified 88 overlapping lipid metabolites showing consistent inverse associations with both maternal BHT-quinol concentrations and GDM status, with enrichment in pathways related to AGE-RAGE signaling in diabetic complications, sphingolipid signaling, and insulin resistance. These findings characterize the maternal–fetal distribution of BHT and its TPs among pregnant women in Southwest China and identify associations of maternal BHT-derived TPs with GDM and related metabolic alterations. Prospective studies are warranted to clarify the potential causal relationships between SPA exposure and maternal metabolic health.

miR-99a associates with CRC progression and prognosis.

Postmenopausal osteoporosis usually happens 5 10 years after menopause. Low awareness, low detection rates and high morbidity have prevented the possibility of early or preventive interventions, thus increasing the social and economic burden on families and societies. A reliable prediction model for postmenopausal osteoporosis has the potential to guide the prevention, but regarding the early prediction of postmenopausal osteoporosis without fracture, this field has not been sufficiently studied. Although many scholars have developed several prediction models to estimate the risk of postmenopausal osteoporosis without fractures, the evidence about the model quality and clinical applicability is scarce. Nine databases (Medline, Embase, Web of science, CINAHL, The Cochrane Library, CNKI, SinoMed, Wanfang, VIP data) were systematically searched from 1 January 2014 to 1 May 2024. Two researchers independently extracted data using the CHARMS checklist and assessed bias using the PROBAST tool. The primary outcomes of interest were related to the model’s discriminative ability (assessed by pooled AUC values) and calibration performance (evaluated using calibration curves or the calibration intercept and slope). We performed meta-regression and sensitivity analyses to explore the influence of important factors, such as data sources, machine learning methods, and types of predictor variables, on the aforementioned. results. Additionally, subgroup analyses were conducted based on data sources, machine learning. methods, and types of predictor variables. The study was registered in the PROSPERO database (registration number CRD42024542498). A total of 8,549 records were initially identified, and 7 studies (comprising 19 models) were ultimately included. All models were developed based on Asian population data. The risk of bias assessment showed: 1 study had a low risk, 1 study had an unclear risk, and 5 studies had a high risk. The sample sizes ranged from 319 to 4,417 participants. The reported AUC of the models ranged from 0.639 to 0.921; however, the vast majority of studies lacked reports on calibration performance. The pooled C-statistic (AUC) was 0.78 (95

EVs from highly metastatic CRC cells promote fibroblast activation.

Background:While large language models (LLMs) show promise in medical education, their comprehensive performance in specialized domains like medical laboratory science remains inadequately assessed. Purpose:This study aimed to evaluate advanced LLMs on medical laboratory questions, assessing accuracy, natural language generation (NLG) quality, reasoning performance, and efficiency. Methods:We conducted a multi-faceted evaluation of three advanced LLMs (DeepSeek-R1, Gemini-2.5 Pro, GPT-5), benchmarking them against medical laboratory scientists and earlier ChatGPT versions. The evaluation utilized 493 questions sourced from the internal Medical Laboratory Test Bank of Wannan Medical College. These questions comprised both knowledge-based and reasoning-based single- and multiple-choice types (SCQs and MCQs). Performance was measured by accuracy, Macro-F1, response time, NLG scores (ROUGE-L, METEOR), and structured logical reasoning assessment. Appropriate statistical tests (including χ2, Wilcoxon, ANOVA, and non-parametric alternatives) with post-hoc corrections were applied to determine significance. Results:DeepSeek-R1's accuracy on total questions was 78.3%, nearing the 79.3% of the higher-performing senior expert. Notably, it excelled at complex reasoning-based MCQ, demonstrating an advantage over senior experts with an accuracy of 64.4%, compared to 58.7% (SMLS-1) and 56.7% (SMLS-2). While ChatGPT-5 was the fastest model, DeepSeek-R1 exhibited intermediate efficiency, aligning with human experts on SCQ but requiring more time for MCQ. In terms of NLG, DeepSeek-R1 consistently achieved the highest scores, with ROUGE-L scores of 0.36 ± 0.14 (Total Q), 0.33 ± 0.15 (SCQ), and 0.38 ± 0.13 (MCQ), and METEOR scores of 0.53 ± 0.19 (Total Q), 0.40 ± 0.17 (SCQ), and 0.63 ± 0.14 (MCQ). Furthermore, it significantly outperformed all other LLMs in logical reasoning comprehensiveness. A critical strength was its consistent integration of key negative findings, vital for diagnosis. Conclusion:DeepSeek-R1 approaches or even surpasses senior expert performance in certain tasks, showing strong potential as an effective tool for education and assessment despite slower processing times.

Perfluorooctanesulfonic acid (PFOS), a persistent organic pollutant and representative per- and polyfluoroalkyl substance (PFAS), is ubiquitously detected in the environment and human tissues, and mounting evidence has implicated it in male reproductive dysfunction. However, the direct impact of PFOS on meiosis in spermatocytes and the underlying molecular mechanisms remain poorly understood. In this study, by combining chromosome spreading with high-resolution microscopy analysis of spermatocyte subtypes and morphology, we revealed that PFOS exposure decreased the proportion of pachytene spermatocytes and induced abnormal DNA double-strand break (DSB) repair, ultimately leading to a reduction in sperm density. Mechanistically, PFOS exposure suppressed the expression of SOX30, a germ-specific transcription factor, leading to downregulation of its downstream targets RPA2 and RAD51—key proteins of homologous recombination repair (HRR). This suppression resulted in unrepaired DSBs, triggering the pachytene checkpoint and leading to spermatocyte apoptosis. Critically, overexpression of SOX30 in PFOS-exposed GC2 spermatocyte cells restored RPA2/RAD51 expression and rescued DSB repair capacity. These findings identify SOX30 as a critical mediator of PFOS-induced meiotic DSB repair defects and establish it as a potential therapeutic target for mitigating PFAS-associated male infertility. This study provides novel insights into the molecular link between environmental pollutant exposure and impaired meiosis, offering a foundation for developing preventive and therapeutic strategies against PFOS-induced reproductive toxicity.

BackgroundSepsis remains a major cause of hospital mortality. Sepsis-induced intestinal injury is regarded as the driving force behind the rapid progression of critical conditions such as shock and sepsis, and serves as the initiating factor of subsequent organ dysfunction. Therefore, the development of effective therapeutic agents to restore intestinal barrier function is crucial for improving outcomes in sepsis.MethodsA caecal ligation and puncture (CLP) model was established in mice to induce sepsis, and intestinal epithelial cells (IEC-6) were treated with lipopolysaccharide (LPS) to simulate sepsis in vitro. These models were used to investigate the protective efficacy and molecular mechanisms of hydroxysafflor yellow A (HSYA) against sepsis-induced intestinal barrier dysfunction.ResultsHSYA alleviated intestinal barrier dysfunction in septic mice, markedly reduced levels of inflammatory factors, and improved survival. In vitro, HSYA enhanced barrier function of IECs, reduced mitochondrial fragmentation and reactive oxygen species (ROS) accumulation, promoted proliferation and inhibited apoptosis by upregulating the expression of Bcl-2 and SOD2.ConclusionThe study demonstrated the therapeutic potential and underlying mechanisms of HSYA in ameliorating sepsis-induced intestinal barrier injury, providing a new strategy for sepsis treatment.

Safety assessment of LY2584702 in mice.

BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) is a common liver condition linked to chronic hepatic dysfunction and systemic metabolic disorders. Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous and persistent environmental pollutants associated with the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, underlying molecular mechanisms linking PAH exposure to hepatic steatosis remain incompletely elucidated. OBJECTIVES:This study aimed to clarify the association between PAHs exposure and NAFLD and unravel the core molecular pathways driving PAHs-induced hepatic lipid metabolism dysfunction. METHODS:Cross-sectional analyses were performed using data from the 2007-2016 National Health and Nutrition Examination Survey (NHANES) to investigate the associations of urinary PAH metabolites with NAFLD prevalence, hepatic steatosis index (HSI), and serum metabolic indicators. The relationships between PAHs and metabolic indicators were further validated in participants from the Preconception Reproductive Health and Birth Outcome Cohort (PREBIC). We then integrated network toxicology, bioinformatics, and both in vivo and in vitro models to elucidate the molecular pathways through which benzo[a]pyrene (BaP), a prototype PAHs, drives hepatic steatosis. RESULTS:Analyses of NHANES data revealed significant positive associations between PAHs exposure and NAFLD incidence, the hepatic steatosis index (HSI), and serum triglyceride (TG) level. Validation in the PREBIC cohort consistently confirmed the robust association between PAHs exposure and increased TG level. Elevated serum TG levels emerged as a key metabolic indictor of PAHs-induced hepatic steatosis. Network toxicology revealed that PPARα is a key molecular involved in lipid metabolism disruption by BaP, contributing to NAFLD. Integrated bioinformatics analyses further revealed that the binding of BaP to PPARα represses the expression of the downstream gene ACAA1. In vivo and in vitro experiments confirmed that BaP inhibits PPARα signaling, impairing peroxisomal function and fatty acid degradation and thus, leadings to hepatic lipid accumulation. CONCLUSION:PAHs exposure is associated with hepatic steatosis and elevated serum TG level, and PPARα/ACAA1 axis suppression constitutes a key pathway through which BaP disrupts hepatic lipid metabolism. This study provides novel insights into the environmental etiology of NAFLD and identifies the PPARα/ACAA1 axis as a potential therapeutic target for PAHs-related NAFLD.

BACKGROUND:Hypertensive disorders of pregnancy (HDP) substantially increase maternal and fetal morbidity and mortality. Although reduced circulating bioavailable testosterone (BT) has been observed in women with HDP, the causal relationship and underlying mechanisms remain unresolved. Based on previous clinical and experimental evidence, we hypothesized a potential causal relationship between BT levels and HDP, with subsequent analyses designed to explore the possible metabolic and anti-inflammatory pathways involved. METHODS:Summary statistics for BT and HDP were obtained from the Integrative Epidemiology Unit OpenGWAS database. A 2-sample Mendelian randomization (MR) framework was implemented to evaluate causality, complemented by extensive sensitivity analyses to strengthen robustness. To explore potential mechanisms, expression quantitative trait loci integration, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes enrichment, and protein-protein interaction (PPI) network analyses were performed. RESULTS:Mendelian randomization analyses provided evidence of a protective causal effect of BT on HDP (inverse variance weighted OR = 0.81; 95% confidential interval, 0.68-0.97; P = .023), with no indication of reverse causality. Sensitivity tests consistently confirmed the reliability of these findings. Genes associated with BT-related single nucleotide polymorphisms were enriched in metabolic and immune pathways, notably the NOD-like receptor and interleukin-17 (IL-17) pathways. Within the PPI network, nuclear factor kappa B inhibitor alpha (NFKBIA) emerged as a pivotal regulator of nuclear factor kappa B (NF-κB) signaling, thereby supporting a role for testosterone-mediated modulation of inflammation in HDP protection. CONCLUSION:From a genetic standpoint, BT appears to act as a protective factor against HDP, potentially safeguarding cardiovascular function through interconnected metabolic and anti-inflammatory mechanisms.

Introduction Mitochondrial homeostasis is intimately associated with the toxic effects of exogenous chemicals, as well as the onset and progression of various diseases. Benzo[b]fluoranthene (BbF) is ubiquitously distributed across various environmental media. The association between BbF exposure and male reproductive damage has been recently discovered. However, the relevant mechanisms remain unexplored. Objectives To investigate the male reproductive toxicity and mechanisms of BbF. Methods We established BbF exposure models in both mice and GC-2 mouse spermatocyte cell lines to investigate BbF-associated reproductive toxicity. By integrating transcriptomic sequencing, bioinformatics analysis, and experimental validation, we demonstrated that disruption of mitochondrial homeostasis was the central mechanism. Furthermore, through N6-methyladenosine (m6A) sequencing combined with functional validation, we revealed the regulatory role of m6A modification in modulating mitochondrial homeostasis. Results BbF exposure triggered mitochondrial homeostasis disruption in spermatocytes and contributed to male reproductive toxicity. Specifically, BbF impaired mitochondrial biogenesis and oxidative phosphorylation via the p53/PGC-1α/TFAM signaling pathway. As a compensatory response, PINK1/Parkin-associated mitophagy was activated, thereby partially alleviating cellular damage. To further investigate the regulatory mechanisms of m6A modification in the aforementioned mitochondrial dysfunction process, we observed that BbF exposure resulted in reduced expression of YTHDF2 in spermatocytes. The downregulation of YTHDF2 slowed the degradation of Trp53 mRNA, leading to elevated levels of both Trp53 mRNA and p53 protein, thereby inducing the p53/PGC-1α/TFAM-mediated mitochondrial damage. On the other hand, we demonstrated that METTL3 exerted a crucial protective effect by regulating mitophagy. Particularly, METTL3 enhanced the m6A modification of Mark4 mRNA, thereby stabilizing the transcript, increasing both mRNA and protein levels of MARK4. Furthermore, the METTL3/MARK4 signaling axis promoted PINK1/Parkin-associated mitophagy, which served as a protective mechanism. Conclusion As a result of the confrontation between YTHDF2/p53/PGC-1α/TFAM-mediated mitochondrial damage and PINK1/Parkin-associated mitophagy regulated by METTL3/MARK4, BbF disrupted mitochondrial homeostasis, ultimately leading to mitochondrial dysfunction and spermatocyte apoptosis.

Circadian disruption, a common consequence of shift work, is associated with neuropsychiatric disorders and cognitive impairment. However, existing occupational studies lack generalizability and the underlying structural mechanisms remain unclear. The present study aimed to investigate the relationships between circadian disruption, cognitive impairment and hippocampal white matter integrity, as well as their changes following circadian rhythm restoration. We analyzed UK Biobank longitudinal cohort data, comparing cognitive performance (including reaction time, numeric memory, fluid intelligence, and prospective memory) and structural connectivity derived from diffusion magnetic resonance imaging (MRI) between shift and non-shift workers. Mouse models of chronic circadian disruption and recovery were established to complement the human findings. Compared with non-shift workers, shift workers exhibited cognitive impairment, with a maximum decrease of 14.81% in fluid intelligence scores; notably, their cognitive performance remained lower than that of never-shift workers even after ceasing shift work, with a maximum reduction of 7.73% in fluid intelligence. Higher Criticism analysis indicated alterations in whole-brain structural connectivity in shift workers, including the hippocampus, with approximately 90% of structural connectivity in the bilateral hippocampi showing a decrease (Cohen's d < 0). Murine models of 8-week circadian disruption confirmed cognitive impairment and myelin loss; furthermore, mice with 8 weeks of circadian rhythm restoration following chronic circadian disruption also displayed hippocampus-related cognitive function inferior to that of controls, as well as slow-to-recover myelin structure. This study indicates that circadian disruption induces slow-to-recover cognitive impairment; this impairment is hippocampus-associated, and the myelin architecture of the hippocampus also exhibits a slow-to-recover pattern.

630 Background: Convergent evidence suggests carcinogenicity of endocrine disrupting chemicals (EDCs). But there is a lack of large-scale epidemiological evidence concerning real-world EDCs mixture exposure and breast cancer (BC). A dataset of emerging knowledge of toxic pathways provides a valuable toolkit to infer the carcinogenicity of chemicals, but current studies of this thus filed are rare. We test whether real-world EDCs exposure, independently or in mixture, increases BC risk in the population, through carcinogenic toxic pathways. Methods: A total of 234,273 women from the UK Biobank cohort were followed for a median of 13.85 years. The annual monitoring record from UK Water Quality Sampling Harmonised was used to estimate the exposure to 13 EDCs (e.g., lead and chlorpyrifos-methyl) for each woman by Kriging interpolation model. The association between EDCs and breast cancer was analyzed by Cox proportional hazard model (for single EDC) and weighted quantile sum (WQS) regression (for mixture). The EDCs were also added to the modified Gail model to test their additional contribution. Twenty-seven Olink proteins were selected via EDC-BC toxic pathway dataset and BC genetic propensity score model to examine their correlation with EDCs. Interaction between EDCs and these proteins and SNPs within their sequence were analyzed by multiplicative model. Results: During the follow-up period, 9,282 women developed BC, 984 of whom died. All the 13 EDCs showed association with increased BC risk. Each unit increase of the 13-EDC mixture was associated with 2.15 fold (95% CI, 2.01-2.31) of BC risk and 4.18 fold of BC-related mortality (95% CI, 3.39-5.17), and 34.38 % of total morbidity and 59.6% of BC-related mortality in the population were attributable to EDC mixture. The risk of hormone receptor-positive BC was higher than that of hormone receptor-negative BC (HR: 2.87 vs HR: 2.03, p = 0.002). The EDCs provided 2.1 % improvement to the modified Gail model of BC prediction. For the 27 Olink proteins referring to BC toxic pathway and genetic propensity score, 26 (96.3%) correlated with at least one EDC (average number ≥8), among which NACC1 protein mediated up to 98.8% (chlorpyrifos-methyl) of the individual EDC’s effect on BC. The EDC mixture showed interaction with multiple proteins, including NACC1 and estrogen receptor 1, on BC-related mortality. Conclusions: Various EDCs in the real world may increase BC morbidity and mortality via common carcinogenic pathways. Future policies of novel EDC emission and safety evaluations must consider the cumulative EDC stressor in the environment because they may act as a whole.

Zoonotic diseases pose a critical threat to global public health, with noroviruses (NoVs) increasingly recognized for their potential to cross species barriers. Traditionally, NoVs were considered host-specific; however, recent evidence suggests the possibility of interspecies transmission. This study investigates the zoonotic potential of porcine NoV (PorNoV) genotype GII.11, which shares high genetic similarity with human NoVs (HuNoVs), by detecting GII.11-specific IgG antibodies in humans and various animals using a Luciferase Immunosorbent Assay (LISA). Seroprevalence was observed in humans (15.2%), pigs (49.3%), dogs (30.6%), wild rats (9.5%), and bats (65.1%), marking the first detection of GII.11 PorNoV antibodies in humans and non-swine species. Bats exhibited the highest seropositivity and antibody levels [vs. humans (P = 0.0011) and pigs (P = 0.0164)], suggesting their potential role as reservoirs. These findings provide serological evidence for anthropozoonotic transmission, challenging the paradigm of strict host specificity in NoVs. Enhanced surveillance of PorNoV in animal reservoirs and high-risk human populations is needed to mitigate zoonotic spillover risks. Further research should aim to elucidate mechanisms of transmission and the clinical significance of cross-species NoVs exposure.