Environment International

Total serum perfluorooctane sulfonate (PFOS) concentration and its isomer composition describe different aspects of internal exposure, but their respective associations with depressive symptoms remain uncertain. We examined adults aged 18-25 years in NHANES August 2021-August 2023 using survey-weighted models of the Patient Health Questionnaire-9 (PHQ-9). Total measured PFOS was the sum of linear PFOS and pooled monomethyl-branched PFOS; composition was their log-ratio. The analytic cohort included 169 participants, with 147 complete cases for core adjustment. Median total PFOS was 1.70 ng/mL, the median linear fraction was 72.2%, and the weighted prevalence of PHQ-9 [≥]10 was 22.6%. In the joint adjusted model, a doubling of total PFOS at fixed composition corresponded to -0.49 PHQ-9 points (95% CI, -1.65 to 0.68); a doubling of the linear-to-branched ratio at fixed total corresponded to 0.21 points (-1.94 to 2.36). Algebraic rescaling across the reported interquartile ranges yielded differences of -0.58 points (-1.95 to 0.81) for total PFOS and 0.13 points (-1.16 to 1.41) for composition. The inverse continuous-score association weakened with adjustment, whereas the screening odds ratio primarily lost precision. Excluding three observations with an isomer below detection shifted both joint coefficients. The data therefore do not establish an independent composition association or equivalent isomer effects. Experimental evidence supports candidate oxidative, inflammatory, and synaptic pathways, but differential protein binding and elimination prevent a serum composition ratio from being interpreted directly as brain dose or toxicity. Larger longitudinal analyses with isomer-resolved exposure and toxicokinetic measurements are needed to test these pathways.

Environmental exposure involves pollutant mixtures. Building on evidence that individual bisphenols alter zebrafish larval physiology and transcriptomic profiles at ng/L concentrations, we assessed the effects of specific mixtures of BPS, BPF, and BPAF without (M1) or with (M2) BPA. Experimentally, M1 and M2 induced 4.16% and 6.54% mortality in zebrafish larvae, despite the concentration addition model predicting no toxicity. Both mixtures reduced swimming-locomotor activities. These behaviors were accompanied by organ-level functional defects, as in vivo optical mapping revealed bradycardia and increased high-frequency (30-80 Hz) brain oscillations for both mixtures, while M2 additionally altered low-frequency (0.2-4 Hz) brain activity. The neurophysiological changes were accompanied by neurovascular remodeling, with in vivo two-photon microscopy revealing decreased vascular length and branching. Finally, transcriptomic analysis revealed common M1- and M2-induced alterations linked to pathways of vascular function, neuronal communication, and metabolism. M2 altered additional pathways of cardiac and neuronal signaling, consistent with the reported organ-physiology effects. We discuss the environmental relevance of mixture exposures and assess whether BPA intensifies mixture-induced responses.

Introduction: Pesticide exposure has been associated with poorer mental health, yet little is known about whether seasonal fluctuations in agricultural pesticide use are associated with cyclical changes in mood among people living in agricultural communities. We evaluated associations between 10 peak and off-peak pesticide spray seasons and ecological momentary assessment (EMA)-derived mood in a floricultural region in Ecuador. Methods: 496 participants completed repeated EMA surveys across 10 assessment administrations over 2.5 years (2022-2024), including one single-assessment administration and nine 10-day bursts (Nobservations=14,332). Mood outcomes included negative affect (sadness, anxiety, stress, anger, tiredness, difficulty concentrating; overall mean=2.79, Standard Deviation [SD]=1.32), positive affect (happiness, motivation; overall mean=4.21, SD=1.60), and behavioral dysregulation (aggression and impulsivity, overall mean=1.86, SD=1.29). Generalized linear mixed models estimated pooled, between-person and within-person associations between peak pesticide spray seasons and mood, adjusting for demographic and longitudinal factors Effect modification by sex, floricultural occupation, and cohabitation with a floricultural worker was assessed. Results: Peak spray seasons were associated with higher negative affect ({beta}=0.11 [0.06, 0.16]) and behavioral dysregulation ({beta}=0.10 [0.05, 0.15]) but not positive affect ({beta}=0.01 [-0.05, 0.07]). Associations were driven by within-person changes. Sex modified associations with negative affect, which were stronger in males than females. Floricultural occupation modified associations, with poorer mood, greater behavioral dysregulation and lower positive affect among floricultural workers than non-workers. Discussion: Peak pesticide spray seasons were associated with worsening of negative affect and behavioral dysregulation. EMA may provide a sensitive approach for detecting short-term neurobehavioral changes associated with seasonal pesticide exposure.

Abstract: Background: Children born very preterm (VPT) are at elevated risk for adverse neurobehavioral outcomes and are vulnerable to environmental exposures. We used untargeted metabolomics analysis to identify environmentally relevant metabolites associated with childhood behavioral problems and to characterize related endogenous metabolic pathways. Methods: We studied 226 children born <30 weeks gestation in a multi-site cohort study. Urine collected at age 4 was profiled using untargeted ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLC-HRMS). Associations between 30 exogenous environmental metabolites and behavioral problems score at age 4 were evaluated cross-sectionally using multivariable linear regression, followed by metabolome-wide association and pathway enrichment analyses. Results: Three exogenous metabolites were nominally associated with child behavior problems. Specifically, 2-(Acetylamino)-3-( henylthiol)propanoic acid was positively associated with overall ({beta}=1.42, p=0.006), externalizing ({beta}=1.50, p=0.006), and internalizing ({beta}=1.34, p=0.021) behavior problems. Diethofencarb was positively associated with overall ({beta}=0.34, p=0.018) and externalizing ({beta}=0.39, p=0.010) behavior problems, while protocatechuic acid was inversely associated with internalizing problems ({beta}=-0.68, p=0.027). No associations remained significant after false discovery rate (FDR) correction. Nevertheless, these metabolites were associated with 151, 131, and 530 endogenous metabolic features, respectively, at FDR<0.05, highlighting perturbations in lipid metabolism, mitochondrial energetics, inflammatory signaling, amino acid metabolism, and neuroactive pathways. Conclusions: Environmental metabolites associated with behavior problems were linked to broad endogenous metabolic differences relevant to neurodevelopment. These findings highlight potentially modifiable environmental influences, including exposures related to combustion-derived pollutants, pesticides, and dietary sources, that may contribute to behavioral vulnerability among children born very preterm

Long-term PM2.5 exposure is associated with increased mortality and is usually represented by annual mean concentration, which does not capture how concentrations are distributed across days. We tested whether the prespecified PM2.5 magnitude-rank index (PMRI), a summary of within-year daily concentration structure, improves mortality prediction beyond the annual mean. Daily modeled PM2.5 estimates were linked to age-adjusted mortality rates for 27,289 county-years from 3,064 U.S. counties during 2003-2011. PMRI is the largest k for which at least k days reached k micrograms per cubic meter. County-grouped 10-fold cross-validation compared models with annual mean alone versus annual mean plus PMRI, with additional geographic, temporal, cause-specific, and specification analyses. Annual mean PM2.5 had the highest standalone predictive performance. Adding PMRI increased county-held-out R-squared from 0.0802 to 0.1391 (increase in R-squared = 0.0589; 95% CI, 0.0499-0.0677) and reduced RMSE and MAE. Improvement persisted across geographic and temporal validations and all six cause-specific mortality outcomes. Within-year PM2.5 exposure structure therefore contains reproducible mortality-predictive information not captured by annual mean concentration.

Background: The incidence of early-onset colorectal cancer (EOCRC), defined as CRC diagnosed age <50, is rising in the United States and is the leading cause of cancer death in among those with early-onset cancer. Epigenetic exposure signatures based on methylation risk scores (MRS) offer a novel approach to identify long-term exposures that may contribute to EOCRC risk. We sought to replicate findings from a recent study in a racially and geographically diverse CRC cohort. Methods: We computed weighted MRS across lifestyle, air pollution, and pesticide exposome traits in 146 participants from the Disparities and Cancer Epidemiology (DANCE) cohort, a diverse population-based CRC study, applying the Maas et al. (2026) framework to tumor tissue. Associations between MRS and age at CRC onset (EOCRC, n=29; intermediate-onset (IOCRC) 50-64 years, n=69; late-onset, [&ge;]65 years, n=48) were evaluated using linear and polytomous regression, with adjustment and stratification for race, geography, Area Deprivation Index (ADI), and Multi-Environmental Exposure Index (MEEI). Spearman correlations were calculated between MRSes and observed exposures. Results: EOCRC cases were predominately Black (65.5% vs. 31.3% among LOCRC) and resided in higher-deprivation neighborhoods. We found higher odds of EOCRC associated with epigenetic exposure signatures for 2,4-D herbicide, heptachlor, coarse particulate matter (PM), Mediterranean Diet Score, and smoking, and borderline associations for fine PM and nitrogen dioxide. IOCRC was associated with signatures for 2,4-D, lindane, and obesity. Heterogeneity was observed by race and area-level factors, though associations were largely consistent across strata. ADI and MEEI were correlated with multiple pesticide and pollutant epigenetic signatures. Conclusions: In a diverse US cohort, epigenetic exposure signatures distinguish CRC cohorts, particularly EOCRC from later-onset disease, with associations consistent with but not identical to previous research. EOCRC in DANCE was characterized by higher epigenetic exposure signatures for air pollution, smoking, and distinct pesticide exposure profiles. IOCRC had overlapping characteristics with early- and late-onset and were the only group with a significant obesity signature. These findings support the hypothesis that exposome-driven epigenetic changes contribute to EOCRC risk and highlight the importance of studying diverse populations to characterize the full spectrum of environmental risk factors.

Objective: Environmental pollutants are increasingly recognized as potential risk factors for metabolic dysfunction-associated steatotic liver disease (MASLD), yet the effects of mixed exposures and underlying mechanisms remain unclear. We evaluated associations between environmental chemical mixtures and MASLD and the mediating role of inflammation-related biomarkers. Methods: We analyzed 60 environmental chemicals across six categories among 39,061 U.S. adults from the National Health and Nutrition Examination Survey (NHANES) 1999-2020. Principal Component Pursuit with Principal Component Analysis (PCP-PCA) identified latent exposure patterns. MASLD was identified using multisociety Delphi consensus criteria and the Hepatic Steatosis Index (HSI [&ge;] 36). Logistic regression, restricted cubic spline models, and mediation analysis were applied. Results: PCP-PCA generated 5-17 dimensions per chemical category, with first-dimension variance contributions ranging from 30.70% to 98.88%. Six dimensions from four categories were retained, with phthalate esters (PAEs) and organophosphate flame retardants (OPFRs) showing the most consistent associations with MASLD. PAEs Dim.1, explaining 90.71% of variance, showed a significant non-linear dose-response association (P-nonlinear = 0.0001). Significant associations were identified for mono-isobutyl phthalate (MiBP; OR 1.12, 95% CI 1.07-1.19), mono(carboxyoctyl) phthalate (MCOP; OR 1.08, 95% CI 1.02-1.14), mono(carboxynonyl) phthalate (MCNP; OR 1.12, 95% CI 1.03-1.21), and bis(1,3-dichloro-2-propyl) phosphate (BDCP; OR 1.15, 95% CI 1.08-1.23). C-reactive protein (CRP) and red cell distribution width (RDW) were the primary mediators, accounting for 32.42% and 19.62% of the MiBP-MASLD association, respectively (both p < 0.0001). Conclusion: Environmental co-exposure, particularly to PAEs and OPFRs, was associated with higher MASLD risk, with systemic inflammation potentially contributing to these associations.

The contribution of environmental reservoirs to antimicrobial resistance (AMR) acquisition in humans remains poorly quantified, despite extensive evidence that resistant bacteria and resistance genes circulate through wastewater, surface waters, food and other environmental matrices. The central difficulty is no longer to demonstrate that these reservoirs are connected, but to quantify the direction and relative contribution of the pathways linking environmental AMR to human acquisition. Here, we synthesize the main processes that need to be represented at the interface between the environment and humans and propose a mechanistic framework for Escherichia coli producing extended spectrum beta lactamases (ESBL Ec), linking human, water and food compartments. The framework explicitly represents contamination of the environment by humans and multiple routes of human exposure to environmental reservoirs, including drinking water, recreational water exposure and food contamination mediated by irrigation. We apply the model to two contrasting illustrative settings, France and Madagascar, and use scenarios involving antibiotic use, environmental contamination and climate to explore how changes in specific drivers propagate across compartments. The simulations show responses that depend strongly on the compartment, while sensitivity analyses identify wastewater treatment efficiency and parameters describing transmission, exposure and environmental selection at specific interfaces as influential components of the system. The framework is used to explore how different transmission pathways and environmental drivers can shape AMR dynamics across interconnected human and environmental compartments. By comparing contrasting scenarios and identifying the parameters that most strongly influence model behaviour, we highlight both potential leverage points and critical gaps in current empirical knowledge. More broadly, this work illustrates how decomposing One Health AMR into tractable reservoir interfaces can help structure future data collection and progressively improve our ability to quantify transmission between reservoirs.

Background: Non-optimal air temperature increases the risk of preterm birth, but how temperature-related risks may translate into future population burden remains uncertain. We aimed to estimate the association between temperature and preterm birth in Sweden and assess how preterm birth burden may change under plausible future temperature conditions. Methods: We conducted a nationwide population-based cohort study of singleton births in Sweden from 1973 to 2018. Weekly mean temperature was assigned at the parish level according to maternal residence. Cox proportional hazards models with a distributed lag nonlinear model were used to estimate nonlinear and delayed associations between temperature and preterm birth. The estimated exposure response relationship and baseline hazards were then incorporated into an individual-based microsimulation of gestational progression under projected temperatures for 2025 to 2055. Future projections were examined across multiple climate models under SSP1-2.6 and SSP3-7.0 scenarios. Outcomes included the annual number and cumulative incidence of preterm births and the temperature-attributable fraction. Results: Among 4,338,825 singleton births, 211,397 (4.9%) were preterm. Temperature preterm birth associations were modest overall. The clearest increase in hazard was observed following exposure to very low temperatures, particularly -10C at short lags. Higher temperatures showed no clear increase in risk. From 2025 to 2055, the annual cumulative incidence of preterm birth and the temperature-attributable fraction was expected to remain broadly stable, with limited differences between emissions scenarios. In contrast, the absolute number of preterm births was expected to over the projection period, primarily reflecting increases in the projected number of pregnancies rather than substantial changes in temperature-associated risk. Conclusions: Very low temperatures were associated with a modest short-term increase in preterm birth risk in Sweden, hot temperatures showed little evidence of increased risk. Applying these associations to future climate conditions suggested limited changes in preterm birth incidence or the proportion attributable to temperature through 2055. However, the absolute burden of preterm birth may increase as the population at risk grows. This highlights the importance of considering demographic change alongside climate projections when assessing future maternal and neonatal health burden.

Background: Lead is a cumulative environmental toxicant for which no safe level of exposure has been identified, and pregnant women and their fetuses are particularly vulnerable because lead readily crosses the placenta and can be mobilised from maternal bone stores. Bangladesh conducted its first nationally representative blood lead testing among pregnant women through the 2025 Multiple Indicator Cluster Survey (MICS), but a detailed, multi-domain analysis of the determinants of elevated blood lead level (BLL) among this population has not yet been reported. Methods: We conducted a secondary cross-sectional analysis of 1,928 pregnant women aged 15-49 years with complete data from the women's dataset of Bangladesh MICS 2025. Elevated BLL was defined as [&ge;]5 g/dL. Survey-weighted logistic regression was used to estimate unadjusted and adjusted odds ratios (aOR) for co-exposure to arsenic, cadmium and mercury and sociodemographic and socioeconomic covariates. Slope Index of Inequality (SII) as well as Relative Index of Inequality (RII) were used to quantify wealth-related inequality. Population attributable fractions (PAF) were estimated for three counterfactual scenarios, and adaptive least absolute shrinkage and selection operator (LASSO) regression was used as a sensitivity analysis. Results: Elevated BLL was present among 6.2% of participants. In the adjusted model, a 2-fold rise in blood cadmium was associated with higher odds of elevated BLL (aOR: 1.54; 95% CI: 1.21-1.96), whereas a 2-fold rise in blood mercury (aOR: 0.63; 95% CI: 0.48-0.83), rural residence (aOR: 0.55; 95% CI: 0.32-0.94), secondary education (aOR: 0.49; 95% CI: 0.28-0.85) and post-secondary education (aOR: 0.22; 95% CI: 0.11-0.46) were associated with lower odds. Belonging to progressively wealthier quintiles was associated with markedly higher odds, BLL rising to an aOR of 10.32 (95% CI: 4.41-24.15) for the richest versus poorest quintile. The RII was 8.59 (95% CI: 4.24-17.40) and the SII was 0.159 (95% CI: 0.101-0.218), indicating a substantial pro-rich gradient in elevated BLL. Counterfactual scenarios suggested that shifting the population to secondary-level education could reduce the prevalence of elevated BLL by 52.9% (95% CI: 20.6-72.0) and shifting to rural residence by 24.3% (95% CI: 1.4-41.9). Adaptive LASSO variable selection produced estimates consistent in direction and magnitude with the fully adjusted model. Conclusion: In this national sample, approximately one out of every 16 pregnant women had blood lead levels that met or exceeded the action threshold set by the World Health Organization, with this issue being particularly prevalent among wealthier, urban, and less-educated women, and was compounded by co-exposure to cadmium. In Bangladesh, the typical pattern observed for maternal and child health indicators does not align with the inverse relationship found between household wealth and lead exposure. This suggests that the sources of exposure are not merely indicators of material poverty. Antenatal blood lead screening, source investigation, and equity-informed lead-reduction strategies that specifically reach wealthier and urban households are warranted.

Microplastics are pervasive environmental pollutants that pose a growing concern for human health. Oral ingestion is a common route of human microplastic exposure, yet the proteomic response of the gut epithelium to microplastics remains unclear. This study aimed to investigate the cellular effects of pristine and artificially digested microplastic exposure in primary rat duodenal epithelial cells using untargeted proteomics. Cells were exposed to pristine or digested 0.5 um polystyrene microplastics at 10 or 100 ug/mL for 72 hours and were then analyzed by tandem liquid chromatography and mass spectrometry (LC-MS). Proteins that were both significantly different in intensity compared to controls, with a threshold change of 1.3 or greater, were considered to be differentially expressed. This criterion identified 41 differentially expressed proteins after 100 ug/mL pristine MP exposure, with 19 downregulated and 21 upregulated. Following exposure to 100 ug/mL digested MP, only 3 differentially expressed proteins were upregulated and 7 were down regulated, demonstrating the impact of microplastic physicochemistry. FGSEA pathway analysis revealed that 270 Reactome pathways were significantly altered following microplastic exposure in either condition at both concentrations. These pathways contributed to functional domains including protein synthesis, DNA replication, cell cycle control and aerobic respiration. Overall, microplastic exposure was associated with upregulated mitochondrial respiration, and downregulation of nuclear-related processes including DNA synthesis, transcription and cell proliferation. This study provides targets for future investigation (mitochondria and nucleus) and emphasizes the need to consider biological and environmental conditions for in vitro models of microplastic exposure.

BACKGROUND: Pesticides are extensively used in agriculture, raising concerns about their potential impact on human health through dietary and environmental exposure. OBJECTIVES: This study evaluated the in vitro cytotoxicity of ten commonly used pesticides and their mixtures (lambda-cyhalothrin, cypermethrin, deltamethrin, tebuconazole, glyphosate, acetamiprid, cyprodinil, piperonyl butoxide, fluopyram, and imazalil) on human intestinal Caco-2 cells. METHODS: Cytotoxicity was assessed using the MTT assay, as a measure of metabolic activity, and the trypan blue exclusion test, as an indicator of cell membrane integrity. FINDINGS: Results showed that high concentrations (100 mg/L) of all pesticides significantly reduced cell viability and vitality. Notably, glyphosate and tebuconazole exhibited significant toxicity even at lower concentrations, respectively 0.1 mg/L and 10 mg/L. Combination treatments (Top 3 and Top 8 pesticide mixtures) retained the cytotoxic effects observed for individual compounds, showing additive (non-synergistic) effects. CONCLUSIONS: Overall, these findings indicate that certain pesticides-based herbicides can exert cytotoxic effects on intestinal cells even at relatively low concentrations and highlight the importance of using the component-based approach in mixture risk assessment for humans. This study was performed as part of the EU SPRINT (Sustainable Plant Protection Transition: A Global Health Approach) project.

Background Staying physically active is essential for healthy ageing. Exposure to high levels of air pollutants such as particulate matter (PM) is associated with less active, more sedentary lifestyles in older adults. Whether results extend to typical fluctuations in daily PM exposure is unclear. We examined associations of higher-than-usual personal exposure to PM (PM2.5 and PM10) with next-day movement behaviour in older adults, assessed using concurrently worn personal air quality monitors and accelerometers. Methods The present study used 304 days of data from 67 adults aged 50-85 years living in the UK. For five days, participants wore accelerometers 24-hours per day and personal air quality monitors during waking hours. Average daily time spent in movement behaviours (moderate-to-vigorous physical activity [MVPA], light physical activity [LPA], sedentary behaviour [SB]) and step count was extracted from accelerometers, and average daily exposure to PM2.5 from personal air quality monitors. PM10 was examined in secondary exploratory analyses. We used linear mixed models to examine within-person associations of deviation from usual PM exposure with next-day movement outcomes, with estimates presented for 'usual' (individual mean) and 'higher-than-usual' (+1 interquartile range, equivalent to 2.6 g/m3 beyond individual mean PM2.5 exposure and 2.8 g/m3 beyond individual mean PM10 exposure) exposure. Analyses were repeated using area-based PM estimates. Results Compared with usual exposure, higher-than-usual PM2.5 was associated with 8 minutes less LPA (95% CI=-14 to -2) and 483 fewer steps (-855 to -82) on the following day. Exposure to higher than usual PM10 was associated with 8 minutes less LPA (-13 to -3), 8 minutes more SB (0 to 15), and 412 fewer steps (-739 to -85) on the following day. There was no association with MVPA, and no associations when area-level PM estimates were used as opposed to estimates from personal air quality monitors. Conclusions Typical daily variability in PM exposure in a setting with relatively low overall PM levels was associated with modest next-day differences in movement behaviour in older adults. Higher-than-usual PM exposure was associated with less next-day activity and more sedentary time. Personal monitoring may be important for capturing short-term exposure-behaviour associations. Trial registration N/A

Fetal development is highly sensitive to environmental influences, including maternal smoking during pregnancy (MSDP) and air pollution. The placenta may play a central role in mediating these effects through epigenetic mechanisms, including small non-coding RNAs (sncRNAs). While most studies have focused on microRNAs (miRNAs), other sncRNA classes remain poorly characterized. Here, we characterized the placental sncRNA landscape and investigated its associations with prenatal exposure to MSDP and air pollution. The sncRNA expression profile of 390 chorionic villi samples from the Barcelona Life Study Cohort (BiSC) was measured using small RNA sequencing and the seqBuster/seqCluster pipeline. MSDP was assessed via questionnaire, and prenatal exposure to black carbon (BC), particulate matter [&le;]2.5 m (PM2.5), and nitrogen dioxide (NO2) was estimated using hybrid dispersion-land-use regression (LUR) spatiotemporal models. Associations were evaluated using linear regressions adjusted for relevant covariates. We identified 979 placental sncRNA clusters, assigned primarily to miRNAs (33.2%), piRNAs (26.4%), snoRNAs (12.2%), tRFs (7.8%), and others (20.4%). MSDP was associated with the downregulation of miR-421 and the upregulation of multiple snoRNAs from the imprinted DLK1-DIO3 locus (SNORD113-4, SNORD114-2, SNORD114-3, and SNORD114-17), as well as the piR-26394. No sncRNAs remained significantly associated with air pollution after multiple-testing correction, although several miRNAs showed suggestive associations. Overall, this study provides a comprehensive characterization of placental sncRNAs and identifies previously unreported smoking-associated sncRNAs within the imprinted DLK1-DIO3 locus, expanding our understanding of placental epigenetic responses to prenatal environmental exposures.

Background: Observational studies have linked air pollution to otitis media, but confounding and reverse causation preclude causal inference. We used two-sample Mendelian randomization (MR) to assess genetic causal effects of six air pollutants on non-suppurative otitis media, represented by otitis media with effusion (OME). Methods: Exposure GWAS for PM2.5, PM2.5 absorbance, PM2.5-10, PM10, NO2 and NOx were obtained from UK Biobank (MRC-IEU), and the outcome was FinnGen R13 H8_NONSUPPNAS (12,397 cases, 464,237 controls). Inverse-variance weighting was primary, with MR-Egger, weighted median and mode, MR-PRESSO, leave-one-out and Steiger analyses, reverse MR and exploratory multivariable MR (MVMR). Asthma, allergic rhinitis and chronic rhinosinusitis served as positive controls, and three suppurative otitis media phenotypes served as negative controls. Results: After false-discovery-rate correction, none of the six pollutants was significantly associated with OME; the sole nominal signal was PM10 (OR=1.555, 95% CI 0.947-2.553, P=0.081), which reversed with the 88-SNP pooled set (OR=0.64, 0.24-1.69, P=0.365). At 80% power, minimum detectable ORs ranged widely from 1.69 to 32.09; only PM2.5-10 and PM10 had values near 2, so moderate effects (OR 1.2-1.5) cannot be excluded. Confirmatory positive controls using phenotype-specific instruments were strongly positive, whereas negative-control outcomes showed no associations (all FDR>0.85). Every nominal reverse-MR signal had a significant MR-Egger intercept (the PM2.5 absorbance signal also showed significant heterogeneity and MR-PRESSO tests), indicating horizontal pleiotropy rather than reverse causation. MVMR was exploratory only, as conditional F statistics were below 10. Conclusions: We found no evidence for large-effect genetic causal associations between the six air pollutants and OME. These null findings argue against large, lifetime-average causal effects, and the associations reported in observational studies may instead reflect residual confounding, shared comorbidity or differences in exposure windows.

Pesticide use is ubiquitous. While pesticide resistance in target species such as insects is a well-known phenomenon, it is less known how pesticide exposures affect the genetics of non-target species. Here, we demonstrate the research value of integrating existing datasets to study the relationship between chemicals and biodiversity from the genetics perspective by analyzing spatial pesticide concentration data and genetic data from Europe that were not initially generated for toxicological purposes. Specifically, we found associations between environmental pesticide concentrations and genetic variation (i.e., single nucleotide polymorphisms, SNPs) in a non-target species, the wild boar. Gene Ontology (GO) terms and biological signaling pathways related to nervous system function were overrepresented for the impacted genes, especially for insecticides and fungicides. Further, we found that external studies characterizing the molecular mechanisms of these pesticides revealed the same pesticide - GO relationships as those observed in our analysis. Our results show that pesticide-induced genetic changes may not be constrained to target species but may also have an impact on the long-term viability of other wildlife populations. We therefore encourage further research into this area and collaboration across disciplines to develop more comprehensive designated datasets for such analyses. This finding also urges the consideration and inclusion of chemical exposure into conservation protection strategies and greater consideration of genetic impacts from chemicals in environmental risk assessment.

Lead (Pb) exposure is strongly associated with cardiovascular diseases, but the effects of developmental Pb exposure on the electrophysiological properties of human cardiomyocytes have not yet been investigated. Using human induced pluripotent stem cell (iPSC)-derived cardiomyocytes, we investigated the effects of human-relevant Pb exposure during ventricular cardiomyocyte differentiation on action potential properties and calcium dynamics in differentiated myocytes. We exposed 2 iPSC lines, from 1 male and 1 female donor, to Pb (0.5 or 5 micromolar) or control during only the first 8 days of differentiation, prior to functional maturation. Differentiation was carried out using an established protocol involving temporal modulation of Wnt signaling, followed by purification and maturation of contractile myocytes. We measured action potential properties and calcium dynamics using fluorescent dyes and optical mapping. We hypothesized that Pb exposure would adversely affect cardiomyocyte function, with effects persisting after cessation of exposure. In keeping with this hypothesis, we found significant Pb-induced changes in calcium (Ca) transients and action potential dynamics that were concentration and cell line specific and persisted well after exposure had ended. In the female cell line, beat frequency significantly increased with Pb exposure for both action potentials and Ca transients, while in the male cell line, beat frequency significantly decreased with Pb exposure for action potentials and increased for Ca transients. For voltage measurements, we observed significantly increased arrythmias with Pb exposure in both cell lines. Significant changes in repolarization and recovery time (for voltage and Ca, respectively) were present with Pb exposure in both cell lines. Gene expression of Ca transporters/channels and K channels were not affected, suggesting that persistent effects of Pb exposure on cardiomyocyte electrophysiology may occur through post-translational mechanisms. Overall, this study paves the way for future work to examine how exposure to Pb impacts long-term cardiac function through developmental programming.

Human metabolism converts inorganic arsenic to the pentavalent methylated species MMA(V) and DMA(V), the forms most people excrete, and the forms long read as the end of a detoxification pathway. Whether a transporter sets how much of these metabolites reaches the genome has not been tested in a mammalian cell. We expressed human AQP3, AQP7, AQP9 or AQP10 in HEK293T and MRC5-SV40 cells and measured gamma-H2AX by flow cytometry across dose series of As(V), MMA(V) and DMA(V), pairing every aquaporin with a GFP-Tubulin control and an untransfected mock acquired in the same replicate. As(V) was inactive in HEK293T cells and only weakly active in MRC5-SV40 cells to 20 micromolar, and both methylated species damaged DNA only in the millimolar range, DMA(V) being the more potent of the two in both cell lines. Against that weak baseline, AQP9 and AQP10 raised DMA(V)-induced gamma-H2AX in HEK293T cells by roughly 17 percentage points over the matched control, more than doubling the damage the same exposure produced in control cells, whereas AQP3 and AQP7 changed it not at all. AQP9 alone remained active with MMA(V). The ranking held in MRC5-SV40 fibroblasts at one-sixth the size, and within single wells the damage rose with the amount of AQP9 a cell carried while the control was flat. Aquaglyceroporins therefore discriminate among arsenic species, and AQP9 and AQP10 turn a weakly genotoxic metabolite into a substantially more genotoxic one.

The anaerobic biotransformation of lindane ({gamma}-hexachlorocyclohexane), a persistent legacy pesticide and challenging subsurface contaminant was modelled using an integrated Monod biokinetics framework. Calibrated against batch experimental data, this model accounted for the dissolution of solid phase lindane and the thermodynamics of reactions involved. The study focused on a methanogenic, lindane-degrading enrichment culture (GT2) that used ethanol as the electron donor, where ethanol fermentation supplied hydrogen to support reductive dechlorination of lindane. A Dehalobacter strain was identified as the lindane-degrading organism, while a member of bacterial order Geobacterales carried out ethanol fermentation. First-order decay constants for lindane-degrading Dehalobacter were estimated from experimental data and showed variation across different growth conditions. The biokinetics model captured interactions among key microbial processes, namely lindane dechlorination, ethanol fermentation, hydrogenotrophic methanogenesis, and acetoclastic methanogenesis. Thirteen biokinetics parameters including maximum substrate utilization rates (k), half-velocity constants (Ks), and decay constants for these microbial processes were estimated through a Bayesian optimization approach. Global sensitivity analysis showed that eight parameters, primarily k and Ks, had significant linear impact on the model output, whereas responses to decay constants were more variable and potentially non-linear. This study proposed an effective modelling approach for characterizing syntrophic microbial growth within enrichment cultures and provides valuable biokinetics parameters estimates for real-world applications of anaerobic lindane bioremediation.

Background: Chronic arsenic exposure in drinking water causes skin lesions and cancers and raises infant, cardiovascular and all-cause mortality in Bangladesh. National surveys tested source water in 2012-13, 2019 and 2025 with different kits, so the trend is uncertain. Objectives: We estimated how arsenic in source water changed after laboratory adjustment of 2012-13 readings, and how many people remained exposed. We also assessed whether districts high in earlier surveys held most people exposed in 2025. Methods: We analysed 11,624 households in three Multiple Indicator Cluster Surveys. We counted arsenic strictly above 10 and 50 parts per billion (ppb). Results: Estimates reproduced published 2019 and 2025 tables. After laboratory adjustment of 2012-13, the share above 10 ppb fell from 24.0% to 14.4% (adjusted ratio 0.61, sampling 95% CI 0.55 to 0.67; 0.69 with interview month). Above 50 ppb it fell from 10.9% to 8.6% (0.80, 0.69 to 0.93; 0.93 with month). Most of the fall at 10 ppb occurred within source types. Without false positives, it would vanish only if later kits detected 61% of sources above 10 ppb. About 26 million people used such water in 2025 (kit scenarios 23 to 32 million). The 25 districts high in 2012-13 and 2019 held 39% of the population but 72% of those exposed (bootstrap 95% interval 60 to 76). Clustering was evident, but no district was a significant hotspot. Conclusions: Arsenic above 10 ppb was lower in 2025 than in 2012-13, but the size of the fall depends on unverified later kits. Change at 50 ppb and since 2019 was unclear after month adjustment. One household in seven exceeded the WHO guideline in 2025. Districts found high earlier held most exposed people, supporting prioritised well testing there alongside broader surveillance. Future surveys need one kit with a laboratory cross-check.