BACKGROUND: While numerous studies have examined associations between prenatal air pollution exposure and fetal growth measures, investigations assessing longitudinal growth trajectories across multiple time points during mid-to-late pregnancy remain limited. OBJECTIVES: The aim of this study is to explore the effects of prenatal exposure to air pollution on fetal growth trajectories. METHODS: From a prospective birth cohort in Wuhan, China, recruited from 2013 to 2016, we included a total of 4283 eligible pregnant women. At 16, 24, 31, and 38 weeks of gestation, we collected ultrasound measurements, including biparietal diameter (BPD), abdominal circumference (AC), femur length (FL), and estimated fetal weight (EFW). Exposure to air pollution during pregnancy was estimated for the participants' residential addresses using a spatial interpolation method. Associations between air pollutants and fetal growth parameters across four exposure windows were examined by using multiple informant models. Group-based trajectory modeling (GBTM) combined with a multinomial logistic regression model was used to explore the effect of air pollution exposure on fetal growth trajectories. RESULTS: Four trajectory groups for AC, FL, and EFW, and three trajectory groups for BPD were selected based on GBTM. Compared with the reference trajectory group, exposure to higher PM2.5 during weeks 1-16 was significantly associated with lower odds of being in the "fast growth group" for AC (OR = 0.68, 95% CI: 0.55, 0.84) and EFW (OR = 0.71, 95% CI: 0.56, 0.91). Exposures to PM2.5, PM10, NO2, SO2, and CO during 1-16 weeks were negatively associated with AC, FL, and EFW at 16 weeks as well as BPD, FL, and EFW at 24 weeks. Similar negative associations were observed between air pollution exposure during 25-38 weeks and AC and EFW at 38 weeks. DISCUSSION: Our study provided evidence of negative associations between air pollution exposure during 1-16 weeks of gestation and the fast growth trajectory group. In addition, we observed distinct lagged associations between air pollution and fetal growth, with early pregnancy exposure negatively related to early and midgestational growth, and mid-to-late pregnancy exposure negatively related to growth in the late window. These results underscore the importance of identifying critical windows of susceptibility during pregnancy and support early intervention strategies to mitigate adverse fetal developmental outcomes.

The environmental factors underlying idiopathic membranous nephropathy (IMN) remain inadequately comprehended. Our purpose is to investigate the environmental factors that contribute to the IMN. Polycyclic aromatic hydrocarbons (PAHs) as a major harmful component of airborne particulate matter, are suspected to be associated with IMN. We employed a 1:1 pair-matched case-control, network toxicology and molecular docking to validate the role of urinary PAHs metabolites in IMN pathogenesis. Urine samples from 146 IMN patients and 146 controls were analyzed for six monohydroxylated PAHs using UPLC-MS/MS. The creatinine-adjusted 1-hydroxynaphthalene (1-OHNAP), 2-hydroxynaphthalene (2-OHNAP), total hydroxynaphthalene (∑OHNAP), and total OHPAHs (∑OHPAHs) were significantly higher in IMN patients (P < 0.05) with odds ratios of 1.42, 1.66, 1.29, and 1.19 respectively, indicating a significantly increased risk of IMN. 8-OHdG were higher in the IMN group. Subgroup analyses indicated stronger associations among males and drinkers. The RCS curve shows that PAHs concentration increases, the risk of IMN generally rises. (P < 0.05). Integrated network toxicology and molecular docking identified TGFβ1 as a key potential target. Molecular dynamics simulations confirmed a stable binding interaction between 2-OHNAP and TGFβ1. This finding was further supported by external RNA-seq data showing elevated TGFβ1 expression in the glomeruli of IMN patients. We report novel evidence suggesting that exposure to PAHs may contribute to the risk of IMN by disrupting immune system, highlighting the environmental factors driving IMN and offering potential therapeutic targets for this increasingly prevalent glomerular disease.

Polycyclic aromatic hydrocarbons (PAHs) are neurotoxicants that may induce cognitive deficits via thyroid dysfunction. Older adults, due to physiological decline, are more susceptible to such toxicants. This crosssectional study involving 433 elderly adults examined the relationships between PAH exposure, cognitive decline and thyroid-mediated pathways. Urinary PAH metabolites were measured and cognitive performance was assessed using the Mini-Mental State Examination (MMSE). Participants were categorized into low-risk (n = 367) and high-risk mild cognitive impairment (MCI) groups (n = 66) based on MMSE scores. Logistic regression results indicated that the odds of MCI risk increased with each one-unit increase in log-transformed levels of 2-OHNap, 2-OHFlu, and 3-OHFlu. Linear modeling further revealed that these metabolites (OH-Nap and OH-Flu) were dose-dependently negatively associated with orientation, attention and memory. In addition, there was a nonlinear dose-response relationship between 1-OHNap and verbal ability, and Sigma OH-PAHs and attention/ memory. Critically, mediating effect analysis showed that the FT3/FT4 ratio mediated the association between PAH metabolites and MMSE scores with a contribution of 22.5 %-26.3 %. This study reveals the mechanism by which PAHs exposure may mediate cognitive decline in the elderly by interfering with thyroid function, providing an important scientific basis for the prevention of environmental factor-induced neurodegenerative diseases.

Disentangling the nonlinear and interactive effects of chemical mixtures remains a central challenge in environmental health, hindering etiologic understanding of immune-mediated diseases such as primary membranous nephropathy (PMN). We developed a multi-stage pipeline integrating exposure clustering, penalized feature selection, interpretable machine learning, and model-based causal inference framework to dissect metal impacts on immune-renal dysfunction. Among 795 adults in Guangxi, China, we quantified 21 plasma metals and three endpoints: PMN diagnosis, estimated glomerular filtration rate (eGFR), and uric acid. Clustering revealed Zn-dominant profiles enriched in PMN patients versus Fe-centered patterns in controls. Tree-based models with SHAP interpretation identified Ba and Tl as being positively associated with PMN, while Co and Ni showed inverse associations. Mo was further linked to elevated uric acid and reduced eGFR, indicating coordinated relationships across metabolic and renal biomarkers rather than definitive evidence of toxicity. Interaction analyses revealed complex, nonlinear relationships, including NiCu antagonism and CoNi dose-modulated associations, highlighting the collective dynamics of metal mixtures in influencing PMN risk. As the first study to couple plasma metal exposomics with interpretable and causal-inspired machine learning in PMN, this work identifies novel exposure patterns and generates etiologic hypotheses, offering a transferable analytic framework for environmental health research.

Aromatic amine antioxidants (AAs) and p-phenylenediamine quinones (PPD-Qs) are novel environmental contaminants derived from tire wear, with emerging neurotoxic concerns, but epidemiological evidence linking them to cognitive health is lacking. This study investigated associations between exposure to these chemicalsand cognitive performance in older adults, and explored the potential mediating role of thyroid hormones. We measured urinary concentrations of nineteen AAs and six PPD-Qs in 439 older adults from Shenzhen, China, and assessed cognitive function using the Mini-Mental State Examination (MMSE). Higher urinary levels of specific compounds, such as N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q), 4-(cyclohexylamino) diphenylamine-quinone (CPPD-Q), and 4-phenylaminodiphenylamine-quinone (DPPD-Q), were significantly associated with lower MMSE scores and increased risks of cognitive impairment. Mixture analyses further indicated that combined exposure to these chemicals was linked to poorer cognitive performance, with 6PPD-Q and CPPD-Q as the most significant contributors. Additionally, specific thyroid hormones were associated with both chemical exposures and cognitive outcomes. Exploratory mediation analysis suggested that thyrotropin (TSH) and total triiodothyronine (TT3) may mediate the association between DPPD-Q exposure and poorer performance in specific cognitive domains. These findings provide the first epidemiological evidence that AAs and PPD-Qs exposure may be associated with cognitive decline in the elderly, potentially via disruption of thyroid hormone homeostasis. These observations warrant confirmation in longitudinal studies.

Pregnancy-triggered shifts in maternal serum elements and gut microbiota may disrupt metabolic balance; yet, their interplay in lipid regulation remains elusive. This study aimed to decode how metal elements and gut microbiota across mid-to-late pregnancy contribute to dyslipidemia and enable early risk prediction. In 689 pregnant women, we measured serum metals and profiled gut microbiota using 16S rRNA sequencing, applying interpretable machine learning and causal inference to unravel element-microbiota-dyslipidemia interactions. Higher serum levels of copper and zinc were linked to adverse lipid profiles, while cobalt showed inverse associations. Metals were also associated with broad alterations in microbial composition and diversity, including shifts in alpha diversity and over 30 significant taxa-level associations, primarily within Firmicutes and Bacteroidota. Microbiota features across pregnancy exhibited extensive associations with lipid metabolism, with reduced alpha diversity linked to elevated levels of triglycerides. Finally, a CatBoost model integrating midpregnancy metals and microbiota robustly predicted late gestational dyslipidemia (AUC = 0.91; AP = 0.94), with SHAP analysis revealing risk-defining microbial thresholds and taxa specific nonlinear effects. These findings demonstrate that maternal elements and microbiota jointly contribute to the development of dyslipidemia, supporting potential strategies for the early identification and prevention of gestational dyslipidemia.

Thyroid function in both pregnant women and newborns is vital for ensuring healthy child growth and development. Existing evidence suggests that exposure to air pollutants during pregnancy may disrupt maternal and neonatal thyroid function; however, findings across studies remain inconsistent. This systematic review and meta-analysis included 24 studies (55,814 pregnant women and 84,645 neonates) published until April 30, 2025. Results indicated that each 10 μg/m3 increase in PM2.5 was associated with a significant decrease in maternal FT4 levels (-0.42%; 95% CI: -0.83%, -0.01%) and neonatal FT4 levels (-0.90%; 95% CI: -1.52%, -0.29%). PM2.5 exposure also increased the risk of maternal hypothyroxinemia (OR = 1.49; 95% CI: 1.16, 1.91). Subgroup analyses revealed stronger effects in the first and third trimesters. Additionally, the study found a nonlinear relationship between PM2.5 exposure and thyroid hormone levels in pregnant women while potential breakpoints vary across thyroid parameters, which range from 20.60 to 71.02 μg/m3, the collective patterns indicate that the most dynamic PM2.5-related effects on maternal thyroid function occur within the 20-60 μg/m3 exposure window. Above approximately 60 μg/m3, response slopes generally diminish, reflecting a sublinear curvature in the exposure-response relationships. These breakpoints notably exceed the World Health Organization air quality guideline (10 μg/m3). These findings underscore the need for stricter air quality regulations to protect maternal and neonatal thyroid health. Further research is warranted to explore the underlying mechanisms and identify critical exposure windows.

To investigate essential metals’ association with anxiety/depression symptoms in the elderly, and explore serum thyroid hormones’ potential mediating role in this association. Study included 416 Shenzhen elderly. The Hamilton Anxiety Scale (HAMA) and the Geriatric Depression Scale (GDS) were utilized to evaluate symptoms of anxiety and depression. Essential metals in urine were measured using inductively coupled plasma mass spectrometry (ICP-MS), while thyroid hormone information was sourced from medical records. Mediation analysis assessed serum thyroid hormones’ mediating effect in the link between essential metals and anxiety/depression. Urinary zinc (Zn) level was negatively linked to the risk of anxiety symptoms [odds ratio (OR) = 0.308, 95

BACKGROUND:Gestational diabetes mellitus (GDM) is common complication in pregnancy. Most studies on the relationship between metal and GDM have centered on a single metal or a few metals mixed, and it remains unclear whether bile acids are associated with this relationship. OBJECTIVE:To investigate the association between exposure to multiple metals in early pregnancy and GDM risk, and the mediating role of serum bile acids. METHODS:Based on a Guangxi Zhuang Birth Cohort, 650 pregnant women recruited were included in the study. Multiple machine models were used to explore the key metal variables and estimate the effects of mixed metal exposure. Then, a nested case-control study was designed with 1:1 individual matching by maternal age and gestational age (n = 304). Mediation analysis was used to assess the mediating role of serum bile acids between metal exposure and GDM. RESULTS:Mo and Sb were found to be negatively associated with GDM risk, while Cd was positively associated with GDM risk. The BKMR model showed that mixed exposure to Mo, Cd and Sb were negatively correlated with GDM risk. Besides, multiple bile acids (such as glycocholic acid (GCA), taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA)) and nine bile acid ratios were correlated with GDM risk. Mo, Cd and Sb were significantly correlated with bile acid levels. The TCA/CA and TCDCA/CDCA played a mediating role in Sb exposure and GDM risk. CONCLUSIONS:Our findings indicate that exposure to Mo, Cd and Sb is significantly associated with the risk of GDM, and bile acids may play a mediating role in this.

Although excessive manganese (Mn) exposure is known to cause neuromotor function in cases of poisoning, its effect on grip strength (a neuromotor marker) in older adults at environmental levels remains unclear. To investigate this issue, we conducted an integrated investigation combining epidemiology and animal experimentation to examine the association between urinary manganese and grip strength. A cross-sectional study of 375 elderly men (60–74 years) was conducted in Guangxi, China, from 2016 to 2017. Urinary Mn concentrations were determined by ICP-MS, and their associations with grip strength were evaluated using generalized linear models and restricted cubic splines. In parallel, 32 six-week-old male C57BL/6J mice were exposed to 0, 5, 10, or 15 mg/kg MnCl2·4H2O via intraperitoneal injection for 6 weeks. Forelimb grip strength of the mice was measured after the final exposure, and mRNA expression of inflammatory markers and cytokines (C reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-α in triceps) in triceps tissue was quantified. The median urinary Mn concentration in the study population was 0.22 μg/g creatinine. After adjusting for confounders, urinary Mn was inversely associated with hand grip strength (highest vs. lowest tertile: β = −3.57 kg; 95% CI: −5.68 to −1.47; p-trend = 0.007). Similarly, in male C57BL/6J mice, grip strengths declined significantly with increasing Mn exposure (p-trend < 0.0001), accompanied by upregulation of the mRNA levels of CRP, IL-6 and TNF-α in muscle tissue. Together, our findings suggest that environmental manganese exposure is inversely associated with grip strength in elderly men. While the manganese doses used in the animal study exceeded typical human environmental exposure, the experimental results further indicate that such grip strength reduction may be linked to muscle inflammation.

BACKGROUND:The long-term effects of early famine exposure on cognitive function remain understudied. This study examined the association between famine exposure and 10-year trajectories of cognitive function, and also assessed the mediating role of depressive symptoms. METHODS:We included 2434 participants from waves 1-5 of the China Health and Retirement Longitudinal Study (CHARLS), with complete baseline data and at least three cognitive assessments. Famine exposure data were obtained from the 2000 China Census, and its severity was determined using the pre-famine Cohort Size Shrinkage Index. Group-based trajectory modeling was used to identify distinct 10-year cognitive function trajectories, and logistic regression was used to estimate the association between famine exposure and trajectory membership. The mediating effect of depressive symptoms was assessed using the Karlson-Holm-Breen method. RESULTS:Among the 2434 participants, two global cognitive function trajectories were identified: persistently low (n = 743, 30.5 %) and persistently high (n = 1691, 69.5 %). Similar patterns were found across cognitive dimensions, including orientation, memory, computation, and drawing. In the fully adjusted model, moderate famine exposure was associated with an increased risk of a persistently low global cognition trajectory [odds ratio (OR) = 1.37, 95 % confidence interval (CI): 1.04-1.82], and severe famine exposure showed a similar trend (OR = 1.57, 95 % CI: 0.97-2.56). Moreover, both moderate (OR = 1.67, 95 % CI: 1.28-2.15) and severe (OR = 1.61, 95 % CI: 1.01-2.54) famine exposures were linked to a heightened risk of a persistently low trajectory for computation, while severe famine exposure was additionally associated with a persistently low trajectory for orientation (OR = 1.90, 95 % CI: 1.15-3.14). Moderate famine exposure, however, was not associated with a persistently low trajectory for orientation (OR = 0.98, 95 % CI: 0.71-1.36). Additionally, while depressive symptoms did not mediate the associations between moderate famine and any cognitive trajectories, they partially mediated the associations between severe famine and global, computation, and orientation trajectories by 20.07 %, 11.76 %, and 10.38 %, respectively. CONCLUSION:Our study identified two distinct cognitive function trajectories, with both moderate and severe famine exposure being linked to persistently low trajectories. Furthermore, depressive symptoms partially mediated the association between severe famine exposure and cognitive function in middle-aged and older adults.

Parabens are among the most prevalent preservatives utilized in daily life. According to studies, parabens are endocrine disruptors that may be harmful to human health. This study used urine (N = 370,460) and blood (N = 19,521) data from 203 publications from 29 countries to calculate the global estimated daily intakes (EDIs) and grouped EDIs (EDIGs) of parabens in different countries and populations, assess the global exposure trends of parabens from 2000 to 2024, and determine the potential health risks of parabens exposure. Global EDIs for methyl -, ethyl -, propyl -, and butyl parabens were 8.00, 1.06, 2.50, and 0.27 μg/kg bw/day in urine, and 0.25, 0.01, 0.19, and 0.01 μg/kg bw/day in blood, respectively. The EDIGs of parabens exhibited significant variations across countries. Compared with the adults, children and pregnant women exhibited higher parabens exposure levels. The hazard quotients of all countries were less than 1; however, potential health risks could not be ignored. Globally, parabens exposure demonstrated a consistent decline from 2000 to 2024, as evidenced by the decrease in methylparaben (MeP) exposure from 12.48 μg/kg bw/day (pre-2005) to 4.97 μg/kg bw/day (post-2020). To our knowledge, this study is the first to evaluate overall parabens exposure levels using published global biomonitoring data, addressing a gap in parabens risk assessment and providing significant insights into the potential health effects of parabens exposure on humans.

The existing studies on the association between multi-metal mixture exposure and cognitive function in the older adults are limited and controversial, with no studies considering the mediating effect of thyroid hormones on the connection between them. This study of 441 urban older adults assessed 21 urinary metal levels and cognitive function using the Mini-Mental State Examination (MMSE). Urinary metal levels were measured via inductively coupled plasma mass spectrometry (ICP-MS), and thyroid hormones levels were obtained from medical records. Mediation analysis evaluated the role of thyroid hormones in the link between metals exposure and cognitive function. The General Linear Model (GLM) showed negative correlations between MMSE scores and titanium (Ti), copper (Cu), rubidium (Rb), and molybdenum (Mo), and positive correlations with selenium (Se) and barium (Ba). Nonlinear inverse U-shaped associations between Mo, Rb, and MMSE scores were identified using Restricted Cubic Splines (RCS) and Bayesian Kernel Machine Regression (BKMR). Mediation analysis revealed that Free Thyroxine (FT4) mediated the relationship between Rb and MMSE scores by 29.10 % and between Zinc (Zn) and language performance by 35.00 %. Total thyroxine (TT4) mediated the link between Cu and orientation score by 24.69 %, and Thyroid Stimulating Hormone (TSH) mediated the association between Cu and attention score by 38.96 %. Ti, Se, Rb, Mo, Ba and Cu were significantly associated with cognitive impairment risk. Mixed exposure to Mo and Rb was linked to an increased risk of cognitive impairment. Additionally, levels of TSH, FT4 and TT4 were associated with cognitive function, mediating the effects of Rb, Zn and Cu on cognitive function.

Polycyclic aromatic hydrocarbons (PAHs) are well-known for their adverse health effects and have garnered significant global attention. This study assessed the levels of ten monohydroxy metabolites of PAHs (OH-PAHs), derived from naphthalene, fluorene, phenanthrene, and pyrene, in urine samples collected from 495 elderly individuals in southern China. OH-PAH concentrations ranged from 0.134 to 183 ng/mL, with OH-Nap (the monohydroxy metabolite of naphthalene) being the most prevalent, accounting for 76.8 % of total metabolites. Significant correlations were observed between urinary OH-PAH levels and demographic factors including gender, smoking, and alcohol consumption, with smoking emerging as the strongest determinant. Regression analyses indicated that steaming significantly reduced PAH exposure (e.g., for 1-OHNap: β = -0.103, 95 % CI: -0.67, -0.04, p < 0.05), while dietary factors, such as fish, mycorrhizal algae, soy products, and coarse grains, influenced OH-PAH concentrations (p < 0.05). Monte Carlo simulations revealed a hazard index below the safety threshold of 1 and an overall carcinogenic risk ranging from 6.40 × 10⁻⁸ to 1.05 × 10⁻⁴, with approximately 85 % of individuals exceeding the acceptable carcinogenic risk threshold (lg(CR) > -6), primarily due to pyrene and naphthalene, which together accounted for 87.2 % of the total. This study delineates the link between PAH metabolites and dietary habits, uncovering health risks for the elderly population in the region. It provides a scientific basis for environmental health and pollution prevention policies aimed at mitigating the adverse effects of PAHs on environmental and public health.

Maternal oxidative stress during pregnancy plays a role as a hazardous factor of offspring neurodevelopment in animal models. However, epidemiological evidence remains limited. In this prospective cohort, we aimed to investigate the associations between maternal oxidative stress biomarkers (OSBs) across pregnancy and neurodevelopmental outcomes in different stages across early childhood. This was a prospective cohort study conducted in 1791 mother–child pairs from Wuhan, China. Three OSBs, including DNA oxidative damage marker (8-hydroxy-2′-deoxyguanosine, 8-OHdG), RNA oxidative damage marker (8-hydroxyguanosine, 8-OHG) and lipid oxidative damage marker (4-hydroxy nonenal mercapturic acid, HNE-MA), were measured in repeatedly collected urine samples in three trimesters across pregnancy. We followed children at age 2, age 3, and age 6 years. At age 2 years, the Bayley Scales of Infant Development of China Revision (BSID-CR) was employed to assess children’s mental and psychomotor development. Brain-derived neurotrophic factor (BDNF) levels were measured in children’s plasma at age 3 years. The Wechsler Preschool and Primary Scale—Fourth Edition (WPPSI-IV) was used to assess children’s intelligence quotients at ages 6 years. Generalized estimating equation models were applied to estimate the associations between OSBs and neurodevelopmental outcomes. Higher maternal HNE-MA levels in late pregnancy were associated with lower mental development index at age 2 years (β = − 0.95, 95

Homocysteine (Hcy) is an independent risk factor for cardiovascular disease (CVD). However, the impact of fructose on Hcy concentrations and whether fructose intake increases disease risk through elevated Hcy remains unclear. We hypothesized that fructose intake is related to Hcy concentrations, and Hcy acts as a mediator linking fructose with CVD and hypertension. We analyzed 2003 to 2006 NHANES data using multivariate logistic regression and restricted cubic spline (RCS) analyses to examine the relationships between fructose intake from different food sources and Hcy concentrations, and to assess whether Hcy mediates the association between fructose intake and CVD or hypertension. After adjusting for confounders, Hcy concentrations were positively associated with the intake of all beverages and foods with added sugars that contain fructose, with an odds ratio of 1.23 (95% CI: 1.01-1.48). RCS analyses showed a "J-shaped" association between Hcy concentrations and the intake of coffee/tea with added sugars, other foods (excluding coffee/tea) with added sugars, tomato catsup, and total juice. An "inverted U-shaped" association was observed with cake intake (all P < .05). Hcy mediated the associations between 4 food sources of fructose (nondiet soft drinks, coffee/tea with added sugars, high-fructose corn syrup sweetened beverages, all beverages and foods with added sugars that contain fructose) and CVD (indirect effects [IE]: 0.03%, 0.03%, 0.04%, and 0.03%) and hypertension (IE: 0.16%, 0.18%, 0.20%, and 0.14%), all P < .05. The findings suggested that various food sources of fructose are associated with Hcy concentrations, and Hcy mediates the relationship between fructose intake and CVD and hypertension.

Background:Hypertension is linked to elevated cardiovascular morbidity and mortality. Research findings regarding cardiovascular benefits of polyunsaturated fatty acids (PUFAs) are inconsistent, possibly due to unbalanced N6FA/N3FA (omega-6 to omega-3 polyunsaturated fatty) ratios and genetic predispositions in PUFAs utilization and cardiovascular disease (CVD) risk. This study investigates the association between plasma PUFAs and CVD risk among hypertensive adults, stratified by the polygenic risk score (PRS) for PUFAs and CVD. Methods:The study analyzed 135,969 hypertensive adults from the UK Biobank. Cox regression models were employed to assess the links between PUFAs and cardiovascular outcomes, as well as the moderating effect of PRS. Results:During the follow-up, 22,084 (16.2%) of participants experienced CVD events, and 2,336 (1.7%) and 13,823 (10.2%) died from CVD and all causes, respectively. Higher blood levels of total polyunsaturated fatty acids (Total PUFA), N3FA, N6FA, docosahexaenoic acid (DHA), and linoleic acid (LA) were associated with lower CVD incidence and mortality, for instance, the hazard ratio for N3FA was 0.745 [95% confidence interval (0.698, 0.796)]. Furthermore, the N6FA/N3FA ratio showed a positive association with CVD incidence and mortality, with the point of minimum risk estimated at approximately 8.70 based on restricted cubic spline analysis. Protective associations of Total PUFA, N6FA, and LA with CVD incidence were stronger in individuals with lower CVD - PRS scores. Conclusion:Despite the general cardiovascular benefits of PUFAs, a higher N6FA/N3FA ratio was associated with an elevated risk of CVD in hypertensive participants. The benefits of PUFAs are greater in those with lower genetic CVD risk. This emphasizes the need to consider N6FA/N3FA balance and genetic predisposition when assessing health impact of PUFAs on CVD.

BACKGROUND:Phthalates are endocrine-disrupting chemicals (EDCs) ubiquitously present in the environment. There are limited studies on the impact of phthalate exposure during the gestational period on neonatal telomere length. OBJECTIVES:The aim of this study is to investigate the correlation between maternal serum phthalate concentrations in early pregnancy and neonatal telomere length and whether this correlation exhibits sex-specificity. METHODS:Between September 2015 and April 2018, 474 pregnant women were selected from the Guangxi Zhuang Birth Cohort (GZBC). Maternal serum samples from early pregnancy were measured for levels of five phthalates and four phthalate metabolites. Umbilical cord blood samples were collected to measure telomere length. The correlations between prenatal phthalate exposure and infant telomere length were assessed using multiple linear regression, Bayesian kernel machine regression (BKMR), quantile g-computation (qg-comp), and restricted cubic spline (RCS) models. RESULTS:Multiple linear regression analyses revealed that per 2.7-fold increase in the concentration of butyl benzyl phthalate (BBP) and mono-ethyl phthalate (MEP), neonatal telomere length decreased by 2.66 % (95 % CI: -5.20 %, -0.05 %) and 3.43 % (95 % CI: -6.46 %, -0.30 %), respectively. Conversely, per 2.7-fold increase in di-butyl phthalate (DBP) concentration corresponded to a 3.01 % (95 % CI: 0.19 %, 5.91 %) increase in neonatal telomere length. Sex-stratified analyses demonstrated that BBP (percent change: -3.60 %; 95 % CI: -6.91 %, -0.18 %); mono-butyl phthalate (MBP) (percent change: -4.13 %; 95 % CI: -7.14 %, -1.01 %) and MEP (percent change: -7.66 %, 95 % CI: -11.53 %, -3.62 %) were inversely associated with neonatal telomere length in female infants only. Neonatal sex significantly modified the association between MEP exposure and neonatal telomere length (P-value for interaction = 0.018). Phthalate mixture was inversely associated with neonatal telomere length in female infants but not in male infants in qg-comp and BKMR models. CONCLUSION:Our study suggests that maternal exposure to phthalates is linked to shorter telomere length in neonates, especially in female infants.

Emerging contaminants (ECs) have garnered growing attention as potential contributors to adverse metabolic outcomes during pregnancy, particularly gestational diabetes mellitus (GDM). Despite increasing recognition of their endocrine-disrupting capabilities, the precise relationship between EC exposure and glucose dysregulation in the gestational context remains inadequately characterized. The scarcity of longitudinal human studies, along with limited mechanistic elucidation, highlights a critical gap in understanding how these ubiquitous environmental pollutants may perturb maternal metabolic homeostasis. This review consolidates current epidemiological evidence linking key classes of ECs, including per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), phthalates (PAEs), bisphenols, organochlorine pesticides (OCPs), parabens, and alkylphenols, with GDM risk and impaired glycemic control. Parallel examination of in vivo and in vitro studies reveals plausible biological mechanisms, including oxidative stress, mitochondrial dysfunction, inflammatory signaling, and insulin resistance (IR), through which these compounds may mediate their effects. By integrating data across human and experimental research domains, this review underscores the urgent need for high-resolution exposure assessments, mixture toxicity frameworks, and mechanistic validation. Such insight is essential for advancing etiological understanding, informing regulatory action, and guiding preventive strategies to mitigate the impact of environmental exposures on maternal-fetal metabolic health.