The aim of this study is to conduct a multi-omics investigation of the metabolic profile of hypothyroidism in the first half of pregnancy and its correlation with the Th17/Treg balance.30 pregnant women with hypothyroidism (hypothyroidism group) and 30 healthy pregnant women (control group) in the first half of pregnancy were included. Results showed that sphingosine (Sph) and BH3 interacting domain death agonist (BID) were significantly upregulated in hypothyroidism group. Sphingolipid signaling pathway was the significantly enriched pathway. Sph and BID in cord blood of hypothyroidism group were also higher. An increase was shown in the Th17/Treg ratio and Th17 cells, and a decrease shown in Treg cells in the hypothyroidism group. The incidence of gestational diabetes mellitus in the hypothyroidism group was significantly higher. Sph and BID were positively correlated with Th17/Treg ratio. Sph levels were positively correlated with Th17 percentage and gestational diabetes.In conclusion, using a multi-omics approach, we identified distinct metabolic alterations in women with hypothyroidism in the first half of pregnancy, characterized by elevated levels of sphingosine and BID and a disrupted Th17/Treg balance. These changes may contribute to the pathogenesis of early gestational hypothyroidism, offering new theoretical insights into its underlying mechanisms.

Trihalomethanes (THMs) are suspected neurotoxicants, yet their relationships with depression remain unclear. This study examined the associations between blood THM concentrations and depressive symptoms, assessed by the Patient Health Questionnaire-9 (PHQ-9), in 2,130 postmenopausal U.S. women. Blood concentrations of bromodichloromethane (BDCM), dibromochloromethane (DBCM), and brominated trihalomethanes (Br-THMs) showed positive dose-response associations with depressive symptoms (PHQ-9 >= 5; all P for trend <0.05). Compared with the lowest exposure category, participants in the highest category of BDCM (T3), DBCM (>= 75th percentile), and Br-THMs (Q4) had increased odds ratios (ORs) for depressive symptoms of 1.38 (95% confidence interval: 1.04-1.82), 1.62 (1.25-2.09), and 1.46 (1.02-2.09), respectively. Further mechanistic experiments in a human neuroimmune organ-on-a-chip model (SH-SY5Y cells cocultured with THP-1 cells) showed that environmentally relevant exposure (0.001 mM BDCM and 0.0005 mM DBCM) increased interleukin-1 beta (IL-1 beta) levels and reduced 5-hydroxytryptamine (5-HT) levels. Low-dose BDCM exposure (0.001 mM) also induced neuronal cytoskeletal changes in SH-SY5Y cells, as reflected by changes in mean fluorescence intensity and skeletonized area. Together, our findings suggest that exposure to Br-THMs may be associated with depressive symptoms in postmenopausal women, potentially via IL-1 beta-mediated neuroinflammation and neurotransmitter imbalance.

Phthalates have been linked to higher mortality, but evidence on their relationship with epigenetic aging remains limited, particularly among older adults. We investigated associations between urinary phthalate metabolites and DNA methylation (DNAm)-derived epigenetic age acceleration (EAA) and examined EAA as a potential mediator for the phthalate-mortality association. We analyzed 611 U.S. adults aged ≥ 50 years without baseline cardiovascular diseases (CVD) or cancer diagnosis from the 1999–2002 U.S. National Health and Nutrition Examination Survey (NHANES), followed for mortality through 2019. Baseline urinary concentrations of four phthalate metabolites and EAA derived from four DNAm clocks were analyzed using survey-weighted linear regression, Bayesian Kernel Machine Regression, and quantile-based g-computation for individual and mixture effects. Higher monobenzyl phthalate (MBzP) was associated with accelerated HannumAge (0.60 years per log-unit increase) and was positively associated with all-cause, cancer, and CVD mortality. Mixture analyses suggest MBzP as the primary contributor to accelerated HannumAge, PhenoAge, and GrimAge, despite no significant overall mixture effects. Mediation analyses indicated that EAA partially explained these associations, with the largest proportion mediated for cancer mortality (3.9%-9.2% across clocks). These findings suggest that among older U.S. adults, urinary MBzP was associated with accelerated epigenetic aging, which partially mediated the MBzP-mortality association, highlighting the need to reduce phthalate exposure and supporting DNAm clocks as sensitive biomarkers of environmental toxicity.

Early-life exposure to di(2-ethylhexyl) phthalate (DEHP) has been associated with compromised immune outcomes in childhood, while evidence regarding DEHP substitutes, such as di-isononyl phthalate (DiNP), di-isononyl cyclohexane-1,2-dicarboxylate (DiNCH) and di(2-ethylhexyl) terephthalate (DEHTP), remains limited. This study analyzed urinary concentrations of 18 phthalate metabolites, including legacy phthalates and the newer substitutes, and examined their associations with overall infection risk among 1989 U.S. children representative of the US population stratified into three vulnerable age groups (3-5, 6-11, and 12-19 years). We applied logistic and mixture models to examine the associations. We found a higher infection risk associated with DiNP metabolite concentrations (MONP: mono-oxo-isononyl phthalate and MCOP: mono-carboxy-isooctyl phthalate) in children aged 3-5 years (3rd vs 1st tertile, MONP OR: 1.94, 95% CI: 1.12, 3.34) and adolescents aged 12-19 years (MONP OR: 5.49, 95% CI: 2.30, 13.06; MCOP OR: 4.91, 95% CI: 2.11, 11.40). Adolescent urinary concentrations of other phthalate metabolites were associated with higher infection odds, including mono-benzyl phthalate (3rd vs 1st tertile OR: 3.39, 95% CI: 1.56, 7.37), mono-(3-carboxypropyl) phthalate (OR: 2.97, 95% CI: 1.47, 5.99), mono-isobutyl phthalate (OR: 1.71, 95% CI: 1.01, 2.87), mono-hydroxy-isobutyl phthalate (OR: 1.95, 95% CI: 1.09, 3.48), and mono-2-ethyl-5-carboxypentyl phthalate (OR: 2.24, 95% CI: 0.97, 5.16). Among adolescents, each tertile increase in mixture concentration was associated with a higher infection risk (OR: 2.45, 95% CI: 1.26, 4.77). Regarding non-phthalate alternatives, only an isolated deleterious association was found for DiNCH in boys but not girls aged 6-11 years. Although these associations should be validated in longitudinal cohorts, our results suggest that children's exposure to specific phthalates and phthalate mixtures may increase susceptibility to infections, and that DiNP does not appear to be a safe substitute for DEHP regarding immune-related outcomes. More observational and toxicological studies are needed, particularly for newer non-phthalate substitutes such as DiNCH and DEHTP.

Trihalomethanes (THMs) are suspected neurotoxicants, yet their relationships with depression remain unclear. This study examined the associations between blood THM concentrations and depressive symptoms, assessed by the Patient Health Questionnaire-9 (PHQ-9), in 2,130 postmenopausal U.S. women. Blood concentrations of bromodichloromethane (BDCM), dibromochloromethane (DBCM), and brominated trihalomethanes (Br-THMs) showed positive dose-response associations with depressive symptoms (PHQ-9 ≥ 5; all P for trend <0.05). Compared with the lowest exposure category, participants in the highest category of BDCM (T3), DBCM (≥75th percentile), and Br-THMs (Q4) had increased odds ratios (ORs) for depressive symptoms of 1.38 (95% confidence interval: 1.04-1.82), 1.62 (1.25-2.09), and 1.46 (1.02-2.09), respectively. Further mechanistic experiments in a human neuroimmune organ-on-a-chip model (SH-SY5Y cells cocultured with THP-1 cells) showed that environmentally relevant exposure (0.001 mM BDCM and 0.0005 mM DBCM) increased interleukin-1 beta (IL-1β) levels and reduced 5-hydroxytryptamine (5-HT) levels. Low-dose BDCM exposure (0.001 mM) also induced neuronal cytoskeletal changes in SH-SY5Y cells, as reflected by changes in mean fluorescence intensity and skeletonized area. Together, our findings suggest that exposure to Br-THMs may be associated with depressive symptoms in postmenopausal women, potentially via IL-1β-mediated neuroinflammation and neurotransmitter imbalance.

The decline in sperm quality has emerged as a major public health concern with significant implications for male fertility and population sustainability. However, high-accuracy biomarkers for sperm quality are lacking, and the environmental drivers remain obscure. Trihalomethanes (THMs), ubiquitous disinfection by-products in drinking water, have been linked to declining semen quality worldwide, yet the molecular mechanisms underlying THM-induced reproductive toxicity remain underexplored. In this propensity score-matched case-control study designed to maximize internal validity, we identified SP biomarkers of oligospermia and teratospermia among Chinese sperm donors and investigated their associations with THM exposure. Using deep data-independent acquisition (DIA) proteomics, we quantified 1666 SP proteins, including 73 proteins enriched in male reproductive tissues. A robust XGBoost machine learning algorithm, validated to mitigate overfitting, determined the optimal biomarker combination, achieving an AUC of 0.95. Ten oligospermia biomarkers—including five testis- or epididymis-specific proteins—were inversely associated with blood THM concentrations. These proteins regulate interconnected pathways related to oxidative stress and energy metabolism. We propose that THM—induced disruption of these fundamental metabolic machineries not only impairs sperm motility but also arrests spermatogenesis, leading to reduced sperm count. This study provides the first evidence linking SP proteomic signatures to THM exposure, offering novel insights into the mechanistic pathways of environmental reproductive toxicity.

Immune modulation is crucial for male reproduction and fertility. Metals and metalloids (metals) have been extensively studied for their immunomodulatory effects. Whether metal exposure affects semen quality through immune modulation is unclear. In the present study, we explored the associations between exogenous metals within immune cells, immune cell proportions, and semen quality among 84 healthy men who repeatedly provided 266 semen samples over 90 days. We employed mass cytometry (CyTOF) technology to identify immune cells in semen and measured exogenous metals in these cells at the single-cell resolution. After adjusting for potential confounders, most detected metals in immune cells were inversely associated with the proportion of immune cells in semen samples (all p < 0.05), indicating the adverse effects of exogenous metals on immune cells. The proportion of immune cells showed N-shaped, nonlinear associations with sperm concentration, total count, progressive motility, and total motility. Mediation analyses showed that the percentage of indirect effects of exogenous metals on sperm quality parameters via immune cells ranged from 15.11% to 54.29%. Overall, our findings unravel the indirect effects of exogenous metal exposure on male reproductive health via immune cells, contributing valuable insights into the complex interplay between environmental factors, immune cells, and human semen quality.

Toxicological studies revealed that exposure to organophosphate esters (OPEs) affects semen quality, but human evidence is controversial. Over a 3-month follow-up, 1,385 healthy young men provided 3,550 urine samples and 6,466 semen samples, which were determined for urinary OPE metabolite concentrations, sperm quality parameters, and sperm mitochondrial DNA copy number (mtDNAcn). Linear mixed models revealed inverse associations between diphenyl phosphate (DPHP) concentrations and sperm concentration [-3.81% (95% CI: -6.31, -1.24) per each 2-fold increment in exposure], total count [-4.07% (95% CI: -7.21, -0.76)], progressive motility [-0.55 (95% CI: -0.93, -0.17)], and total motility [-0.54 (95% CI: -0.91, -0.17)]; and between bis(2-butoxyethyl) phosphate (BBOEP) and diocresyl phosphate and di-p-cresyl phosphate (DoCP and DpCP) concentrations and sperm concentration [-3.61% (95% CI: -5.53, -1.58) and -3.27% (95% CI: -5.92, -0.48), respectively] and total count [-5.13% (95% CI: -7.53, -2.67) and -3.87% (95% CI: -7.21, -0.35), respectively]. These inverse associations persisted only for DPHP, DoCP and DpCP, and BBOEP measured during the epididymal storage period. Sperm mtDNAcn mediated 67.7% and 52.5%, respectively, of the associations between BBOEP and sperm concentration and total count [beta coefficient of average causal mediation effects = -0.15 (95% CI: -0.25, -0.07) and -0.18 (95% CI: -0.29, -0.08), respectively].

Toxicological studies show that disinfection byproducts (DBPs) adversely affect neurological and psychiatric symptoms, which have been linked to poor sleep quality. This cohort study explored the associations between DBP exposure, oxidative stress, and sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI) questionnaire among young healthy Chinese men who provided 710 blood and 2647 repeated urinary samples over 3 months. We measured trihalomethanes in blood and haloacetic acids and oxidative stress markers in urine samples. In adjusted models, each 2.7-fold increase in urinary trichloroacetic acid (TCAA) concentrations was associated with a greater PSQI score of 0.29 (95% confidence interval: 0.07, 0.50). A clear dose-response relationship was observed when TCAA concentrations were included as quartile variables (P for trend = 0.01). In the analyses of individual PSQI components, TCAA was associated with a greater risk of difficulty in falling asleep, short sleep duration, and daytime dysfunction (odds ratios = 1.33 (1.04, 1.70), 1.35 (1.03, 1.78), and 1.39 (1.08, 1.78), respectively, per 2.7-fold increase in TCAA concentrations). Mediation analyses showed that 4-hydroxy-2-nonenal-mercapturic acid mediated 22.24% (4.44%, 80.00%) of the association between TCAA concentrations and PSQI scores. In summary, TCAA exposure may affect sleep quality, which is partly mediated by oxidative stress.

Agricultural soil has become an important reservoir and transmission source of antibiotic resistance genes(ARGs)because of the extensive application of organic fertilizers such as livestock and poultry manure in organic agriculture production.This greatly increases the risk of foodborne transmission of ARGs in organic agricultural products.However,the extent of ARGs contamination in different types of organic vegetables and its driving factors remain unclear.Therefore,two organic and traditional farming species:green radish(Raphanus sativus L.)and coriander(Coriandrum sativum L.)species were selected as representatives to compare and analyze the abundance of ARGs and mobile gene elements(MGEs)and microbial community structure of the vegetable surface bacteria and endophytic bacteria using real-time PCR and 16S rRNA sequencing technology.Compared to conventional farming practices,organic farming significantly increased the abundance of ARGs among both epiphytic and endophytic bacteria on vegetables.The enrichment levels reached up to 78.9 times and 1.99 times,respectively.Furthermore,compared with that in coriander,green radishes exhibited a higher accumulation of ARGs.Similarly,the relative abundance of MGEs in endophytic bacteria of organically grown vegetables was significantly higher than those of the conventionally grown vegetables.Additionally,the abundance of MGEs positively correlated with the abundance of ARGs(P<0.05),indicating that the organic farming practices increased the abundance of ARGs in the microbiomes of the vegetables by promoting horizontal gene transfer.Furthermore,network analysis showed that the interactions between ARGs and bacteria were more complex under organic farming practices,enriching 30 bacterial genera as potential hosts.Among them,14 bacterial genera(e.g.,Microbacterium,Aeromicrobium,and Glutamicibacter)were significantly associated with high-risk ARGs(aadA,tetM,and floR).These findings demonstrated that organic farming practices can increase the risk of human intake of ARGs by introducing potential ARG host bacteria and enriching MGEs,and root vegetables are more significantly affected by organic farming practices compared to leafy vegetables.This study provides a theoretical basis for assessing the health risks of ARGs contamination in edible vegetables under organic agricultural ecosystems.

Organophosphate flame retardants (OPFRs) can increase fat accumulation and exert neurotoxic effects. In this study, we enrolled 1019 young men who provided 3,550 urine samples over a 3-month follow-up period. We measured nine OPFR metabolite concentrations in urine samples and assessed depressive symptoms using the Beck Depression Inventory questionnaire. In the fully adjusted linear regression models, a 2.7-fold increase in urinary diphenyl phosphate (DPHP) concentrations was associated with a 0.44 unit (95% confidence interval (CI): 0.06, 0.82) higher depressive symptom scores. When men were categorized as having any depressive symptoms (score: > 10 vs ≤ 10), Poisson regression models showed an increased risk of depression across DPHP tertiles (P trend = 0.08). Further, we found stronger associations between urinary OPFR metabolite concentrations and depressive symptom scores among men with a higher waist circumference, waist-hip ratio, or waist-height ratio (P interaction < 0.15). The machine learning algorithm identified three different patterns of obesity, and the strongest association between urinary DPHP concentrations and depressive symptom scores was observed among men with a waist-hip ratio of ≥ 0.89 and a body mass index of <24 kg/m2. In summary, exposure to OPFRs may be associated with depressive symptoms among young men, especially in those with abdominal obesity.

Declining semen quality has become a global concern, with environmental exposures implicated as key contributors. In this prospective cohort study of 649 men in Wuhan, China, we investigated associations between fine particulate matter (PM2.5) components, ambient temperature, and semen quality, and explored underlying mechanisms using untargeted seminal plasma metabolomics. Bayesian Kernel Machine Regression and generalized linear models revealed that higher exposures to nitrate (NO3-), sulfate (SO42-), and temperature were independently associated with reduced sperm concentration. Specifically, a 2.72-fold increase in NO3-, SO42-, and temperature corresponded to decreases of 19.41 × 106/mL, 47.89 × 106/mL, and 36.05 × 106/mL in sperm concentration, respectively. Metabolomic profiling identified distinct metabolic signatures associated with each exposure: SO42- and temperature predominantly disrupted lipid metabolism, while NO3- exposure primarily disrupted nucleotide metabolism. Notably, three metabolites-3-hydroxybutyrylcarnitine, eicosapentaenoic acid, and uridine-were consistently linked to all exposures, indicating shared pathways involving mitochondrial dysfunction, membrane instability, and oxidative stress. These findings provide molecular evidence that co-occurring environmental stressors can impair male reproductive health via convergent metabolic mechanisms, highlighting the importance of addressing both individual and combined exposure risks.

The preservation of groundwater quality is essential for maintaining the integrity of the water ecological cycle. The preservation of groundwater quality is crucial for sustaining the integrity of the water ecological cycle. Nitrate (NO3−) has emerged as a pervasive contaminant in groundwater, attracting significant research attention due to its extensive distribution and the potential environmental consequences it poses. The primary sources of NO3− pollution include soil organic nitrogen, atmospheric nitrogen deposition, domestic sewage, industrial wastewater, landfill leachate, as well as organic and inorganic nitrogen fertilizers and manure. A comprehensive understanding of these sources is imperative for devising effective strategies to mitigate NO3− contamination. Technologies for tracing NO3−-polluted groundwater include hydrochemical analysis, nitrogen and oxygen isotope techniques, microbial tracers, and numerical simulations. Quantitative isotope analysis frequently necessitates the application of mathematical models such as IsoSource, IsoError, IsoConc, MixSIR, SIAR, and MixSIAR to deduce the origins of pollution. This study provides a summary of the application scenarios, as well as the strengths and limitations of these models. In terms of remediation, pump and treat and permeable reactive barrier are predominant technologies currently employed. These approaches are designed to remove or reduce NO3− concentrations in groundwater, thereby restoring its quality. The study offers a systematic examination of NO3− pollution, encompassing its origins, detection methodologies, and remediation approaches, highlighting the role of numerical simulations and integrating multidisciplinary knowledge. Additionally, this review delves into technological advancements and future trends concerning the detection and treatment of NO3− pollution in groundwater. It proposes methods to control the spread of pollution and acts as a guide for identifying and preventing pollution sources.

BACKGROUND:Plastic pollution is a major environmental and health issue. To cover knowledge gaps, this study aimed to examine the association between population exposure to plasticiser mixtures and mortality, estimate the attributable public health burden, and explore potential nutritional mitigation measures. METHODS:This prospective population-based study included non-pregnant US adults aged 20 years or older free from cardiovascular diseases and cancer at baseline from the US National Health and Nutrition Examination Survey 2005-16. The main outcome was mortality status and cause of death, which was confirmed using ICD-9 and ICD-10 codes. Baseline urinary concentrations of eight phthalate metabolites and bisphenol A were selected a priori based on a comprehensive review of the toxicological and epidemiological evidence and modelled as a plasticiser mixture by quantile-based g-computation. Vitamin concentrations were examined as effect modifiers. FINDINGS:8378 adults were included. Over 71 127 person-years of follow-up (average 8·5 years per person), 633 deaths occurred. Each tertile increase in the mixture concentration was positively associated with all-cause mortality (hazard ratio 1·35, 95% CI 1·02-1·78), cancer mortality (1·79, 1·06-3·03), and cardiovascular disease mortality (1·83, 1·04-3·22). An estimated 10·31% (95% CI 0·78-20·38) of total deaths were attributable to a tertile increase in the mixture, equating to 256 471 annual excess deaths in the USA. The mixture association with all-cause, cancer, or cardiovascular disease mortality was observed only in individuals with serum vitamin D or red blood cell folate concentrations in the lowest tertile, but not in the upper tertiles. INTERPRETATION:Exposure to a mixture of common plasticisers was associated with increased all-cause, cancer, and cardiovascular disease mortality risk. Vitamin D and folate appeared to mitigate these associations. The findings underscore the need to reduce plasticiser exposure, optimise vitamin intake, and regulate chemicals by class. FUNDING:Instituto de Salud Carlos III (Spain) and NextGeneration EU.

BACKGROUND AND AIMS:Uric acid (UA) to high-density lipoprotein cholesterol (HDL-C) ratio (UHR) is a new indicator of inflammation and metabolism proposed by recent researches. Previous researches have confirmed a positive association between UHR and the risk of cardiovascular death. However, it is undetermined that the association between UHR and peripheral arterial disease (PAD). METHODS AND RESULTS:The research is a prospective cohort study that included a total of 6,867 participants from the Chinese Hypertension Registry Study. 328 participants were identified with PAD during a median follow-up period of 48 months. Multiple logistic regression analysis and smooth curve fitting were applied to explore the association between UHR and PAD among men and women. After adjusting for potential confounders, UHR was positively associated with PAD both in men (HR: 1.27, 95 % CI: 1.07-1.51) and women (HR: 1.45, 95 % CI: 1.19-1.77). Subgroup analyses showed that the association between UHR and PAD remained stable across subgroups of men and women (all P for interaction >0.05). CONCLUSIONS:There is a significant positive association between UHR and new-onset PAD in the Chinese hypertensive population both in men and women. An elevated UHR predicted increased risk of PAD.

Polycyclic aromatic hydrocarbons (PAHs) are persistent organic pollutants that present potential health threats to children. Hydroxy-PAHs (OH-PAHs), as the metabolites of PAHs, are widely used in biological monitoring due to less physiological burden than blood or tissue sampling. However, the association between PAHs exposure through inhalation and the urinary OH-PAHs concentration is not clear and whether OH-PAHs can reflect the short-term exposure levels of respiratory PAHs remains controversial. In this study, child participants from an indoor coal combustion environment were selected, and a panel study was conducted after dietary control. A total of 10 OH-PAHs in morning urine were measured by a LC-MS/MS method. PAHs and Nitro-PAHs (NPAHs) associated with PM2.5 were collected by a personal sampler and measured by the GC-MS method. The response significance of urinary OH-PAHs to inhalation PAHs exposure was tested by Spearman analysis. The theoretical urinary OH-PAH values were estimated based on inhalation exposure and compared with the method limits of detection (LOD). Finally, the negative health influence of PAHs inhalation on children was quantitatively estimated. The results showed that no significant correlation was observed between urinary OH-PAHs and the inhalation exposure dose. Furthermore, the theoretical urinary OH-PAHs concentration estimated was much less than the current method LOD. The carcinogenic risk based on urine OH-PAHs (average risk: 1.79 × 10-5) was approximately two orders of magnitude higher than the risk derived from inhalation (average risk: 3.26 × 10-8). The study showed that urinary OH-PAHs were not suitable as indicators for short-term inhalation exposure in routine studies. The accurate assessment of inhaled PAH related health risks of children requires a comprehensive analysis combining environmental monitoring, biological monitoring, dietary exposure assessment, and behavioral data of the target population.

Although epidemiological studies have explored the association between poly- and perfluoroalkyl substances (PFAS) concentrations and semen quality, existing findings are often inconsistent. Our work aimed to explore the association of PFAS in plasma and semen with repeated measures of semen quality parameters in healthy adults. Plasma was collected at the initial recruitment and semen was collected at least once within five predetermined intervals during an approximately 3-month period. Semen volume, concentration, motility, and total sperm count were measured in each semen specimen. PFAS was measured in individual plasma samples (n = 1252) and pooled semen samples (n = 1019) from multiple collections (or in a single semen sample if no multiple collection was available). The results reveal seminal perfluorooctanoic acid, perfluorooctanesulfonic acid, perfluorohexanesulfonic acid, and 6:2 chlorinated polyfluoroalkyl ether sulfonate were significantly associated with decreased sperm progressive motility and total motility, while multiple seminal PFAS were positively associated with sperm concentration and total sperm count. By contrast, null associations were observed between plasma PFAS and semen quality. Our study provides epidemiological evidence that PFAS exposure may affect male fertility and seminal PFAS should be measured for precise assessment of the impact of PFAS on male reproductive performances.

Evidence from both epidemiology and toxicology suggests that exposure to individual air pollutant during pregnancy can impair intrauterine skeletal development, but the joint effects of pollutant mixtures and the mediating biological pathways are poorly understood. Within a Chinese birth cohort comprising 470 mother-infant pairs, we investigated the associations between joint exposure to six common air pollutants (fine particulate matter and inhalable particulate matter, nitrogen dioxide, sulfur dioxide, carbon monoxide, and ozone) and markers of intrauterine skeletal development (intrauterine femur length and birth length). We further explored the potential mediating role of placental metabolites in these observed associations. Our results show that joint exposure to air pollutants during the third trimester was inversely associated with femur length in utero and birth length, in which PM2.5 was the primary contributor. Specifically, each quintile increase in the mixture was linked to decreases in femur length (β = -0.08 SD; 95 % CI: -0.16, -0.01) and birth length (β = -0.11 SD; 95 % CI: -0.19, -0.03). Placental metabolomic analysis identified that arachidonic acid metabolism was significantly linked to both air pollutants and intrauterine skeletal development. Specifically, arachidonic acid-metabolomic score was positively associated with joint exposure to air pollutants but negatively associated with birth length. Prostaglandins, including prostaglandin E2 and prostaglandin F2α mediated 4.16-7.24 % of the observed inverse associations. Our findings suggest that maternal third trimester joint exposure to air pollutants may adversely affect intrauterine skeletal growth, potentially through disrupting placental arachidonic acid metabolism.

BACKGROUND:Exposure to certain chemicals in disinfectants has been associated with vascular dysfunction in toxicological studies, but the association between disinfectant exposure and clinical cardiovascular disease (CVD) remains unclear. OBJECTIVE:The aim of this study was to evaluate the association between occupational exposure to disinfectants and subsequent risk of CVD among US nurses. METHODS:We included 75,675 participants from The Nurses' Health Study II who maintained a nursing job and reported data on occupational disinfectant exposure. We estimated hazard ratios (HR) and 95% confidence intervals (CIs) of incident CVD, including coronary heart disease (CHD) and stroke, using Cox proportional hazard models comparing job types and general disinfection tasks between participants. We also used a job-task-exposure matrix to evaluate the risk of CVD by frequency of cleaning/disinfection tasks and exposure levels of seven specific disinfectants (formaldehyde, glutaraldehyde, hypochlorite bleach, hydrogen peroxide, alcohol, quaternary ammonium compounds, and enzymatic cleaners). RESULTS:During 10 y of follow-up (2009-2019), we documented 726 incident cases of CVD. In fully adjusted models, the hazard ratio of CVD among nurses who worked in operating rooms was 1.72 [95% confidence interval (CI): 1.25, 2.36], in comparison with those working as educators or administrators. A similar pattern of associations was found when we separately assessed the risk for CHD and stroke [HR=1.69 (95% CI: 1.11, 2.58) and HR=1.69 (95% CI: 1.05, 2.74), respectively] among operating room nurses, in comparison with those working as educators or administrators. Those who used disinfectants weekly had modest elevations in CVD risk (HR=1.21; 95% CI: 1.04, 1.40), in comparison with women who never used disinfectants. The highest CVD risk was observed among nurses using disinfectants or spray or aerosol products 4-7 d/wk and those exposed to the highest levels of the seven specific disinfectants listed above. CONCLUSION:Exposure to disinfectants in real-world health care settings was associated with a higher risk of CVD, including CHD and stroke, among US nurses. https://doi.org/10.1289/EHP14945.