Ecotoxicology and Environmental Safety

Hormesis is an important consideration in chemical risk assessment across most aquatic environments. Evidence suggests that hormetic responses are shaped by organismal physiological processes. Accordingly, predictions of hormesis under environmentally realistic conditions should account for physiological traits. Yet the role of these traits remains largely unexplored. This study investigated how baseline growth rate modulates antibiotic responses in the harmful cyanobacterium Microcystis and the underlying mechanisms. Results showed that at an antibiotic concentration of 200 ng L-1 (representing environmental concentration levels), slow-growing Microcystis populations exhibited an obvious growth enhancement more than 4-fold greater than that of fast-growing populations, and this enhancement was positively correlated with cellular reserves. A baseline growth rate below 0.19 day-1 emerged as the threshold below which hormetic responses were consistently observed. This study provides pioneering insights into how organisms' physiological states influence pollutant-induced hormetic responses in aquatic environments. Our findings point to a central principle for extrapolation that laboratory-derived toxicological responses may not translate directly to the field unless key physiological traits of the organisms are explicitly considered. In this regard, baseline growth rate and energy reserves may be key physiological traits for reliably predicting toxic effects at the population level. This study also makes an initial attempt to conceptualize a physiology-anchored framework for strengthening risk assessment of low-level emerging contaminants.

Urban green infrastructure is increasingly promoted as a public-health intervention, yet the biological features that determine exposure to potentially beneficial plant-derived volatile compounds remain poorly understood. Here we quantified airborne terpenes and terpenoids across five contrasting urban greenspaces in Oxford, UK, and related chemical profiles to plant diversity, vegetation structure and surrounding habitat characteristics. Ambient air samples collected across spring and summer were analysed by thermal-desorption gas chromatography-mass spectrometry, alongside field surveys of taxonomic richness, canopy cover, vegetation volume and ground composition. Terpene and terpenoid scentscapes differed strongly among sites and through time, with monoterpenes dominating detected profiles. Sites with greater plant richness and greater vegetation volume below 1.5 m consistently showed higher terpene/terpenoid abundance, whereas total vegetation volume, canopy cover and tree abundance were weaker and less consistent predictors. These relationships were specific to plant-associated chemical classes and were not observed for predominantly anthropogenic volatile compounds. These patterns were resolved across only five independent sampling sites, and the relationships reported here should therefore be considered exploratory. Our findings suggest that human exposure to plant-derived volatiles in cities may be maximised not simply by increasing tree cover, but by designing biodiverse, structurally complex lower-to-mid-storey vegetation within the breathing zone. These results provide an empirical basis for incorporating scentscape ecology into health-oriented urban greenspace design.

Benzyl paraben (BzP) and butyl paraben (BuP) are used as preservatives and antimicrobial agents in cosmetics, pharmaceuticals, and foods. BzP and BuP have been detected in urine, placental tissue, and ovarian follicular fluid and are understudied with regards to their endocrine activity, raising concerns on their impact to the reproductive system. We tested the hypothesis that BzP and BuP are toxic to the ovary and behave similarly to other structurally similar endocrine disrupting chemicals, such as phthalates and terephthalates, by altering hormone levels and impacting cell growth and gene expression in vitro. Untreated mouse antral follicles were exposed to vehicle, 0.1, 1, 10, or 100 g/mL BzP, BuP, or the BuP analog monobutyl terephthalate (MBuTP) for 96 hours. The highest dose of BzP and BuP were cytotoxic to follicles, suggesting that medium chain length hydroxybenzoates are more cytotoxic to the ovary than corresponding terephthalic acids. BzP significantly increased levels of estradiol and testosterone compared to control. BuP decreased follicle growth and disrupted expression of cell cycle regulators, similar to phthalates. The peroxisome proliferator-activated receptor gamma (PPARg)-transcriptionally controlled gene Fabp4 was significantly upregulated by both BzP and BuP, whereas MBuTP upregulated all four PPAR target genes and decreased follicle growth. Overall, BzP, BuP, and MBuTP disrupted hormone levels, follicle growth, and cell cycle progression, suggesting similarities in toxicity to phthalates and potential endocrine disruption. Further study should be done on the reproductive toxicity and endocrine disrupting effects of chemicals similar in structure to phthalates to reduce exposure to endocrine disruptors and inform design of safer replacements.

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.

Per- and polyfluoroalkyl substances (PFAS) and phthalate metabolites are understudied in follicular fluid of women undergoing assisted reproduction. We characterized these in previously collected follicular fluid from patients at a Nebraska fertility clinic (August 2022 to June 2025) and retrieved demographics and clinical characteristics from fertility records. Spearman correlations and nonparametric tests evaluated PFAS and phthalate correlations and exposure differences by age, race, BMI, and urbanicity. Seven PFAS and four phthalate metabolites were detected in at least half of participants. PFOS and PFHxS concentrations were higher in younger women, and mono-isobutyl phthalate (MiBP) was higher in younger and non-White women. PFAS and phthalate correlations were weak, and exposures did not differ by urbanicity, indicating multiple chemical exposures in follicular fluid with sociodemographic disparities.

Background: Millions of textile and agricultural workers inhale organic dust containing endotoxin, an exposure associated with impaired respiratory function. However, the underlying biological pathways remain unclear. We conducted a two-cohort epigenome-wide association study (EWAS) to identify airborne endotoxin-associated DNA methylation (DNAm) alterations and pathways. Methods: In the discovery phase, we compared blood DNAm in 281 endotoxin-exposed cotton workers and 253 unexposed silk-workers from the Shanghai Textile Worker Study (STWS) measured using Illumina MethylationEPICv2 arrays. STWS endotoxin assessment combined detailed work histories and onsite measurements. For targeted parallel validation, we tested STWS signals in 686 incident lung cancer cases and 683 matched controls from the Shanghai Women's Health Study (SWHS), using occupation-derived low, medium, or high exposure-intensity ranks based on published evidence. To gain biological insight, we analyzed pathway enrichment, immune-cell composition, DNAm inflammation risk scores (IRSs), and respiratory phenotype associations in STWS. Results: In STWS, we identified 36 epigenome-wide significant DNAm sites (P<5e-8), of which, 35 were hypomethylated. Among 30 sites testable in SWHS, 18 had concordant effect directions, and four were nominally significant: cg11869499 (POLG; P=0.041), cg16290931 (TSKS; P=0.044), cg05019530 (EPIC1; P=0.042), and cg26033526 (PSMB9/TAP1; P=0.013). Enrichment implicated immune and signal-transduction pathways, including IgSF cell-adhesion-molecule signaling (FDR=8.2e-6;). Neutrophil were higher in cotton workers than in silk workers (63.5% vs 58.9%, p=7.52e-10). Cumulative endotoxin was associated with higher CRP-based IRSs, which showed the most consistent associations with lower lung function and airflow obstruction. Conclusions: Our EWAS findings suggest that occupational endotoxin may operate partly through immune-cell composition and inflammatory pathways.

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

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.

Inhalation of airborne per- and polyfluoroalkyl substances (PFAS) represents an important yet understudied exposure route. While volatile organic compounds (VOCs) have been widely explored as biomarkers of toxicant exposure, their potential for early detection of PFAS-induced pulmonary toxicity remains largely unexplored. This study investigated VOC profiles in human alveolar (A549) and bronchial (BEAS-2B) epithelial cells following exposure to environmentally relevant PFAS concentrations (1, 5, and 10 ppb) for 12, 24, and 48 h. VOCs were analyzed using headspace solid-phase microextraction coupled with gas chromatography-Orbitrap mass spectrometry. We observed significant concentration- and time-dependent alterations in VOC profiles in both cell models. The principal VOCs associated with PFAS exposure include butanal, acetone, 2-butanone, 2-nonanone, (E)-2-nonenal, (E)-2-octenal, (E)-2-heptenal, 2,4-heptadienal, 2,4-nonadienal, 2,4-decadienal, 1-pentanol, and 1-hexanol. Cell type-specific regulations were observed, reflecting differential metabolic responses between transformed and non-transformed lung epithelial cells. Metabolite set enrichment analysis indicated perturbations in ketone body metabolism, consistent with altered cellular energy metabolism. Complementary qPCR analysis revealed altered expressions of CYP1A1, CYP2E1, ALDH1A1, and ALDH2, supporting a mechanistic link between PFAS exposure and oxidative stress, lipid peroxidation, and impaired aldehyde detoxification. These findings demonstrate that VOC profiling, combined with transcriptional analysis, can reveal PFAS-induced metabolic perturbations in pulmonary epithelial cells.

Importance: Long-term exposure to higher average air pollutant concentrations is associated with poorer cognitive health, but annual averages can obscure substantial differences in day-to-day exposure. Whether recurrent high pollution days are associated with long-term cognitive aging trajectories among people with similar overall air pollution exposure is unclear. Objective: To determine whether the annual number of days exceeding World Health Organization daily guideline values for nitrogen dioxide (NO2) and particulate matter (PM2.5 and PM10) is associated with subsequent cognitive decline after accounting for annual mean air pollutant exposure. Design: Prospective cohort study using data from waves 1-10 (2002-03 to 2021-23) of the English Longitudinal Study of Ageing. Setting: Population-based cohort of community-dwelling adults in England. Participants: 12,235 adults aged 50+ years at analytic baseline. Exposures: Number of days exceeding World Health Organization daily guideline values ('exceedance days') for NO2, PM2.5, and PM10, derived from residence-linked environmental estimates during the calendar year preceding the analytic baseline. Main Outcomes and Measures: Baseline cognitive performance and model-estimated 14-year cognitive decline (corresponding to the 75th percentile of follow-up duration) in episodic memory and verbal fluency. Results: Exceedance days were not associated with baseline memory or verbal fluency after adjustment for annual mean air pollutant exposure. More NO2 exceedance days were associated with faster cognitive decline: comparing the 75th percentile with the median of NO2 exceedance days, the difference in 14-year decline was -0.09 SD (95% CI, -0.17 to -0.01; p = 0.02) for memory and -0.10 SD (95% CI, -0.19 to 0.00; p = 0.04) for fluency. PM2.5 and PM10 exceedance days were not associated with cognitive decline. Conclusions and Relevance: In this cohort study of older adults, a higher number of NO2 exceedance days was associated with faster subsequent cognitive decline after adjustment for annual mean air pollutant exposure. This suggests that daily exposure to high NO2 concentrations may be related to accelerated cognitive aging even when offset by lower exposure on other days, potentially providing a new rationale for identifying and prioritizing areas with recurrent high NO2 exposure and the local emission sources contributing to it.

Current health risk assessments from thirdhand exposure to methamphetamine (meth) to occupants of contaminated residences when no cooking or use is still occurring assume that inhalation exposure is insignificant. After Wright et al. (2021) reported substantial meth concentrations in a contaminated residence, the present study was conducted to further test the hypothesis that concentrations were high enough to contribute to total occupant dose. Air sampling was conducted in contaminated residences that had been previously sampled for surface contamination. Samples were collected on personal sampling pumps in fixed locations on treated glass fiber filters is cassettes and analyzed by gas or liquid chromatography with mass spectroscopy. Sixty-nine samples were collected from eighteen residences for the study. Meth concentrations ranged from 0.02 to 15 ug/m3. Concentrations in supply air vents were significantly higher than in return vents or in ambient air. Residences with no HVAC systems (baseboard heat) had airborne concentrations similar to residences with HVAC systems turned off, and lower than when HVAC was on. Whether a residence was occupied or not did not show differences. All data from residences with HVAC had a significant correlation with surface concentrations (R2 = 0.61) but some factors that affected results were not determined in the study. In the context of the risk assessment and regulatory standard established by California and adopted in several other states, the inhalation exposure would approximately double total occupant dose for infants, and this population would exceed the California reference dose by approximately 100%. Further studies should be conducted to refine these estimates and determine the factors that influence airborne concentrations.

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants with the potential to disrupt metabolic processes and contribute to carcinogenesis; however, molecular evidence linking alternative and emerging PFAS to ovarian cancer (OC) remains limited. We conducted a biomarker-based case-control study integrating exposureomics with multi-omics profiling. Plasma samples from 128 patients with OC and 128 controls were analyzed for 26 PFAS, untargeted metabolomics, lipidomics, and clinical phenotypes, while urine samples from an additional 100 patients and 100 controls underwent untargeted metabolomic and clinical profiling. Single-compound, burden-based, and mixture models were integrated with PFAS-omics association scans, cross-matrix metabolite prioritization, observational exposure-omics-clinical association-chain analyses, and repeated internal cross-validation. Higher PFAS burdens were consistently associated with OC case status, and DONA, GenX, PFNA, PFPeS, PFUdA, and PFTrDA constituted an OC-prioritized six-PFAS mixture. DONA and GenX exhibited the broadest lipid-related bridging signals, particularly across phospholipids, lysophospholipids, sphingolipids, neutral lipids, and acylcarnitines. Integrated plasma and urine analyses further identified five shared metabolites-elaidic acid, hippuric acid, betaine, corticosterone, and taurocholic acid-that provided incremental and complementary discrimination beyond reference models based on clinical variables and tumor markers in internal cross-validation. Collectively, these findings demonstrate that both alternative and emerging PFAS are associated with a distinct OC-related molecular phenotype involving coordinated lipidomic, metabolomic, and hematologic alterations, while highlighting DONA and GenX as the most prominent exposure-related signals.

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.

Genetic variation impacts biological response to chemical and environmental exposures, contributing to differences in resistance or susceptibility. Forward genetic screens of genetically diverse cell populations can be used to identify the precise genetic variants that drive response variation. Cell lines from laboratory mouse genetic reference populations like the Diversity Outbred (DO) population are well powered for genetic mapping. Diverse stem cell panels are especially beneficial for studying early developmental effects of chemical exposures like triphenyl phosphate (TPHP), an organophosphate flame retardant linked to adverse developmental effects, including altered cell cycle in stem cells. Self-renewal and pluripotency are defining properties of stem cells during development; therefore, it is important to understand how chemicals like TPHP may alter these critical characteristics. To better understand the influence of genetic variation on TPHP exposure response, we utilized a genetically diverse panel of DO induced pluripotent stem cells (DO iPSCs). Our analyses characterize interline variation in gene expression through differential gene expression analysis and expression quantitative trait locus (eQTL) mapping. We identified genomic loci that contribute to variation in gene expression following TPHP exposure, including a regulatory hotspot on chromosome 15. Gene set enrichment highlighted several pathways affected by TPHP including lipid metabolism, steroid hormone signaling, and cell cycle. Our study shows that genetic variation modulates the effects of TPHP on gene expression and cell cycle in stem cells. Additionally, our work demonstrates that genetically diverse cell panels like the DO iPSC resource offer a tractable and scalable approach for identifying the genetic determinants of chemical toxicity.

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: Cardiovascular disease is an important competing cause of death in men with metastatic prostate cancer, and ambient air pollution may increase cardiovascular vulnerability. We evaluated associations of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) with all-cause, cardiovascular, and prostate cancer-specific mortality, including joint associations with androgen deprivation therapy (ADT). Methods: We analyzed 33,384 men from 11 US state registries diagnosed with metastatic prostate cancer during 2000-2015 and followed through 2018. Residential PM2.5 and NO2 concentrations at diagnosis were assigned using 1-km exposure models. Multivariable Cox models estimated all-cause mortality, and inverse-probability-weighted Cox models assessed cause-specific mortality. Results: Each interquartile-range increase in PM2.5 was associated with higher cardiovascular mortality (HR 1.04, 95% CI 1.02-1.07; p-trend=0.008). Cardiovascular mortality was also higher in the fourth and fifth PM2.5 quintiles versus the first (HR 1.18 and 1.21, respectively). Higher NO2 was associated with prostate cancer-specific mortality in the highest quintile (HR 1.07, 95% CI 1.01-1.13). In joint analyses, ADT-treated men with high versus low PM2.5 exposure had higher cardiovascular mortality (HR 1.19, 95% CI 1.05-1.34), without clear evidence of effect modification (p-interaction=0.051). Conclusions: In men with metastatic prostate cancer, higher PM2.5 exposure was associated with cardiovascular mortality, particularly among ADT-treated patients, supporting further study of environmental exposures and systemic therapy in cardio-oncology.

Micro/nanoplastics (MNPs) are increasingly recognized as a persistent environmental contaminant of concern, yet polyisobutylene (PIB), an industrially significant polymer used as industrial sealants, adhesives, cable insulation, lubricant additives, and chewing gum bases, remains poorly studied relative to more commonly studied plastics such as polyethylene terephthalate (PET), polystyrene (PS), and polyethylene (PE). This study investigated the multisystem toxicological effects of chronic dietary exposure to PIB-MNPs in Drosophila melanogaster. PIB-MNPs (> 5 micron) were synthesized via the solvent evaporation method and characterized using scanning electron microscopy (SEM) and Fourier Transform Infrared spectroscopy (FTIR), confirming successful synthesis. Flies were chronically exposed to PIB-MNPs (1, 2, or 3 mg) alongside an SDS control and a water control to 50 mg of yeast over 21 days, with toxicological outcomes assessed via survival analysis, climbing assays, fluorescence brain imaging, fertility/fecundity assays, the Smurf gut-permeability assay, Ellman's AChE activity assay, and RT-qPCR analysis of Stat92E expression, a marker of inflammation. Chronic exposure to PIB-MNPs reduced survival, with females exhibiting markedly greater susceptibility than males. Exposure progressively impaired locomotor performance and induced brain vacuolization suggestive of neurodegeneration, peaking at day 15. AChE activity declined in a concentration-dependent manner by day 21. Female fecundity, egg-hatching rate, and ovarian egg-chamber maturation were significantly reduced, while male gonadal cyst cell numbers remained largely unaffected. PIB-MNPs exposure also induced a positive Smurf phenotype, indicating compromised intestinal barrier integrity and upregulated Stat92E expression, consistent with activation of a systemic stress response. Notably, several endpoints showed non-monotonic, concentration-independent trends, suggesting particle aggregation may influence effective bioavailability. Collectively, these findings establish PIB-MNPs as a multi-system toxicant in Drosophila.

ObjectivesTo estimate the prevalence of objective peripheral neuropathy, and to test whether self-reported use of personal protective equipment (PPE) is associated with lower neuropathy risk, among adults attending a community hospital in a Nigerian population exposed to both agrochemicals and mining. DesignClinic-based cross-sectional study (June-November 2025), reported per STROBE. SettingInfant Jesus Community Hospital, Ishiagu, Ebonyi State, a community combining smallholder farming with granite and lead-zinc mining. Participants285 adults ([&ge;]18 years) attending the outpatient screening department; people with known diabetes were excluded. Main outcome measuresPeripheral neuropathy on the Michigan Neuropathy Screening Instrument (MNSI) examination -- an instrument validated in diabetic populations -- defined a priori as an abnormal 10 g monofilament test or absent/reduced ankle reflexes; three alternative case definitions were pre-specified. PPE use was scored 0-12. Associations were estimated by multivariable logistic regression adjusted for age and sex. ResultsThe proportion screening positive was 47.0% (95% CI 41.2-52.8) under the primary definition and ranged from 29.8% to 56.8% across definitions. PPE use was near-absent (89.1% never used gloves; 43.2% used none) and showed no detectable protective association (adjusted OR 0.97 per point, 95% CI 0.88-1.06). Men used PPE more than twice as often as women (55.1% vs 24.5%, p<0.001), yet neuropathy did not differ by sex (41.6% vs 49.5%, p=0.27). Only age was associated with neuropathy (adjusted OR 1.02 per year, p=0.02). ConclusionsNearly half of the adults sampled screened positive for peripheral neuropathy, and protective equipment showed no detectable protective association. Because PPE use was near-absent, the study cannot separate ineffective protection from too little protection to measure, and the cross-sectional design precludes causal inference. The equal burden across sexes despite markedly unequal protective behaviour is consistent with community-wide environmental exposure; reducing the total toxic load is a plausible priority that direct exposure measurement should now test.

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.

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.