BACKGROUND:Fine particulate matter (PM2.5) and hyperglycemia are established risk factors for stroke, but whether PM2.5 and its constituents influence the progression from pre-diabetes mellitus (pre-DM) to diabetes mellitus (DM) and stroke remains unclear. METHODS:We used longitudinal data from 118,811 adults in the Guangzhou Older Longitudinal Dynamic Health Cohort who were free of hyperglycemia and stroke at baseline. A multistate model evaluated the effects of PM2.5 and five major constituents, including black carbon (BC), organic matter (OM), sulfate, nitrate, and ammonium, on six glycemic and cerebrovascular transitions: normal glucose to pre-DM, normal to DM, normal to stroke, pre-DM to DM, pre-DM to stroke, and DM to stroke. Accelerated failure time models estimated how exposures influenced transition timing. RESULTS:Over 378,568 person-years of follow-up, 2018 participants developed stroke. PM2.5 was associated with higher risks of all transitions, including normal to pre-DM (HR 1.014, 95 % CI 1.014-1.014), pre-DM to DM (1.029, 1.028-1.030), and DM to stroke (1.048, 1.037-1.058). Direct progressions to stroke from normal and pre-DM stages were also elevated. BC showed the strongest associations with stroke, with HRs of 1.833 and 1.954. Accelerated failure time models indicated that high PM2.5 exposure shortened the transitions to stroke by 2.89 years from normoglycemia, 1.43 years from pre-DM, and 1.29 years from DM. OM contributed most to these accelerations, reducing transition times by 2.77, 1.56, and 1.45 years. CONCLUSIONS:PM2.5 and its constituents increase risk and accelerate progression from normoglycemia and pre-DM to stroke, supporting constituent-specific air quality regulation.

Background:Environmental exposures may influence irritable bowel syndrome (IBS) pathogenesis, but the interplay between genetic risk, residential green/blue space, and IBS incidence remains unexplored. Methods:We aimed to study the association between green/blue space and incident IBS, and to assess effect modification by genetic susceptibility. The study included 376 749 UK Biobank participants at baseline. Residential green space was measured using the normalised difference vegetation index (NDVI), and blue space was defined by distance to the nearest water bodies. For time-to-event analyses, we used Cox proportional hazards models, polygenic risk scores (PRS), and mediation analysis to test gene-environment interactions. Results are presented as hazard ratios (HRs) with 95% confidence intervals (95% CIs). Results:During a follow-up of 11.73 years, 7091 incident IBS cases were documented. Higher residential green space exposure was associated with reduced risk of incident IBS. Specifically, within a 1000 m buffer, each interquartile range (IQR) increase in NDVI corresponded to a 5% lower IBS risk (HR = 0.95; 95% CI = 0.91-0.98), with consistent effects observed at 800 m and 500 m buffers. Conversely, a greater distance to water bodies was associated with reduced IBS risk. Stratification by PRS revealed a significant interaction: increased green space (1000 m buffer) reduced IBS risk by 8% exclusively among high-genetic-risk individuals (HR = 0.92; 95% CI = 0.88-0.96), whereas no interaction was observed for blue space. Moreover, physical activity mediated the association between green space and IBS. Conclusions:Increased residential green space exposure is associated with reduced IBS incidence, particularly among individuals with high genetic susceptibility. These findings underscore the importance of urban greening as a public health strategy to mitigate IBS risk, highlighting the potential for targeted environmental interventions to offset genetic predispositions.

Cholera outbreaks are prevalent in coastal regions, where hydroclimatic factors play a critical role. However, evidence on their associations with different genotypes remains limited, and global projection remains lacking. We compiled cholera data from EnteroBase and WHO weekly reports covering 110 coastal countries from 1980 to 2022. A generalized additive model was used to examine the associations between hydroclimatic factors and different cholera serotypes and genotypes. We further projected future cholera occurrences for each coastal country under three climate change scenarios from 2025 to 2100. During the study period, Wave 3 of O1 replaced Wave 1 as the predominant genotype of cholera, while cholera O139 remained at low levels and only occurred in Asia. At the country–year level, each 1 °C increase in sea surface temperature (SST) was significantly associated with cholera occurrence (OR: 1.032, 95% CI: 1.023 to 1.040) and Wave 3 of O1 (OR: 1.149, 95% CI: 1.097 to 1.203). Drainage density (m/km2) and coastline ratio (%) were positively related to cholera, with ORs of 1.067 (95% CI: 1.046 to 1.087) and 1.022 (95% CI: 1.019 to 1.027). For future projections, five trend patterns were identified under different emission scenarios, with most countries showing increased cholera risk due to global hydroclimatic changes, peaking under the SSP585 scenario. Our findings reveal associations between hydroclimatic factors and different cholera genotypes and project future cholera risk across coastal countries, thereby providing evidence to inform genotype-specific surveillance and targeted prevention strategies at the global scale.

Non-methane volatile organic compounds (NMVOC) are widespread ambient pollutants with documented toxicological properties, yet population-level evidence on their long-term health impacts remains limited. We analyzed data from 394,153 adults in a large prospective cohort study. Individual exposure to NMVOC was estimated by linking residential addresses with modeled concentrations. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) per standard deviation (SD) increase in exposure for 14 major mortality categories and 97 specific causes. Population attributable fractions were calculated to characterize the potential mortality burden, and accelerated failure time models assessed the impact of exposure on timing of death. Over a median follow-up of 13.71 years, 32,310 deaths occurred. Long-term NMVOC exposure was associated with increased mortality risks across a range of disease systems. Of the major disease categories, mortality from respiratory system diseases exhibited the strongest and positive association (HR = 1.048, 95% CI: 1.028-1.069). Notably, subtype analysis highlighted particularly strong associations with asthma (HR = 1.130) as well as phlebitis and thrombophlebitis (HR = 1.129). The estimated population attributable fractions of mortality associated with NMVOC exposure ranged from 2.243% for circulatory diseases to 7.673% for other symptoms. In addition, accelerated failure time models suggested that higher exposure levels were associated with differences in survival time corresponding to 1.517 to 3.935 years earlier mortality. These findings suggest associations between long-term NMVOC exposure and increased and earlier mortality across multiple organ systems, highlighting potential public health relevance.

Background: Early puberty has been associated with various adverse health outcomes. We aimed to characterize the spatiotemporal patterns of age at menarche or spermarche in China and to identify potential associated factors. Methods: We leveraged data from six consecutive nation-wide cross-sectional surveys in China conducted in 1995, 2000, 2005, 2010, 2014, and 2019. A total of 519 940 girls aged 9 to 18 years and 392 813 boys aged 11 to 18 years from 30 provinces in Mainland China were included. Probabilistic analysis was used to estimate the median ages at spermarche or menarche as surrogate measures of pubertal development. We used Bayesian spatiotemporally varying series models with the spatiotemporal variance partitioning index to assess the spatiotemporal heterogeneity of ages at menarche or spermarche across 30 provinces and to quantify the relative contributions of the socioeconomic and environmental factors. Results: Almost all provinces experienced decreases in the median ages at spermarche and menarche during the study period. Regional disparities were identified, as a faster decreasing trend was generally observed in eastern provinces when compared with western provinces. Socioeconomic factors explained 34.58% of the spatiotemporal heterogeneity for boys and 34.17% for girls, while environmental factors explained 55.68 and 56.22%, respectively. Among these, temperature, nighttime light, nitrogen dioxide, relative humidity, and illiteracy rate showed the largest contributions (each >5%). In general, higher levels of economic indicators and environmental stressors were observed in provinces with lower initial ages at spermarche and menarche and/or faster declining trends. Conclusions: A significant trend toward early puberty was observed in China over the past 25 years, especially in eastern provinces. Both socioeconomic and environmental factors were strongly associated with the observed spatiotemporal patterns.

Background To evaluate the associations of fine particulate matter (PM2.5) and its constituents with the risk of different stages of chronic kidney disease (CKD), as well as the modification by lifestyle and genetic risk and the mediation by accelerated biological aging. Methods A total of 448,282 participants without CKD were included in this study. Bilinear interpolation approach was utilized to assess annual levels of PM2.5 and constituents. Cox proportional hazard model was utilized to evaluate the associations of PM2.5 constituents with risks of CKD stages. We examined the potential modifying role of lifestyle and genetic risk. Mediation analyses were conducted to investigate the mediation role of biological aging in PM2.5 constituents-CKD stages associations. Results During a median follow-up of 13.66 years, 17,724 participants developed incident CKD. Long-term exposure to PM2.5 and constituents was associated with increased CKD risk in different stages, with hazard ratios [HRs (95% confidence intervals, CIs)] ranging from 1.05 (1.03, 1.08) for elemental carbon (EC)-CKD association to 1.25 (1.12, 1.40) for Organic matter (OM) -CKD stage 5 association. Additive interactions of PM2.5, sulfate, OM, and EC with lifestyle were observed in relation to CKD risk. Biological aging acceleration served as a mediator in PM2.5 constituents-CKD stages relationships; the mediation proportions ranged from 4.56% (sulfate-CKD stage 1–2 association) to 28.32% (sulfate-CKD stage 5 association). Discussion Long-term exposure to PM2.5 and its constituents might increase the risk of CKD in different stages, especially in those with unhealthier lifestyles, with biological aging involved in the mechanisms potentially.

The biomolecular pathways linking fine particulate matter (PM2.5) and its constituents to depression remain elusive. With 24,940 depression-free participants in the UK Biobank, exposure to PM2.5 and its 5 constituents (ammonium, nitrate, sulfate, elemental carbon, and organic carbon) was estimated. We integrated Olink-based proteomics and NMR-based metabolomics using Cox proportional hazards models, mediation analyses, functional enrichment analyses, and drug predictive analyses. We identified 982 depression cases during a mean follow-up of thirteen years. PM2.5 and its constituents was associated with increased depression risk, with HRs up to 1.20 per SD increment in ammonium. We identified 140 proteins and 3 metabolites as statistically-significant mediators, with mediation proportions up to 8.00% and 3.42%. These mediators were enriched in lipid and unsaturated fatty acid metabolism, immune regulation, and inflammation responses. Drug predictive analyses showed potential drug repurposing. Shifts in biomolecules partially explained PM2.5-depression associations, highlighting inflammation and lipid dysregulation as potential pathways.

AIMS:Weight fluctuation and changes in relative fat mass (RFM) are independently linked to mortality, but few studies have examined the joint effects of weight and RFM changes on all-cause and cardiovascular disease (CVD) mortality among older community-dwellers. METHODS:We followed 203 962 Guangzhou residents aged ≥ 65 years (mean 71.9 years) who had baseline weight, waist and height measurements in 2018 and repeat assessment in 2019-2020. Weight and RFM changes were categorized as stable (±5%), 5%-10% increase, > 10% increase, 5%-10% decrease or > 10% decrease. Mortality from follow-up visit until December 31, 2023. Multivariable Cox regression and restricted cubic splines analysis were used to explore the associations of changes in weight, RFM, or both with all-cause and CVD mortality among participants. RESULTS:During median follow-up of 5.6 years, 14 712 all-cause and 6536 CVD deaths occurred. U-shaped relationships were seen for both exposures. Compared with stable weight, all-cause mortality was higher in participants who decreased > 10% (HR 1.89, 95% CI 1.76-2.03) or increased > 10% (1.50, 1.39-1.63); similar patterns were observed for RFM decrease. In joint analyses, the highest all-cause mortality risk was seen when both weight and RFM decreased > 10% (HR 2.09, 1.82-2.41), whereas the highest CVD risk occurred with > 10% weight decrease coupled with > 10% RFM increase (HR 2.02, 1.53-2.67). Similar associations of changes in weight, RFM or both, and all-cause and CVD mortality were observed in different subgroups. CONCLUSIONS:Weight change exceeding 10% and any RFM decrease are associated with elevated all-cause and CVD mortality among older community-dwellers. Concurrent changes of more than 10% in both metrics confer the greatest risk. Maintaining stable weight and RFM may reduce premature mortality among older community-dwellers. TRIAL REGISTRATION:ClinicalTrials.gov identifier: ChiCTR2400089945.

Gastrointestinal (GI) diseases represent a significant global health burden, and emerging evidence suggests air pollution may be a risk factor. We reviewed relevant literature and performed a meta-analysis. We searched original studies investigated the associations between long- and short-term exposure to particulate matter (diameter ≤ 2.5 µm [PM2.5], ≤ 10 µm [PM10]) and gaseous pollutants (nitrogen dioxide, sulfur dioxide, carbon monoxide, and ozone [O3]) and GI diseases. DerSimonian and Laird random-effects meta-analyses were conducted when at least 2 studies were available for a given pollutant (per 10 μg m-3 increment) and a specific GI disease. A total of 70 studies were included. Long-term exposure to PM2.5 was significantly associated with increased mortality rate from all GI cancers (OR = 1.128; 95% CI, 1.019-1.248), with the strongest association observed for colorectal cancer (OR = 1.214; 95% CI, 1.061-1.389). For non-cancer GI diseases, long-term exposure to PM2.5 was significantly associated with increased risks of duodenal ulcer (OR = 1.073; 95% CI, 1.057-1.089) and irritable bowel syndrome (OR = 1.353; 95% CI, 1.222-1.497); PM10 was also linked to the latter (OR = 1.108; 95% CI, 1.012-1.213). Short-term exposure, particularly to PM2.5, PM10, and O3, was significantly associated with appendicitis hospitalization (OR = 1.003 [95% CI, 1.001-1.004]; OR = 1.017 [95% CI, 1.015-1.019]; and OR = 1.001 [95% CI, 1.000-1.003], respectively). PM2.5 was also associated with peptic ulcer bleeding (OR = 1.006; 95% CI, 1.001-1.011). Long- and short-term exposures to air pollution, especially PM2.5, are associated with increased risks of GI diseases.

BACKGROUND:Chronic obstructive pulmonary disease (COPD) is a leading global cause of mortality, with ambient fine particulate matter (PM2.5) recognized as a key environmental risk factor. However, the circulating proteomic alterations that may underlie the association between long-term PM2.5 exposure and incident COPD remain incompletely characterized. METHODS:We included 48,219 participants from the UK Biobank. Baseline plasma proteins were measured using the Olink Explore 3072 platform, and PM2.5 concentrations were assigned using the ESCAPE land-use regression model. The PM2.5-protein associations were estimated using multivariable linear regression. An elastic net model was used to construct a PM2.5-related proteomic score. Cox proportional hazards models were then applied to evaluate the associations of PM2.5 and PM2.5-related proteomic score with incident COPD. Statistical mediation, pathway enrichment, protein-protein interaction, and druggability analyses were further performed. RESULTS:Over a median follow-up of 12.6 years, 1955 participants developed COPD. We identified 1629 proteins associated with PM2.5 exposure and 1185 proteins associated with incident COPD. Among proteins associated with both PM2.5 exposure and incident COPD, 500 showed evidence consistent with statistical mediation in exploratory analyses. The largest estimated statistical mediation proportions were observed for PLAUR (24.7%), GDF15 (17.4%), and MMP12 (16.3%). Enrichment analyses highlighted inflammatory and stress-response pathways, and protein-protein interaction analysis identified IL1B, TGFB1, and CXCL8 as network hubs. Database screening and molecular docking further prioritized PLAUR, MMP12, and CXCL8 as potentially druggable candidate proteins for future experimental evaluation. CONCLUSION:Long-term PM2.5 exposure was associated with widespread plasma proteomic alterations, and a subset of proteins showed evidence consistent with statistical mediation of the PM2.5-COPD association. These systems-level findings provide pathway-level biological plausibility and prioritize candidate biomarkers and potentially druggable proteins for external replication, mechanistic validation, and future translational research.

Air pollution is associated with Alzheimer’s disease (AD), and the susceptibility of AD from air pollution may be affected by genetic characteristics, but the underlying mechanisms remain unknown. Data from the UK Biobank, in conjunction with PLINK2, was utilized to conduct a genome-wide analysis of a gene-air pollution (PM2.5, PM10, NO2, and NOx) interaction in AD. Functional annotation, positional gene mapping, expression Quantitative Trait Loci (eQTL) analysis, 3D chromatin interactions mapping (ciMap), and gene expression analysis were conducted using FUMA. Potential biological pathways was analyzed by Metascape. A total of 322,958 participants were included in the study. Genome-wide gene-air pollution interaction analysis (GWIA) identified 38, 36, 66, and 101 genomic risk loci that interacted with PM2.5, PM10, NO2 and NOx (p < 5 × 10–8). The functional annotation positional gene mapping, eQTL, ciMap mapping, and quantitative gene prioritization prioritized 26, 25, 46 and 70 prioritized genes for PM2.5, PM10, NO2 and NOx, including PTCH1, UNC80, TUBGCP3, RUNX2, RCAN2, SUPT3H, DNPH1, TTBK1, and RSPH9, and we found significantly high expression of NOx-related prioritized genes in the heart atrial appendage, the modulation of smoothened signaling was associated with PM2.5 and PM10, hemopoiesis was associated with nitrogen oxides, and learning or memory processes may be involved in the interaction between PM2.5, NO2, NOx, and genes, affecting Alzheimer’s disease. We prioritized genetic risk loci that interact with air pollutants in AD and revealed that learning or memory are crucial pathways through which these pollutants interact with genes PDE1B, SRF, ZNF385A, and TTBK1.

AIMS:The life-course joint effects of specific fine particulate matter (PM2.5) components and genetic susceptibility on the progression from atrial fibrillation (AF) to heart failure (HF) remain uncertain. We aimed to investigate these associations for both incident AF and its subsequent progression to HF. METHODS AND RESULTS:In this prospective study of 464 541 UK Biobank participants, we estimated life-course residential exposures to PM2.5 and its key components-including elemental carbon (EC), organic carbon (OC), ammonium (NH₄⁺), nitrate (NO₃⁻), and sulfate (SO₄²⁻)-using a validated spatiotemporal model, and constructed a polygenic risk score for AF and HF. We used Cox models to assess non-linear associations and gene-environment (G × E) interactions on both additive and multiplicative scales and quantile-based g-computation to evaluate mixture effects. During follow-up for a median 12.3-years (IQR: 11.70, 13.23), 27 655 participants (mean age 56.5, SD 8.1; 54.8 female) developed AF, with 12.3% progressing to HF. Life-course exposure to components such as EC was associated with increased risks for both incident AF (HR per 1-SD increase: 1.03; 95% CI: 1.02, 1.04) and progression to HF (HR: 1.04; 95% CI: 1.01, 1.08), often with non-linear threshold effects. We also identified a stage-dependent G × E interaction, shifting from a significant multiplicative interaction for incident AF to an additive interaction for the progression to HF, with a relative excess risk due to interaction of up to 0.46. CONCLUSION:Our findings highlight that minimizing cumulative pollution exposure is crucial for preventing incident AF and subsequent HF, especially in genetically susceptible individuals, guiding precision prevention strategies.

BACKGROUND:Black carbon (BC) has been linked to adverse health outcomes, yet underlying mechanisms remain unclear. Integrating metabolomic and metagenomic data across tissues may clarify BC-induced biological pathways. METHODS:We performed human epidemiology and mice experimental approaches. We included 248,288 participants with annual BC exposure estimates and plasma metabolomic profiles. Elastic net regression identified BC-associated metabolites. Male C57BL/6J mice were exposed to filtered air or BC (1 mg/m3, 1 h/day, 5 days/week, 12 weeks). Multi-tissue metabolomics and cecal contents microbiota sequencing were conducted, with histology and gene expression measurements. RESULTS:In humans, long-term BC exposure significantly altered plasma metabolites, notably increasing saturated fatty acids (β = 0.048), while decreasing docosahexaenoic acid (β = -0.002). Amino acid metabolism was broadly disrupted, involving elevated valine (β = 0.011) and reduced glutamine (β = -0.006). In mice, metabolomic profiling showed organ-specific shifts, including increased glutathione and cortisol in the liver (2.88-fold and 2.06-fold), increased PC(16:0/18:1(9Z)) in the heart (3.22-fold), elevated anandamide and arachidonic acid in the kidney (2.35-fold and 1.48-fold), and decreased multiple fatty acids and lysophospholipids across organs. Cecal microbiota exhibited reduced alpha-diversity (Shannon: 3.67 vs. 4.50, P < 0.05) and taxonomic shifts, including an increased abundance of g_Akkermansia and decrease in g_Bacteroides. Multi-omics integration revealed significant microbiota-metabolome correlations in the cecum and plasma (Mantel r = 0.276, P = 0.012). Histological examination confirmed organ injuries, notably lung inflammation, cardiac edema, and neuronal condensation. Gene expression analysis showed increased Il-6 in the lung (5.35-fold, P = 0.047), increased Mb in the heart (5.18-fold, P = 0.010), and increased Igfbp7 in the kidney (3.03-fold, P = 0.001), while Tjp1 expression in cecum was reduced (0.42-fold, P = 0.004). CONCLUSIONS:Our findings suggest that BC exposure may alter systemic metabolism and gut microbiota, potentially contributing to tissue injury and inflammation. The gut-organ axis could be a target for mitigating BC-related health effects.

This study aims to explore the association of outdoor ALAN exposure with T2DM and the mediating effects of obesity in Chinese rural adults. A total of 38,108 participants were recruited from the Henan Rural Cohort. ALAN was positively associated with T2DM and FPG, and negatively associated with insulin, HOMA-IR, as well as HOMA-β, and the effect sizes of per-quartile increase in ALAN were 1.24(1.19, 1.28), 0.14(0.13, 0.16), -1.19(-1.24, -1.14), -0.22(-0.25, -0.20), and -27.30(-29.11, -25.48), respectively. The elderly, men, current smokers, individuals with lower education or income, or physical inactivity were more vulnerable to ALAN-related adverse health effects. The associations of ALAN with T2DM and glucose metabolism were mediated by WC, BMI, WHtR, WHR, VFI, and BFP, with estimated mediation proportions of 36.41%, 25.14%, 33.98%, 22.33%, 24.39%, and 25.85%, respectively, for T2DM. These findings emphasize the need for targeted public health interventions for reducing ALAN-related adverse health effects in rural areas.

BACKGROUND:Evidence is limited concerning whether and to what extent fine particulate matter pollution (particulate matter with an aerodynamic diameter less than 2.5 μm [PM2.5]) is linked to the risk and the time to occurrence of site-specific cancers along with the key constituents of PM2.5 and the sensitive exposure window. METHODS:By using data from 277,446 participants in the UK Biobank, the authors estimated exposures to PM2.5 and its 15 constituents during each participant's lifetime and at different life stages using a bilinear interpolation method. The incidence and time to occurrence of 14 cancers were ascertained. Cox proportional hazard models and accelerated failure time models were applied to investigate the associations between air pollutants and incidence risk and occurrence time of 14 cancers. RESULTS:During a mean follow-up of 11.15 years, 25,820 patients with incident cancer were identified. Lifetime exposure to PM2.5 and to its constituents was associated with an increased incidence risk of 12 of 14 cancers, with hazard ratios and 95% confidence intervals ranging from 1.04 (95% confidence interval, 1.01-1.07) for breast cancer to 1.18 (95% confidence interval, 1.10-1.27) for esophageal cancer. The constituents chloride ion, ammonium, nitrate, and sodium demonstrated the most pronounced effects. The middle-aged and elderly life stage (individuals aged 45 years and older) comprised the sensitive exposure window. The time to occurrence of cancers was earlier by from 0.05 years (ovarian cancer) to 1.95 years (esophageal cancer) because of overexposure to PM2.5 levels greater than 5 μg/m3. CONCLUSIONS:Lifetime exposure to PM2.5 and its constituents might increase the risk and accelerate the onset of various cancers. Combustion-sourced and agriculture-sourced components mainly account for this influence, with the middle-aged and elderly life stage (aged 45 years and older) a sensitive exposure window.

To examine the association between ambient temperature and pregnancy outcomes of in vitro fertilization/intracytoplasmic sperm injection and embryo transfer (IVF/ICSI-ET) participants. We included 10,988 infertile participants who underwent their first IVF/ICSI-ET at a major assisted reproduction specialist hospital in Chengdu, China, between 2019 and 2022. Ambient temperature was assessed using daily mean temperatures from the European Centre for Medium-Range Weather Forecasts Reanalysis v5 (ERA5) dataset, matched to the women’s residential addresses, and eight exposure periods were defined based on key stages of IVF treatment. We used a generalized linear model to explore the association between ambient temperature and clinical pregnancy and live birth, constructing dose–response curves to examine non-linearity. Among the participants, 5,805 (52.83

BACKGROUND:Emerging evidence suggests associations between air pollution, multimorbidity, and atrial fibrillation (AF), but their interplay remains unclear. We evaluated these relationships in a prospective cohort. METHODS:We retrieved a total of 480 344 individuals from the UK Biobank. The quantification of air pollutants (particulate matter with a diameter ≤2.5 μm (PM2.5), particulate matter with a diameter ≤10 μm (PM10), nitrogen oxides (NOx) and nitrogen dioxide (NO2)) was conducted at the geocoded residential locations of each participant. Multimorbidity clusters were determined using latent class analysis using 35 long-term conditions (LTCsc. Three latent classes were identified: non-cardiovascular disease (non-CVD) multimorbidity, mental health multimorbidity and cardiometabolic multimorbidity. These were compared with no LTCs and singular LTCs. Cox models examined the effects of air pollution and multimorbidity status on AF incidence. Counterfactual analyses were performed to calculate the proportion of preventable AF. RESULTS:During a median follow-up of 12.5 years (IQI 11.8 to 13.2), 28 977 incident AF cases occurred. Exposure to PM2.5 was associated with a 37% higher AF risk per 1 µg/m³ higher PM2.5 (HR 1.37, 95% CI 1.36 to 1.38), with similar patterns for PM10 (HR 1.18, 95% CI 1.17 to 1.18), NOₓ (HR 1.06, 95% CI 1.06 to 1.06) and NO2 (HR 1.03, 95% CI 1.03 to 1.03). Compared with no multimorbidity, cardiometabolic multimorbidity showed a 1.84-fold higher AF risk (95% CI 1.76 to 1.93), while non-CVD multimorbidity showed a 2.13-fold higher risk (95% CI 1.97 to 2.30). Additive interactions were observed between air pollution and multimorbidity. For example, participants with high PM2.5 exposure and non-CVD multimorbidity had a sixfold higher AF risk (95% CI 5.25 to 6.82; relative excess risk due to interaction (RERI) 2.31, 95% CI 1.55 to 3.07), exceeding the sum of individual risks. Counterfactual analysis suggested that reducing PM2.5 to the 10th percentile could prevent 26-52% of AF cases in multimorbidity subgroups, with the largest reductions in cardiometabolic (52%) clusters. CONCLUSION:Air pollution and multimorbidity were independently and synergistically associated with higher AF risk. Mitigation strategies targeting pollution may reduce AF burden, particularly in high-risk populations.

The current evidence regarding the relationship between sunlight exposure and dementia is limited and inconclusive, with potential modifiers and underlying mechanisms remaining largely unexplored. A total of 499,627 participants from the UK Biobank were included in the study. Sunshine duration and other meteorological exposures for each participant were estimated using the bilinear interpolation approach and time-weighted method. The association between sunshine duration and incident dementia was assessed using the time-dependent Cox proportional hazard model and generalized propensity score model. Multiplicative and additive interaction models were employed to identify the potential modifying effects of sociodemographic, lifestyle, environmental, and genetic factors. Brain age was predicted using machine learning methods based on neuroimaging phenotypes. The individual and joint parallel mediating effects of serum vitamin D, calcium, and brain age acceleration were further assessed using causal mediation analysis. With an average follow-up of 12.3 years, 7636 incident dementia cases were identified. Shorter sunshine duration was found to be associated with increased incidence of dementia with a hazard ratio of 1.05 (95% CI: 1.03, 1.07) for a 10-h decrease in average monthly sunshine duration. The adverse impact of reduced sunshine duration was modified by age, smoking status, household income, and time spent outdoors. The decrease in sunshine duration was also positively associated with brain age acceleration. The mediating effects of serum vitamin D, calcium, and brain age acceleration were estimated to be 16.20% (95% CI: 8.45%, 24.00%), 6.77% (95% CI: 4.01%, 9.78%), and 7.95% (95% CI: 6.48%, 9.00%), respectively, with a combined mediating proportion of 35.2%. Reduced sunshine duration associates positively with incident dementia and the brain aging process. Serum vitamin D, calcium, and brain age acceleration appear to serve as the underlying mechanism mediating the adverse impacts of reduced sunshine duration on dementia. The elderly, smokers, individuals with lower household income, and those with less time spent outdoors should be particularly vigilant.