Benzo[a]pyrene (BaP) exhibits high stability, low bioavailability, and strong ecotoxicity in soil, limiting its natural degradation. This study evaluated whether bioaugmentation with the BaP-degrading bacterium Bacillus subtilis MSC4 combined with biostimulation using Lactobacillus plantarum fermentation liquor (LPS) or Yarrowia lipolytica extracellular metabolites (YEM) could improve BaP removal and reduce soil phytotoxicity. Results demonstrated that the application of MSC4 at 5 & times; 108 CFU kg-1 with 5% (v/w) LPS or YEM increased BaP removal rate by 29.82% and 25.92%, respectively. The combined treatments improved the soil quality, as indicated by increasing dissolved organic carbon, total nitrogen, and total phosphorus availability. At the same time, LPS treatment increased lipase and polyphenol oxidase activities by 35.77% and 20.05%, respectively, while YEM increased them by 26.63% and 32.49%. Microbial analysis showed that biostimulation reduced bacterial Alpha diversity but promoted selective enrichment of BaP-responsive taxa and regulated microbial co-occurrence networks. LPS and YEM increased positive bacterial correlations by 3.14% and 6.62%, respectively, suggesting enhanced potential cooperation or co-occurrence among bacterial taxa, whereas fungal networks showed stronger niche differentiation after biostimulation. Phytotoxicity assessments showed that the combined remediation significantly alleviated BaP-induced inhibition of Arabidopsis thaliana growth, tissue structure, and photosynthesis, reduced oxidative stress levels, and mitigated its molecular and genotoxic effects. Overall, LPS and YEM significantly improved remediation efficiency and ecological risk reduction of BaP-contaminated soils through soil environment improvement, microbial network regulation, and ecotoxicity attenuation, providing theoretical support for the systematic bioremediation of PAH-contaminated soils.

Dextromethorphan (DXM), a centrally acting non-narcotic antitussive, is subject to abuse worldwide, yet the risks associated with its long-term intake remain unclear. In this study, we examined the behavioral effects of repeated once-daily intraperitoneal administration of DXM at doses of 30 mg/kg and 50 mg/kg for 14 consecutive days in male mice and evaluated the toxic effects and underlying mechanisms in the intestine and brain using exploratory magnetic resonance imaging and physiological and biochemical indicators. The results suggested that DXM administration may attenuate neuronal activity in the prefrontal cortex and hippocampus and was associated with intestinal and brain tissue damage as well as apoptosis. At the high dose, the pro-inflammatory cytokine IL-1β was increased by 30% in both intestinal and brain tissues, whereas the anti-inflammatory cytokine IL-10 was decreased by 15% in the intestine and by 35.7% in the brain. DXM exposure also altered the gut microbiota composition. In parallel, serum lipopolysaccharide (LPS) levels were increased by 1.3-fold, suggesting potential disruption of the intestinal barrier and possible systemic effects via circulation. DXM was associated with alterations in gut microbiota composition, and gut-derived metabolites were correlated with dysregulation of lysophosphatidylcholine (LPC) metabolism in the brain. The abnormal accumulation of LPC was associated with lipid metabolic disturbances, which were in turn correlated with alterations in the brain microenvironment and neuroinflammation. Collectively, these results suggest that long-term DXM exposure may be associated with intestinal injury and alterations in brain metabolism, providing insights into the potential health risks associated with chronic DXM abuse.

The electrocatalytic nitrite reduction reaction (NO2--RR) presents a sustainable route to remediate nitrogen pollution and produce valuable ammonia (NH3), yet its development is hindered by the lack of efficient catalysts. Herein, we fabricate cuprite nanostructures (Cu2O NSs) with highly exposed high-index facets via a facile in-situ electrochemical reconstruction strategy. The catalyst exhibits an exceptional NO2--RR performance, achieving a remarkable NH3 production rate of 5.02 mg h(-1) mg(cat)(-1) with a Faradaic efficiency of 96.2% at -0.4 V. Experimental and theoretical results reveal that high-index facets such as (311) facets not only thermodynamically favor the adsorption and activation of key intermediates but also kinetically accelerate the reaction through rugged surfaces and porous architecture. By integrating the NO2--RR cathode with a hydrazine oxidation reaction (HzOR) anode, an electrolyzer was constructed for simultaneous NH3 electrosynthesis and wastewater purification at an ultralow cell voltage of 0.19 V (10 mA cm(-2)), achieving an 83% reduction in energy consumption compared to conventional systems. An alkaline Zn-NO2- battery was further demonstrated, delivering a high open-circuit voltage of 1.312 V and a superior power density of 10.02 mW cm(-2), through which dual-functional nitrogen management and energy conversion are successfully realized.

In recent years, propoxate (PPO), a structural analogue of etomidate (ETO), has been illicitly added to e-cigarette liquids, while its neurotoxic and addictive mechanisms remain unclear. In this study, 8-week-old male C57BL/6 J mice were used to evaluate the toxic and addictive effects of 3 mg/kg and 5 mg/kg PPO exposure through behavioral tests, molecular biology, and molecular docking. The results showed that PPO induced conditioned place preference, reduced locomotor activity, and anxiety- and depression-like behaviors. It accumulated dose-dependently in the brain and other tissues and increased blood-brain barrier (BBB) permeability by significantly downregulating tight junction-related genes (Ocln, Tjp1, Cldn5) and interfering with the ZO-1/Occludin complex via direct binding. PPO also induced oxidative stress, local inflammation, and neuronal apoptosis in the hippocampus and striatum. In addition, GABA_A receptor α1 expression was upregulated in the hippocampus, and PPO was found to bind to the α/γ2 subunit interface of the receptor, potentially modulating its function. Transcriptomic analysis further confirmed that PPO mediates neurotoxicity and addictive potential by suppressing genes associated with tight junction proteins and disrupting the GABAergic system. This study reveals the dual mechanisms underlying PPO-induced neurotoxicity and addiction, providing a molecular-level explanation for its environmental and public health risks.

Chlorinated hydrocarbons (CHCs) persistently threaten ecosystems. Using eco-friendly biostimulants to enhance the remediation capacity of indigenous microorganisms is a core strategy in bioremediation. This study aims to elucidate the mechanisms by which Yarrowia lipolytica extracellular metabolites (YEMs) promote trichloroethylene (TCE) biodegradation from multiple perspectives, including environmental factor correlation, community structure, interaction networks, and functional genes. Results showed that the maximum biostimulation efficiency of YEMs for microbial degradation of TCE reaches 93.93%, while simultaneously improving soil chemical properties and enzyme activities. Fungal (tyrosol) and bacterial (C6-HSL and C8-HSL) quorum sensing signal molecules significantly increased on days 40 and 120, respectively. Community analysis revealed distinct changes in the bacterial community structure, with significant correlations between their abundance changes and the levels of TCE and signal molecules. Interactions between bacteria-bacteria and bacteria-fungi became more intense. Moreover, specific dehalogenase-encoding gene pceA and nonspecific monooxygenase gene clusters pmoABC-amoABC and dmpKLMNOP were significantly enriched, while the abundance of metagenome-assembled genomes (MAGs) associated with acid production, hydrogen production, and cobalamin (Vitamin B12) synthesis also increased, providing functional support for redox dechlorination of TCE. This study reveals the mechanism of YEMs-induced microbial TCE degradation and provides theoretical support for its application in actual CHC-contaminated sites.

Isopropoxate (IPPO), an emerging imidazole ester-type new psychoactive substance, poses potential risks to public health and the environment, yet its neurotoxic mechanisms remain poorly understood. In this study, 8-week-old C57BL/6 J mice were used to evaluate the effects of IPPO on the blood-brain barrier (BBB), oxidative stress, neuroinflammation, and neurotransmitter receptor systems through UPLC-MS/MS-based tissue distribution analysis, quantitative real-time PCR, TUNEL staining, and molecular docking. At a dose of 3 mg/kg, IPPO accumulated in brain tissue and induced cerebral edema. Marked reductions in the tight-junction proteins Occludin and Claudin-5, together with decreased expression of the efflux transporter genes Abcb1a and Abcb1b, indicated impairment of blood-brain barrier (BBB) integrity. In brain tissue, malondialdehyde (MDA) increased by approximately 30%, catalase (CAT) activity decreased by approximately 20%, and glutathione (GSH) content declined by approximately 8%, demonstrating enhanced lipid peroxidation (LPO) and weakened antioxidant defenses. IPPO exposure also upregulated components of the NLRP3 inflammasome and the pro-inflammatory mediators IL-1β, IL-6, and TNF, while reducing the anti-inflammatory cytokine IL-10 by approximately 26%, indicating disruption of the pro-/anti-inflammatory balance. Within neurotransmitter systems, DRD1 and GABRA1 protein levels increased, Taar1 expression decreased, and the immediate-early genes Fos and Arc were markedly upregulated, consistent with dysregulation of dopaminergic, GABAergic, and neuronal activity-related signaling. Molecular docking further indicated stable interactions of IPPO with GABAA and DRD1 receptors, supporting a potential direct influence on neurotransmission through key receptor targets. Transcriptomic profiling corroborated suppression of tight-junction-related genes and disturbance of neurotransmitter-associated pathways. Collectively, these findings identify a coordinated neurotoxic mechanism in which IPPO disrupts the BBB, promotes oxidative stress and neuroinflammation, and alters neurotransmitter receptor signaling.

ABSTRACT The electrochemical CO 2 reduction reaction (CO 2 RR) to multicarbon (C 2+ ) products offers a promising route for sustainable carbon cycling and renewable energy storage. Copper (Cu)‐based nanocatalysts are indispensable for enabling C‐C coupling; however, conventional synthesis methods struggle to consistently produce and stabilize ultrasmall Cu(0) nanoparticles, which are prone to oxidation and aggregation, and fail to preserve their high‐energy facets critical for C 2+ selectivity. In this work, we overcome these challenges by constructing a well‐defined Cu/Ti 3 C 2 heterointerface that leverages a lattice matching mechanism. This approach not only stabilizes ultrasmall Cu(0) nanoparticles under ambient conditions but also promotes the preferential exposure and stabilization of high‐energy (110) facets. The resulting Cu/Ti 3 C 2 composite catalyst exhibits exceptional performance in the CO 2 RR, achieving a total C 2 Faradaic efficiency of 72.5%, with acetate alone reaching 42.5% at an industrially relevant current density of 235 mA·cm −2 . Combined spectroscopic and computational studies reveal that the electronic metal‐support interaction and epitaxial growth are key to stabilizing the active structure, while the exposed Cu(110) facets lower the kinetic barriers for the critical C‐C coupling step toward acetate. This study underscores the vital importance of precise interfacial and crystallographic control in developing efficient and stable electrocatalysts for CO 2 conversion.

As a representative agent of bicyclic antidepressants, venlafaxine (VEN) has become widely used worldwide and is frequently detected in surface waters with concentrations ranging from ng/L to µg/L. To evaluate the toxicological effects of such medications on aquatic species, studies on environmentally relevant concentrations are essential. Zebrafish were used as a model organism to assess growth and development in larvae and examine tissue accumulation, oxidative stress, and DNA methylation in adults. The results showed adverse effects, including an 18.5% decrease in embryo hatching rate and an increase in mortality by 18.5%. There was also a reduction in body length (4.5%) and eye area (12.2%) in the larvae, along with abnormal developmental issues, such as pericardial edema, yolk sac edema, and spinal curvature. Venlafaxine and its metabolites induced oxidative stress, leading to observable toxic effects. In adult zebrafish, VEN and O-desmethylvenlafaxine (ODV) accumulated primarily in the liver, followed by the brain and intestines, and caused a reduction in DNA methyltransferase activity, leading to DNA hypomethylation. VEN had the most significant impact on DNA methyltransferase 1 and altered its conformation more than ODV. Overall, venlafaxine was found to be more toxic than its metabolites, providing a scientific basis for evaluating the toxic effects and ecological risks of antidepressant residues on aquatic organisms.

The pronounced stability of water-in-heavy oil (W/O) emulsions complicates efficient demulsification, necessitating energy-intensive thermal-chemical methods with environmental trade-offs. To mitigate these challenges, 27 biosurfactant-producing bacterial strains (surface tension <40 mN/m) were systematically screened, identifying Pseudomonas-derived rhamnolipids as optimal biodemulsifiers. HPLC-MS resolved structural homologs: mono-rhamnolipid (Rha-C10:1-C10:2) and di-rhamnolipid (Rha-Rha-C10-C10). Di-rhamnolipids outperformed mono-variants in demulsification efficiency and interfacial activity. Molecular dynamics simulations revealed stronger di-rhamnolipid-resin interactions, evidenced by binding free energy and enhanced hydrogen bonding, which destabilized interfacial films. Field trials demonstrated di-rhamnolipid fermentate achieved 99 % demulsification at 50 degrees C lower than conventional polyether agents-reducing energy costs by 15.14 % and annual expenses by 31.31 %, alongside enabling 150,000 t waste water recovery. This work establishes a structure-guided framework for biodemulsifier design, linking molecular specificity to functional efficacy, and advances sustainable strategies for heavy oil processing.

Various anabolic androgenic steroids (AAS) are frequently detected in aquatic environments, yet the potential ecotoxicological impacts of their increased load have not received adequate attention. This study investigates the effects of exposure to the androgen nandrolone on sex differentiation, gonadal development, and the expression of hormones, enzymes, and proteins related to the hypothalamic-pituitary-gonadal (HPG) axis in zebrafish. The results indicate that exposure to nandrolone at 60 days post-fertilization promotes the maturation of spermatogonia, inhibits the development of oocytes, and induces their apoptosis. Additionally, there were dose-dependent changes in male differentiation and hormone levels within the HPG axis: in the high-dose group (5 μg/L), males constituted 73 % of the population, and levels of E2 hormones in gonadal tissues decreased by 33 %, while T hormone levels increased by 55 %. Furthermore, the expression of genes essential for ovarian differentiation were downregulated, whereas the expression of testicular differentiation-related genes were upregulated. The molecular docking results show that the drug can form hydrogen bonds with key proteins, which have high affinity, and are more likely to cause conformational changes in the proteins, thereby altering their activity. KEGG analysis suggests that the MAPK signaling pathway is likely the target pathway through which nandrolone exposure induces reproductive toxicity.

The frequent detection of psychoactive drugs in aquatic environments has caused various toxic effects on aquatic organisms, highlighting the urgent need to explore remediation methods and mechanisms. Against the backdrop of toxicity induced by the typical benzodiazepine (BZD) flunitrazepam (FLZ) in zebrafish, this study evaluates the mitigating effects of vitamin C (VC) on FLZ-induced embryonic developmental toxicity, larval behavioral anomalies, apoptosis, oxidative stress, and mitochondrial dysfunction at environmentally relevant concentrations through reactive oxygen species (ROS)-mediated pathways. Furthermore, molecular dynamics simulations were utilized to decipher the mechanism underlying ROS inhibition. Results demonstrated that co-exposure to 0.5 μg/L VC with FLZ (0.05 μg/L and 0.2 μg/L) significantly elevated the hatching rate of zebrafish embryos at 72 hpf and decreased the larval malformation rate at 96 hpf. In terms of physiological and biochemical indicators, VC significantly inhibited the FLZ-induced increase in ROS and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. VC also upregulated the activity of mitochondrial uncoupling protein 2 (UCP2), a key regulator of ROS production. Molecular docking and dynamics simulations revealed that VC competitively binds to the LYS 38 and LYS 240 sites of UCP2, destabilizing FLZ-UCP2 interactions via steric hindrance and hydrogen bond competition. With the restoration of UCP2 activity, its proton leak function was enhanced, suppressing excessive ROS generation. Consequently, uqcr2b, cox4i1l, and atp5g3b were normalized, restoring ATP synthesis capacity and significantly alleviating FLZ-induced mitochondrial dysfunction. This study elucidates the mechanism by which VC counteracts ROS-mediated FLZ toxicity, providing critical insights for assessing environmental risks and formulating protective strategies against pollutants.

The quorum sensing (QS) system can regulate and enhance the degradation of petroleum pollutants. Enhancing the indigenous microbial QS system by adding environmentally friendly biostimulants is currently a preferred strategy for achieving high stability, sustainability, and cost-effective biodegradation of petroleum contaminants. However, the intrinsic mechanisms by which biostimulants induce QS-mediated regulation of petroleum hydrocarbon degradation remain unclear. Unlike traditional QS regulation strategies, the aim of this study was to explore the mechanisms of the extracellular metabolites of euglena (EME) stimulant to enhance the degradation of diesel by Pseudomonas aeruginosa LNR1 through QS inhibitor (eugenol) damaging QS system. Results showed that the addition of eugenol reduced the degradation rate of diesel, down-regulated the expression of degradation-related hydroxylation and dehydrogenation genes, and inhibited the synthesis of extracellular polymeric substances (EPS) and biofilm. Further, we found that eugenol reduced the intracellular synthesis of three signal molecules (C4-HSL, 3-oxo-C12-HSL, and PQS) of Pseudomonas aeruginosa, among which 3-oxo-C12-HSL showed obvious intracellular accumulation. The genes of the three signaling molecules synthesis and the 3-oxo-C12-HSL transport system (MexAB-OprM) were down-regulated. Eugenol had a strong affinity with the peripheral plasma membrane fusion protein (MexA) of the 3-oxo-C12-HSL transport system, and the transport function was obviously inhibited. Eugenol also has hydrogen bond interaction with translocase and receptor protein of signal transduction that regulate signal transduction. The above results indicated that the biostimulant controlled the QS system by inducing microorganisms to change the synthesis, transport and signal transduction of signal molecules, thus affecting metabolic functions related to degradation and promoting the degradation of pollutants.

Microbial remediation of polycyclic aromatic hydrocarbons (PAHs) often leads to a decrease in microbial metabolic activity due to limited living conditions and nutrient deficiencies. The application of eco-friendly biostimulants is an effective strategy to overcome this problem. In this study, a biostimulant was developed using tea residue fermentation liquid (TRF), and the physiological responses of Pantoea dispersa MSC14, a benzo [a]pyrene (BaP) -degrading strain, under TRF stimulation were investigated in terms of cell morphology, oxidative stress, and energy metabolism. Special attention was given to the role of quorum sensing (QS) mediated by N-acyl homoserine lactone (AHL) in the BaP degradation process. Results showed that a 10 % (v/v) dosage, the stimulation efficiency of TRF on the degradation of BaP by MSC14 was 212.6 %. TRF preserved morphology, promoted cell growth, reduced oxidative stress, increased electron transport system activity (ETSA) by 70.3 %, and raised the activities of Na+/K+-ATPase, Mg2+-ATPase, and Ca2+-ATPase by 24.6 %, 103.2 %, and 194.3 %, respectively. TRF activated the QS system, enhancing microbial response to BaP stress, as reflected in the synergistic increases of biofilm, EPS, and rhamnolipid production, thereby significantly promoting BaP degradation. Genomic analysis and RT-qPCR confirmed that the expression of AHL-synthesis gene luxI increased by 98.9 %. Furthermore, BaP degradation-related genes aaeA, phnP, nagA were upregulated by 215.0 %, 95.1 %, and 49.5 %. These findings confirm that TRF effectively promotes the degradation of BaP by Pantoea dispersa through regulating signaling molecules, providing theoretical guidance for the application of "waste-to-treat-waste" strategy in environmental remediation and demonstrate significant ecological benefits.

Wastewater-based epidemiology (WBE) has been widely used as a public health surveillance tool worldwide, especially since the COVID-19 pandemic. In China, the WBE approach has been adopted for monitoring illicit drug use since the early 2010s and further extended to monitoring consumption or exposure to other chemicals. Establishing a nationwide monitoring program for substance consumption has increased the population coverage from 3.5 to 382 million. However, previous similar to 200 WBE studies in China are mostly chemical-focused, with limited focus on pathogenic bacteria or viruses. Moreover, there are still challenges for the methodology as multiple factors affect the accuracy and reliability of the final back estimations. With emerging public health challenges, especially after the COVID-19 epidemic, WBE can play a more important role in China. This study summarizes achievements made in various WBE applications in China and research efforts in enhancing the accuracy and reliability of WBE results over the past decade. Future perspectives were also discussed, considering the achievements in other countries and the unique features of China. Integrating WBE estimation, both chemical and biological data, with other data would promote the development of more evidence-based strategies for public health.

Although prokaryotic microbes in coking wastewater (CWW) treatment have been comprehensively studied, the ecological functions of viruses remain unclear. A full-scale CWW biological treatment AOHO combination was studied for the virus-bacterium interactions involved in element cycles by metaviromics, metagenomics and physicochemical characteristics. Results showed the unique viromic profile with Cirlivirales and Petitvirales as the dominant viruses infecting functional bacteria hosts. The auxiliary metabolic genes (AMGs) focused on element cycles, including metabolisms of carbon (fadA), nitrogen (glnA), sulfur (mddA and cysK) and phosphorus (phoH). Other AMGs were involved in toxic tolerance of hosts, improving their cell membrane and wall robustness, antioxidant, DNA repair and cobalamin biosynthesis. Vice versa, the bloomed host provided fitness advantages for viruses. Dissolved oxygen was found to be the key factor shaping the distributions of viral community and AMGs. Summarizing, the study exposed the mutual virus-bacterium interaction in the AOHO combination providing stable treatment efficiency.

Benzo[a]pyrene (BaP) is a highly carcinogenic persistent organic pollutant, and biostimulation is an effective strategy to enhance its degradation. This study utilized Bacillus subtilis MSC4 as a BaP-degrading bacterium to investigate the effects of two different fermentation waste liquids as stimulants on BaP degradation. The mechanisms were analyzed and compared at both the cellular and molecular levels. The results showed that the stimulation percentages of yeast Yarrowia lipolytica extracellular metabolites (YEMs) and Lactobacillus plantarum fermentation waste solution (LPS) on the biodegradation of BaP reached 52.8% and 63.4%, respectively, compared to B treatment without biostimulant. Physiological analyses showed that both stimulants repaired cell morphology, more than doubled bacterial biomass, increased EPS secretion, enhanced bacterial activity, and significantly reduced oxidative stress by lowering ROS levels to 75-78% of those in the BaP-stressed group, allowing for repair of oxidative damage. Transcriptomic analysis indicated that both stimulants upregulated pathways related to central carbon metabolism, enhancing cell proliferation and energy supply. Additionally, YEMs promoted electron transport and BaP transmembrane transport and upregulated the synthesis of various monooxygenases, while LPS induced the upregulation of genes encoding quercetin dioxygenase and played a more active role in biofilm formation and enhancing BaP bioavailability. This study reveals the shared and distinct mechanisms by which YEMs and LPS enhance BaP biodegradation, providing theoretical guidance for the application of YEMs and LPS in the bioremediation of BaP-contaminated environments.

Wastewater-based epidemiology has emerged as a transformative surveillance tool for estimating substance consumption and monitoring disease prevalence, particularly during the COVID-19 pandemic. It enables the population-level monitoring of illicit drug use, pathogen prevalence, and environmental pollutant exposure. In this perspective, we summarize the key challenges specific to the Chinese context: (1) Sampling inconsistencies, necessitating standardized 24-hour composite protocols with high-frequency autosamplers (≤ 15 min/event) to improve the representativeness of samples; (2) Biomarker validation, requiring rigorous assessment of excretion profiles and in-sewer stability; (3) Analytical method disparities, demanding inter-laboratory proficiency testing and the development of automated pretreatment instruments; (4) Catchment population dynamics, reducing estimation uncertainties through mobile phone data, flow-based models, or hydrochemical parameters; and (5) Ethical and data management concerns, including privacy risks for small communities, mitigated through data de-identification and tiered reporting platforms. To address these challenges, we propose an integrated framework that features adaptive sampling networks, multi-scale wastewater sample banks, biomarker databases with multidimensional metadata, and intelligent data dashboards. In summary, wastewater-based epidemiology offers unparalleled scalability for equitable health surveillance and can improve the health of the entire population by providing timely and objective information to guide the development of targeted policies.

Wastewater-based epidemiology (WBE) is a powerful tool for monitoring biomarkers of human health conditions. The WBE approach could deliver robust public health data with high temporal and spatial resolution, making it highly effective for assessing the impact of public health interventions across different populations. This study applied WBE to compare substance use and explore public health implications across two distinct populations: a general urban population and a university population. Daily and weekly wastewater samples were collected from 2017 to 2018, originating from a wastewater treatment plant serving the urban catchment and a pump station encompassing 10 universities. Consumption of over-the-counter (OTC) medications, prescribed drugs, and chronic disease medications in these two populations were estimated. Additionally, previously published data on recreational substances, respiratory and allergy medications, sweeteners, stress markers, and anabolic steroids were analyzed to present a comprehensive overview of human lifestyles and health status. Our results indicated that the university population consumed more OTC painkillers, including ibuprofen and paracetamol, but fewer prescribed opioids, such as codeine and morphine, compared to the general population. In contrast, higher consumption of chronic disease medications in the urban catchment indicated poorer overall health compared to the younger university population. These findings highlight significant differences in pharmaceutical consumption patterns and associated public health profiles between younger and general populations. This study underscores the utility of WBE in identifying public health disparities and guiding targeted health interventions based on population-specific needs and behaviors.

Benzodiazepines (BZDs) have been widely detected in aquatic environments, but their neurotoxic effects and potential mechanisms are still unclear. This study focuses on flunitrazepam (FLZ) and its metabolite, 7-aminoflunitrazepam (7-FLZ), as representative psychotropic BZD. We investigated their neurotoxic effects on adult zebrafish following a 30-day exposure to environmentally relevant concentrations. The findings reveal that exposure to these drugs induces anxiety-like and aggressive behaviors in zebrafish. Additionally, notable morphological damage to brain tissue and mitochondrial structures was observed. Through TUNEL staining, an increase in apoptotic cells was detected in the brain tissue of the exposed group, accompanied by marked elevations in ROS and caspase-3/9 levels. The upregulation of apoptosis-related genes Bax, p53, and Bcl-2 confirmed the occurrence of apoptosis. Furthermore, exposure to the drugs resulted in decreased acetylation levels of brain histones H3 and H4. The upregulation of histone deacetylation enzyme genes (HDAC1, HDAC3, HDAC4, and HDAC6) supported this result. Molecular docking results suggest that compared to 7-FLZ, FLZ has a higher binding affinity with HDAC3 and HDAC4, explaining why it causes lower histone acetylation levels. This study in zebrafish elucidates the neurotoxicity and molecular mechanisms induced by FLZ and 7-FLZ, which is significant for further understanding the impact of BZDs on human health and assessing their ecological risks.

The psychotropic drug flunitrazepam (FLZ) is frequently detected in aquatic environments, yet its neurotoxicity to aquatic organisms has not received sufficient attention. In this study, microbiome, metabolome, and genome analyses were conducted to study the effects of FLZ and its metabolite 7-aminoflunitrazepam (7-FLZ) on the zebrafish nervous system and understand their toxic mechanisms. The results demonstrated that drug exposure induced gut dysbiosis, decreased short-chain fatty acids and promoted the production of lipopolysaccharides (LPS). LPS entered the brain and interacted with Toll-like receptors to cause neuroinflammation by upregulating the expression of proinflammatory cytokines TNFα and NF-κB. The increased ratio of S-adenosylmethionine to S-adenosylhomocysteine in brain tissues indicated abnormal expression of Dnmt1 gene. Whole-genome bisulfite sequencing displayed an increase in differentially methylated regions (DMRs) associated-genes and pertinent biological pathways encompassed the MAPK signaling pathway, calcium signaling pathway, and Wnt signaling pathway. Correlation analysis confirmed connections between gut microbiota, their metabolites, inflammatory factors, and DNA methylation-related markers in brain tissue. These findings indicate that while the toxicity is somewhat reduced in metabolized products, both FLZ and 7-FLZ can induce DNA methylation in brain tissue and ultimately affect the biological function of the nervous system by disrupting gut microbiota and their metabolites.