BACKGROUND:Previous studies have revealed a relationship between plasma branched-chain amino acids (BCAAs) levels and non-alcoholic fatty liver disease (NAFLD). However, this connection has not been thoroughly explored due to potential biases such as confounders or reverse causality. We performed a bidirectional Mendelian randomization (MR) analysis to explore the potential causal association between plasma BCAAs levels and NAFLD at the genetic level. METHODS:Publicly available summarized data from genome-wide association studies (GWASs) on plasma BCAAs levels (n = 115,079) and NAFLD (2275 cases and 375,002 controls) were obtained from Integrative Epidemiology Unit Genome-Wide Association Study Database (IEU GWAS database) and Finnish Genome biobank (FinnGen biobank), respectively. The inverse variance weighted (IVW) method was used in the main analysis, followed by maximum likelihood (ML) method, simple median (SM) method, and Mendelian randomization robust adjusted profile score (MR-RAPS) and leave-one-out method in the sensitivity analyses. Heterogeneity was analyzed using Cochran's Q statistic, and horizontal pleiotropy was assessed via MR-Egger regression. RESULTS:The bidirectional MR study revealed that genetically determined high plasma valine level was significantly associated with an increased risk of NAFLD via IVW method (odds ratio [OR], 1.944; 95% confidence interval [CI], 1.226-3.084; P = 0.004), with consistent effect estimates across alternative MR methods. Heterogeneity and horizontal pleiotropy were not detected by sensitivity analysis, supporting the reliability of our findings. Results of reverse MR do not support an effect of NAFLD on plasma BCAAs levels at the genetic level. CONCLUSIONS:The present bidirectional MR study support a potential directional association between genetically predicted higher plasma valine levels and increased susceptibility to NAFLD.

Prenatal polycyclic aromatic hydrocarbon (PAH) exposure may contribute to neural tube defects (NTD), but combined effects and underlying mechanisms remain unclear. We conducted a matched case-control study (128 pairs) in six high-risk counties in Shanxi Province, China (2004-2016). At delivery or pregnancy termination, placenta samples were collected. Sixteen placental PAHs and 11 hydroxylated metabolites were quantified by GC-MS/MS as biomarkers of fetal intrauterine exposure, alongside 16 DNA adducts measured by UPLC-MS/MS. Complementary ICR mouse experiments with benzo[a]pyrene (BaP, 100 mg/kg) validated mechanistic findings. Statistical analyses used conditional logistic regression, WQS and BKMR (for parent PAHs and hydroxylated metabolites, respectively), followed by mediation analysis. Results showed that increased fresh vegetable intake and kitchen-living separation significantly reduced placental PAH concentrations. A dose-dependent increase in NTD risk was observed across tertiles of measured placental PAHs. The highest versus lowest tertile was associated with increased NTD risk for total PAHs (OR=5.04, 95%CI:1.96-12.96), phenanthrene (OR=4.96, 95%CI:2.05-11.97), and low-molecular-weight PAHs (OR=4.47, 95%CI:1.87-10.67) after adjustment for confounders. In subtype analyses, higher phenanthrene, low-molecular-weight PAH and total PAH related to anencephaly, whereas benzo[b]fluoranthene, indeno[1,2,3-cd]pyrene, and 9-hydroxyfluorene were associated with spina bifida. Mixture models confirmed significant joint effects of multiple PAHs. Mediation analyses showed 5-HmdC changes explained 10.7% (phenanthrene) and 12.4% (total PAHs) of NTD risk. In mice, BaP increased NTD incidence (5.7% vs. 1.8%), stillbirths (1.8% vs. 0%), and fetal resorptions (3.6% vs. 1.8%) versus controls. BaP-exposed groups showed reduced 5-HmdC in fetal tissues, consistent with human findings. This study provides evidence that individual and mixed PAH exposures are associated with an increased risk of NTD. DNA damage, particularly 5-HmdC alterations, may partially contribute to this association. These findings further support preventive strategies, including dietary and household environmental modifications.

In recent years, as childhood obesity rates soar globally, there has been a concomitant increase in the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD). The intent of this analysis is to explore the correlation between four novel obesity indices and pediatric MAFLD, and to compare their varying screening performance for MAFLD. We used data from the Wuxi (China) Children's Nutrition and Health cohort. Logistic regression and restricted cubic spline (RCS) were employed to assess the associations between the obesity indices, including visceral adiposity index (VAI), lipid accumulation product (LAP), body roundness index (BRI), and weight-adjusted waist index (WWI) with MAFLD in children. Furthermore, Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive performance of the four novel obesity indices, and DeLong's test was applied to compare the AUC of the best-performing index (BRI) with those of traditional anthropometric measures (BMI, WC, and WHtR). A total of 1,214 children (aged 6-14 years) were enrolled in this study, with a mean age of 10.3 years and a boy proportion of 56.4%. Among them, 205 (16.8%) were diagnosed with MAFLD, while the remaining 1,009 (83.1%) served as controls. The multivariate logistic regression revealed that the VAI, LAP, BRI and WWI displayed a marked association with MAFLD in children (all p < 0.001). Among them, BRI exhibited high and consistent screening performance for pediatric MAFLD across all analyzed subgroups. For instance, in the subgroup with CAP ≥ 248 dB/m, it achieved an AUC of 0.929 (95% CI: 0.913-0.945), comparable to traditional BMI and WHtR, and significantly outperformed WC. Our findings demonstrated four the novel obesity indices are significantly associated with MAFLD in children. The BRI emerges as a simple, reliable, and clinically useful screening tool that captures visceral fat distribution and may aid in early risk stratification.

Background:Liver steatosis in children can be non-invasively assessed by the controlled attenuation parameter (CAP) derived from transient elastography. This study aimed to identify determinants of longitudinal changes in liver steatosis in a Chinese pediatric population. Methods:We established a prospective cohort in Wuxi, China, to investigate risk factors of fatty liver among school-aged children. A total of 1498 children aged 6 to 13 years were enrolled in 2023 and 1195 children completed follow-up assessments in 2024. Biomarkers based on blood, urine, and body composition were measured. The progression of liver steatosis was evaluated using CAP values. Regression analyses were conducted identify determinants of both longitudinal changes in CAP and the progression of liver steatosis. Results:The average CAP of the participants in 2023 was 193.5 dB/m, and in 2024 it was 189.0 dB/m. During the one-year follow-up period, 68 children developed new liver steatosis. Regression analyses revealed 10 biomarkers significantly associated with changes in CAP, which were further categorized into two distinct clusters characterized primarily by metabolic and inflammatory processes. Additionally, the ratio of neutrophils to albumin constituted a separate subgroup. For liver steatosis progression, stepwise logistic regression identified four independent determinants: sex, BMI z-score, lymphocyte count, and trunk body fat mass, and demonstrated good discriminatory power (AUC = 0.80). Conclusion:Several inflammatory and body composition markers were significantly associated with the progression of liver steatosis in Chinese children. These findings underscore the roles of inflammation and fat distribution in the early development of fatty liver disease, which may inform screening strategies for school-aged children.

Background/Objectives: Folate plays a key role in one-carbon metabolism and may influence reproductive function, but evidence regarding its association with fecundability remains inconsistent. This study examined the association of folic acid (FA) supplementation, dietary folate intake, and folate status with time to pregnancy (TTP) among women planning to conceive. Methods: This study is a secondary analysis of a prospective cohort study included women enrolled during premarital health examinations in two counties in Shanxi Province (2009-2012). Folate-related exposures were assessed at baseline and included FA supplementation, dietary folate intake, and red blood cell (RBC) folate concentrations. Discrete-time proportional hazards model was used to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs). Results: A total of 1475 women without a history of previous pregnancy were included, among whom 24 (1.6%) reported FA supplementation at baseline. Higher intake of several food groups was associated with increased RBC folate concentrations. In separate models, only seafood intake (1-3 times per week) was significantly associated with higher fecundability (FR: 1.23, 95% CI: 1.04, 1.44). In joint models, FA supplementation was associated with higher fecundability at 6 months (FR: 2.07, 95% CI: 1.01, 3.77), 12 months (FR: 1.91, 95% CI: 1.00, 3.30), and 24 months (FR: 1.91, 95% CI: 1.00, 3.30). Conclusions: Preconception FA supplementation showed a potential positive association with fecundability when considered alongside dietary intake and folate status, although the evidence was limited by the low use of supplementation. Further studies are needed to clarify the role of folate in human fecundability.

Neonatal necrotizing enterocolitis (NEC) is a severe inflammatory disease primarily affecting premature infants, characterized by high mortality and morbidity, with limited therapeutic options available. While emerging evidence links microbiota to NEC pathogenesis, the role of commensal metabolites in NEC and safe metabolite-based therapies remain unexplored. Metabolomic profiling reveals a significant reduction in 3-indoleacrylic acid (IA), a tryptophan-derived metabolite, in NEC infants and animal models. IA supplementation alleviates intestinal inflammation and tissue damage. Single-cell RNA sequencing analysis reveals the activation of STAT1 signaling as a necroptosis driver in intestinal epithelial cells, which is suppressed by IA. Protection is abolished by aryl hydrocarbon receptor (AhR) inhibitor CH-223191 or in intestinal epithelium-specific AhR knockout mice. Oral administration of Bifidobacterium longum subsp. infantis containing the IA-producing fldI gene prevents NEC in mice. Our study uncovers IA as a microbiota-derived therapeutic inhibiting STAT1-driven necroptosis via the AhR-SOCS5 axis, offering a targeted strategy for NEC management.

BACKGROUND:Environmental exposure to volatile organic compounds (VOCs) may adversely affect liver function, particularly in adolescents; however, the evidence remains scarce. OBJECTIVE:This study aimed to evaluate the individual and combined effects of VOCs exposure on liver function in adolescents, as well as the potential mediating role of lactate dehydrogenase (LDH) and possible intervention strategies. METHODS:In total, 1,280 adolescents aged 12-19 years from the National Health and Nutrition Examination Survey were studied to examine the associations between 15 VOC metabolites and 4 liver function indicators. Four statistical models were employed to assess the associations, including weighted linear regression, restricted cubic splines, weighted quantile sum (WQS), and Bayesian kernel machine regression (BKMR). Mediation analysis was performed to evaluate whether LDH mediated or partially explained these associations. RESULTS:Among the 15 individual VOC metabolites, 8 were observed to have a significant association with specific liver function indicators. The WQS and BKMR models consistently identified significant associations between VOC mixtures and elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Additionally, AMCC [parent VOC (pVOC): N, N-dimethylformamide] and HMPMA (pVOC: crotonaldehyde) were identified as major contributors to the combined effect. Mediation analysis showed the potential mediation effect of serum LDH on these associations. Moreover, the adverse effect of VOC exposure on adolescent liver function was significantly mitigated with adequate vitamin D intake. DISCUSSION:The results indicate that VOC exposure is positively associated with elevated liver function indicators in adolescents, with AMCC and HMPMA as main contributors. The mediating role of LDH suggests that oxidative stress may serve as a key mechanistic pathway underlying VOC-induced liver injury. Additionally, adequate vitamin D intake appears to mitigate these adverse effects. CONCLUSION:Our findings revealed a positive association between exposure to VOC and liver function in adolescents, and suggest that LDH may be a potential mechanism for VOC-induced liver injury. Supplementing with vitamin D may help protect adolescent liver function from the effects of VOC exposure.

Abstract Background Pediatric obesity is a major public health challenge with adverse effects on health and long-term metabolic outcomes. Although diet and genetic susceptibility contribute to obesity across the life course, pediatric obesity may be particularly influenced by early-life developmental and maternal factors. Protein palmitoylation is linked to lipid metabolism, but whether palmitoylation-related programs differ between pediatric and adult obesity remains unclear. Methods We analyzed transcriptomic datasets from pediatric and adult obesity using differential expression analysis and weighted gene co-expression network analysis (WGCNA). Candidate genes were further evaluated in a juvenile high-fat diet-induced obesity mouse model and online obesity databases. Results In both age groups, palmitoylation-related candidate common hub genes were significantly enriched in lipid metabolic pathways. However, pediatric-specific palmitoylation-related candidate common hub genes were prominently enriched in branched-chain amino acid (BCAA) metabolic and catabolic processes. Least absolute shrinkage and selection operator regression prioritized seven candidate genes. In the juvenile obesity model, four genes (Cldn2, Mccc2, Pcca, and Vdac2) were consistently downregulated in adipose tissue from obese offspring, correlating significantly with fat mass. Downregulation was less pronounced in obese adult mice, whereas total protein palmitoylation was markedly elevated in both ages, with a greater increase in juveniles. Among the four genes, Mccc2 and Pcca were directly involved in BCAA catabolism, suggesting an association between BCAA metabolism and pediatric obesity. Conclusion These findings provide a basis for future mechanistic studies of age-related differences in adipose tissue metabolism in obesity.

Previous studies have primarily examined the benefits of calorie restriction and fasting for metabolic dysfunction-associated steatotic liver disease (MASLD). However, the impacts of eating timing and frequency on MASLD remain uncertain. This study comprised 2128 participants aged 12 to 19 years, drawn from the National Health and Nutrition Examination Survey (NHANES) data collected during the period 2017 to 2023. Chrononutrition patterns were determined with two 24-h dietary recalls. Logistic regression, accounting for potential confounders, was used to examine the relationship between chrononutrition patterns and MASLD. Subgroup analyses stratified by demographic and clinical variables were used to evaluate their potential impact on the associations observed. Mediation analysis was conducted to assess the indirect effects of metabolic indicators on MASLD risk. Logistic regression demonstrated that the timing of the first (continuous: OR: 1.07; 95

Metabolic dysfunction-associated fatty liver disease (MAFLD) and chronic kidney disease (CKD) have shown a marked global increase in prevalence, placing a substantial burden on public health and healthcare systems worldwide. Epidemiological data demonstrate a significant overlap between these two conditions, with further evidence from research identifying common pathophysiological features, such as lipid metabolism dysregulation, disrupted energy balance, and chronic systemic inflammation. Mitochondria are central to the pathophysiology of both diseases. In addition to their role in energy production, mitochondria are involved in numerous critical cellular processes, including biosynthesis, lipid metabolism, oxidative phosphorylation, signal transduction, and apoptosis regulation. Mitochondrial dysfunction, characterized by increased reactive oxygen species, impaired adenosine triphosphate synthesis, disrupted mitophagy, and changes in mitochondrial morphology, is implicated in the progression of both MAFLD and CKD. Given the pivotal role of mitochondria in maintaining cellular metabolism homeostasis, dysfunction of this organelle is increasingly recognized as a key mechanistic link that connects the pathophysiological processes underlying both MAFLD and CKD. This review underscores mitochondrial dysfunction as a pathogenic nexus between MAFLD and CKD and examines the mechanisms that drive their pathogenesis

BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common chronic liver disease that progresses from simple steatosis to inflammation, fibrosis, and cirrhosis. Currently, no effective targeted therapy is available. Exercise is a well-recognized non-pharmacological intervention with clear benefits. However, the biological mechanisms by which skeletal muscle responds to regular exercise and contributes to MASLD improvement remain poorly understood. AIM To identify exercise-responsive biomarkers in skeletal muscle associated with MASLD and explore their diagnostic and therapeutic potential. METHODS We analyzed skeletal muscle transcriptomic datasets from the gene expression omnibus. Differentially expressed genes (DEGs) were detected and then analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment methods. To identify key genes, we employed weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) regression. Correlation with diagnostic efficacy was performed utilizing a validation group and receiver operating characteristic (ROC) analysis. Finally, an obese mouse model was established and subjected to endurance aerobic training. Gastrocnemius muscle tissue was validated at the messenger RNA, protein, and secretion levels to confirm the identified biomarkers. RESULTS Transcriptomic analysis identified 61 DEGs between pre-exercise and post-exercise samples, with 40 upregulated and 21 downregulated genes. GO enrichment analysis showed that extracellular matrix (ECM) organization and collagen fibril formation were significantly enriched. KEGG pathway analysis further highlighted cytoskeleton dynamics in muscle cells and ECM-receptor interactions. Integrated DEGs, WGCNA and LASSO analysis identified 12 hub genes. Validation cohort and ROC analysis demonstrated strong diagnostic performance for nine hub genes (COL3A1, COL1A2, BGN, LAMB1, PECAM1, LAMA4, THBS4, PXDN and THY1). In the mouse model, three hub genes (Lama4, Pecam1 and Pxdn) were significantly upregulated, while Thbs4 was downregulated after exercise in skeletal muscle tissue. CONCLUSION This study identified four exercise-responsive skeletal muscle-expressed genes (LAMA4, PECAM1, PXDN and THBS4). These genes are mechanistically associated with MASLD and may serve as myokine-like candidates. Our research offers new perspectives on the pathophysiology of MASLD and suggest possible strategies for precision diagnosis and therapy.

BACKGROUND:Bronchopulmonary dysplasia (BPD) is a common lung disease in premature infants. Hyperoxia-induced oxidative stress and ferroptosis are key pathological mechanisms leading to alveolar epithelial (AT) cell injury and impaired alveolar development. M2 macrophage-derived exosomes (M2-Exo), as intercellular communication carriers, have potential protective effects in regulating oxidative stress-related diseases, but the molecular mechanism by which they exert effects by regulating ferroptosis in BPD remains unclear. OBJECTIVE:To explore the protective effect of M2-Exo on hyperoxia or inflammation-induced BPD models and clarify its antioxidant mechanism. METHOD:In vitro AT cell injury models and in vivo BPD models were constructed by hyperoxia or LPS induction. M2-Exo were isolated, identified, and used to intervene in models. Oxidative stress and ferroptosis-related indicators (ROS, MDA, iron accumulation, GPX4), AT cell functional markers (AQP5, SPC), and ZAKα-p38 pathway activation contents were detected. ZAKα overexpression was used to verify pathway dependence. RESULTS:M2-Exo intervention significantly enhanced AT cell viability, upregulated the expression of AQP5 and SPC, and reversed alveolar simplification. Concurrently, it effectively suppressed hyperoxia or LPS-induced oxidative stress and ferroptosis, as evidenced by reduced contents of ROS and MDA, diminished iron accumulation, and GPX4 expression. Mechanistically, M2-Exo significantly inhibited the activation of the ZAKα-p38 pathway, and ZAKα overexpression could antagonize the antioxidant, anti-ferroptotic, and AT cell protective effects of M2-Exo. CONCLUSIONS:M2-Exo alleviate AT cell oxidative stress and ferroptosis by inhibiting the ZAKα-p38 pathway, thereby improving hyperoxia or inflammation-induced BPD and providing a new strategy and molecular target for the antioxidant treatment of BPD.

ABSTRACT A recent study suggested an increase in male births associated with maternal preconception high blood pressure. Our objective was to examine this association. Data were obtained from the China‐US Collaborative Project for Neural Tube Defects Prevention, a large population‐based cohort study. We included 44 399 singleton pregnancy to women who were registered before pregnancy in seven counties in southern China. Blood pressure was measured during registration by trained health care workers and other health‐related information was recorded prospectively. We used log‐binomial regression to evaluate the associations between preconception blood pressure and the risk of male delivery, adjusting for potential confounders. The study size had 99% power (α = 0.05) to detect an increase of 50% over the unexposed rate of 51.94% for male delivery. The prevalence of hypertension in the preconception study population was 4.61% (2045/44 399). The prevalence of male delivery was 51.10% for the hypertension group and 51.79% for the non‐hypertension group. Compared with the non‐hypertension group, the hypertension group did not show significantly increased chance for male delivery [adjusted risk ratio (RR) = 0.99, 95% confidence interval (CI): 0.94, 1.03]. Our results do not support an association between hypertension or higher blood pressure prior to pregnancy and increased likelihood of male delivery.

Environmental elements are persistent exposures with both toxic and physiological roles. However, evidence regarding their individual and combined effects on maternal liver function during pregnancy, as well as the potential biological mechanisms, remains limited. In this study, we included 620 pregnant women from the Wuxi Birth Cohort. Maternal blood concentrations of 20 elements and 11 liver function markers were measured. Associations between individual elements and liver function markers were evaluated using generalized linear model (GLM) and generalized additive model (GAM). Mixture effects were assessed via quantile g-computation (Qgcomp) and weighted quantile sum (WQS) regression. Interaction and joint effects were further examined, and an adverse outcome pathway (AOP) framework was constructed to explore potential mechanistic pathways. Among the 20 measured elements, 13 had detection rates above 70%. Single-element analyses identified positive associations of manganese (Mn), lead (Pb), mercury (Hg), cobalt (Co), cadmium (Cd), and selenium (Se) with multiple liver enzyme levels, whereas strontium (Sr) and titanium (Ti) were inversely associated with liver function markers. Both Qgcomp and WQS analyses consistently demonstrated positive associations between element mixtures and multiple liver function markers, particularly ALT, AST, and LDH. Significant interactions between Sr and Hg were observed for several liver function markers. Furthermore, computational AOP analysis suggested that exposure to selected elements may be mechanistically linked to liver dysfunction through activation of the TNF–NF-κB signaling pathway. In conclusion, our findings provide integrated epidemiological evidence and computational AOP analysis, suggesting that gestational exposure to element mixtures may be associated with altered maternal liver function markers. Sr was inversely associated with liver function markers and may modify the association between element exposure, particularly Hg exposure, and liver function during pregnancy.

Necrotizing enterocolitis (NEC) remains one of the most devastating gastrointestinal emergencies in preterm infants and is associated with high morbidity, mortality, and long-term complications. Increasing evidence suggests that breast milk and probiotics may act synergistically to reduce NEC risk by modulating the intestinal microbiota, its metabolites, and host immune responses. As the optimal nutritional source for preterm infants, breast milk provides a wide range of bioactive components, including human milk oligosaccharides (HMOs), lactoferrin, and immunoglobulins, which promote intestinal maturation, strengthen epithelial barrier function, inhibit pathogen colonization, and support immune development. Probiotics further complement these protective effects by enhancing the colonization of beneficial bacteria, suppressing the overgrowth of potential pathogens, improving barrier integrity, and regulating inflammatory signaling. In this context, microbial metabolites emerge as critical proximal mediators linking microbial composition to host protection. Among them, short-chain fatty acids (SCFAs) and tryptophan-derived indole metabolites play essential roles in maintaining intestinal homeostasis, promoting mucosal integrity, and modulating immune tolerance. Therefore, the preventive effects of breast milk and probiotics should be understood not only as independent benefits, but also as coordinated ecological and metabolic regulation of the immature gut. A better understanding of these interactions may provide a mechanistic basis for developing personalized and evidence-based strategies for NEC prevention in preterm infants.

Necrotizing enterocolitis (NEC) is a life-threatening acquired inflammatory bowel disease in neonates, whose pathogenesis is intricately linked to aberrant inflammatory activation of macrophages within the innate immune system. Emerging research underscores that NEC progression involves M1/M2 polarization dysregulation in macrophages, dysregulated secretion of pro-inflammatory cytokines , and aberrant activation of signaling pathways such as NF-κB and MAPK. In this study, we utilized Sprague-Dawley (SD) neonatal rat models of NEC and bone marrow-derived macrophage (BMDM) inflammatory models to assess the therapeutic potential of exogenous interventions with peony seed oil enriched in α-linolenic acid (ALA) and purified ALA. H&E staining and qRT-PCR analyses revealed that both peony seed oil and ALA significantly suppressed intestinal cytokine expression (Il-1β, Il-6, Tnf-α) and attenuated histological intestinal injury. Notably, ALA can suppress the M1 polarization of bone marrow-derived macrophages (BMDMs) and intestinal macrophages, as well as inhibit the expression of p-IκB and p-NF-κB. This study demonstrates that dietary supplementation with peony seed oil rich in ALA may alleviate intestinal inflammatory responses in necrotizing enterocolitis (NEC) by modulating macrophage polarization balance and inhibiting the NF-κB signaling pathway, thereby reducing the release of pro-inflammatory mediators.

Per- and polyfluoroalkyl substances (PFASs) are persistent environmental contaminants with potential hepatotoxicity. Their impact during pregnancy remains poorly characterized. We investigated 601 pregnant women from the Wuxi Birth Cohort, measuring serum concentrations of 23 PFASs and 11 liver function markers. Associations between individual PFASs and liver function markers were evaluated with generalized linear model (GLM) and generalized additive model (GAM), while mixture effects were assessed using weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR). Independent validation was performed using National Health and Nutrition Examination Survey (NHANES) data. To explore underlying mechanisms, pregnant rats were exposed to perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA) followed by liver function assays and RNA sequencing. In the present study, twelve PFASs had detection rates above 90%, with perfluoropentanoic acid (PFPeA) being the predominant compound. Serum perfluorooctanoic acid (PFOA), PFNA, PFDA, and perfluoroundecanoic acid (PFUdA) were significantly associated with alanine aminotransferase (ALT) [β (95% CI): 0.100 (0.023, 0.178), 0.080 (0.033, 0.126), 0.068 (0.025, 0.111), 0.061 (0.021, 0.101), respectively], and were also associated with higher levels of aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), and alkaline phosphatase (ALP). Both WQS and BKMR models indicated positive associations between PFAS mixtures and liver function markers, particularly ALT, AST, and ALP. Similar patterns were observed in NHANES data. In animal experiments, gestational exposure to PFDA (0.3 mg/kg/day) and PFNA (0.2 mg/kg/day) at human-relevant levels altered maternal liver function markers in pregnant rats, while transcriptomic analyses revealed disruptions in key hepatic metabolic pathways, including unsaturated fatty acid biosynthesis, peroxisome, and PPAR/AMPK signaling. This study provides epidemiological and experimental evidence supporting an association between PFAS exposure and altered maternal liver function during pregnancy, suggesting potential implications for maternal health.

OBJECTIVES:Previous studies had reported the association between famine exposure in early life and subsequent non-communicable diseases risk. In current study, we aimed to evaluate the associations between famine exposure on multimorbidity prevalence and incidence in middle-aged and older Chinese population. METHODS:A total of 13,254 participants from the China Health and Retirement Longitudinal Study 2011 were included in cross-sectional analyses. 5,780 participants were including in longitudinal analyses and were followed up in 2020. Based on the questionnaire, participants were divided into non-exposed, mild famine, moderate famine and severe famine subgroups. RESULTS:In cross-sectional analyses, both mild, moderate and severe famine groups were significantly associated with higher multimorbidity prevalence. During the 9 years of follow-up, a total of 2,643(45.73%) participants with multimorbidity incident were identified. After adjusting for all covariates, individuals who experienced mild famine, moderate famine and severe famine were significantly associated with increased risk of multimorbidity incident, with the corresponding ORs (95%CI) being 1.32(1.14-1.52), 1.54(1.21-1.96) and 1.62(1.32-1.99), respectively. DISCUSSION:Our findings indicate that famine exposure in mild, moderate and severe famine groups might be associated with an increased multimorbidity risk.

Introduction:This study aimed to explore the relationship between the timing of physical contact and the level of estradiol contamination in the skin after application of estradiol gel. Estradiol gel is a common medication used in menopausal hormone therapy (MHT) and understanding its potential for contamination is crucial for ensuring patient safety and effective treatment. Purpose:The purpose of this hospital-based case-control study was to determine the correlation between the timing of physical contact and the degree of estradiol contamination following the administration of estradiol gel. This information is vital for advising patients on appropriate precautions to minimize the risk of estradiol transfer to others. Methods:This study was conducted in the gynecology department of Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University between 2021 and 2022. The participants included 40 menopausal women aged 40-60 years who required MHT and 40 women who did not use estradiol. The intervention involved physical contact after the administration of estradiol gel, and the main outcome measure was estradiol concentration on the skin. Skin estradiol levels were assessed at 10 min, 30 min, 60 min, and 120 min post-application. Results:The results indicated that the estradiol levels in the skin of the estradiol gel group were 205.29 ± 79.33, 193.64 ± 61.17, 99.15 ± 37.34, and 110.83 ± 69.81 at 10 min, 30 min, 60 min, and 120 min, respectively. In contrast, the estradiol content in the skin of the physical contact group was significantly lower, with levels of 65.87 ± 32.75, 59.06 ± 24.99, 7.95 ± 4.89, and 12.09 ± 3.71 at the same time points. Estradiol contamination was detected in all participants in the physical contact group; however, the levels were markedly lower than those in the estradiol gel group. In the estradiol gel group, estradiol levels remained stable within the first 30 min (p >0.05), rapidly decreased at 60 min (p <0.001) and remained stable from 60 min to 120 min (p >0.05). The trend in skin estrogen concentration over time in the physical contact group was consistent with that in the estradiol gel group. Conclusion:The study concludes that physical contact following application of estradiol gel can lead to skin contamination. Therefore, it is recommended that patients avoid skin exposure for at least 60 min after applying estradiol gel and refrain from physical contact with others, especially infants, children, individuals with breast cancer or other sex hormone-dependent tumors, and pets to minimize the risk of estradiol transfer.

Bioactive components in breast milk offer a new therapeutic strategy for bronchopulmonary dysplasia (BPD). While osteopontin (OPN) is supplemented in formula to promote neonatal growth, the therapeutic role of its derived peptide, SVVYGLR (SV), in BPD remains unexplored. This study aimed to elucidate SV's therapeutic mechanisms in BPD. The results revealed that SV significantly enhances cell viability, inhibits hyperoxia/LPS-induced apoptosis, and repairs alveolar epithelial injury. Molecularly, SV restores mitochondrial integrity, upregulates the anti-apoptotic protein BCL-2, and downregulates the pro-apoptotic protein Bax. In vivo experiments showed SV reduced hyperoxia/LPS-triggered BPD-like injury, evidenced by neonatal mice gaining weight, improved lung histology, and increased alveolar counts and septal thickness. Preliminary mechanistic studies revealed that SV interacts with KIF5B and enhances its binding to mitochondria. In conclusion, SV improves BPD by repairing mitochondrial damage and inhibiting apoptosis via KIF5B interaction. This study identified new potential targets and therapeutic strategies for BPD management.