Ultra short-chain perfluoroalkyl substances (USC PFAS) with C1-C3 chain lengths are increasingly important. Globally, trifluoroacetic acid (TFA) makes up the largest proportion of PFAS in the environment, however, knowledge about human internal exposure to these substances is scarce. We present a new, fast and robust human biomonitoring (HBM) method to quantify simultaneously 5 USC PFAS in urine. A simple dilute and shoot method based on liquid chromatography-tandem mass spectrometry using isotope dilution was developed, validated and applied in a HBM pilot study using samples from a population-based subsample of the general population. It showed linearity up to 75 µg/L, low limits of quantification (LOQ 0.05–1.5 μg/L), satisfactory matrix spiked mean relative recoveries (95–107 %) and overall precision (VC 2.9–12 %). In an initial set of two longitudinal samples from 150 participants, aged 21–69 years, of the German National Cohort Hamburg study center, TFA was detected in all samples, ranging from 2.96 to 1512 µg/L. Trifluoromethanesulfonic acid (TFMS) was detected in 73 % and quantified in 8 % of samples, providing first evidence of its occurrence in urine. All other analytes were below LOQ in all samples. Adjusted linear regression analyses showed that baseline TFA levels increased across five age groups and year of examination. From baseline (2015–2019) to follow-up (2020–2024) median of TFA increased on average by 1.6-fold, independent of aging. These are the first longitudinal data on TFA internal exposure among adults from a German metropolitan region, revealing the need for analyzing potential predictors of exposure over time.
Mycotoxin contamination of food and feed is an increasing global health concern, particularly due to Fusarium toxins such as the regulated deoxynivalenol (DON) and the emerging enniatin B (ENNB). However, the combined mechanisms of action of these toxins remain poorly understood. This study aimed to assess their toxic effects, alone and in combination, using the HepaRG liver cell model. Toxicity, individually and in combination at concentrations equivalent to those used in single exposures (5:1 DON to ENNB ratio), was assessed in HepaRG cells. Several endpoints were investigated, including viability (cell number), γH2AX formation and apoptosis (active caspase-3) by High Content Analysis (HCA) as well as the pro-inflammatory response (IL-8 sretion) by ELISA. DON induced a concentration-dependent decrease in cell number and increased the levels of active caspase-3, γH2AX and IL-8. In contrast, ENNB only slightly reduced cell viability. Interestingly, the combination limited DON-induced cell death, DNA damage and apoptosis. To further investigate which pathways are involved in toxicity, proteomics and metabolomics analyses were performed. DON increased long-chain saturated dicarboxylic acids, suggesting impaired fatty acid oxidation (FAO), histones and proteins related to mitochondrial respiration while reducing FAO-related proteins. These effects were mitigated by ENNB, suggesting opposite effects of the toxins. This mitigation appeared to be consistentwith the involvement of peroxisome proliferator-activated receptor alpha (PPARα) signaling, though without direct receptor activation by either substance. We present insights into DON and ENNB toxicity and highlight the importance of considering combined effects in risk assessment.
Prenatal and early life exposure to phthalates has been increasingly implicated in adverse neurodevelopmental outcomes. However, associations between phthalate exposure in early life and later adolescent mental health remain understudied, particularly when also considering co-exposure to early life psychosocial stressors. We examined the independent and combined associations of prenatal and early life (ages three, five, and seven) phthalate exposure with adolescent internalizing symptoms in a longitudinal cohort of 563 Black and Latiné mother–child dyads living in a low-income urban neighborhood. We further explored whether early life stress modified these associations or predicted internalizing symptoms independently. Exposure to eleven common phthalates was assessed using urinary metabolites measured in the third trimester of pregnancy and in children ages three, five, and seven. Early life stress was operationalized by a composite measure of material hardship and maternal demoralization measured concurrently with phthalate exposure. Youth self-reported anxiety and depression symptoms were measured between ages 13–15 with the Revised Children’s Manifest Anxiety Scale and Center for Epidemiological Studies Depression Inventory, respectively. Bayesian kernel machine regression assessed effects of the phthalate mixture on anxiety and depression symptoms. False discovery rate-corrected, pooled linear regressions tested individual phthalate effects, stratified by sex, and tested early life stress as an effect modifier. We did not detect significant associations between prenatal or postnatal phthalate exposure—either independently or jointly—and adolescent depression or anxiety; early life stress did not modify these associations or independently predict symptomology. However, uncertainty in effect estimates necessitates future research to clarify if these null effects hold in larger samples. If replicated, our findings suggest that there may be important, as yet unknown resilience factors protecting youth from long term effects of early phthalate exposure.
Micro- and nano-plastics (MNPs) have emerged as ubiquitous environmental contaminants and are increasingly implicated in adverse cardiovascular outcomes, yet their induced cardiotoxicity and potential mechanisms remain poorly understood. This study integrated in vivo mouse models, AC16 cardiomyocytes and a human cardiac organoid-on-a-chip (COoC) platform to multi-dimensionally evaluate polystyrene nanoparticles (PS-NPs)-induced cardiac injury and clarify its key molecular mechanisms. We found that PS-NPs exposure induced pronounced structural and functional cardiac injury in mice and caused impaired myocardial contraction, disrupted calcium transients and increased injury biomarkers in vitro. Notably, PS-NPs exposure perturbed myocardial energy metabolism, producing a metabolic reprogramming profile characterized by suppressed fatty acid oxidation (FAO) and enhanced glycolytic activity. Metabolic interventions further showed that activation of FAO or promotion of mitochondrial pyruvate oxidation improved myocardial energy status and alleviated cardiotoxicity, whereas direct inhibition of glycolysis aggravated energy depletion and cellular injury, suggesting that enhanced glycolysis provided partial energetic compensation but was insufficient to offset impaired oxidative metabolism. Mechanistically, our findings indicated a functional role of the SDHA/succinate/HIF-1α signaling axis in this metabolic reprogramming. PS-NPs-induced SDHA downregulation promoted succinate accumulation and HIF-1α stabilization, thereby rewiring myocardial energy metabolism and contributing to cardiac dysfunction. Collectively, we revealed myocardial metabolic reprogramming as an important mechanism underlying PS-NPs-induced cardiotoxicity and identified the SDHA/succinate/HIF-1α axis as a potential molecular link between PS-NPs exposure and cardiac injury.
Fish and seafood consumption provides essential nutrients for fetal and child development but is also the main source of human exposure to methylmercury, a neurotoxic substance of public health concern. To ensure safe consumption during pregnancy and early life, food safety authorities have issued recommendations; however, their integration into clinical guidelines and practice remains unclear.This study assessed whether fish consumption advice during pregnancy in Spain adequately addresses mercury exposure by integrating evidence from biomonitoring studies, guideline analysis, and healthcare professionals’ practices. A scoping review identified studies measuring mercury biomarkers in pregnant women and children. In parallel, international, national, and regional guidelines in Spain were reviewed to evaluate the presence, accuracy, and clarity of recommendations. Additionally, a nationwide cross-sectional survey was conducted among healthcare professionals involved in maternal and childcare.The scoping review showed consistent evidence of mercury exposure in pregnant women and children, largely influenced by fish consumption patterns. Guideline analysis revealed substantial heterogeneity, frequent omissions of official recommendations, and the use of outdated or incomplete information. Survey results indicated limited awareness of official guidance among healthcare professionals and inconsistent communication of advice to pregnant women.Overall, despite the availability of scientific evidence and official recommendations, fish consumption advice during pregnancy in Spain is inadequately integrated into clinical guidelines and healthcare practice. Strengthening dissemination and implementation of clear, updated, and evidence-based recommendations is essential to support healthcare professionals and ensure safe fish consumption during pregnancy.
Diquat (DQ) is one of the most widely used bipyridyl herbicides and has been identified as a potential neurotoxin; however, its primary central nervous system (CNS) targets and the underlying mechanisms remain unclear. In cases of acute human DQ poisoning, subcortical white matter lesions have been reported to emerge approximately two weeks after exposure, with demyelination representing the predominant pathological finding. We used an acute oral DQ exposure rat model that mimics human DQ poisoning. Magnetic resonance imaging (MRI) revealed prominent white matter abnormalities in the corpus callosum, while histological analyses confirmed demyelination, impaired myelin integrity, reduced myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) expression, and marked mitochondrial ultrastructural damage. RNA sequencing indicated significant enrichment of ferroptosis-associated pathways. DQ induced sustained intracellular reactive oxygen species (ROS) accumulation and reduced nuclear factor erythroid 2-related factor 2 (Nrf2) expression. DQ exposure also reduced ferroportin (FPN) expression, accompanied by intracellular Fe2⁺ accumulation, enhanced lipid peroxidation, and ferroptotic cell death. In vivo, ferrostatin-1 pretreatment significantly attenuated DQ-induced demyelination. In vitro, N-acetylcysteine (NAC) partially restored Nrf2 expression and attenuated DQ-induced lipid peroxidation, whereas FPN overexpression reduced intracellular Fe2⁺ accumulation and lipid peroxidation. Collectively, these findings suggest that DQ disrupts redox balance and iron homeostasis in association with reduced Nrf2 signaling and FPN expression. Targeting FPN-mediated iron homeostasis warrants further investigation as a potential strategy for limiting DQ-induced neurotoxicity.
Chlorination of drinking water effectively prevents waterborne infections but also results in the formation of potentially carcinogenic disinfection by-products, including trihalomethanes (THMs). Experimental animal studies indicate that the liver and kidney are target organs for THM carcinogenicity, yet epidemiological evidence remains limited for these sites. In this study we assessed the association of long-term exposure to THMs in drinking water with incidence of liver and kidney cancer in two large Swedish population-based cohorts. We included 58,664 adults from the Swedish Infrastructure for Medical Population-Based Life-Course and Environmental Research (SIMPLER), who were supplied by public drinking water. Individual residential histories were linked to a national database of drinking-water monitoring results to estimate long-term exposure to total THMs. Incident liver and kidney cancer cases were ascertained through linkage to the Swedish National Cancer Register. Multivariable adjusted Cox proportional hazards regression models were fitted to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 25 years of follow-up, 183 liver cancer cases and 347 kidney cancer cases were ascertained. Residential drinking water THM exposure was not associated with liver cancer. For kidney cancer, THM was dose-dependently associated with higher risk (p-trend = 0.047) among men with HR 1.54 (95% CI 1.00, 2.38) comparing ≥15 µg THM/L with no drinking water chlorination. No association was observed among women. Although based on a limited number of cases, these findings provide novel prospective cohort evidence on the potential association between long-term THM exposure and kidney cancer at exposure levels below current regulatory limits for drinking water. The observed association warrant confirmation in future independent studies.
The widespread use and non-biodegradable nature of polyethylene microplastics (PE-MPs) have prompted significant public concern about their safety. However, the mechanisms underlying their adverse effects on human health remain largely elusive. Male rats were orally administered 34-μm PE-MPs via daily gavage for 28 consecutive days, with three dose groups set at 0.6, 6.0, and 60.0 mg/kg body weight (bw), respectively. The results showed that exposure to PE-MPs induced a decrease in serum triiodothyronine (T3) levels, accompanied by an increased incidence of thyroid follicular dilation, both of which displayed a distinct dose-response relationship. The 28-day oral toxicity study in male rats identified a no-observed-adverse-effect level (NOAEL) of 0.6 mg/kg bw and a lowest-observed-adverse-effect level (LOAEL) of 6.0 mg/kg bw for PE-MPs, corresponding to approximately 10 and 100 times the estimated daily human intake of microplastics, respectively. Toxicokinetics revealed that PE-MPs were absorbed and markedly accumulated in major organs, and the organ burdens correlated strongly with the severity of thyroid toxicity. Integrative multi-omics analysis implied that PE-MPs exposure altered the expression of thyroid toxicity-related genes Ddit3, Zbtb16 and the levels of associated metabolites. This study provides exploratory experimental evidence identifying the thyroid as a target organ for PE-MPs-induced toxicity. It should be noted that conclusions drawn from multi-omics and toxicokinetic analyses are limited by the relatively small sample size in the present work. Further validation with larger sample sizes is required in future studies. These findings contribute valuabledata to human health risk assessment and regulatory oversight of PE-MPs.
Per- and polyfluoroalkyl substances (PFAS) accumulate in the hippocampus, yet their effects on adult hippocampal neurogenesis (AHN) remain unclear. In this study, adult male mice were orally exposed to PFOA or GenX (2 or 10 mg/kg/day) for 28 days. Behavioral performance, AHN, synaptic remodeling, microglial morphology, and redox status were evaluated using behavioral assays, Nissl and Golgi staining, BrdU immunolabeling, microglial morphometric analyses, and Western blotting. PFOA exposure and high-dose GenX exposure reduced time spent and distance traveled in the center area of the open field and impaired spatial learning and memory performance in the Morris water maze, as indicated by increased escape latency and fewer platform crossings. In contrast, PFOA and low-dose GenX exposure reduced exploration of the open arms in the elevated plus maze. PFOA and GenX reduced dendritic spine density with fewer mushroom/thin spines and more stubby spines. PFOA preferentially decreased PSD95 (postsynaptic marker), whereas GenX reduced synaptophysin (presynaptic marker). In the subgranular zone (SGZ), survival and neuronal differentiation of neural stem cells were diminished, and asymmetric divisions of radial glia-like cells increased, suggesting stem-cell pool depletion. Microglia exhibited a hyper-ramified/bushy reactive phenotype. Hippocampal ROS/MDA rose, NOX2 components (GP91phox/P22phox) were upregulated, and ferroptosis defenses (SLC7A11/GLS2/GPX4) were downregulated. Collectively, PFOA and GenX disrupt hippocampal synaptic remodeling and AHN and are associated with increased oxidative stress and ferroptosis-related alterations. Differential pre- versus postsynaptic vulnerabilities may contribute to the distinct behavioral alterations observed following PFOA and GenX exposure. This work provides new insights into the neurotoxic effects of PFOA and GenX and identifies potential pathways involved in PFAS-induced hippocampal dysfunction.
Polychlorinated biphenyls (PCBs) are persistent organic pollutants of global concern, yet their associations with predicted cardiovascular risk remain unclear. In this prospective Wuhan-Zhuhai cohort study, concentrations of seven serum PCBs (PCB-28, 52, 101, 118, 138, 153, and 180) were measured using GC-MS/MS. The validated China-PAR equation was used to calculate predicted 10-year atherosclerotic cardiovascular disease (ASCVD) risk, and urinary 8-iso-prostaglandin F2α (8-iso-PGF2α) served as a marker of oxidative stress. Multivariable linear and logistic regression models were fitted to evaluate PCB-related differences in continuous predicted risk and predicted high-risk status. Cross-sectionally, each one-unit increase in ln-transformed PCB-118, PCB-138, PCB-153, and ΣPCB was associated with 1.249-, 1.253-, 1.457-, and 1.829-percentage-point higher predicted 10-year ASCVD risk, respectively (all P < 0.05). The associations for PCB-118, PCB-138, and PCB-153 remained significant after FDR correction. Longitudinally, persistent high PCB-118 exposure was associated with a 0.510 percentage-point greater increase in predicted 10-year ASCVD risk (95 % confidence interval [CI]: 0.023-0.996, P < 0.05) and a higher risk of transitioning to predicted high-risk status (RR = 1.432, 95 % CI: 1.012-2.027, P < 0.05) compared with persistent low exposure, although neither association remained significant after FDR correction. Exploratory mediation analysis suggested that urinary 8-iso-PGF2α was statistically consistent with partial indirect pathways for the associations, with estimated indirect proportions ranging from 3.29 % to 11.62 %. Database-derived bioinformatics analyses highlighted TNF/NF-κB/IL-17 pathways and identified IL-6, TNF, IL-1β, and ICAM1 as candidate hub genes. Overall, several PCB measures were cross-sectionally associated with higher predicted ASCVD risk, whereas longitudinal evidence was limited and was strongest for persistent high PCB-118 exposure. Exploratory mediation and bioinformatics findings highlighted possible oxidative-stress and inflammation-related pathways that require further validation.
Background The C8 Science Panel previously conducted studies of perfluorooctanoic acid (PFOA) exposure in Ohio Valley residents, finding probable links with kidney and testicular cancers, raised cholesterol, ulcerative colitis, thyroid disease, and pre-eclampsia. Findings were largely based on a cohort of 32,254 persons with high PFOA exposure followed through 2011 for disease incidence. We have now followed this cohort through 2021 for mortality. Methods Deaths were ascertained via the National Death Index (NDI). We extended cumulative PFOA serum estimates from 2011 until 2021. We used internal comparisons via Cox regression models to analyze cause-specific mortality for 22 causes of death in relation to natural log transformed cumulative PFOA exposure (continuous and in quartiles) with a variety of lags, controlling for confounders. We also considered multiple cause of death. Results There were 5709 deaths in the cohort through 2021. We found a positive significant trend (p < 0.05) in underlying cause of death analyses between the log cumulative serum level and brain cancer [HR 1.25 (1.05, 1.50)] and a suggestive but non-statistically significant association with bladder cancer [HR 1.17 (0.98, 1.39). . In stratified analysis, pancreatic cancer showed a positive significant trend among older participants (>72 years) [HR 1.23 (1.05, 1.43)]. No other causes showed marked positive trends, except for stroke among workers (13 % of total cohort). Conclusion PFOA exposure was significantly associated with mortality from brain cancer, and pancreatic cancer among older subjects. Pancreatic cancer has been associated with PFOA in animal studies, with equivocal evidence in other cohort studies. There was some suggestion of an increase of bladder cancer Caution is warranted due to multiple comparisons.
Aromatic amine antioxidants (AAs) and p-phenylenediamine quinones (PPD-Qs) are novel environmental contaminants derived from tire wear, with emerging neurotoxic concerns, but epidemiological evidence linking them to cognitive health is lacking. This study investigated associations between exposure to these chemicalsand cognitive performance in older adults, and explored the potential mediating role of thyroid hormones. We measured urinary concentrations of nineteen AAs and six PPD-Qs in 439 older adults from Shenzhen, China, and assessed cognitive function using the Mini-Mental State Examination (MMSE). Higher urinary levels of specific compounds, such as N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q), 4-(cyclohexylamino) diphenylamine-quinone (CPPD-Q), and 4-phenylaminodiphenylamine-quinone (DPPD-Q), were significantly associated with lower MMSE scores and increased risks of cognitive impairment. Mixture analyses further indicated that combined exposure to these chemicals was linked to poorer cognitive performance, with 6PPD-Q and CPPD-Q as the most significant contributors. Additionally, specific thyroid hormones were associated with both chemical exposures and cognitive outcomes. Exploratory mediation analysis suggested that thyrotropin (TSH) and total triiodothyronine (TT3) may mediate the association between DPPD-Q exposure and poorer performance in specific cognitive domains. These findings provide the first epidemiological evidence that AAs and PPD-Qs exposure may be associated with cognitive decline in the elderly, potentially via disruption of thyroid hormone homeostasis. These observations warrant confirmation in longitudinal studies.
Nitrogen-containing organic compounds (NOCs) are important constituents of fine particulate matter emitted from household solid-fuel combustion, yet their personal-exposure characteristics and potential biological relevance remain insufficiently understood. We conducted an exploratory cross-sectional study among 15 rural homemakers, including 12 solid-fuel users and three electric-heating controls. Personal breathing-zone PM2.5 and PM0.25 samples were collected during two consecutive 24-h periods, and six classes of filter-collected PM-associated NOCs were quantified. Urinary inflammatory and oxidative-stress-related biomarkers and a targeted panel of 62 amino-acid-related metabolites were also analyzed. Personal exposure concentrations of the measured NOC classes were substantially higher in solid-fuel households than in electric-heating households, with particularly pronounced differences in free amino acids (FAAs) and C6-C20 alkyl nitriles. Urea dominated the total measured NOC mass, whereas FAAs constituted the largest non-urea fraction in the solid-fuel group. Correlation and exploratory mixture-response analyses indicated that FAAs and alkyl nitriles were the NOC classes most consistently associated with urinary C-reactive protein and vascular endothelial growth factor. Targeted urinary amino-acid profiling identified lower urinary concentrations of 4-hydroxyphenyllactic acid and methylguanidine in solid-fuel users based on nominal criteria, together with a borderline reduction in serotonin. Exploratory KEGG analysis further organized the measured metabolites into broad amino-acid-related biochemical categories, but was not interpreted as evidence of pathway activation or impairment. Overall, household solid-fuel use was associated with an NOC-rich personal PM exposure profile and selected urinary biomarker and targeted amino-acid-related patterns. Given the small and imbalanced sample and cross-sectional design, these findings should be interpreted as hypothesis-generating associations rather than confirmed biomarkers, causal effects, or mechanistic evidence.
Since the outbreak of the COVID-19 pandemic, the reinforcement of personal hygiene practices has led to a significant increase in surfactant residues in municipal wastewater. As a reservoir of antibiotic resistance genes (ARGs), municipal wastewater has been reported to facilitate the conjugative transfer of ARGs by surfactants. However, the intrinsic mechanisms driving this process and the broader impact of surfactants on ARGs fate in real wastewater systems remain poorly understood. Here, we demonstrate that residual cetyltrimethylammonium bromide (CTAB) and sodium dodecylbenzenesulfonate (SDBS) promote ARGs transfer both between Escherichia coli (E. coli) strains and from E. coli to municipal wastewater indigenous microbiota. Exploration of the underlying mechanisms revealed that CTAB exerts its effects primarily by increasing cell membrane permeability, inducing oxidative stress, and activating the SOS response. Further investigation showed that CTAB increases membrane permeability through direct binding to membrane proteins. SDBS primarily acted by enhancing bacterial motility and reducing barriers to cell contact. Additionally, modulation of glutamate and aspartate metabolism supported the conjugative transfer process by providing supplementary energy. Furthermore, we found that harboring multidrug-resistant plasmids conferred a survival advantage to bacterial hosts in municipal wastewater environments, thereby promoting the enrichment of ARGs. These findings elucidate novel mechanisms underlying surfactant-facilitated dissemination of ARGs, revealing a significant but overlooked environmental risk associated with residual surfactants in wastewater.
Objective To examine the association between prenatal exposure to a mixture of EDCs and attention-deficit/hyperactivity disorder (ADHD) symptoms in children Methods Participating were mother–child pairs from the Environmental influences on Child Health Outcomes (ECHO) Cohort (n = 3,962, 18 Sites, 2001–2021). Maternal spot urine samples collected during pregnancy were sent to the Wadsworth Center Human Health Exposure Analysis Resource laboratory and analyzed using a single assay workflow. From those samples, 24 urinary metabolites of EDCs with detection frequency > 70%, were grouped as molar sum of high- and low-molecular-weight (HMW, LMW) phthalates, polycyclic aromatic hydrocarbons, bisphenol S, organophosphate esters, and organophosphate and pyrethroid pesticides. Child ADHD symptoms were assessed using raw scores from the Child Behavior Checklist for preschool-aged (CBCL/1½-5) and school-aged (CBCL/6–18) Attention-Deficit/Hyperactivity Problems subscale. Scores ≥ the 85th and 95th percentiles were respectively classified as borderline and clinical thresholds. Quantile g-computation estimated the expected change in ADHD outcome associated with a one-quartile increase in all prenatal EDC mixture concentrations, using negative binomial models for raw scores and binomial models for percentile thresholds. Results Prenatal exposure to the EDC mixture was not associated with child ADHD symptoms in preschool-aged or school-aged children in adjusted models for either continuous raw scores or percentile thresholds. Conclusion Overall our findings on prenatal EDC mixture exposure and ADHD symptoms were not robust to full adjustment. Future research that can delineate factors such as windows of vulnerability and trajectories of ADHD-related symptoms may help clarify mixed findings in the literature.
Despite widespread environmental detection of 2,4-di-tert-butylphenol (2,4-DTBP), its neurotoxic impacts on cognitive behavior remain largely unexplored. In this study, adult zebrafish were exposed to 0.01, 0.1, and 1 μM 2,4-DTBP for 28 days. T-maze testing revealed dose-dependently longer path lengths to the food-baited target zone, indicative of impaired spatial memory. Evans blue extravasation demonstrated that 2,4-DTBP increased blood-brain barrier permeability and bioaccumulated in the zebrafish brain. Ultrastructural analysis confirmed impaired synaptic plasticity and neuron injury. Targeted metabolomics identified six significantly alterated neurotransmitter-related metabolites (threonine, glycine, arginine, aspartic acid, histidine, and tyramine) implicated in neuroinflammation. 2,4-DTBP disrupted intestinal barrier integrity (reduced ZO-1 and occludin) and elevated nitric oxide (NO) levels and expressions of pro-inflammatory cytokines gene (il1b and il6). These gut-derived inflammatory mediators (NO, IL-1β, IL-6, and TNF-α) entered systemic circulation and subsequently translocated into the brain. Decreased brain NF-κB and iNOS expression indicated that neuroinflammation was driven by a gut-to-brain inflammatory cascade rather than de novo cerebral synthesis. Although bdnf and mmp9 transcripts were up-regulated, the mature brain-derived neurotrophic factor (mBDNF) levels were not proportionally increased, indicating impaired neurorepair. Our findings provide novel mechanistic insights into the potential contribution of environmental SPA contaminants to the pathogenesis of neurodegenerative disorders.
Fragrance products are ubiquitous in UK homes, yet the associated indoorPM2.5 exposure remains poorly quantified under real residential conditions. Using high time-resolution measurements from 112 London homes between 2022 and 2024, together with a source-resolved framework, our study found that fragrance use markedly elevated indoor PM2.5 exposure, with hourly peaks up to 1293 μg/m3 for incense, 858 μg/m3 for oil diffusers, and 622 μg/m3 for candles. Across homes using those fragrance products, incense and oil diffusers each accounted for nearly 50 % of bedroom PM2.5 exposure, whereas candles contributed 14 %.Exceedance of the WHO 24-hguideline (15 μg/m3) was frequent, with a median exceedance rate of 40 %in candle-using homes, and in some incense-using households, exceedances occurring on the majority of monitored days. Exposures were highest in compact dwellings and under inadequate room ventilation. As UK housing moves toward greater airtightness, these findings identify fragrance products as a dominant indoor PM2.5 source and provide empirical evidence relevant to source-aware ventilation design and Net Zero housing assessments.
Malodorous compounds (MCs) feature ultra-low olfactory thresholds, episodic emissions and rapid dispersion, which complicate the analysis of their spatiotemporal behaviors and hinders real-time identification and spatial mapping of individual odorants in industrial park malodor management. Here, we developed a cost-effective sensor array network guided by source-specific emission fingerprints. The network, calibrated in situ using XGBoost models, achieved species-specific, real-time concentration mapping of multiple MCs across a 3 km2 industrial park. A standardized protocol integrating olfactory screening and multi-platform instrumental analysis identified trimethylamine, ethanethiol, hydrogen sulfide and ammonia as the dominant MCs. Dedicated sensor arrays were then constructed based on these source-specific signatures and calibrated in situ against co‑located Fourier transform infrared (FTIR) measurements. A high-density monitoring network of 42 monitors equipped with sensor arrays was established, acquiring data at 10-minute intervals. Real-time concentration mapping based on the monitoring network directly linked MCs to their respective sources. Validated by independent mobile FTIR measurements, the network localized hotspots with <150 m deviation. This source fingerprint-guided spatial monitoring network transforms odor management from a complaint-driven response to source-targeted precision monitoring, offering a paradigm for industrial environmental supervision.
BACKGROUND:Air quality improvements have reduced PM2.5 mass, but particle surface area, which primarily contributes to inflammatory responses, may not follow the same trend, potentially creating health-relevant exposure. METHODS:To investigate this potential decoupling, we analyzed three years of observations in Fuzhou, China. Potential inflammatory responses were estimated from the lung-deposited surface area (LDSA) exceeding PM2.5-based expectations, using an animal-derived dose-response relationship that relates particle surface area to pulmonary inflammation. RESULTS:We identified that 6.6% of PM2.5 attainment hours (<35 μg m-3) exhibited elevated LDSA, with surface area exposure 7.5-fold greater than expected from the LDSA/PM2.5 ratio during other attainment hours, and 82% of potential inflammatory risk was undetected by mass-based assessment. During these periods, despite median PM2.5 mass concentrations of only 3.0 μg m-3 (well below air quality standards), toxicological dose-response assessment predicts potentially clinically relevant inflammatory responses (27% lung neutrophil infiltration). Machine learning reveals that photochemical oxidation (elevated O3 and secondary organic carbon importance) contributes to these periods by producing abundant 50-100 nm particles during summer-autumn afternoons under warm, high-radiation conditions. CONCLUSIONS:These photochemical ultrafine particle events represent a mechanistically distinct pollution regime where mass-based frameworks may underestimate potential inflammatory effects, a gap that may widen as emission controls reduce primary sources and climate warming enhances photochemistry.
