BACKGROUND:Diabetic kidney disease (DKD) is a major complication of diabetes, but circulating proteins linking glycaemic stress to kidney injury remain unclear. We aimed to identify glycaemia-linked plasma proteins associated with DKD risk and assess their treatment responsiveness. METHODS:We integrated Mendelian randomization, cis-protein quantitative trait locus-based summary-data-based Mendelian randomization (cis-pQTL-based SMR), deCODE protein genome-wide association study (GWAS) validation, prospective UK Biobank analysis, and semaglutide-associated proteomic assessment. We screened 2,923 plasma proteins for hemoglobin A1c (HbA1c)-driven effects, and evaluated incident DKD. RESULTS:Fifty proteins were associated with genetically predicted HbA1c, and 10 were supported by independent HbA1c datasets. Cis-pQTL-based SMR analyses prioritized ITGBL1 and KLK13. In deCODE validation, KLK13 was the only candidate supported across both glycaemic trait-to-protein and protein-to-DKD analyses (OR 1.13, 95% CI 1.02-1.24). Among 9,936 UK Biobank participants without baseline DKD, 107 developed incident DKD. Higher KLK13 was associated with incident DKD (HR 1.52, 95% CI 1.13-2.06), whereas serine peptidase inhibitor Kazal type 6 (SPINK6) showed stronger association (HR 2.02, 95% CI 1.49-2.74). KLK13 decreased with semaglutide, but attenuated after weight and HbA1c adjustment. CONCLUSIONS:KLK13 was prioritized as a glycaemia-linked circulating protein associated with DKD, implicating protease-inhibitor biology in DKD progression.

Background:The 2021 World Health Organization and United Nations Children's Fund definition of minimum dietary diversity (MDD) includes breast milk as an eighth food group. However, cross-country evidence under this revised definition remains limited. We estimated MDD achievement among children in low- and middle-income countries (LMICs) and examined its associations with anaemia, stunting, underweight, and overweight/obesity (OWOB). Methods:We analysed the most recent Demographic and Health Survey completed between 2000 and 2023 in 62 LMICs, comprising 123,569 children aged 6-23 months. We constructed MDD from standard DHS recode food-consumption variables according to the 2021 WHO/UNICEF definition, with achievement defined as consumption of at least five of eight food groups in the previous 24 hours. We estimated associations using survey-weighted logistic regression with country fixed effects and prespecified covariates. Complementary analyses included restricted cubic splines, a two-stage individual-participant-data meta-analysis, and ecological analyses. Results:Overall, 27.0% of children achieved MDD and 73.0% did not, with rates increasing from 17.7% in low-income countries to 42.9% in upper-middle-income countries. Binary MDD achievement was associated with lower odds of stunting across income groups (adjusted odds ratio (aOR) ranging from 0.677 to 0.822) and underweight (aOR ranging from 0.695 to 0.782). Continuous-score and categorical analyses showed similar patterns, whereas individual-level with anaemia and OWOB were not consistent. National MDD prevalence was inversely correlated with stunting (weighted R = -0.686; P < 0.001), underweight (weighted R = -0.678; P < 0.001), and anaemia (weighted R = -0.373; P = 0.003), but not with OWOB (weighted R = 0.068; P = 0.597). Conclusions:In our study, MDD achievement was low across 62 LMICs and varied substantially across countries and by urban or rural residence and household wealth. Greater dietary diversity was associated with lower odds of stunting and underweight across the primary income-stratified models, whereas individual-level associations with anaemia and OWOB were not consistently observed across model specifications. Policies should prioritise equitable access to affordable, nutrient-dense complementary foods, particularly in sub-Saharan Africa and socioeconomically disadvantaged populations.

Excessive classroom noise is an important, but under-addressed, environmental health concern in schools, with potential implications for students' listening conditions, learning, and hearing health. This study examined classroom noise exposure among Chinese students and evaluated whether a Classroom-oriented Distributed Acoustic Equalization Intervention (C-DAEI) improved classroom acoustics, speech intelligibility, and hearing-related outcomes. The study combined large-scale cross-sectional surveillance with a six-month cluster-randomized, parallel-group field intervention. Surveillance data from 398,629 students selected through stratified cluster sampling between 2019 and 2023 were used to assess classroom indoor noise across school settings. The intervention included 295 students and compared classrooms equipped with C-DAEI with classrooms using standard sound reinforcement. Outcomes included standardized acoustic indicators, speech intelligibility, and pure-tone audiometry in a symptomatic subsample. Nearly half of student-linked classrooms exceeded national noise limits, with non-compliance more frequent in urban than rural schools. Compared with standard sound reinforcement, C-DAEI improved sound-field uniformity and speech transmission conditions. Students in the intervention group achieved higher post-intervention speech accuracy than controls. Audiometric changes were modest, but hearing thresholds showed favourable trends. These findings suggest that optimized classroom sound reinforcement may be a practical school-based strategy for improving listening environments and supporting hearing health.

AIMS/BACKGROUND:The coexistence of gestational diabetes mellitus (GDM) and preeclampsia (PE) significantly increases the risk of adverse neonatal outcomes. However, effective predictive tools for this high-risk population remain limited. This study aimed to evaluate the predictive value of inflammatory and placental-related biomarkers for adverse neonatal outcomes in pregnant women with GDM and PE. METHODS:This retrospective observational study enrolled 230 pregnant women with GDM and PE between February 2022 and February 2025. Participants were divided into an event group (n = 53) and a non-event group (n = 177) based on the occurrence of adverse neonatal outcomes. Baseline characteristics, inflammatory markers, and placental growth factor (PlGF) levels were collected. Independent predictive factors were identified using univariate and multivariate logistic regression analyses, with collinearity diagnostics performed. Receiver operating characteristic (ROC) curves were plotted to evaluate the discriminative performance of individual markers and combined predictive models. RESULTS:Univariate analysis indicated that fasting blood glucose, PlGF, glycated hemoglobin (HbA1c), neutrophil-lymphocyte ratio (NLR), systemic immune-inflammatory index (SII), and systemic inflammatory response index (SIRI) were significantly associated with adverse neonatal outcomes (all p < 0.05). Multivariate logistic regression, after adjustment for collinearity, identified elevated fasting blood glucose, reduced PlGF, increased HbA1c, and elevated SII as independent risk factors for adverse neonatal outcomes (all p < 0.001). ROC curve analysis demonstrated that the combined model incorporating these four variables achieved the highest predictive accuracy, with an area under the curve (AUC) of 0.944 (95% confidence interval [CI]: 0.902-0.986), sensitivity of 94.3%, and specificity of 84.7%, significantly outperforming individual markers. CONCLUSION:In pregnant women with GDM and PE, fasting blood glucose, PlGF, HbA1c, and SII represent independent predictors of adverse neonatal outcomes. A composite panel integrating metabolic, placental, and inflammatory biomarkers exhibits strong discriminative value and may provide objective evidence for neonatal risk stratification in this high-risk population, thereby informing targeted clinical management.

To investigate the association between weekend catch-up sleep (WCS) duration and depressive symptoms among young adults in China and the United States, and to explore potential associated factors. We conducted a binational cross-sectional study comprising 1,440 Chinese young adults (collected in 2024) and 892 US young adults (from NHANES 2021-2023). Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9 ≥ 10). WCS duration was categorized. Logistic regression, restricted cubic splines (RCS), and threshold effect models were employed to examine the relationship. Subgroup analyses were conducted by sex, education, and lifestyle factors. A U-shaped association was observed in both populations. Compared to no catch-up sleep (0 h), a WCS duration of 0-1 h was associated with significantly lower odds of depressive symptoms (China: Odds Ratios (OR) = 0.495, 95% Confidence Intervals (CI) 0.339-0.724; US: OR = 0.412, 95% CI 0.209-0.812). Restricted Cubic Spline (RCS) and threshold analyses confirmed this non-linear pattern, with inflection points at approximately 0.58 h (China) and 1.01 h (US). Subgroup analyses indicated the associations were modified by sex and alcohol drinking status. This study reveals a consistent U-shaped association between WCS and depressive symptoms among young adults in two distinct national populations. Moderate weekend catch-up sleep (around 0-1 h) may be associated with lower odds of depressive symptoms. These findings highlight the importance of balanced sleep patterns for mental health in young adults.

Objective:To map the current landscape of wearable and sensor-based fall detection and pre-impact prediction technologies relevant to older adults and to evaluate their translational maturity within public health contexts. Methods:A scoping review was conducted following PRISMA-ScR guidelines. Four electronic databases (PubMed, Web of Science, Scopus, and IEEE Xplore) were systematically searched for studies published between January 2005 and September 2025. Eligible studies reported the development or validation of fall detection or pre-impact prediction systems incorporating wearable, vision-based, environmental, or multimodal sensing modalities. In total, 243 studies were included in the overall synthesis, with a predefined subgroup of 21 studies involving real-world or mixed real-world validation in older adult populations (≥65 years). Results:Across the 243 included studies, wearable inertial measurement unit (IMU)-based systems constituted the dominant technological stream, and post-fall detection remained the most frequently investigated functional objective. However, more than half of studies relied primarily on laboratory-based simulated fall protocols. Within the real-world validated older adult subgroup (n = 21), 71.4% focused on post-fall detection, 19.0% investigated pre-impact prediction, and 9.5% addressed fall risk modeling. While technical performance metrics such as sensitivity and specificity were frequently reported under controlled conditions, evidence regarding long-term adherence, workflow integration, and health economic impact was limited. A maturity gradient emerged across modalities, with wearable detection systems demonstrating stronger ecological grounding than predictive, multimodal, and ecosystem-level approaches. Conclusion:Although technological innovation in fall-related sensing systems has expanded rapidly, translational maturity remains uneven. Bridging the gap between algorithmic performance and scalable public health implementation will require robust real-world validation, longitudinal adherence evaluation, implementation science frameworks, and economic assessment. Advancing along a continuum from reactive detection toward predictive and personalized prevention represents a critical pathway for supporting safe and independent aging.

Given widespread antibiotic use and residues, this study examined associations of multi-class urinary antibiotic exposure with childhood overweight and obesity (OWOB) risk, identified potential dietary sources, and explored lipidomic signatures and potential indirect effects. We analyzed two cohorts from China: the 4C cohort (Inner Mongolia, 2024; n = 692) for diet-exposure analyses and the CBPEF cohort (Xiamen, 2018/2020; n = 594) for repeated-measures exposure-adiposity and lipidomics analyses. Twenty-four urinary antibiotics across six classes were measured by LC-MS/MS. BMI percentile, OWOB, and untargeted serum lipidomics were assessed, with lipidomics performed in a CBPEF subsample of 73 children. Multi-class antibiotic exposure and co-exposure were common in both cohorts, with >94% of children in the 4C cohort and ≥98% in the CBPEF cohort having at least two detected antibiotics. In the 4C cohort, fish/seafood intake was associated with higher detection of sulfonamides, tetracyclines, and quinolones, with the strongest diet-exposure association observed for seafood intake and sulfonamide detection (OR = 2.17, 95% CI: 1.05-4.48), whereas plant-based intake was inversely associated with total detected antibiotic counts (β = -0.492). In the CBPEF cohort, each additional antibiotic detected was associated with a 0.63-point increase in BMI percentile (95% CI: 0.34-0.92), and each additional human antibiotic detected was associated with 14% higher odds of OWOB (OR = 1.14, 95% CI: 1.04-1.24). Cumulative sulfonamide, quinolone, macrolide, tetracycline, and phenicol counts were positively associated with BMI percentile (β range: 1.15-2.45). Lipidomic analyses identified 102 candidate lipids shared by urinary antibiotic exposure metrics and BMI percentile, with PC1-based indirect-effect signals across multiple antibiotic classes and pathway annotations mainly involving steroid/cholesterol-related metabolism. These findings suggest that contemporary Chinese children and adolescents commonly experience multi-class antibiotic exposure, particularly involving quinolones and macrolides, which may partly reflect dietary and environmental sources and contribute to childhood obesity risk, with lipidomic signatures suggesting involvement of steroid/cholesterol-related metabolism.

Background:Benign prostatic hyperplasia (BPH) is a prevalent disease in elderly men. However, the plasma proteomic signatures for incident BPH are absent, hindering early prediction and risk stratification. We aimed to identify plasma proteins associated with incident BPH and the implicated biological pathways. Methods:This prospective cohort was constructed based on the UK Biobank, enrolling 20 996 BPH-free males at baseline. We used the Olink Explore platform to determine the abundances of 2920 plasma proteins. We used Cox regression models to evaluate associations and the Extreme Gradient Boosting model to perform feature selection and predictive modelling. We performed pathway enrichment and Mendelian randomisation analyses to elucidate the molecular pathways involved and assess causality. Results:During the median follow-up period of 13.38 years, 2405 incident BPH cases were recorded. Cox regression identified 92 plasma proteins significantly associated with BPH risk (false discovery rate <0.05). Extreme Gradient Boosting model prioritised a three-protein signature: TSPAN1 (hazard ratio (HR) = 1.24) and KLK3 (HR = 1.34) as risk factors, and EDA2R (HR = 0.83) as a protective factor. This three-protein panel achieved an AUC of 0.71 (95% confidence interval = 0.69-0.73) for predicting BPH onset. Enrichment analysis revealed the associated proteins were mainly involved in immune-inflammatory pathways and stromal remodelling. As revealed by Mendelian randomisation, TSPAN1 and KLK3 were causally associated with incident BPH. Conclusions:We identified a three-protein panel (TSPAN1, KLK3, EDA2R) which can predict incident BPH. The findings highlight potential targets for non-invasive risk assessment and therapy.

Little research has explored the association of exposure to phthalates and phenols with obesity in Chinese children and adolescents, especially with regard to co-exposure. The mechanisms by which exposure to phthalates or phenols contributes to obesity in children and adolescents remain unclear. Therefore, this case-control study was aimed at examining the effects of multiple phthalate and phenol exposures on obesity and further exploring the potential key role of insulin. The cross-sectional study involved 293 pairs of children and teenagers with obesity and normal weight matched on age (± 1 year) and sex. In addition, 21 urinary endocrine-disrupting chemicals (EDCs), including 11 phthalate metabolites and 10 phenols, were measured. The associations of individual EDCs and EDC mixtures with obesity were investigated using conditional logistic regression models, weighted quantile sum (WQS) analyses, and Bayesian kernel machine regression (BKMR). Mediation analyses were performed to evaluate the mediated effects of insulin on the relationships between EDCs and obesity. In the single-EDC model, the highest quartiles of mono-iso-butyl phthalate (MiBP), mono-2-ethyl-5-hydroxyhexyl phthalate (MEHHP), mono-2-carboxymethylhexyl phthalate (MCMHP), and bisphenol A (BPA) were positively associated with obesity compared to their lowest quartiles. In mixed-exposure analyses, the WQS and BKMR model results consistently suggested that exposure to phthalate and phenol mixtures showed a positive association with obesity. BPA was identified as an essential exposure in the mixture with dominant effects on obesity in children and adolescents. Further mediation analysis revealed that insulin partly mediated the relationship between BPA and obesity, with the proportion of mediation at 50.13

Depression is highly prevalent among individuals with cancer, yet the pathways remain incompletely understood. This study utilized cross-sectional data from the 2018 wave of the China Health and Retirement Longitudinal Study. Cancer was identified from harmonized and health files. Depression was assessed using the 10-item Center for Epidemiologic Studies Depression Scale. Sleep quality was proxied by a single item, which captures one dimension of sleep disturbance. Social participation diversity was constructed from 6 types of activities and summarized as a variety index. Covariates included age, sex, education, partnership, urban residence, retirement, drinking, smoking, and comorbidities. Mediation analysis was conducted using nonparametric bootstrap with 5000 resamples. Moderation was tested via linear models incorporating a sleep quality × social participation interaction term. The analytical sample included 17,550 adults aged 45 years and above. The total effect of cancer on depression was 2.157 (95% confidence interval [CI]: 0.458-3.856). The indirect effect mediated through poor sleep quality was 0.265 (95% CI: 0.028-0.587, P = .026), accounting for 12.29% of the total effect, indicating that sleep quality partially statistically mediated the relationship between cancer and depression. The direct effect of cancer on depression was 1.892 (95% CI: 0.246-3.538, P = .024). Social participation diversity attenuated the path from sleep to depression (sleep × participation interaction: β = -0.134, standard error = 0.043, P = .002). Among Chinese adults aged 45 and older, sleep quality statistically accounted for a modest portion of the cancer-depression association, and social participation diversity modified the sleep-depression association. Given the cross-sectional design and the single-item sleep measure, findings should be interpreted cautiously with respect to temporality and causality. Interventions addressing sleep problems and supporting social engagement warrant further evaluation in longitudinal and interventional studies.

Atopic dermatitis (AD) is a chronic inflammatory skin disease affected by environmental factors. However, the influence of residential environment space on AD has not been well understood. This study aimed to investigate the potential associations between environment space with AD. This study analyzed data from 422,899 participants from the UK Biobank, with 2,462 incident cases of AD documented over a median follow-up of 12.45 years. Cox proportional hazards models were used to assess the association between residential environment space and the risk of developing AD. The risk of AD was negatively associated with the percentage of green space, with a hazard ratio (HR) of 0.81 (95

Background Rapid hypobaric hypoxia exposure damages oxygen-sensitive organs like the kidneys. Ferroptosis and pyroptosis, oxygen-dependent cell death mechanisms, remain understudied in this context, as does the role of mitochondrial DNA (mtDNA) methylation. Methods We established a rat model of hypobaric hypoxia (6000 m/7000 m, 6 h/72 h). Kidney ferroptosis (Prussian blue staining, LPO/MDA/GSH assays, ACSL4/GPX4 expression) and pyroptosis (Caspase1/GSDMD activation) were analyzed. mt-cox1/2/3 methylation was assessed in renal mitochondrial DNA, cytoplasmic DNA, and serum cell-free DNA (cf mtDNA) via pyrosequencing. PCA identified biomarkers. Results Hypobaric hypoxia induced renal iron accumulation, lipid peroxidation, and tubular injury. Ferroptosis was mediated by ACSL4 upregulation and GPX4 suppression, while pyroptosis activated Caspase1/GSDMD. Mitochondrial damage and mtDNA leakage were observed via TEM. mt-cox3 pos2 hypermethylation in serum cell-free mtDNA distinctly distinguished hypoxia-exposed rats via PCA. Conclusion Ferroptosis and pyroptosis synergize to drive hypobaric hypoxia-induced renal injury. mt-cox3 pos2 methylation in cell-free mtDNA emerges as a novel biomarker for renal pathogenesis.

Aging and age-related diseases share convergent pathways at the proteome level. Here, using plasma proteomics and machine learning, we developed organismal and ten organ-specific aging clocks in the UK Biobank (n = 43,616) and validated their high accuracy in cohorts from China (n = 3,977) and the USA (n = 800; cross-cohort r = 0.98 and 0.93). Accelerated organ aging predicted disease onset, progression and mortality beyond clinical and genetic risk factors, with brain aging being most strongly linked to mortality. Organ aging reflected both genetic and environmental determinants: brain aging was associated with lifestyle, the GABBR1 and ECM1 genes, and brain structure. Distinct organ-specific pathogenic pathways were identified, with the brain and artery clocks linking synaptic loss, vascular dysfunction and glial activation to cognitive decline and dementia. The brain aging clock further stratified Alzheimer's disease risk across APOE haplotypes, and a super-youthful brain appears to confer resilience to APOE4. Together, proteomic organ aging clocks provide a biologically interpretable framework for tracking aging and disease risk across diverse populations.

OBJECTIVE:Our objective was to investigate the associations of polyunsaturated fatty acids (PUFAs) intake with rheumatoid arthritis (RA) risk, alongside the role of genetic predisposition and the potential mediating effects of circulating proteins. METHODS:Using data from 188,597 RA-free participants in the UK Biobank, Cox proportional hazard models assessed the association of PUFAs intake with RA risk. The polygenic risk score for RA further allowed evaluation of genetic predisposition's modifying effects. Olink proteomics identified protein signatures associated with PUFAs intake and RA risk, with mediation analyses highlighting specific proteins as potential mediators. RESULTS:Over a median follow-up of 9.1 years, 1,640 RA cases were documented. Each one-SD deviation increase in the intakes of stearidonic acid (SDA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) reduced RA risk by 9% to 10%. Among individuals with high genetic risk, omega-3 fatty acids (n-3 PUFAs) intake (including SDA, EPA, DPA, and DHA) significantly decreased RA risk, with antagonistic additive interactions against genetic predisposition. Olink-based proteomic analysis displayed that RA risk and specific n-3 PUFAs intake (DHA, DPA, and SDA) were primarily associated with immune response and inflammation, cytokine interactions, signal transduction, cell adhesion and migration, and metabolic pathways. Mediation analyses identified 55 mediating proteins involved in immune regulation, inflammation, and cell homeostasis. Notably, CD80 and tumor necrosis factor receptor superfamily 4 emerged as vital mediators in the relationship between specific n-3 PUFAs intake and RA risk. CONCLUSION:These findings indicated the potential benefits of n-3 PUFAs intake in reducing RA risk and provided new insights into the mechanisms by which n-3 PUFAs influence RA risk.

Non-pharmaceutical interventions (NPIs) during the COVID-19 pandemic significantly reduced influenza transmission. This study explores the hypothesis of "immunity debt" which suggests increased vulnerability to influenza following reduced exposure during the pandemic. World Health Organization aggregated data on influenza from 116 countries and its association with NPI intensity as measured by the COVID-19 Stringency Index is analyzed. Where individual-level data available (France, the United Kingdom, Spain, Italy, Belgium, and Romania), the analyses of influenza monthly rates in six European countries (France, the United Kingdom, Spain, Italy, Belgium, and Romania) are replicated. The results indicate globally a 46.3% (95%CI: 15.79-70.78%) reduction in influenza cases during COVID-19 restrictions in the winter season, followed by a 131.7% (95%CI: 34.95-255.78%) increase in the first postrelaxation winter and a 161.2% (95%CI: 31.88-382.16%) increase in the summer as compared to the predicted level based on historical influenza epidemic trends. In addition, a positive association between the Stringency Index and post-relaxation influenza surge is observed globally (R2 = 0.14-0.17) and replicated regionally. The findings support the population immunity debt hypothesis for influenza and call for proactive preparations against its consequences in future pandemics.

Phthalates (PAEs) exposure and triglyceride-glucose (TyG) index—an indicator of insulin resistance (IR), remains not fully understood. To investigate the predictive and mediating role of IR markers in associations between PAEs exposure and puberty initiation, adjusting for sex hormones. A cohort was implemented in May 2017-October 2020. Urinary creatinine-adjusted PAE levels were measured at baseline. IR surrogates including TyG, TG/HDL-c, the metabolic score for IR (METS-IR) and TyG-BMI, sex hormones were measured at multiple visits. Early puberty onset was defined as occurring at an age below the first quartile age specific to age and sex. Group-based multi-trajectory modeling was performed to identify longitudinal patterns of IR surrogates and sex hormones. Multinomial logistic regressions were used to analyze the relations among PAEs exposure, IR surrogates’ trajectories and earlier pubertal onset. Th mediating effects of IR surrogates’ trajectories was performed by mediation analyses. Of 800 children, 88.88 % initiated puberty. PAEs exposure significantly increased the risk of larger trajectories of IR surrogates and earlier puberty, while the “largest” trajectories for METS-IR (OR=2.74, 95 %CI=1.22, 6.14) and TyG-BMI (OR=2.85, 95 %CI=1.28, 6.38) could increase the odds of early pubertal onset, and had a stronger predictive ability than TyG or BMI alone. METS-IR and TyG-BMI exhibited significant mediating effects of associations between PAEs exposure and early pubertal onset with the mediating proportions of 24.17 % and 29.0 %. Trajectories of METS-IR and TyG-BMI mediated the relationship of PAEs exposure—earlier pubertal initiation independent of sex hormones. Reducing PAEs and screening IR markers are crucial for pubertal health.

Childhood hypertension is a growing public health concern, predisposing affected individuals to long-term cardiovascular complications. The cardiovascular and metabolic effects of exposure to bisphenol A (BPA) substitutes, emerging endocrine-disrupting chemicals, remain poorly understood in children. This study investigated associations between childhood BPA substitutes exposure and blood pressure, focusing on the modifying role of latent insulin resistance (LIR) and potential lipid metabolic pathways. A total of 747 children from a prospective cohort in Xiamen, China, were included. Associations between repeated bisphenol measurements and blood pressure were assessed using mixed-effects models and generalized estimating equations. A random subsample underwent lipidomic profiling; participants were grouped by bisphenol exposure and triglyceride-glucose (TyG) index. Differentially expressed lipids were identified, tested for associations with blood pressure, and analyzed by enrichment and mediation approaches. Exposure to bisphenol AF and AP was positively associated with higher systolic blood pressure z-scores (β = 0.075 and 0.144, both P < 0.001) and with increased risk of elevated and high blood pressure (OR = 1.218 and 1.364, P < 0.001 and = 0.002; OR = 1.281 and 1.539, both P < 0.001). Children with concurrently higher bisphenol AF or AP exposure and TyG exhibited lipid dysregulation, which was associated with increased childhood blood pressure. Dysregulated lipids were predominantly enriched in lysoglycerophospholipids and lipid-mediated signaling pathways. Specific lipids, including two glycerolipids and five glycerophospholipids, potentially mediated the association between bisphenol AF/AP × LIR and blood pressure, with indirect effects ranging from 0.114 to 0.626. In conclusion, bisphenol AP and AF were significantly associated with elevated childhood blood pressure. LIR amplified these adverse effects, partly through lipidomic perturbations, highlighting glycerophospholipid and glycerolipid metabolism as potential pathways underlying this association.

Objectives:This study aimed to estimate the combined effects of long-term fine particulate matter (PM2.5) exposure and physical activity (PA) on cardiovascular disease (CVD) risk and to assess whether the cardiovascular benefits of PA outweigh the potential adverse effects of PM2.5 exposure. Methods:Data were obtained from the China Health and Retirement Longitudinal Study and the ChinaHighAirPollutants datasets. Cox proportional hazards models were used to assess the independent and combined effects of PA and long-term PM2.5 exposure on CVD. Interaction analyses were conducted to determine whether the cardiovascular effects of PM2.5 or PA were modified by each other. Results:PA was negatively associated with CVD risk. Each IQR increase in PA significantly reduced the risk of CVD by 10% (HR=0.90, 95% CI 0.83 to 0.98). While PM2.5 exposure was positively associated with CVD, a 10 μg/m3 increase in PM2.5 significantly increased 5% risk of CVD (HR=1.05, 95% CI 1.00 to 1.09). Compared with participants with high PA and low PM2.5 exposure, those with low PA and high PM2.5 exposure had the highest risk of CVD (HR=1.56, 95% CI 1.15 to 2.13). Long-term PM2.5 exposure increased the risk of CVD in participants with low and moderate PAs, but not high PA. Conclusion:The beneficial effects of high levels of PA may mitigate the detrimental effects of PM2.5 exposure, indicating that PA is an effective strategy for reducing the risk of CVD, even among individuals living in areas with elevated PM2.5 concentrations.

Childhood respiratory diseases remain a major global health concern, with school-centered exposures to air pollution and extreme temperatures posing significant risks. We conducted a spatiotemporal stratified multi-city, school-based design to evaluate underexplored risk patterns of fine particulate matter with an aerodynamic diameter <= 1 mu m, nitrate, sulfate, ammonium, chloride, black carbon, and temperature exposures including daily mean, extremes, and short-term variability. The analysis included 265,076 pneumonia and/or tracheitis cases among schoolchildren in Jiangsu Province, China. We observed significant urban-rural disparities and spatial clustering in air pollution and temperature variation. Cumulative exposure to all pollutants was positively associated with increased risk of illness-related absences, with stronger effects observed in urban schools and during low-temperature conditions overall. Boys showed higher initial sensitivity to air pollution, while girls exhibited greater vulnerability after 10-14 days. Notably, urban children were most affected by combined exposures to low temperature-high pollution, whereas rural children experienced greater combined risks under high-temperature conditions. In contrast, short-term temperature variability contributed minimally to the observed health effects. These findings support the development of early warning systems for composite exposures, informed by exposure-risk profiles, to enable timely school intervention and protect schoolchildren's respiratory health.

Social isolation, loneliness, and fine particulate matter (PM2.5) exposure are significant social and environmental factors that frequently cooccur in vulnerable populations. The joint effects of these factors on the risk of cardiovascular disease (CVD), however, are not well supported by data. This study aimed to evaluate the independent and combined effects of social isolation, loneliness, and long-term PM2.5 exposure on CVD risk and to assess the interactions between social isolation or loneliness and PM2.5 exposure on CVD risk. We used Cox proportional hazards models to estimate the independent and combined effects of loneliness, social isolation, and long-term PM2.5 exposure on CVD incidence. We also conducted interaction analyses to investigate whether the effects of social factors on CVD are modified by the level of PM2.5 exposure. This study included 12,544 participants, with mean age of 58.7 ± 9.4 years. The median follow-up was 7 years, with 1761 CVD events occurred. Individuals with loneliness presented a 29