Environment International

Prenatal air pollution exposure is associated with childhood asthma, particularly among biological males. The mechanisms remain unclear, but may involve lasting epigenetic changes, such DNA methylation (DNAm), that occur during gestation in response to oxidative stress and inflammation. Higher maternal intake of "protective" micronutrients, like antioxidants, could buffer pollution-induced oxidative stress and inflammation to mitigate potentially adverse DNAm differences contributing to asthma. Using data from 515 CANDLE participants, we examined associations between prenatal NO2, PM2.5, and PM10 and cord blood DNAm, evaluated DNAm mediation of pollution associations with childhood wheeze phenotypes (transient, persistent, and late-onset), and assessed buffering of DNAm by maternal polyunsaturated fatty acid, vitamin C, or folate intake, and overall diet quality measured by the Alternative Healthy Eating Index-Pregnancy (AHEI-P). We identified 19, seven, and five regional DNAm differences associated NO2, PM2.5, and PM10. Mediation analyses suggested a role for HLA-DPA1/DPB1 DNAm in NO2 and PM2.5 associations with transient wheeze. To assess buffering, we fit pollutant-by-diet interaction models, defining buffering as an interaction opposite in sign to the main pollutant effect. One or more micronutrients or AHEI-P attenuated pollutant effects at 16 of 19 NO2-associated DMRs, including HLA-DPA1/DPB1, and all PM2.5- and PM10-associated DMRs. However, attenuation of HLA-DPA1/DPB1 DNAm did not significantly reduce the indirect effect of NO2 on transient wheeze. In sex-stratified analyses, biological males exhibited lower PM2.5-associated DNAm in SERPINB9, a gene linked to lung function. These findings suggest prenatal air pollution alters DNAm, which may contribute to transient wheeze, with some differences partially buffered by maternal diet. Significance StatementPrenatal air pollution exposure contributes to child wheeze and asthma, potentially through the oxidative stress response and subsequent changes to infant DNA methylomes. Here, we used data from the CANDLE cohort to identify cord blood DNAm differences associated with NO2, PM2.5, or PM10. We examined if any alterations mediated the relationship between prenatal air pollution exposures and transient, persistent, or late-onset wheeze at age 4 to 6 years. Some of these DNAm differences appeared to be at least partially buffered by maternal micronutrients and/or overall diet quality.

Managing post-weaning diarrhoea (PWD) in piglets is difficult due to limits on antibiotics and zinc. Chitosan is emerging as a potential feed additive. We analysed a chito-oligosaccharide hydrochloride (COS-HCl), a low molecular weight (LMW) chitosan, and a medium molecular weight (MMW) chitosan, and assessed their effects on growth, faecal consistency, microbiota, and potential interference with enterotoxigenic Escherichia coli (ETEC). The three chitosans were characterised using {superscript 1}H-NMR, SEC-RI-MS, and SEC-RI-MALLS. COS-HCl had an Mw of 0.824 kDa; LMW and MMW showed Mw ranges of 14.4 kDa (0.3-30 kDa) and 116 kDa (15-600 kDa). Degrees of acetylation were 9.5%, 6.5%, and 15%. Two 42-day field studies evaluated average daily gain (ADG), faecal consistency, and microbiota. In the first trial, COS-HCl at 0.025-0.1% did not significantly affect ADG (-33 to - 12 g/d). In the second, LMW and MMW at 0.01% did not significantly change ADG (-7 and +3 g/d). Faecal consistency, ETEC shedding, and microbiota composition were similar to controls. An enzymatic HPLC-MS method enabled quantification of MMW chitosan in premix. Our results highlight the importance of advanced chitosan characterisation for precision nutrition and suggest that a threshold dosemay be needed to benefit growth and gut health in PWD management. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/714014v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@19c9e23org.highwire.dtl.DTLVardef@152461aorg.highwire.dtl.DTLVardef@7886e0org.highwire.dtl.DTLVardef@df0d9b_HPS_FORMAT_FIGEXP M_FIG C_FIG

As toxicology shifts towards non-animal testing, quantitative models are essential to predict adverse health effects from molecular or cellular perturbations. Quantitative Adverse Outcome Pathways (qAOPs) represent such models, building on mechanistic knowledge and quantifying the Key Event Relationships (KERs) described in AOPs. Despite the recognized need, the number of qAOPs remains limited. Bayesian-based approaches are often chosen for developing qAOP for their flexibility, but most use discretized variables, limiting their predictive power. In addition, these models are mainly built from newly generated data, underexploiting the large amount of information available. This study successfully leverages data from public literature and presents an innovative framework based on continuous variables to develop a Bayesian-based quantitative model for a central KER towards liver fibrosis. The model predicts the probability of the expression fold change for two key markers of hepatic stellate cell activation (aSMA and COL1A1), given the effects on tissue injury, using in vitro data from 9 chemicals. We propose a newly developed workflow to assist in knowledge identification, organization, and extraction from scientific literature and chemical databases. Based on in vitro data and in vivo information from the Open TG-GATEs (Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System) database, we estimate a biologically relevant range in COL1A1 fold change that indicates an activated state of stellate cells and high liver fibrosis odds ratios. Our study provides a case example of integrating published data and continuous variables to build a Bayesian-based model, which constitutes an essential step for predicting liver fibrosis from in vitro data.

Rapid urbanisation has profoundly shaped microbial diversity across different ecosystems. Freshwater microbiomes are particularly affected by urbanisation activities, such as eutrophication, pollution, runoff, and sewage. This is of significant concern as marginalised communities often depend on waterbodies for their livelihood. Freshwater bodies play a crucial role in maintaining both human and ecological health at population level. Currently, we lack a systematic understanding of the global impacts of urbanisation on freshwater microbiomes in relation to human health, ecosystem functioning, and sustainability. We identified 90 eligible papers from the last 25 years after screening based on the inclusion exclusion criteria. We extracted data that examined changes in the functional traits such as antimicrobial resistance (AMR), nutrient cycling of the microbiome in urban waterbodies and several other factors. Data were extracted by a thematic analysis followed by a narrative synthesis on specific functional traits. This systematic review presents a comprehensive analysis on the changes and challenges brought about by urbanisation on freshwater bodies. Our results indicate that urbanisation leads to reduced bacterial diversity of urban waterbodies, with a striking increase in reporting of Proteobacteria, Cyanobacteria and Coliform bacteria. These insights will help inform public health strategies and sustainable urban planning. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/715732v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@18db38dorg.highwire.dtl.DTLVardef@70a79org.highwire.dtl.DTLVardef@40aaaborg.highwire.dtl.DTLVardef@184ecca_HPS_FORMAT_FIGEXP M_FIG C_FIG Waterbodies in urban areas function as convergence platforms for anthropogenic and environmental microbiomes. Runoffs, wastewater and effluents contain antimicrobial resistance genes and other pathogens that survive in water due to inadequate treatment. Disposal, use, and overflow of wastewater cause restructuration of microbial communities, proliferation of opportunistic microorganisms, and spread of antimicrobial resistance in aquatic ecosystems.

Bullous pemphigoid (BP) is an autoimmune blistering disease with a growing incidence, and environmental factors are receiving increasing attention. Tetrabromobisphenol A (TBBPA), a widely used brominated flame retardant, is a significant environmental pollutant. However, the molecular mechanisms by which TBBPA contributes to BP pathogenesis remain unclear. This study integrated network toxicology, molecular docking, and molecular dynamics (MD) simulations to systematically investigate the molecular mechanisms of TBBPA-induced BP. Using network toxicology, we identified 797 potential targets of TBBPA and 446 BP-related targets. A Venn diagram analysis revealed 48 common targets. Protein-protein interaction (PPI) network and topological analyses further identified five core hub targets: TNF, CXCL8, MMP9, ICAM1, and ITGB1. Gene enrichment analysis indicated that these targets were significantly enriched in immune-inflammatory pathways, such as leukocyte migration, inflammatory responses, and the IL-17 signaling pathway, as well as in various pathogen infection and cancer-related pathways. Molecular docking revealed that TBBPA stably binds to all five core targets with binding energies [≤] -5 kcal/mol, driven primarily by hydrophobic interactions and {pi}-{pi} stacking. Subsequent MD simulations confirmed that TBBPA complexes with TNF, CXCL8, and MMP9 remained stable throughout the 100 ns simulation. The overall protein structures remained compact, and the ligands were effectively encapsulated within the binding pockets, forming stable networks of hydrogen bonds and hydrophobic interactions. In conclusion, this study, for the first time, proposes a systematic molecular framework using integrated computational biology. Our findings suggest that the environmental pollutant TBBPA may act as a potential risk factor in BP pathogenesis by targeting core proteins (TNF, CXCL8, and MMP9). These interactions potentially disrupt critical signaling pathways related to immune inflammation, cell migration, and tissue remodeling. This study offers a novel mechanistic hypothesis regarding environmental chemical exposure in autoimmune blistering diseases, although further experimental validation is required. HighlightsO_LINetwork toxicology identified 48 common targets linking Tetrabromobisphenol A(TBBPA) exposure to Bullous Pemphigoid (BP). C_LIO_LIFive core targets (TNF, CXCL8, MMP9, ICAM1, ITGB1) were screened as potential mediators. C_LIO_LITBBPA stably binds to TNF, CXCL8, and MMP9 with binding energies [≤] -5 kcal/mol. C_LIO_LIMolecular dynamics simulations confirm stable binding and structural integrity of complexes. C_LIO_LIThis study provides a mechanistic framework for TBBPA as an environmental risk factor in BP. C_LI

Establishing whether real-world environmental chemical (EC) exposure can induce heritable epigenetic modifications in large, outbred mammals is key to determining long-term developmental impacts of the human exposome. Using an established biosolids-treated pasture (BS) sheep model, we investigated whether gestational exposure to low-level mixtures of EC induced heritable changes in DNA methylation across three generations of sheep. Reduced-representation bisulfite sequencing of liver, blood, and sperm, combined with a structured, lineage-controlled breeding design, revealed widespread but lineage- and sex-specific differentially methylated loci (DML) in F1 offspring, with detectable alterations evident in F2 and F3 descendants. Although most DML were unique to individual sire lineages, or to a single generation, subsets of loci showed repeated involvement across generations and were associated with altered gene expression in F3 descendants. Sperm from F1 males exhibited reduced methylation at numerous loci and, together with seminal plasma, revealed differential expression of several microRNAs. These effects, however, showed limited persistence in F2 males, indicative of intergenerational rather than fully transgenerational persistence. Collectively, these findings demonstrate that complex, low-level chemical exposures can elicit recurrent, sexually dimorphic epigenetic responses in outbred species, but underscore the challenge of disentangling exposure-induced inheritance from genetically regulated methylation variation. Significance StatementEnvironmental chemical (EC) exposures are ubiquitous, yet their capacity to induce heritable epigenetic changes in large, genetically diverse mammals is poorly understood. Using a real-world exposome-based sheep model, we demonstrate that low-level gestational EC exposure leads to sexually-dimorphic and lineage-dependent alterations in DNA methylation that can extend to unexposed descendants. Although genetic ancestry exerts a dominant influence over these responses, repeated alterations at specific loci suggests that environmentally induced epimutations can reoccur across generations in certain genomic contexts.

Characterizing aroma and flavours generated during cheese production is of high relevance for the food industry. A deeper comprehension of flavour generation can be achieved by understanding the role of microbial population governing milk processing, and in particular their metabolic activity governed by gene expression. In this work we considered two independent experiments in which gene expression of the microbial population involved in cheese processing is sampled, together with final volatile products quantification. We estimated the final volatile compound profile from the measured metatranscriptomic expression by using machine learning with two different strategies for model training and validation, and we were able to associate specific biochemical pathways to the identified gene signatures.

Per- and polyfluoroalkyl substances (PFAS) are widespread environmental contaminants with documented toxic effects, yet their multi- and transgenerational impacts on neurodevelopment and underlying mechanisms remain poorly understood. Here, we present a comprehensive study delineating the effects of developmental exposure to environmentally relevant concentrations of PFOS and PFBS on behavior, transcriptome, and genome-wide DNA methylation patterns in the directly exposed generation (F0) and their unexposed offspring (F1 and F2) in zebrafish. Both PFOS and PFBS altered larval behavior, linked to transcriptomic and DNA methylation changes in neuro-related pathways, even in the unexposed offspring. Importantly, specific DNA methylation changes in F0 were associated with behavioral outcomes in F2 animals, suggesting that these alterations could underlie transgenerational effects. Pathways associated with differentially methylated genes were prominently enriched for response to light and circadian regulation. Our findings demonstrate that developmental exposure to PFAS causes transgenerational behavioral effects in zebrafish and suggest that epigenetic changes induced by direct exposure may serve as markers for predicting outcomes in subsequent, unexposed generations. TEASERPFAS induce circadian-related epigenetic changes in zebrafish associated with behavioral impacts in unexposed offspring.

Per- and polyfluoroalkyl substances (PFAS) are chemicals linked to obesity and metabolic dysfunction, but their role in bariatric surgery remains poorly understood. This prospective pilot study examined correlations between plasma PFAS concentrations, body composition, and glycemic measures in adults undergoing bariatric surgery. Thirty-two patients (91% female; 66% Black; mean age 43 years) were enrolled preoperatively; twenty-two completed follow-up at a mean 8.6 months post-surgery. Three PFAS (PFHxS, PFNA, and PFOS) were quantified by plasma liquid chromatography-mass spectrometry; body composition and insulin sensitivity were assessed by dual-energy X-ray absorptiometry and intravenous glucose tolerance testing. At baseline, higher plasma PFNA and PFOS concentrations tracked with lower total lean mass ({rho}s = -0.46 and -0.48, respectively) and lean mass index ({rho}s = -0.46 and -0.42), and PFNA was inversely correlated with body weight ({rho}s = -0.40). No baseline associations were observed with adiposity or glycemic indices. Postoperatively, PFHxS concentrations decreased (median = -1.103 ng/mL, p < 0.001), whereas PFNA and PFOS did not change. Average PFNA was positively correlated with postoperative changes in HOMA-IR ({rho}s = 0.51) and total lean mass ({rho}s = 0.49). No significant associations were observed for average PFHxS or PFOS. These findings suggest that PFNA and PFOS may be linked to reduced lean tissue at baseline, and that PFNA burden modestly tracks with attenuated metabolic and body composition recovery. In an ANCOVA, baseline PFNA was not significantly associated with postoperative HOMA-IR or total lean mass. Larger, longitudinal studies are needed to clarify how PFAS influence these associations.

Bisphenol A (BPA) is a prevalent chemical used in the production of plastics. While adverse effects on the reproductive system have been documented, more recent studies also associated BPA exposure with carcinogenesis as well as genomic instability. However, these studies were generally performed using BPA concentrations much higher than those observed in the serum or urine of the general population, making their relevance unclear. To address this, we report here an unbiased genetic study to identify mechanisms responding to environmentally relevant BPA exposure. We performed genome-wide CRISPR knockout screens in HeLa and RPE1 cells upon continuous exposure to 0.5uM BPA, a concentration similar to the mean BPA concentration found in the urine of plastics manufacturing workers, for 19 days. We found genome stability genes among the top common hits between the two cell lines, suggesting that BPA causes DNA damage at this environmentally relevant exposure dose. We validated the DNA repair gene RAD51C and the RNA helicase DDX21 as genes required for BPA resistance. Moreover, we show that BPA exposure increases the formation of R-loops which are resolved by DDX21. Our study suggests that BPA exposure at environmentally relevant doses can cause DNA damage, highlighting the relevance of BPA for carcinogenesis.

Background Ambient air pollution is a leading global health risk and disproportionately affects populations of Low- and Middle-Income Countries (LMICs). In 2021, WHO revised its Air Quality Guidelines (AQG), lowering recommended annual limits for Particulate Matter 2.5 (PM2.5) and Nitrogen Dioxide (NO2). We estimated the potential health and economic impacts of achieving WHO Interim Target 3 (IT3) and AQG concentrations across LMICs. Methods We conducted a health impact assessment across 136 LMICs to quantify one-year changes in all-cause and cause-specific mortality (chronic obstructive pulmonary disease [COPD], ischaemic heart disease [IHD], and stroke) and disease incidence (COPD, dementia, IHD, and stroke) under WHO IT3 and AQG counterfactual scenarios for PM2.5 and NO2. Concentration-response functions were applied at 1km x 1km resolution. Economic welfare impacts of mortality risk reductions were estimated using country-adjusted values of a statistical life (VSL, Int$ PPP-adjusted 2021). Direct medical and productivity-related costs associated with incident cases were estimated using a cost-of-illness (COI) framework. Uncertainty intervals (UI) reflect uncertainty in concentration-response functions. Results Attainment of WHO IT3 and AQG concentrations for PM2.5 was associated with an estimated 16.04% reduction (6.58million, UI: 6.10-7.07million) and 22.97% reduction (9.43million, UI: 8.75-10.11million) in annual deaths, respectively. Corresponding VSL-based estimates of deaths averted were Int$5.5 trillion (7.0% of aggregate LMIC GDP) and Int$8.4 trillion (10.6% of GDP), respectively. For NO2, IT3 and AQG scenarios were associated with estimated reductions of approximately 1.06% (approximately 435,000 deaths, UI: 388,000-483,000) and 2.79% (435,000 deaths; UI: 388,000-483,000), yielding gains of Int$0.6 trillion (0.7% of GDP) and Int$1.5 trillion (1.9% of GDP). Disease-specific mortality reductions were most prominent for IHD and stroke in Asia and Africa. Under the PM2.5 AQG scenario, an estimated 2.82million (1.67-2.97) COPD, 1.10million (0.83-1.37) dementia, 7.3million (6.41-8.19) IHD, and 2.3million (2.19-2.41) stroke cases could be delayed or averted in one year. Associated reductions in direct medical and productivity-related costs were greatest for IHD, COPD, and stroke. NO2-related morbidity reductions were smaller across all outcomes. All estimates represent one-year changes in risk relative to counterfactual exposure and may reflect delayed rather than permanently avoided events. Discussion Achieving both WHO IT3 and AQG values in LMICs could yield substantial reductions in premature mortality and disease incidence, particularly for cardiovascular and respiratory conditions, alongside large, monetised welfare gains from reduced mortality risk. These findings underscore the considerable societal value of air quality improvements and support accelerated action toward meeting WHO guideline levels in regions bearing the highest pollution burden.

Background Prenatal exposure to pesticides and psychosocial factors often co-occurs, particularly in low- and middle-income settings, yet their joint effects on epigenetic age acceleration (EAA) in early life remain unknown. We investigated the joint associations of prenatal pesticides metabolites and psychosocial factors on EAA in the first five years of life in the South African Drakenstein Child Health Study. Methods In 643 mothers, we measured 11 urinary pesticide metabolites and seven psychosocial factors during the second trimester of pregnancy. Child DNA methylation was measured in whole blood at ages 1, 3, and 5 years. EAA was estimated using the Horvath, Skin & Blood Horvath (skinHorvath), and Wu epigenetic clocks. Longitudinal associations were estimated using generalized estimating equations, adjusted for confounders. Joint mixture associations were evaluated using weighted quantile sum regression (WQS) and quantile g-computation (QGCOMP). Results The joint prenatal exposure mixture was positively associated with Wu ({beta} per one quintile increase in the mixture [95% CI]: 0.41 years [0.15, 0.80]), skinHorvath (0.11 years [0.06, 0.16]), and Horvath EAA (0.31 years [0.20, 0.46]) over time using WQS. Psychosocial factors, particularly food insecurity, physical interpersonal violence, and stress biomarkers, contributed most to the total mixture effect for all clocks. Pyrethroid metabolites PBA and TDCCA were top pesticide contributors to Wu EAA. Pathway enrichment analyses of clock-specific CpGs revealed distinct biological architectures, with the Wu clock enriched for neurodevelopmental and immune pathways, and metabolic pathways for the Horvath clock. Discussion Joint prenatal exposure to pesticides and psychosocial factors was associated with increased EAA across early childhood, with psychosocial factors contributing the most to the total effect. These findings highlight the importance of assessing chemical and non-chemical stressors jointly and clock-specific biological interpretation in epigenetic aging research.

Hydrocarbons are recalcitrant organic matter that are released into the environment via natural and anthropogenic activities. We hypothesized that abiotic and biotic factors, including salinity, temperature, seasonality, microbial interactions, and functional redundancy, influence the abundance and activity of potential hydrocarbon degraders in the Delaware and Chesapeake Bays. We identified key genes in hydrocarbon degradation pathways in metagenomes, metatranscriptomes, and metagenome assembled genomes (MAGs) from these estuaries. Aerobic aromatic and alkane degradation pathways predominated in both estuaries, with higher gene abundances observed in low-salinity spring and summer samples. Hydrocarbon degrading MAG abundance were significantly structured by salinity, temperature, nitrate, and silicate concentrations. Metatranscriptomic analyses revealed consistently higher expression of aerobic alkane and aromatic degradation genes in the Delaware compared to the Chesapeake Bay, with the highest occurring under low-salinity spring conditions in the former. Catechol degradation pathways exhibited high functional redundancy, whereas the naphthalene degradation pathway showed restricted distribution. Co-expression analysis revealed that Burkholderiales displayed condition dependent metabolic coupling while Pseudomonadales integrated hydrocarbon degradation with fermentation and central metabolism, demonstrating complementary strategies that support multi-scale ecosystem resilience. In conclusion, environmental gradients and taxon-specific metabolic strategies together govern hydrocarbon degradation potential in these estuaries, with implications for predicting ecosystem responses to hydrocarbon inputs under changing conditions. ImportanceCoastal estuaries are among the most contaminated aquatic environments on Earth, receiving continuous hydrocarbon inputs from industrial activity, urban runoff, and natural sources. Microorganisms are the primary agents of hydrocarbon breakdown in these systems yet predicting when and where this capacity is active and how resilient it is to environmental change remains a major challenge. Using paired genomic and transcriptomic data from microbial genomes across two major mid-Atlantic estuaries, we show that hydrocarbon degradation capacity is not uniformly distributed but is instead shaped by salinity, nutrients, and seasonality in pathway-specific ways. Critically, dominant degrader taxa employ fundamentally different metabolic strategies to sustain this function across fluctuating conditions, providing a form of community-level insurance against environmental disturbance. These findings advance our ability to predict microbial hydrocarbon degradation in coastal systems and inform nature-based approaches to bioremediation under increasing climate and anthropogenic pressures.

As climate change intensifies, health risks from extreme heat are rising. Accurate assessment of heat vulnerability at high spatial resolution is crucial for developing effective adaptation strategies, particularly in socioeconomically heterogeneous urban settings. However, the identification of key indicators underlying heat vulnerability remains challenging. Using Chicago, Illinois (USA) as a case study, we systematically compare different variable selection strategies in community-level heat vulnerability assessments. We take the conventional unsupervised principal component analysis (PCA)-based Heat Vulnerability Index (HVI) as a baseline, and compare it with supervised approaches that incorporate variable selection, including machine learning algorithms (Lasso regression, Random Forest, and XGBoost) as well as traditional statistical methods (simple linear regression and polynomial regression). Using the vulnerability indicator subsets identified by each variable selection method, we construct multiple HVIs and evaluate their performance against heat-related excess mortality. Our work indicates that supervised variable selection improves the performance of HVIs in capturing heat-related health risks. Among all methods, the Random Forest-based variable selection algorithm achieves the best overall results, highlighting the potential of machine learning to enhance heat vulnerability assessment tools. Our results demonstrate that poverty rate, lack of air conditioning, and proportion of residents aged 65 and above are robust determinants of heat vulnerability in Chicago.

Ethylene oxide (EtO) is primarily used as an intermediate in the manufacture of chemicals, with a minor use as a sterilant for medical equipment and food products. It is a direct-acting alkylating agent that reacts with cellular macromolecules, including proteins and DNA. EtO has been shown to induce tumors in rodents and humans. DNA reactivity has been the postulated mode of action (MOA) for its carcinogenicity. The current study has investigated the dose response for EtO-induced genetic damage to inform the biological plausibility of a dose-response model for cancer risk assessment. Male and female B6C3F1 mice were exposed to 0, 0.05, 0.1, 0.5, 1, 50, 100, or 200 ppm EtO by whole-body inhalation (6 hours/day for 28 days, 7 days/week). Mutagenicity was assessed by determining the frequency of mutant Pig-a phenotype in reticulocytes (RET) and mature red blood cells (RBC) on Day 28. Cytogenetic damage was evaluated by the erythrocyte micronucleus (MN) test in blood samples collected on Days 5 and 28. EtO is a relatively weak genotoxicant with treatment-related increases in Pig-a and MN frequencies being seen primarily at 200 ppm. The hockey-stick shaped dose response for genetic damage may be conservatively interpreted as being no more than a linear response with a single slope. Thus, a cancer risk assessment dose-response model consisting of a single linear slope throughout the exposure range is biologically plausible and consistent if EtO were acting through a mutagenic MoA for its carcinogenicity.

The East Asian region, known for its high levels of human and fishery activities, experiences serious plastic pollution in the marine environment, especially in seawater and along coastlines. Wharf roaches (Ligia spp.) collected from the coast of western Japan frequently ingest expanded polystyrene (EPS), which is then excreted as microplastic through their feces. However, the impact of EPS exposure and ingestion on the gut microbiome of wharf roaches remains unclear. Thus, this study aimed to investigate the effects of EPS ingestion on the gut microbiota of wharf roaches by examining their gut microbiota and gene expression. The expression levels of more than 400 genes, including those associated with xenobiotic metabolism, and the abundance of gut microbial community were altered. Microbial analysis revealed that at least five archaeal types, two to four bacterial types, three to seven eukaryotic types, and three viral types were involved in a correlation network composed of strong associations. Among them, Haloquadratum, Halalkalicoccus, and Methanospirillum (archaea); Volvox (eukaryote); and Varicellovirus and T4-like viruses showed significantly increased abundance. Furthermore, covariance structure analysis indicated that the viruses and methanogens played key causal roles as characteristic factors related to EPS administration. In conclusion, EPS disrupts the intestinal environment of wharf roaches and serves as a potential material for viral activation and methane production. Building on our previous field study that identified wharf roaches as potential indicators of coastal EPS pollution, this study provides novel insights into the ecological impacts of EPS ingestion and consequences of plastic pollution.

Bisphenol A (BPA) and Bisphenol S (BPS) exposure disrupt ovarian function and granulosa cell (GC) steroidogenesis. Extracellular vesicles (EVs) and their miRNA cargo, as mediators of cellular response to environmental stimuli, might be involved in fertility and folliculogenesis. This study explored modulation of microRNA expression after 48h BPA or BPS exposure (10 {micro}M) in ovine primary GC and EVs from corresponding conditioned medium (CM EVs). Small RNA sequencing of control (0h) and 48h treated GC, CM EVs as well as follicular fluid EVs allowed identification of 533 ovine miRNAs, including 129 new sequences. BPA did not alter miRNA expression in GC, while BPS decreased cellular oar-24b miR. In contrast, BPA modified expression of 4 miRNAs in CM-EVs, including 3 new sequences, and two miRNAs were modified by BPS. Both compounds reduced expression of sequence homologous to miR-1306. Further studies are required to decipher their roles in bisphenol toxicity in GC.

Background & Aims: Per- and polyfluoroalkyl substances (PFAS) are persistent endocrine-disrupting chemicals associated with metabolic dysfunction, including metabolic dysfunction-associated steatotic liver disease (MASLD). While PFAS perturb lipid and bile acid (BA) metabolism in a sex-specific manner, the underlying mechanisms remain unclear. We tested whether steroid hormones mediate PFAS-associated metabolic alterations. Methods: In 104 patients with biopsy-characterized MASLD, we performed sex-stratified analyses applied liquid chromatography coupled to mass spectrometry (LC-MS) for chemical analysis, integrating circulating steroids, PFAS exposure, hepatic lipidomics and BA profiles. Results: Steroid hormones were associated with MASLD severity in a sexually-dimorphic manner. Dihydrotestosterone showed consistent inverse associations with steatosis, fibrosis, necroinflammation and insulin resistance, particularly in females. PFAS exposure was associated with altered steroid profiles, predominantly indicating suppressed steroidogenesis in females. These PFAS-associated hormonal changes were linked to downstream alterations in hepatic lipids and BAs. Mediation analysis supported indirect effects of PFAS on metabolic pathways via steroids, including testosterone/epi-testosterone-mediated effects on ether phospholipids and estradiol-mediated effects on lithocholic acid. Females exhibited stronger PFAS-steroid-BA associations, whereas males showed weaker, lipid-centric effects. Conclusions: PFAS exposure is associated with sex-specific disruption of steroid hormone pathways that may link environmental exposure to lipid and BA dysregulation in MASLD. These findings identify steroid hormones as potential key mediators of PFAS-associated metabolic dysfunction and highlight sex as a critical determinant in environmental liver disease.

Antimicrobial resistance (AMR) is a significant and growing threat to human, plant and animal health, the global economy, and food security. The One Health approach to AMR recognises the role of the environment in the evolution, emergence, and dissemination of AMR. In part, this is due to anthropogenic pollution that releases AMR organisms alongside cocktails of compounds that may select for AMR in situ, which then pose an exposure risk to humans and animals. This has spurred growing interest from cross-sectoral stakeholders in environmental risk assessment (ERA) of antibiotics, with regards to their selective potential. Many different experimental and modelling approaches have been used to determine the lowest concentration of an antibiotic that may select for AMR. Debates continue regarding which individual approach, if any, may be best for determining concentrations of antibiotics that may select for AMR, for ERA purposes. This paper contributes to this ongoing discourse by refining and using a previously published method SELECT (SELection Endpoints in Communities of bacTeria) to rapidly generate predicted no effect concentrations for resistance (PNECRs) for 32 antibiotics on the premise that reduction in growth of complex community of bacteria correlates with selection for AMR resistance genes. The database of PNECRs of antibiotics presented here is the largest generated using a single experimental, empirical approach that will aid future efforts towards creating a standardised test. PNECR data were used to conduct ERAs using measured environmental concentrations of antibiotics to rank antibiotics by potential selection risk in different environments. The experimental approach and statistical code have been made open access, with online tutorials available to facilitate other laboratories using the SELECT 2.0 method. Finally, we discuss the limitations of this approach and how these could be addressed in future studies.

Microbial communities play a central role in compost-bedded pack (CBP) systems by driving organic matter decomposition and nutrient cycling. The objective of this study was to characterize and compare the bacterial community structure of CBP from two dairy farms in Cordoba, Argentina, using 16S rRNA gene sequencing. Two CBP systems were evaluated: Martin Bono (MB; 30 months in operation) and Angela Teresa (AT; 20 months). The MB system was established on natural soil without bedding addition and included concrete feed alleys, whereas AT was initiated with peanut shell bedding and lacked concrete alleys. In both systems, compost was tilled twice daily. Two samples per farm were collected at a depth of 30 cm during winter 2019. Raw Illumina reads were processed using the DADA2 pipeline, including quality filtering, error modeling, denoising, and chimera removal. A total of four samples yielded 2,503 amplicon sequence variants (ASVs), with approximately 76% of reads retained after filtering and chimera removal, indicating high-quality sequencing data. Taxonomic analysis revealed that bacterial communities in both systems were dominated by phyla typically associated with compost environments, including Actinobacteriota, Proteobacteria, and Firmicutes. Differences in relative abundance between systems suggested shifts in community composition associated with management conditions.