Quaternary ammonium compounds (QACs) have raised concerns due to their widespread use in disinfectants and unknown bioaccumulation behavior. However, conventional bioaccumulation assessments are costly, time-consuming, and low-throughput, limiting their utility for screening the growing array of emerging QACs. In this study, we developed a protein affinity ultrafiltration mass spectrometry (PA-UF-MS) strategy using human serum albumin (HSA) as a molecular bait to selectively isolate bioaccumulative QACs from disinfectants. We identified 12 traditional and emerging QACs, including several silanol alkyltrimethylammonium compounds (silanol-ATMACs), with strong HSA binding affinities [fold changes (FCs): 10.1-60.0]. Five silanol-ATMACs (C10-C18) were further structurally elucidated by MS/MS characterization and confirmed via a hydrolysis-based transformation experiment. In silico toxicokinetic modeling and in vivo rat experiments revealed longer elimination half-lives for silanol-ATMACs compared to ATMACs, indicating their bioaccumulation potential. These silanol-ATMACs were mainly detected in medical disinfectants with a median total concentration (∑silanol-ATMAC) of 779 mg/L. While detected at modest levels in indoor dust (median: 8.04 ng/g), silanol-ATMACs exhibited elevated concentrations in human serum, comparable to those of 18 traditional QACs (medians: 10.6 and 13.9 ng/mL, respectively). Our findings demonstrate the application of PA-UF-MS for prioritizing emerging bioaccumulative contaminants and highlight the need for further toxicological evaluation and human exposure assessment of silanol-ATMACs.

Environmental exposure to toxic chemicals has long been suspected an important factor contributing to autism spectrum disorder (ASD) in children. Our study developed a suspect screening strategy to broaden the understanding of neurotoxicant exposure in children with ASD (n = 307) and healthy controls (n = 461) and the association between ASD and mixed chemical exposure. Suspect screening of urine samples from the study population identified a total of 94 neurotoxicants designated as confidence level 1, with additional 16 and 34 compounds designated as confidence level 2 and 3, respectively. Among identified level 1 compounds, 48 had a detection frequency >70% in the study population, covering plasticizers, polycyclic aromatic hydrocarbons, insecticides, flame retardants, ultraviolet filters, antimicrobial agents and synthetic antioxidants. The results reveal a complexity of exposure spectrum in ASD children. Conditional logistic regression analyses with level 1 compounds revealed significant associations between ASD and increasing urinary levels of 28 neurotoxicants. Mixed exposure analysis revealed a strong association between combined neurotoxicant exposure and the ASD diagnosis. Among the diversity of neurotoxicants, 1,3-diphenylguanidine (DPG), diphenyl phosphate (DPP) and mono (2-ethyl-5-carboxypentyl) phthalate (mECPP) were identified as the key substances contributing to the exposure-ASD associations. Collectively, our work reported a complex neurotoxicant exposure spectrum in ASD children and associations between neurotoxicant exposure and ASD. The findings highlight the complexity of neurotoxicant exposure in children and the importance of exploring environmental factors of ASD.

Micro- and nanoplastics (MNPs) can enhance the toxicity of co-occurring chemicals via a proposed "Trojan horse" effect, yet the underlying mechanisms remain unclear. Here, we investigated the estrogenic effects of coexposure of ultraviolet filter homosalate (HMS) and polystyrene nanosphere (PNS) using ovariectomized mice (HMS: 0.1 and 1 mg/kg; PNS: 2.5 mg/kg) and human cell models (HMS: 0.01 - 1 μM; PNS: 1 mg/L). In mice, HMS-PNS coexposure significantly increased uterine weight, promoted mammary gland proliferation, and upregulated estrogen receptor 1 and its downstream targets amphiregulin and progesterone receptor. Integrated metabolomic and transcriptomic analyses identified endogenous 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) as a key mediator of these effects in mammary glands. In MCF-7 cells, HMS-PNS coexposure elevated 15(S)-HETE levels, promoting cell proliferation via the estrogen receptor alpha-arachidonate 15-lipoxygenase (ERα-ALOX15) axis. At a concentration of 100 nM 15(S)-HETE, pharmacological inhibition of phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) abrogated cell proliferation and serum and glucocorticoid-regulated kinase 1 (SGK1) activation. Moreover, immunoprecipitation and docking analyses suggested a direct interaction between 15(S)-HETE and SGK1. Knockdown of ALOX15, or PI3K/AKT inhibition, suppressed HMS-PNS-induced cell proliferation. Taken together, these results demonstrated that HMS-PNS coexposure amplifies estrogenic responses through ERα-ALOX15-dependent 15(S)-HETE production and PI3K/AKT/SGK1 signaling. Our findings uncover a mechanistic pathway beyond the canonical "Trojan horse" effect, providing new insight into how MNPs modulate endocrine-disrupting activity of co-occurring contaminants and informing future risk assessment of combined environmental exposures.

The rapid expansion of the global renewable energy industry has led to increasing environmental release of LiFePO₄ (LFP) and polyvinyl chloride-derived micro/nanoplastics (PVC), yet their combined impacts remain largely unexplored. Here, we demonstrate that chronic co-exposure to environmentally relevant levels of PVC and LFP exerts synergistic hepatotoxicity through a gut-liver axis. Multi-omics integration reveals that co-exposure disrupts intestinal microbial homeostasis, depletes short-chain fatty acids, barrier integrity, and elevates plasma lipopolysaccharide (LPS) and pro-inflammatory cytokines. This gut barrier disruption permits portal translocation of LPS, PVC, and iron, initiating a hepatic inflammatory cascade. Concurrently, PVC and iron enrichment in both the intestine and liver, and lithium depletion in the liver under co-exposure exacerbate oxidative stress. Transcriptomic profiling identifies activation of the p38-cPLA₂-arachidonic acid axis and TGF-β/α-SMA signaling, linking metabolic inflammation to extracellular matrix remodeling and fibrosis. In vitro assays further confirm that co-exposures induce synergistic cytotoxicity and upregulate fibrogenic proteins. Collectively, these findings provide the first mechanistic evidence that co-exposure enhances hepatic fibrosis. This study not only underscores the overlooked health risks posed by composite pollution from renewable energy systems but also highlights the urgent need for sustainable material management and toxicity-informed design in the clean energy transition.

Quaternary ammonium compounds (QACs) are widely used in cleaning and disinfectant products, and their extensive use since the COVID-19 pandemic has raised increasing concerns about the potential health effects. However, exposure to QACs in different indoor environments remains insufficiently characterized. In this study, 18 QACs were determined in house dust (n = 45) and automotive cabin air filter (ACAF) dust (n = 50) from South China. The median & sum; QAC concentrations were 6968 and 7982 ng/ g in house and ACAF dust, respectively. Alkyltrimethylammonium compounds (ATMACs) predominated, comprising 51.5% in house dust and 65.0% in ACAF dust, with median concentrations of 3298 and 5600 ng/g, respectively. Dwelling factors did not significantly affect QAC concentrations in house dust, whereas in ACAF dust, benzyldimethyldecylammonium chloride (C10-BAC) decreased with mileage, and C10-BAC and benzyldimethyloctylammonium chloride (C8-BAC) varied with vehicle manufacturers. Toddlers exhibited higher estimated daily intakes of QAC (median: 124 ng/kg bw/day) than adults (4.02 ng/kg bw/day) under high exposure scenarios. Although the estimated health risks of QACs in this study were relatively low, ACAF dust showed comparable & sum; QAC concentrations with house dust and demonstrated its value as a passive sampling matrix for assessing long-term accumulation and human exposure in vehicle environments. (c) 2025 Publishing services by Elsevier B.V. on behalf of KeAi Communications Co. Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Membrane separation provides an efficient alternative to alleviate water scarcity. However, it remains challenging to mitigate membrane fouling, especially biofouling, and surpass performance trade-off limitation. Here we report an antibiotic membrane with broad-spectrum antibacterial properties for highly permeable and selective water purification. Using the antibiotic kanamycin and trimesoyl chloride as monomers, a polyamide-polyester membrane was constructed through interfacial polymerization. This membrane exhibits competitive separation performance, with a high water permeance of 47.9 l m(-2) h(-1) bar(-1), solute rejection of 99.6% and solute-solute selectivity of similar to 10,000, outperforming most existing membranes. Moreover, this membrane can effectively inactivate Gram-negative/positive, single/multiple-resistant and disinfectant-resistant bacteria at high concentrations of 3 x 10(7) colony-forming units per millilitre, showing mortality ratios of 93.6-99.9%. In addition, this membrane maintains long-term antibacterial durability during crossflow filtration for at least 170 h. These concepts and findings offer an alternative route to the design of high-performance and antifouling membranes for water treatment.

CONTEXT:The association between copper exposure and gestational diabetes mellitus (GDM) remains inconclusive. OBJECTIVE:Our study aimed to investigate the prospective relationship between urinary copper and GDM and the mediating role of DNA methylation and proteomic biomarkers in this association. METHODS:A nested case-control study was conducted based on the Tongji-Huaxi-Shuangliu Birth Cohort. Urinary copper levels and genome-wide DNA methylation were measured in early pregnancy for 432 pregnant women, and 737 circulating proteins were measured in a subset of 150 pregnant women. RESULTS:Urinary copper levels were positively associated with risk of GDM (adjusted odds ratio = 1.48 for each 1-unit increase in the log-transformed levels of copper, 95% CI, 1.15-1.91). A total of 73 differential cytosine-phosphoguanine sites (CpGs) were identified as associated with copper. Of these CpGs, cg23773809 annotated to SNX10 mediated 24.7% and 22.4% of the copper-GDM and copper-1 hour plasma glucose (1-h PG) association, respectively. cg04168577 annotated to PPFIBP2 and cg06105935 located in the intergenic region mediated 23.4% and 13.9% of the copper-1-h PG association, respectively. The protein CD2AP was found to be a reliable predictor for GDM. The 73 differential CpGs mediated 64.1% of the copper-CD2AP association. CONCLUSION:Copper exposure may induce alterations in DNA methylation patterns, which can subsequently lead to changes in the expression of proteins associated with GDM and elevate the risk of developing GDM.

Baby skincare products are extensively used on infant skin, yet their contamination with plastic additives (PAs) remains poorly understood. This study employed an integrated analytical approach combining high-resolution mass spectrometry-based suspect screening and target quantification to investigate PAs in 55 commercial baby skincare products, including lotions, powders, and shampoo-bath foams. A total of 121 PAs were identified, with 99 compounds confirmed and quantified using reference standards. Among the identified PAs, over 20 were reported for the first time in baby skincare formulations, including emerging plasticizers and transformation products (specifically derivatives of organophosphate esters, synthetic antioxidants, and UV stabilizers). The identification of these transformation products highlights a significant yet often overlooked source of chemical complexity and potential risk in these products. Target analysis revealed a median total concentration of PAs at 3,220 ng/g, with non-phthalate plasticizers constituting the most abundant group (median: 1,090 ng/g), followed by organophosphate esters (289 ng/g), ultraviolet stabilizers (227 ng/g), phthalate esters (205 ng/g), synthetic antioxidants (77.8 ng/g), parabens (13.9 ng/g), and bisphenols (7.45 ng/g). The levels and composition profiles of PAs also exhibited distinct product-specific patterns. Although estimated dermal exposure levels in infants and toddlers were generally low, the frequent detection and wide chemical diversity of PAs raise concerns about cumulative and mixture exposures during sensitive developmental windows. Our work provides a systematic characterization of chemical profiles in baby skincare products, offering critical data for product safety assessment.

Recent studies have reported the presence of 6:2 fluorotelomer ethoxylates (FTEOs) as an emerging group of perfluoroalkyl and polyfluoroalkyl substances. However, the environmental relevance of additional FTEO homologues and analogues remains rarely investigated. Through a combination of suspect screening and homologue-based nontargeted analysis, we identified a total of 60 FTEO homologues and 30 perfluoroalkyl ether ethoxylate (PFAEE) homologues in commercial antifog products. They included homologue groups of 4:2 FTEOs (n = 16), 6:2 FTEOs (n = 17), 8:2 FTEOs (n = 12), 10:2 FTEOs (n = 8), 12:2 FTEOs (n = 7), perfluorobutyl ether ethoxylates (n = 15), and perfluorohexyl ether ethoxylates (n = 15). Among them, 4:2 FTEOs, 6:2 FTEOs, and perfluorobutyl ether ethoxylates were also frequently detected in house dust (n = 120) collected from South China, with semiquantified concentrations measured to be 30.4, 36.0, and 55.3 ng/g. Among each homologue group, the composition profiles of individual homologues with different numbers of repeated ethoxy units resembled between antifog products and house dust. A toxicological priority index (ToxPi) approach revealed the highest risk of 6:2 FTEOs among all of the identified FTEOs and PFAEEs, although the risks from other groups should not be overlooked. Collectively, our work reveals the complexity of diverse FTEO homologues and reports the presence of PFAEEs for the first time in indoor environments, raising the need for further investigating their sources, environmental distribution, and potential human exposure.

The potential neurotoxicity of biomicroplastics has attracted increasing attention with the global expansion of bioplastics. Our recent findings revealed that starch-based microplastics (SB-MPs) can disrupt fatty acid metabolism, a perturbation strongly linked to neurotoxicity disorders. However, systematic investigations into the neurotoxic potential of chronic SB-MP exposure and its underlying mechanisms remain scarce, limiting comprehensive risk assessment. Here, we exposed mice to food-relevant concentrations of SB-MPs for 180 days and evaluated the risk of Alzheimer's disease (AD). SB-nanoparticles (SB-NPs) were found in the brain, accompanied by significantly impaired locomotor activity, learning, and memory, while increasing cerebral Aβ-42 protein levels, indicating a strong potential to promote AD-like pathology. Multiomics integration further revealed that SB-MPs are driving the expansion of bacterial taxa and metabolic pathways associated with short-chain fatty acid (SCFA) production. The resulting SCFAs overload and SB-NPs entered circulation and accumulated in brain tissue, where they disturbed fatty acid homeostasis and provoked neuroinflammation, ultimately increasing AD risk. Collectively, these findings demonstrate that chronic exposure to SB-MPs can elevate AD risk by perturbing the gut-brain axis. Continued research is needed to clarify the neurotoxicity of SB-MPs and to inform the design of greener bioplastics with reduced health impacts.

Abstract Gestational diabetes mellitus (GDM) reflects metabolic dysregulation that becomes clinically apparent during pregnancy and shares key pathophysiological features with broader forms of diabetes. Gut microbiome‐host metabolic interactions may contribute to this process, yet their role in early pregnancy remains incompletely understood. In this prospective nested case‐control study within the Tongji‐Huaxi‐Shuangliu Birth Cohort, 784 pregnant women, including 222 who developed GDM, underwent first‐trimester gut metagenomic and plasma lipidomic profiling. Cross‐omics analyses were performed to identify microbiome‐lipid associations and potential mediation patterns. Women who later developed GDM showed reduced gut microbial diversity and altered microbial profiles in early pregnancy. We identified 26 microbial species associated with GDM risk, with seven species, including Ruminococcus bicirculans ( R. bicirculans ), showing concordant associations in external type 2 diabetes populations. Microbial pathways related to fatty acid and lipid biosynthesis were enriched in women at higher risk. Plasma lipidomics revealed widespread alterations, particularly among glycosphingolipid‐related metabolites. Integrated analyses suggested that lipidomic variation statistically accounted for part of the microbiome‐GDM association. A class‐level dihexosylceramide feature, DHC 24:1, consistent with lactosylceramide‐related metabolites, emerged as a potential mediator and was prioritized for exploratory follow‐up. Experimental analyses provided functional support for a microbiome‐lipid‐host interaction axis. R. bicirculans promoted lactosylceramide 24:1 production in vitro , bacterial colonization and metabolite administration improved insulin tolerance in vivo , and lactosylceramide 24:1 modulated insulin‐stimulated AKT signaling dynamics in hepatocytes. These findings identify a gut microbiome‐lipid axis associated with metabolic dysregulation in pregnancy and suggest a potential mechanism linking microbial metabolism to host insulin signaling.

Ultrashort-chain per- and polyfluoroalkyl substances (USC-PFAS) have gained increasing attention due to their ubiquitous environmental presence and escalating environmental concerns. However, data on their presence in corals remain lacking. This study investigated the concentrations of USC-PFAS, including trifluoroacetic acid (TFA), perfluoropropionic acid (PFPrA), trifluoromethanesulfonate (TFMS), perfluoroethanesulfonate (PFEtS), perfluoropropanesulfonate (PFPrS), and bisperfluoromethane sulfonimide (bis-FMeSI), along with other legacy and emerging PFAS in reef-building coral samples (n = 54) from the Beibu Gulf of the South China Sea. Among the USC-PFAS, TFA, PFPrA, and bis-FMeSI exhibited detection rates of 100%, 74%, and 72%, respectively, in coral samples. TFA dominated the PFAS profile, accounting for 86% of the total concentrations by weight, with concentrations (median: 23 ng/g dw) far exceeding those of all other legacy and emerging PFAS. The wet-weight-based logarithm bioaccumulation factors (log(10) BAFs) from seawater to coral were estimated to be 1.85-3.60 for TFA, 2.07-4.09 for PFPrA, and 0.56-3.43 for bis-FMeSI, suggesting their bioaccumulative potential in reef-building corals. This study provides the first evidence of the widespread occurrence of USC-PFAS, particularly TFA, in reef-building corals, underscoring the need for further research into their potential ecological risks.

Mangrove ecosystems, located at the land-sea interface, are especially susceptible to land-based runoff carrying persistent environmental pollutants such as per- and polyfluoroalkyl substances (PFAS). Despite their ecological importance, the dynamics of PFAS contamination in China's mangroves remain poorly understood. We systematically assessed 15 mangrove wetlands across four southern provinces, revealing significant spatial variation in PFAS contamination. Mangrove sediments from Fujian exhibited significantly higher levels of PFOA and ΣPFAS compared to the other three provinces, while Guangdong showed notably higher concentrations of FOSA and N-EtFOSAA. PFOS levels were also significantly higher in Fujian and Guangdong than in Guangxi and Hainan, whereas PFPeA, PFTeDA, PFHxS or 6:2 FTS showed no significant differences. Sediment PFAS profiles across the four provinces showed some overlap, particularly for C5 − C7 PFCAs, C4 and C6 PFSAs, N-EtFOSAA and NaDONA. In contrast, surface seawater from Beihai and Guangzhou displayed distinct PFAS compositions: Beihai was dominated by PFBA, while Guangzhou had higher ratios of PFBS, C6 − C8 PFCAs, and 6:2 FTS. Both log KD and log KOC values exhibited significant positive correlations with carbon-chain length, with emerging PFAS exhibiting comparable or higher log KOC values than long-chain PFAAs. Socioeconomic indicators, including population size, GDP, and urbanization rate, were positively correlated with long-chain PFAAs, and negatively correlated with short-chain PFAAs, suggesting that urbanization and industrialization are potential factors associated with PFAS contamination patterns in mangrove sediments, and contributed to elevated PFOS risk in parts of Fujian and Guangdong.

Due to the limited documentation on thermal treatment of per- and polyfluoroalkyl substances (PFAS), this study investigated the thermal degradation behavior, mechanisms, mineralization, and gaseous product toxicity of five environmentally ubiquitous PFAS, including perfluorooctanesulfonic acid (PFOS), perfluorooctane sulfonamide (PFOSA), 6:2 chlorinated polyfluoroalkyl ether sulfonate (F-53B), perfluorooctanoic acid (PFOA), and 1H,1H,2H,2H-perfluoro-1-decanol (8:2 FTOH). Results showed that thermal stability of PFAS is dictated by their functional groups, presenting a stability hierarchy of sulfonic acid (PFOS, F-53B) > sulfonamide (PFOSA) > carboxylic acid (PFOA) > hydroxyl (8:2 FTOH). Thermal decomposition of these PFAS was initiated with cleavage of bonds connecting the functional group to the perfluorinated chain followed by stepwise chainshortening reactions, yielding various perfluoroalkanes, perfluoroalkenes, and hydrofluoroalkanes. Calcium hydroxide remarkably enhanced fluorine mineralization into calcium fluoride and suppressed the formation of organofluorinated compounds during PFAS thermal treatment. Toxicity predictions indicated reduced acute toxicity for thermal degradation products compared to parent PFAS, but they still pose potential risks to human health. This implies that optimizing thermal treatment conditions is essential, focusing not only on mineralization efficiency but also on suppressing the formation of harmful by-products. These findings provide a systematic understanding of PFAS thermal decomposition and identify potentially hazardous gaseous by-products.

CONTEXT:Renal function may play a crucial role in the development of gestational diabetes mellitus (GDM). However, prospective studies on this topic are scarce and the mechanisms remain unclear. OBJECTIVE:This work aimed to assess the associations of early-pregnancy renal function with GDM and the mediating role of carnitine metabolites. METHODS:The study was based on the Tongji-Huaxi-Shuangliu Birth Cohort. Renal function was routinely assessed before 15 gestational weeks. Plasma carnitine metabolites in early pregnancy were quantified using ultrahigh-performance liquid chromatography-tandem mass spectrometry. GDM was diagnosed at 24 to 28 gestational weeks by a 2-hour oral glucose tolerance test. Multivariable logistic regression was used to examine the associations of renal function indicators with GDM. Mediation analyses were applied to assess the mediating effects of carnitines. RESULTS:The mean age of 6770 participants was 26.6 ± 3.7 years. Serum uric acid, uric acid to creatinine ratio, and estimated glomerular filtration rate (eGFR) were positively associated with GDM, and the odds ratios (95% CIs) were 1.67 (95% CI, 1.25-2.23), 1.94 (1.47-2.57), and 1.53 (1.17-2.01) for the extreme-quartile comparison. Increased creatinine, cystatin C, and creatinine to weight ratio were associated with lower GDM risk, with ORs of 0.62 (0.47-0.82), 0.72 (0.52-0.99), and 0.69 (0.53-0.91) for the extreme-quartile comparison. Serum creatinine-, creatinine to weight ratio-, and eGFR-related carnitine scores played positive mediating roles, and the mediation proportions were 43.1%, 81.9%, and 56.7%, respectively. CONCLUSION:Renal function should be monitored for GDM, and the potential roles of carnitine metabolites require further evaluation and validation.

With the widespread use of antibiotics, the distribution of antibiotic resistance genes (ARGs) in the aquatic environment has become a globally environmental issue. However, traditional disinfection techniques are generally ineffective in the ARGs elimination. In this study, A piezocatalysis nanofibrous membrane was facilely fabricated by incorporating BaTiO3 (BTO) nanoparticles into polyvinylidene fluoride (PVDF) nanofibers via electrospinning approach. A novel aeration-driven peroxymonosulfate (PMS) piezoactivation system using PVDF-BTO piezoelectric membrane was developed to effectively eliminate ARGs from water. Under the external forces generated by aeration or periodic hydraulic pressure, the piezocatalytic PVDF-BTO membrane can efficiently remove 5.6-log ARGs under optimal conditions. Radical quenching and quantitative experiments confirmed the participation of singlet oxygen (1O2), hydroxyl radical (HO•), sulfate radical (SO4•-) and superoxide radical (•O2-) in the ARGs elimination process. Furthermore, the nanofibrous membrane exhibited excellent reusability, achieving a stable ARGs elimination efficiency in the tested five-cycle experiments. This study provides an attracting ARGs elimination method that could be simply integrated into the current membrane-based water treatment systems.

The pervasive environmental presence of N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its transformation product, 6PPD-quinone (6PPDQ), has raised concerns about their potential toxicity, yet their interactions with the gut microbiota at environmentally relevant concentrations remain poorly understood. Here, we investigated the effects of 6PPD and 6PPDQ on the gut-liver axis in zebrafish (Danio rerio). Zebrafish larvae exposed to 0.01, 1, and 100 μg/L of 6PPD or 6PPDQ for five days exhibited intestinal and hepatic developmental toxicity, including hepatic lipid accumulation and hepatomegaly. Adult zebrafish exposed for 21 days displayed compromised intestinal barrier integrity, gut dysbiosis, and lipidomic disturbances in the liver. Statistical analysis using the multi-response permutation procedure confirmed significant shifts in gut microbial community structure. Dysbiosis was characterized by reduced beneficial bacteria and an increase in pathogenic taxa, accompanied by elevated circulating lipopolysaccharide (LPS) and upregulated hepatic expression of lbp (LPS-binding receptor). Hepatic lipid accumulation resulted from increased triglyceride (TG) and total cholesterol synthesis, with lipidomics revealing distinct disruptions: 6PPD impaired phosphatidylinositol phosphate synthesis, while 6PPDQ affected TG homeostasis. Correlation analysis linked gut microbial shifts to hepatic lipid dysregulation. These findings suggest that 6PPD and 6PPDQ exposure disrupts gut-liver axis homeostasis, potentially driving non-alcoholic fatty liver disease development. This study underscores the need to integrate gut-liver-microbiota endpoints into environmental risk assessments for aquatic organisms.

Urinary exposome analysis faces analytical challenges due to the lack of reference standards for biotransformed products and the wide structural diversity of metabolites. This study developed a chemically labeled exposome analysis (CLEAN) strategy for nontargeted identification of urinary metabolites. The strategy uses dansyl chloride (DnsCl) and N-methylphenylethylamine (MPEA) to label exogenous and endogenous molecules with phenolic hydroxyl, primary amine, and carboxyl groups and develops an integrated screening workflow based on diagnostic fragment ion filtering and machine learning-assisted retention time prediction and structure annotation. We applied the CLEAN strategy to screen for key environmental chemicals in pregnant women associated with small vulnerable newborns (SVN) in a nested case-control study of 80 SVN cases and 160 matched controls. Among 97 identified exogenous substances, 29 were detected in more than 70% samples. The BKMR analysis revealed a significant and positive association between mixed exposure and the SVN risk and identified 1-hydroxypyrene, monoisopropyl phthalate and pentabromophenol as the key exposure markers. Among the identified endogenous metabolites, four amino acids exhibited the strongest mediation effects on the environmental exposure-SVN associations. Collectively, our work demonstrates the ability of CLEAN to achieve high-throughput and accurate urinary exposome characterization, supporting large-scale human biomonitoring and epidemiological studies.

Following restrictions on the use of phthalate esters (PAEs), the industry has increasingly manufactured non-PAE plasticizers (NPPs) to meet the continuous demand for plastic products. However, the environmental occurrence of NPP diversity remains insufficiently investigated. This study established a suspect and category-specific characteristic fragment-dependent non-targeted screening strategy based on liquid chromatography-high resolution mass spectrometry (LC-HRMS) to identify 14 categories of emerging NPPs in house and car dust. Application of the screening strategy in house dust (n = 45) and car dust (n = 50) collected from South China resulted in the identification of 48 NPPs with various confidence levels, many of which had very scarce or no environmental data. Among these, the cumulative concentrations of 32 target analytes reached a median level of 34.1 and 20.0 µg/g in house and car dust, respectively. The overall distribution patterns of NPPs in household and car dust were broadly similar, dominated by citrate, adipate, and oleate ester chemicals. Variations between the two environments were primarily attributed to differences in their specific applications. Collectively, our findings demonstrate the complexity of NPP contamination in indoor and vehicle environments and call for further research on potential human exposure and health risks.

The industrial use of monomeric halogenated flame retardants has now gradually been phased out due to their toxicity to humans and ecosystems. Polymeric flame retardants are emerging as a 'safe' alternative and so have a high production and consumption volume. However, the environmental fate and toxicity of their derivatives remain unknown, making it difficult to understand and adequately manage the associated risk. We take two tetrabromobisphenol A-based polymers (polyTBBPAs) that are widely used in electronics as model flame-retardant chemicals, and we study their behaviour when they break down in the environment and the toxicity of the derivative products. Our results show that polyTBBPAs break down into smaller products in the environment. Using a non-target screening strategy called BrMiner developed by us, we identified 76 breakdown products of polyTBBPAs with molecular weights in the range 400-2,000 Da. These were detected in environmental samples taken from electronic waste recycling facilities in South China. Toxicity tests with zebrafish embryos showed that when they break down in the environment, polyTBBPAs become more toxic, with mitochondrial dysfunction representing a key toxicity mechanism. This study reveals that there are environmental risks associated with polymeric flame retardants, and therefore, their use should be adequately assessed and regulated.