There are mixed findings on the associations of particulate matter (PM) with amyloid beta (Aβ) and phosphorylated tau (pTau) proteins, key pathologies of Alzheimer's disease (AD). The associations of airborne manganese (Mn) with AD biomarkers remain underexplored. We investigated the associations of PM with diameters ≤10 μm (PM10) and ≤2.5 μm (PM2.5) and their Mn constituents (Mn10, Mn2.5) with AD biomarkers. We included 340 cognitively unimpaired adults. Air pollution exposure was assessed using PM sampling and spatial modeling. Plasma Aβ40, Aβ42, pTau-181, and their ratios were measured using highly sensitive assays. Associations between air pollution exposure and the AD biomarkers were evaluated using single- and two-pollutant linear regression models per interquartile-range increase, with stratified analyses assessing potential effect modification. PM2.5 was inversely associated with the Aβ42/Aβ40 ratio (β = -0.002, 95% CI = -0.004, -0.001, p = 0.001). Mn2.5 was positively associated with pTau-181 (β = 0.387, 95% CI = 0.084, 0.691, p = 0.013) and the pTau-181/Aβ42 ratio (β = 0.057, 95% CI = 0.005, 0.108, p = 0.032). In the two-pollutant model, PM2.5 remained inversely associated with the Aβ42/Aβ40 ratio (β = -0.002, 95% CI = -0.003, -0.001, p = 0.008), and Mn2.5 remained positively associated with pTau-181 (β = 0.400, 95% CI = 0.073, 0.727, p = 0.017). Neither PM10 nor Mn10 exposure showed significant associations with any biomarker. The positive association between PM2.5 and the pTau-181/Aβ42 ratio appeared stronger in APOE-ε4 carriers (β = 0.109, 95% CI = 0.016, 0.201, p = 0.022) than in non-carriers (β = 0.007, 95% CI = -0.046, 0.060, p = 0.804) (p for interaction = 0.054). PM2.5 exposure was associated with the amyloid biomarker, whereas Mn2.5 exposure was nominally associated with the tau biomarker. These findings suggest differential associations of PM2.5 and its Mn constituent with amyloid- and tau-related biomarkers.

Microplastics (MPs) generated from plastic degradation in municipal solid waste landfills pose a persistent threat to subsurface soils and groundwater, yet their vertical distribution and migration mechanisms in deep soils remain poorly understood. We established nine soil and five groundwater sampling locations across an informal landfill site. Soil cores were collected at ∼1 m intervals to 6 m depth to analyze MP distribution and ecological risks. The results indicate pronounced MP abundance in both deep soils and groundwater, with average abundances of 57,740 ± 42,355 particles/kg dry weight and 55 ± 51 particles/L, respectively. The dominant polymers in soil were polytetrafluoroethylene (PTFE) and polyethylene (PE), accounting for 60.14% and 22.58%, respectively. In contrast, groundwater was primarily characterized by PE and polypropylene (PP), with PE representing the highest proportion at 58.82%. MP abundance in soils decreased significantly with increasing depth, indicating attenuation during vertical migration. Notably, distinct polymer-specific migration behaviors were observed: PTFE was preferentially retained in shallow soils, whereas PE exhibited greater vertical mobility and became relatively enriched in deeper soils and groundwater. Ecological risk assessment revealed that although the abundance of MPs was observed to decrease significantly in depth, the potential ecological risk index remained relatively stable across soil depths due to the increasing proportion of mobile polymers such as PE and HDPE in deeper layers. This indicates that risk assessments based solely on abundance may systematically underestimate the MP threat in deep subsurface environments. This work elucidates that polymer-specific migration is a key mechanism controlling the subsurface transport and fate of MPs from landfills, providing a scientific basis for developing polymer-informed risk management strategies.

Lambda-cyhalothrin (LCT) is a widely used type II pyrethroid insecticide commonly found in global aquatic environments. However, how it impairs cognitive function in non-target aquatic organisms at environmentally relevant concentrations remains poorly understood. In this study, adult zebrafish were chronically exposed to LCT at 0.1, 0.2, and 0.4 μg/L for 28 days. Behavioral tests, histopathological observations, multi-omics, and biochemical analyses were combined to explore the underlying neurotoxic mechanisms. Our results showed that exposure to 0.4 μg/L LCT significantly impaired spatial learning and memory in zebrafish and caused marked neuronal damage along with disrupted mitochondrial ultrastructure in the brain. LCT markedly inhibited key rate-limiting enzymes of glycolysis and the TCA cycle and blocked mitochondrial respiratory chain function, leading to insufficient ATP production and excessive ROS accumulation. Multi-omics integration revealed a severe depletion of cerebral α-ketoglutarate (α-KG) alongside inhibited α-ketoglutarate dehydrogenase (α-KGDH) activity and downregulated ogdh transcription. Critically, dietary supplementation with the cell-permeable α-KG analog dimethyl α-ketoglutarate (DM-KG) during LCT exposure restored brain α-KG levels, rescued TCA cycle flux and ATP production, attenuated oxidative stress, and recovered glutamate and GABA contents. These rescue experiments provide direct evidence that α-KG depletion is a key metabolic driver of LCT-induced disruption of energy metabolism and neurotransmitter homeostasis. While behavioral recovery was not assessed in the rescue experiment, these findings establish α-KG as a critical metabolic node in LCT neurotoxicity and offer a potential target for mitigating pyrethroid-induced neurological damage.

We report here dual impacts of atmospheric humic-like substances (HULIS) on climate forcing and oxidative potential in the northwestern Himalayas. Neutral HULIS (H-n) dominantly constrained the seasonal water-soluble organic carbon (WSOC) mass (53-63%) as well as bulk brown carbon (BrC) absorption (37-53%). The combined HULIS relative radiative forcing (RRF) at 300-400 nm ranged from 15±1% to 27±8% seasonally, and contributed 53-75% to BrC RRF. HULIS also accounted for more than half of the observed bulk volume-normalized oxidative potential (OPv), with greater contribution from H-n (31-37%) than that from H-a (14-18%). The intrinsic efficiency of reactive oxygen species (ROS) production (in terms of mass-normalized oxidative potential; OPm) was also higher for H-n than H-a (1.5-3.2 times), and a clear trend of increased OPm was observed in the photochemistry-dominated summer as compared to the primary emission-dominated winter. Three-dimensional fluorescence showed that H-n and H-a corresponded, respectively, to condensation-type HULIS associated with highly conjugated aromatic structures and degradation-type HULIS generated via photochemical and atmospheric processes. Clustered principal component analysis indicated that OPv of H-n was consistent with contributions from primary emissions and the degree of humification whereas that of H-a aligned more closely with secondary aerosol formation. These findings establish HULIS as a critical, yet overlooked, driver of both regional warming and oxidative stress in Himalayan environments.

Neonicotinoids (NEOs) are widely used systemic insecticides, and several individual NEOs have been associated with neurotoxic effects. Humans are commonly exposed to mixtures of parent NEOs (p-NEOs) and their metabolites (m-NEOs), yet the biological correlates of such mixed exposure in cerebrospinal fluid (CSF), particularly those relevant to neurotoxicity, remain insufficiently characterized. We quantified 6 p-NEOs and 4 m-NEOs in CSF samples from 159 patients with neurological disorders, most of whom had neuromyelitis optica spectrum disorder, and explored their associations with routine serum and CSF biochemical indicators to identify potential neurotoxicity-related biological signals. Associations were evaluated using multivariable linear regression (MLR), weighted quantile sum (WQS) regression, quantile g-computation (Qgcomp), and Bayesian kernel machine regression (BKMR). Dinotefuran (DIN) and imidacloprid-olefin (IMI-olefin) showed the highest median concentrations among the p-NEOs and m-NEOs, at 0.064 and 0.283 ng/mL, respectively. MLR identified nominal associations between at least one NEO and 24 biochemical indicators spanning several physiological domains. WQS regression showed a negative association with carbohydrate antigen 19-9 (β = -0.23, 95% CI: -0.45, -0.02; p = 0.04), whereas Qgcomp identified a negative association with mean platelet width (β = -0.13, 95% CI: -0.23, -0.04; p = 0.01). BKMR further identified a positive overall association with absolute lymphocyte count, driven mainly by IMI. Across mixture models, imidacloprid (IMI), IMI-olefin, and DIN were the most influential contributors. Overall, these findings suggest that NEO mixtures in CSF may be associated with biochemical changes potentially relevant to neurotoxicity and support the prioritization of key contributors in health effect assessment.

GenX (hexafluoropropylene oxide dimer acid, HFPO-DA), a widely used alternative to perfluorooctanoic acid (PFOA), has raised significant concerns due to its multi-system toxicity and potential human health risks. Accumulating evidence indicates that both the toxicokinetics and toxicity of GenX exhibit marked sex-specific differences. The current reference dose (RfD) derived by the U.S. Environmental Protection Agency (U.S. EPA) relies on allometric scaling for cross-species extrapolation, which may not adequately capture physiological determinants of toxicokinetics or account for sex-related variability. To address this gap, we developed the first sex-specific physiologically based toxicokinetic (PBTK) models for GenX in mice and extrapolated them to humans to derive sex-specific RfDs and assess population risks. A literature search identified nine mouse toxicokinetic publications contributing 14 sex-specific datasets for model calibration and evaluation, including nine male and five female datasets. The calibrated sex-specific models showed coefficients of determination (R[2]) exceeding 0.87 for both sexes, with 52.4% to 70.2% of predictions falling within twofold of the observations. The models were subsequently extrapolated to humans and evaluated using an independent human toxicokinetic dataset, with population biomonitoring data used for a separate consistency assessment. Using hepatocellular hypertrophy as the critical endpoint, the sex-specific RfDs were lower in males than in females (9.03 × 10[-6] vs. 5.10 × 10[-5] mg/kg/day). Risk assessment further indicated potential GenX-related health risks among populations living near fluorochemical industrial facilities. Overall, this study provides the first sex-specific PBTK models for GenX and supports more refined, sex-informed risk assessment and management.

Eutrophication, often caused by excess nitrogen, currently affects over 40% of water bodies globally. However, little is known about nitrate's sublethal toxicity on species considered hardy against this stressor, like crayfish. Pollutants can alter behaviour through long-term physiological changes or after short exposures by interfering with stimuli detection. To investigate whether nitrates affect crayfish behaviour, two experiments were conducted whereby crayfish were exposed to ecologically relevant moderate (50 mg NO3[-]/L) and high (150 mg NO3[-]/L) nitrate concentrations for 2 weeks or 30 min. They were then tested for their food-searching response to chemical food cues and their antipredator response to damage-released chemical alarm cues. Nitrates did not interfere with alarm cue responses but instead caused activity reductions in response to both alarm cues and water disturbances after high-level exposures for 2 weeks. Crayfish reduced food searching at both nitrate concentrations after two weeks while 30 min of nitrate exposure only caused effects at high concentrations. These results suggest that nitrates do not interfere with chemical cue detection, and likely elicit effects by decreasing oxygen availability for the musculoskeletal and sensory systems required for food-searching and antipredator behaviours. Furthermore, this is the first study demonstrating that crayfish can be affected by sublethal nitrate toxicity at ecologically relevant levels after exposures as short as 30 min, which could occur with point-source pollutant releases. Crayfish should not be overlooked when considering species vulnerable to eutrophication as it continues to spread, especially as sublethal toxicity can decrease fitness and result in indirect mortalities.

Various water-repellent consumer spray products (CSPs) are widely available and easily accessible. However, information on airborne per- and polyfluoroalkyl substance (PFAS) emissions during product use remains limited. This study quantified airborne PFAS emissions from thirty water-repellent CSPs categorized into four groups-tire, furniture, textile, and general-purpose-using a controlled chamber experiment designed to simulate typical indoor spray use conditions. Airborne PFAS concentrations, emission rates, emission factors, doses per event, and hazard indices were evaluated. The general-purpose group showed the highest airborne PFAS concentration (518.0 ± 100.1 ng/m[3]), followed by textile, furniture, and tire groups. The most frequently detected PFAS were 6:2 FTS, 8:2 FTS, PFOA, and PFHxA. Measured concentrations were substantially higher than PFAS levels typically reported in indoor air, indicating that spray product use can act as a significant short-term indoor emission source. The general-purpose group also showed the highest emission rate ((2.3 ± 0.5) × 10[5] ng/min) and emission factor ((1.9 ± 0.7) × 10[4] ng/g). Although hazard index under general consumer use conditions remained under 1, those estimated for professional-use scenarios exceeded 1, suggesting potential adverse health risks associated with repeated occupational exposure. Although the experiments were conducted under controlled conditions, the study provides realistic insight into short-term indoor PFAS exposure during CSP use. Furthermore, the detection of both legacy and alternative PFAS compounds in bulk materials and airborne samples adds significance to the findings and suggests the need for future management strategies to reduce exposure.

Air pollution is an increasingly recognized risk factor for late-life neurodegenerative and cerebrovascular diseases, yet its impact on brain structure remains incompletely understood.Here we investigate the association of long-term exposure to ambient air pollution with longitudinal changes in brain structure in middle-aged and older adults. In a longitudinal cohort of 4,276 middle-aged and older adults with repeated brain MRI, we quantified global, grey matter and white matter volumes, as well as white matter hyperintensities (WMH). Residential exposures to major air pollutants were estimated using high-resolution spatiotemporal models and linked to individual neuroimaging trajectories over follow-up. Using fully adjusted multivariable regression models, we show that higher long-term exposure to ambient particulate air pollution (PM2.5 and PM10) is associated with accelerated loss of global and regional grey matter and greater progression of WMH burden.Our findings provide longitudinal, population-based evidence that ambient air pollution is linked to both neurodegenerative and cerebrovascular pathways of brain ageing, supporting the brain as a key target organ of air pollution and underscoring the potential brain health benefits of improving air quality.

Tralopyril has been approved as an active substance in antifouling products under the European Biocidal Products Regulation since 2015. Its release into aquatic environments has raised concerns about its environmental fate and potential ecological impacts, yet its transformation behavior in natural waters remains insufficiently understood. In this study, a 288-day leaching experiment was conducted to investigate the long-term release of tralopyril from antifouling coatings. The hydrolysis of tralopyril was examined in natural waters and pH-buffered waters, while the photodegradation of its hydrolysis product and the effects of environmental factors were investigated under natural sunlight using coastal and seawater samples. Phototransformation products were identified by high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry, and possible transformation mechanisms were proposed. The toxicity of tralopyril and its transformation products was further assessed using zebrafish embryo tests, ECOSAR modelling, and ToxPi analysis. The results showed that tralopyril was rapidly released from antifouling coatings into the water phase and subsequently hydrolyzed to BCCPCA, indicating that tralopyril is unlikely to persist in aquatic environments. The hydrolysis half-lives of tralopyril in natural waters were less than 7 h. The photodegradation of BCCPCA was mainly driven by natural organic matter, with half-lives of 15 and 38 h in collected harbor water and seawater, respectively. Several phototransformation products were formed, including 4-chlorobenzamide. The LC50 of 4-chlorobenzamide was 5.78 mg L[-1], lower than that of BCCPCA at 6.56 mg L[-1], suggesting increased toxicity after transformation. In addition, six phototransformation products showed higher ToxPi scores than BCCPCA, indicating that sequential phototransformation may increase the ecological risks of tralopyril-derived products in marine and coastal waters.

Rice-paddy amphibians are routinely exposed to neonicotinoids, yet whether such exposure causes endocrine, mitochondrial, and neuromuscular toxicity remains poorly understood. Herein, we combined field surveillance across 39 rice-paddy sites in Zhejiang, China, with a 60-day exposure of adult Pelophylax nigromaculatus to thiamethoxam. Field monitoring in July detected all five neonicotinoids in 69.2% of rice-paddy water samples with summed thiamethoxam-equivalent concentrations ranging from 52.18 to 1282.69 μg/L, while concentrations in wild tadpoles ranged from 6.45 to 113.39 μg/kg. Laboratory thiamethoxam exposure (0.5 and 5 mg/L) resulted in predominant hepatic accumulation and detectable brain residues. Notably, thiamethoxam reduced serum T3, T4, FT3, and FT4, increased L-tyrosine, epinephrine, and dopamine, with dysregulation of HPT-axis-related genes. In skeletal muscle, thiamethoxam inhibited mitochondrial membrane potential, respiratory chain complexes I, II, III, V, as well as basal and maximal mitochondrial respiration (up to 55%). These defects coincided with fragmented AChR clusters, reduced receptor content, and impaired gastrocnemius force across 20-60 Hz in the 5 mg/L group. Some responses varied between sexes, with AChR fluorescence intensity significantly reduced only in females in 5 mg/L. Structural equation modeling supported a thyroid to mitochondrial pathway, in which thiamethoxam reduced integrated thyroid hormone status (β = -0.91), while thyroid hormone status positively predicted mitochondrial membrane potential (β = 0.79) and maximal respiration (β = 0.71). These findings identify thyroid hormone-linked mitochondrial dysfunction as a mechanistic bridge between thiamethoxam exposure and neuromuscular impairment.

Heavy metal contamination is widespread in large river basins, yet its ecological consequences are often inferred mainly from concentration exceedances, leaving community-level biological responses insufficiently resolved. Given that β-diversity captures spatial community reorganization that may not be detected by local α-diversity, we examined whether taxonomic and functional β-diversity can reveal ecological responses to metal pollution beyond conventional chemical assessment. Surface water, sediments, and benthic macroinvertebrates were sampled at 23 sites in the Xiangjiang River basin, China, during the wet and dry seasons in 2023. Arsenic, cadmium, chromium, copper, manganese, nickel, and lead, together with physicochemical variables, nutrients, sediment particle size, and taxonomic and functional diversity metrics, were quantified. All metals were detected in nearly all water and sediment samples in both seasons. Arsenic, cadmium, and lead frequently exceeded guideline values for the protection of aquatic life, with maximum water-phase concentrations of 141, 2.90, and 52.2 μg/L, respectively. Among 59 recorded macroinvertebrate taxa, moderately pollution-tolerant taxa dominated. Biological Monitoring Working Party scores indicated moderate-to-bad ecological quality in the wet season, with improvement in the dry season. Taxonomic and functional α-diversity were generally higher in the dry season, whereas taxonomic and functional β-diversity were higher in the wet season. β-Diversity responded more strongly than α-diversity to environmental gradients (marginal R[2]: 0.73-0.87 vs. 0.25-0.59) and was significantly associated with turbidity, sediment texture, and water-phase heavy metals. Path analysis further suggested direct effects of these variables and indirect seasonal effects through turbidity and water-phase metals. These findings indicate that concentration exceedance screening alone does not fully characterize the community-level ecological consequences of metal pollution, highlighting the value of integrating chemical monitoring with multidimensional biomonitoring in large river basins.

The increasing microplastics (MPs)/nanoplastics (NPs) pollution in the ocean has ecotoxicological effects on marine organisms, affecting their ecological function related to the sulfur cycle. Ciliated protozoa play an important role in dimethyl sulfide (DMS) emission in the microbial food chain. DMS is a negative greenhouse gas associated with the global climate. However, fewer studies were done on the influences of MPs or NPs on DMS and its related dimethyl sulfur compounds production caused by ciliates feeding. Here, we have investigated the ecotoxicological effects of 5 μm and 50 nm polystyrene (PS), alone and in combination with lead (Pb) on ciliates Euplotes vannus, and their impacts on DMS, dissolved and particulate dimethylsulfoniopropionate (DMSPd,p), and dissolved and particulate dimethyl sulfoxide (DMSOd,p) production. Our study indicated that MPs/NPs and Pb exposure slowed the growth rate of E. vannus, reduced its abundance and biomass, increased superoxide anion (O2·[‒]) generation rate, malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity, decreased glutathione (GSH) content. The co-exposure to NPs and Pb exerted a synergistic effect on the O2·[‒] generation rate and GSH content. In addition, exposure to MPs/NPs and Pb alone reduced the ingestion rate of ciliates, leading to inhibited production of DMS and DMSOd. These findings enhance our understanding of the ecotoxicological impacts of MPs/NPs and Pb, both alone and in combination, on protozoa and their importance on dimethyl sulfur compounds cycling.

Springtime ozone (O3) pollution has shown an earlier annual onset in recent years, yet its chemical drivers remain less understood compared to summer. Using an observation-based model, this study investigates the chemical drivers of this earlier spring O3 onset by comparing two contrasting spring episodes, emphasizing the role of specific volatile organic compounds (VOCs). More severe O3 pollution occurred in spring 2024 than 2023, with higher concentrations and earlier onset. The increased pollution level of O3 is primarily driven by elevated VOCs level and meteorological conditions, with meteorological factors showing a stronger influence. OVOC could accelerate the formation of peroxy radicals through photolysis and acyl peroxy radicals (RCO3·) reactions, while active alkenes through reactions with hydroxyl radical or Criegee Intermediates decomposition. The consistently higher peroxy radical formation rates in spring 2024 are key to the worsened O3 pollution. Source analysis, excluding meteorological influences, identified gasoline vehicles and industrial processes as the dominant contributors to VOCs and O3 in spring 2024. These sources emitted substantial amounts of active alkene and OVOC, respectively, enhancing photochemical activity and leading to higher O3 formation potential in 2024 (32.70% and 36.90%). Controlling the two sources could significantly reduce the peroxy radicals and O3 formation through RCO3·-related pathway. In summary, the elevated emissions of gasoline vehicles and industrial processes are identified as key drivers of the intensified photochemical activity in the 2024 episode. These findings quantitatively resolve the previously underrecognized roles of alkenes and OVOC in promoting peroxy radical formation under spring conditions, extending insights from summer studies and highlighting the need for season specific control measures.