Environmental Health Perspectives

Wildfire smoke poses a growing health risk worldwide, yet the magnitude and temporal evolution of mortality after episodic exposure remain poorly resolved, limiting burden assessment. Using monthly county-level wildfire PM2.5 and mortality data from the United State, we exploit episodic exposure contrasts to deconvolve overlapping mortality responses and recover the impulse-response function. The excess mortality response peaks approximately three years after an exposure pulse and subsides by five years. We estimate 1.7 (95% uncertainty interval: 1.1-2.3) million smoke-associated deaths during 2011-2023, approximately ten times estimates using long-term ambient PM2.5 mortality relative risks. Circulatory and respiratory diseases contribute comparably and dominate this burden. Responses are markedly greater among adults [≥]65 years; during the COVID-19 pandemic, population-wide cumulative responses are significantly higher over at least the first seven months after exposure. Reducing wildfire smoke exposure can thus yield substantial health benefits over multiple years, particularly when population vulnerability is heightened.

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.

Researchers must often rely on observational data to draw conclusions about the causal relationship between an exposure and an outcome. This is common in environmental epidemiology research, where the assignment to an exposure can be unethical or impossible. Consider a setting in which we seek to estimate excess mortality during heat waves, but are unable to randomize individuals to moderate or extreme heat. We propose to follow a causal framework for non-randomized time series that uses what we call historical time series matching to construct hypothetical randomized experiments, in which background covariates are balanced. We applied this framework and assessed the following causal question: Are daily mortality counts among elderly Americans higher during hot versus warm summer time periods? We addressed this causal question by drawing frequentist, Fisherian, and Bayesian inferences for five American cities. We estimated the average treatment effect of heat on three-day mortality with 95% Fisherian intervals to be 0.5 [-3.6, 4.4] deaths in Pittsburgh, 3.7 [0.7, 6.6] deaths in Seattle, 12.5 [6.1, 18.9] deaths in Chicago, 8.5 [1.4, 15.6] deaths in Los Angeles, and 20.3 [11.2, 29.5] deaths in New York.

Background: Environmental noise and air pollution are both shaped by road traffic and the built environment, and exposure assessment increasingly folds them into composite indices or proxies both by traffic exposure. Whether the two share a social distribution has rarely been tested against direct measurement of several exposures in the same communities, and community noise is almost always characterized by A-weighted levels alone, which discount low-frequency energy. Methods: At 176 sites across Rhode Island, spanning the contiguous urban area of Providence, Central Falls, and Pawtucket together with four rural municipalities, we measured the acoustic environment under A- and C-weighting (LAeq, LCeq), fine particulate matter (PM2.5), night-time illuminance, and relative humidity across four session types over roughly one year (704 site-sessions). Exposures were linked to census-tract composition (American Community Survey), and mixed-effects models were fitted for each of eight area-level markers of disadvantage, adjusting for campaign and session. Relative humidity was carried through the identical model as a negative control. Results: A-weighted noise was consistently higher in more disadvantaged tracts, rising with non-White, poverty, renter, and no-vehicle shares and falling with income and older-resident share (six of eight markers significant; 1.3 to 1.8 dBA per standard deviation; 6.6 dBA between the least and most racially diverse neighborhoods). C-weighted levels followed the same gradient on every marker and exceeded their A-weighted counterparts at block-group scale for renter occupancy and vehicle absence. Night-time illuminance was also socially patterned, whereas short-term PM2.5 was roughly an order of magnitude weaker and relative humidity showed no gradient. The acoustic gradient persisted within the urban core alone. Conclusions: Measured burden was carried by the acoustic environment, including its low-frequency component, and by night-time light, not by short-term particulates. The exposure metric and the averaging time determine which disparities are visible at all.

Biodiversity is globally threatened by chemical pollution, yet toxicity data remain unavailable for millions of species and tens of thousands of chemicals, severely limiting our ability to assess ecological impacts. Here we present TRIDENT-2, a multimodal artificial intelligence model for predicting chemical toxicity across evolutionarily diverse eukaryotic species. Trained on 560,780 toxicity assays spanning 82,775 chemicals, 6,793 species, and multiple exposure scenarios, TRIDENT-2 accurately predicts toxicity across Eukaryota with an average median absolute error ranging from 1.76 to 3.80. By jointly learning from chemical, biological, and experimental information, it remains accurate across broad chemical and taxonomic distances, allowing for toxicity assessment for species and chemicals beyond the current experimental evidence. Our findings demonstrate that artificial intelligence can help overcome longstanding data limitations in ecotoxicology, paving the way for improved decision-making and reducing chemical impacts on biodiversity and ecosystems.

Hydroclimate whiplash, defined as the rapid transition between unusually wet and dry conditions, is expected to intensify under climate change, yet its population health impacts remain largely unknown. Here we quantified the association between hydroclimate whiplash and mortality across the contiguous United States from 2003 to 2023 using monthly county-level mortality records, standardized precipitation evapotranspiration index data, and two-stage time-series models. We identified overall and direction-specific dry-to-wet and wet-to-dry whiplash events at seasonal and sub-annual timescales and across 5-, 10-, and 20-year recurrence intervals. More severe whiplash events were associated with higher all-cause mortality risk; 5-, 10-, and 20-year sub-annual overall whiplash events increased mortality risk over five months by 3.4%, 4.5%, and 5.7%, respectively. Elevated risks were observed across cause-specific mortality outcomes, with the strongest association for infectious diseases. We estimated that 103,471 deaths were attributable to overall whiplash during the study period. These findings identify hydroclimate whiplash as an emerging climate-related public health threat and suggest that adaptation strategies focused on single hazards may underestimate the health burden of rapid, sequential hydroclimatic extremes.

Large-scale chemical screens are important tools for hazard identification and chemical prioritization, but they less commonly progress from identifying a phenotype to identifying its mechanism. Here, we used zebrafish embryos to screen 4,657 chemicals from the U.S. EPA ToxCast Phase III library for disruption of embryonic development and advanced selected hits through sequential validation using original library stocks, independently sourced chemicals, concentration-response analysis, transcriptomics, and functional experiments. Of 61 primary hits subjected to repeat testing, 33 reproduced the original phenotype, and four of eight compounds subsequently tested using independently sourced chemicals exhibited reproducible concentration-dependent developmental toxicity. We then investigated purpurin, an understudied anthraquinone pigment that caused pericardial edema, circulation defects, and body-axis abnormalities. Transcriptomic analysis of purpurin-exposed embryos revealed coordinated suppression of pathways involved in calcium regulation, ion transport, and neuronal signaling. Increasing extracellular calcium produced a concentration-dependent rescue of purpurin-induced developmental abnormalities, whereas equivalent magnesium supplementation did not, supporting a role for calcium availability or homeostasis in purpurin developmental toxicity. These results demonstrate that large-scale in vivo toxicity screening can be integrated with independent chemical validation and functional follow-up to move beyond hazard identification toward mechanistic understanding of how environmental chemicals disrupt embryonic development.

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.

Per- and polyfluoroalkyl substances (PFAS) are present throughout the environment due to decades of use in many commercial products and industrial processes. These molecules contain a hydrophobic fluorocarbon tail and a functional headgroup (typically a carboxylic or sulfonic acid) that allows hydrophilic interactions with the surrounding environment. These properties make them inherently resistant to degradation, difficult to track through the environment, readily bioaccumulative, and likely to impact human health. Through collaboration with town officials, multiple meetings with local sustainability committee members and school officials, and direct contact with individual homeowners, we conducted community-driven sampling of PFAS in well water from 105 houses in Tremont, ME, a rural coastal town that relies on private wells for drinking water. The rate of PFAS detection for one or more analytes across all wells (N=105) was 69%. Of all wells tested, 16 (15%) exceeded the current public drinking water standard in Maine (20 ng/L for 6 PFAS), and an additional 17 (totaling 31% of all wells tested) exceeded Maine's newly adopted public drinking water standards for the state (based on EPA 2024 standards). Because private wells are unregulated, homeowners may use these results as a guide for taking action to maintain safe drinking water. Both hierarchical cluster analyses and pairwise Spearman's rank correlation of PFAS test results revealed similar profiles in households near and far from one another. Along with the absence of obvious, large-scale potential point sources of PFAS contamination, these findings support septic systems as the primary source of PFAS contamination in drinking water across this town. The community-driven approach to the sampling effort has enabled information sharing on the importance of water filtration options, discussion of long-term pollution abatement strategies for individual households and the town, and focused efforts for future well water testing and PFAS mitigation.

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.

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.

Many urban health outcomes are shaped by environmental stressors that occur together rather than in isolation, yet methods for measuring such co-occurrence at the neighbourhood scale remain underdeveloped. We developed a multi-metric framework for joint co-exposure assessment and applied it to characterise the joint spatial distribution of summer surface heat and fine particulate matter (PM2.5) across 42,304 census tracts in 48 large US metropolitan areas during summers 2015 to 2020, covering approximately 174.6 million residents. The framework combines a composite co-exposure index, a joint exceedance indicator, a conditional exceedance ratio that compares observed joint occurrence to within-group statistical independence, and an upper tail dependence parameter estimated using both the non-parametric Caperaa-Fougeres-Genest estimator and a Gumbel copula, with bias-corrected and accelerated (BCa) confidence intervals obtained from a 5,000-replicate metropolitan-area block bootstrap. Among residents of predominantly Black tracts, 13.21% lived in neighbourhoods that simultaneously exceeded the within-metropolitan-area 80th percentile for both heat and PM2.5, compared with 3.33% of residents of predominantly White tracts; the corresponding heat-only and PM2.5-only ratios were 2.88 and 2.48. Residents of Home Owners Loan Corporation grade D tracts had 3.97 times the odds (95% confidence interval 2.79 to 5.66) of joint hotspot residence compared with grade A residents after adjustment for contemporary tract racial composition, poverty, renter-occupancy, and pre-1960 housing. The within-group conditional exceedance ratio at the 80th percentile was 2.29 in predominantly White tracts (95% BCa CI 1.81 to 2.78), 1.27 in predominantly Black tracts (0.71 to 1.56), and 1.13 in predominantly Hispanic tracts (0.70 to 1.41); the White interval excluded one while the Black and Hispanic intervals included one, which we interpret as power-limited given fewer contributing CBSAs. Magnitudes attenuated under near-surface air temperature surfaces but the direction and statistical significance of the primary findings were preserved. The framework is portable to other compound-exposure questions and supports cumulative-impact assessment.

Plastic products have greatly improved convenience in daily life. However, diverse pollutants released from these materials pose substantial risks to human health. Lactiplantibacillus plantarum PD01 has previously been demonstrated to reduce microplastic (MP) bioaccumulation and toxicity in murine model. In this study, we conducted a randomized, double-blind, placebo-controlled trial to further evaluate the efficacy of L. plantarum PD01 in reducing MPs and MP-associated chemicals in humans. A total of 106 participants were recruited in November 2025. Eligible participants were randomly assigned to either the placebo or intervention group, and orally received placebo or 1.0x1010 colony-forming units (CFU) L. plantarum PD01 after meals three times a day, respectively. Fecal, urinary, and blood samples were collected to determine the MPs contents, plasticizer levels, gut microbiota composition, blood metabolic profiles and biochemical indicators. Among these measurements, the analysis of urinary phthalate metabolites was completed first and revealed a significant reduction after the probiotic intervention. Compared with the placebo group, 6-week L. plantarum PD01 supplementation resulted in significant relative reductions in urinary levels of MCMHP by 60.2% (P = 0.0343), MMP by 51.2% (P < 0.001), MEHP by 49.6% (P = 0.0058), MiBP by 45.7% (P = 0.0085), MnBP by 35.8% (P = 0.0478), and {Sigma}DEHP by 46.2% (P = 0.0461). The interim results presented here provide the first clinical evidence that the probiotic strain PD01 can significantly reduce residual MP-associated chemicals in human body. To the best of our knowledge, this is the first randomized controlled trial (RCT) to evaluate probiotic intervention targeting MPs and MP-associated chemicals in humans.

Vaccine hesitancy remains a major public health challenge, highlighting the need for effective strategies to boost vaccine uptake. We conducted a county-randomized trial to evaluate whether a social media campaign grounded in alerts driven by community-level wastewater surveillance could increase COVID-19 and influenza vaccination. Forty New York State counties were selected for an 11-week campaign during fall 2024, with 20 counties assigned to the intervention and 20 serving as controls. The campaign reached more than 16.6 million impressions, with over 77K clicks on the call-to-action link, demonstrating substantial public engagement. During the campaign period, intervention counties administered significantly more COVID-19 vaccine doses ({beta} = 76.7, P = 0.01) but fewer influenza vaccine doses ({beta}= -140.9, P = 0.04) per 100,000 residents per week than control counties. However, season-level analysis showed no significant differences in COVID-19 or influenza vaccination uptake between groups. These findings highlight the potential of alerts from community-level wastewater surveillance to promote vaccination.

Background: In coastal Bangladesh, saline drinking water has been linked to raised blood pressure. The 2025 Multiple Indicator Cluster Survey (MICS) measured electrical conductivity (EC), a salinity indicator, in source water, but its report gave no population counts or district estimates. Objectives: To estimate how many people live in households whose tested source has high EC, and to describe patterns by place, household characteristics, source type and arsenic. Methods. EC was measured in source water of 6,040 households in 64 districts, February to June. In 14.5% of households the tested source was not the main drinking-water source. Primary outcomes were EC above 1,500 and 3,000 microsiemen/cm, survey risk classes that are not health-based standards. Estimates were survey weighted; comparisons were observational. Results: EC exceeded 1,500 microsiemen/cm in 5.3% of households (95% CI 4.7 to 5.9), about 9.0 million people, including 1.8 million above 3,000 microsiemen/cm. Coastal-zone districts held 26% of households but 70% of those above 1,500 microsiemen/cm. Shares varied little by wealth or in households with young children or pregnant women. Nationally, deep tube wells more often had high EC because most are coastal. In the coastal zone, deep and shallow wells had similar shares (16.1% and 17.9%). After district adjustment, EC was about 18% lower in deep wells (geometric mean ratio 0.82, 0.73 to 0.92). Within upazilas (restricted sample) it was 0.93 (0.80 to 1.07). Arsenic above 10 ppb was more common where EC was high, but this link weakened after district adjustment. Conclusions: Millions of people live in households whose tested source has high EC, mostly in coastal and south-central districts. Deep wells had modestly lower EC after geographic adjustment, but the difference shrank within upazilas and depended on the handling of implausibly low readings. The findings support measuring EC alongside arsenic, with documented meter calibration.

Current insecticide toxicology still lacks an integrated understanding of how lethal and sublethal exposure shape organismal performance across biologically and environmentally relevant contexts. In particular, insecticide susceptibility may vary with physiological state, environmental conditions, and recent exposure history, factors that are only partially captured by standardized toxicity assessments. Here, using Drosophila melanogaster, we systematically compared responses to three insecticides with distinct modes of action - acetamiprid, chlorantraniliprole, and deltamethrin - across developmental stages, sexes, adult ages, and ambient temperatures. Insecticide sensitivity varied substantially across these conditions, with temperature modulating toxicity in a compound-dependent manner. Notably, deltamethrin caused substantial lethality at concentrations more than 10,000-fold below approved field application rates. Beyond these context-dependent differences in acute toxicity, sublethal pre-exposure to each insecticide rapidly reduced lethality during a subsequent challenge with the same compound, with increased tolerance already detectable after 24 h. Importantly, these exposure conditions that enhanced insecticide tolerance were associated with reduced resistance to environmental challenges, including heat and nutrient starvation, revealing a potential trade-off in organismal stress resilience. Acetamiprid exposure further altered reproductive performance in a concentration-dependent manner, with higher exposure reducing egg production while increasing developmental success among the resulting offspring, such that the number of offspring reaching adulthood remained largely unchanged. Together, these findings demonstrate that insecticide susceptibility is highly context dependent and can be rapidly modified by recent exposure history. We identify short-term, compound-specific, and potentially costly tolerance as an underappreciated consequence of insecticide exposure and highlight the importance of incorporating biological context, environmental conditions, and sublethal exposure history into pesticide risk assessment.

Typical environmental exposures to the toxic class of chemicals known as polycyclic aromatic hydrocarbons (PAHs) involve complex mixtures; however, relatively few mechanistic toxicity studies have evaluated them as environmental mixtures, instead focusing on individual compounds or simple mixtures. In this study, we first derived Republic Sediment Extract (REPSE), a complex PAH mixture extracted from sediment at the Republic Creosoting site of the Elizabeth River in Norfolk, Virginia. After characterizing the PAH contents of REPSE, we evaluated its mechanisms of developmental neurotoxicity in three evolutionarily distinct taxa, leveraging the unique strengths of Atlantic killifish, zebrafish, and Caenorhabditis elegans as model species, with a focus on the Aryl hydrocarbon Receptor (AhR) pathway. Embryonic REPSE exposure caused induction of CYP1A in both fish species at sub-teratogenic concentrations, consistent with activation of the canonical AhR pathway. These sub-teratogenic exposures nevertheless induced neurotoxicity across both fish species, altering neurobehavioral phenotypes in fish, and induced dopaminergic neuronal damage in worms, again at non-teratogenic concentrations. To determine whether these effects were linked to canonical AhR response pathways, we examined killifish offspring from the pollution-adapted Republic Creosoting population, which exhibited characteristic recalcitrance to CYP1A induction, but remained susceptible to the neurobehavioral effects of REPSE. The induction of neuronal damage in worms provides orthogonal evidence for a non-AhR mechanism, because C. elegans AhR is not transcriptionally activated by PAHs as in vertebrates. Further probing of potential mechanisms underlying REPSE-induced neurotoxicity in worms revealed altered neuronal redox status (roGFP) and energy availability (ATP:ADP ratio). Collectively, our multispecies approach reveals conserved mechanisms of PAH mixture neurotoxicity, including effects that extend beyond canonical AhR signaling.

Essential for nutrient growth, due to intensive farming practices nitrate has become a common water contaminant in agricultural states. US nitrate regulations are designed to protect the health of newborns and infants, but have never been revised to consider potential harms of prenatal exposure. Recent evidence, however, suggests that exposure below the 10 mg/L regulatory limit may be associated with adverse birth outcomes. This current study examines whether first-trimester exposure below the regulatory limit is associated with adverse birth outcomes in Iowa (an intensive agricultural state). Finished drinking-water nitrate measurements from Iowa public water systems were linked to birth records. Nitrate measures were aggregated to a balanced county-quarter panel (1983 to 1988). Each pregnancy was assigned an average nitrate exposure over a 98-day first-trimester window. All births with a first trimester county-quarter nitrate measure >= 10 mg/L were excluded. Linear probability models with county-by-year and year-by-conception-quarter fixed effects, with standard errors clustered by county, estimated both uncorrected and Sidak corrected inference. The final analytic sample included 113,328 singleton births. Relative to lowest exposure category (0.1 mg/L or below), exposure to 5 mg/L or more nitrate was associated with a 1.04 percentage-point increase in the probability of preterm birth (CI = 0.24 to 1.83), a 13.5% relative increase, and associated with a 0.53 percentage-point increase in very preterm birth (CI = 0.08 to 0.97), a 46.2% relative increase. The statistical significance of both estimates persisted after correction for multiple tests. Exposure to > 0.1 mg/L and < 5 mg/L was not associated with any outcome. These preterm and very preterm birth associations were consistent across several sensitivity checks. Because nitrate concentrations between 5 to <10 mg/L comply with current rules, these findings warrant reassessing approaches to protect the health of pregnant women and their children.

Cadmium (Cd) is an emerging environmental risk factor for cognitive decline and Alzheimer's disease, and few interventions limit its effects on the brain. Akkermansia muciniphila, a human gut commensal, is neuroprotective through mechanisms that remain unclear. Building on our finding that A. muciniphila prevented Cd-induced memory deficits without reducing brain Cd burden (Wang et al., 2026a), we tested whether it reprograms Cd-disrupted hippocampal RNA regulation. Male C57BL/6J mice received A. muciniphila (1x10^9 CFU, oral gavage, 5 days/week) before and throughout 9 weeks of 3 mg/L CdCl2 exposure; hippocampi were analyzed by RNA-seq, m6A epitranscriptomic profiling, and rMATS-based alternative-splicing analysis. Cd disrupted hippocampal neuropeptide signaling, neuronal excitability, and synaptic plasticity. Co-exposure with A. muciniphila reversed signatures enriched for Nrf2-centered cytoprotective signaling and opposed m6A and splicing changes across more than a thousand genes, largely without changes in total mRNA abundance. Restored events converged on machinery governing local translation, calcium-dependent plasticity, and synaptic transmission. Projected onto predicted protein structures, most introduced a premature termination codon predicted to trigger nonsense-mediated decay or edited short loop and linker segments rather than rebuilding folded domains, regulation largely invisible to gene-level expression analysis. Among these, paired events amplifying semaphorin-plexin signaling, an axis linked to oligodendrocyte injury and memory consolidation, were reversed. These findings identify restoration of hippocampal transcript fate and splice-isoform selection as a mechanism potentially underlying A. muciniphila-mediated protection against Cd neurotoxicity, and establish post-transcriptional RNA regulation as a gut-brain target for mitigating environmentally driven neurotoxicity.

Environmental factors including chemical exposures are important contributors to Parkinsons disease (PD). Nearly all well-validated chemicals involved in PD affect mitochondria, and the great majority of those identified inhibit mitochondrial complex I, causing ATP depletion and oxidative stress. We hypothesized that inhibition of mitochondrial complex III would also cause dopaminergic neurotoxicity. Using Caenorhabditis elegans to evaluate the in vivo effects of complex III-inhibiting pesticides antimycin A and pyraclostrobin, we found that both caused selective dopaminergic neurotoxicity. We evaluated exacerbation of dopaminergic neurotoxicity by the presence of -synuclein, and pdr-1/PRKN and pink-1/PINK1 mutant backgrounds and found increased neurotoxicity for pdr-1. Complex III inhibition caused a more-oxidized cellular environment in those neurons and pharmacological and genetic antioxidant interventions rescued neurotoxicity, but energetic rescue attempts did not. Finally, optogenetic production of superoxide anion specifically at complex III caused dopaminergic neuronal damage. Thus, redox stress at complex III following chemical exposure causes dopaminergic neurotoxicity in vivo in C. elegans.