Ecotoxicology and Environmental Safety最新文献_第7页

Impact of silver nanoparticles on dye conversion and detoxification potential during long-term operation of an aerobic granular sludge sequencing batch reactor for textile wastewater treatment 纳米银对纺织废水好氧颗粒污泥序批式反应器长期运行过程中染料转化和脱毒潜力的影响

IF 6.1 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety

Pub Date : 2025-12-01 DOI: 10.1016/j.ecoenv.2025.119473

Rita Dias Guardão Franca , Sofia Sousa , Carolina Almeida , Ana Marta Rodrigues , Helena Maria Pinheiro , Cristina Anjinho Viegas , Nídia Dana Lourenço

Textile industry wastewater (TWW) is characterized by high organic loads and recalcitrant dyes, but the increasing use of silver nanoparticles (AgNP) in textiles has added a new environmental challenge. This study evaluates the impact of AgNP on aerobic granular sludge (AGS) sequencing batch reactors (SBRs) under long-term operation, including granulation and reactivation after an 18-day idle period at 4 ºC. Two SBRs were operated for 246 days: SBR1, fed with synthetic TWW containing 20 mg L⁻¹ AgNP, and SBR2, an AgNP-free control. Granulation was achieved after 40–50 days in both reactors, with AgNP enhancing AGS settling and biomass accumulation in long-term operation, including reactivation. Despite the accumulation of AgNP on the biomass, treatment performance was not affected, 80 % of color and organic load removal being reached after 1 and 2 weeks of operation, respectively, and maintained along the experimental run in both SBRs. However, only the AgNP-fed SBR1 effectively converted a recalcitrant aromatic amine, deriving from azo dye reduction, for prolonged periods of time during the experimental run. No significant differences in detoxification trends were observed between the reactors, and no correlation was found between the potential cytotoxicity/genotoxicity of mixed liquor samples and the azo dye or its metabolite. This study, with novel insights on the impact of AgNP on AGS granulation, stability and reactivation, assessed by direct comparison with a AgNP-free control SBR, and including toxicity aspects, supports the application of AGS in TWW treatment, considering its irregular discharges containing increasing concentrations of emerging pollutants like AgNP.

纺织工业废水具有高有机负荷和难降解染料的特点，但纳米银在纺织品中的使用日益增加，给环境带来了新的挑战。本研究评估了AgNP在长期运行下对好氧颗粒污泥（AGS）序批式反应器（sbr）的影响，包括在4ºC下闲置18天后的造粒和再激活。两个SBRs手术246天：SBR1，用含有20 mg L -¹ AgNP的合成TWW喂养，SBR2，不含AgNP的对照。两个反应器在40-50天后均实现了造粒，AgNP在长期运行（包括再激活）中增强了AGS的沉淀和生物质的积累。尽管AgNP在生物质上积累，但处理性能不受影响，运行1周和2周后分别达到80% %的颜色和有机负荷去除，并在两个sbr的实验运行中保持不变。然而，在实验过程中，只有agnp喂养的SBR1在很长一段时间内有效地转化了一种顽固性芳香胺，这种胺来自偶氮染料还原。反应器间的解毒趋势无显著差异，混合液样品的潜在细胞毒性/遗传毒性与偶氮染料及其代谢物之间无相关性。本研究对AgNP对AGS造粒、稳定性和再活化的影响有了新的认识，通过与不含AgNP的对照SBR进行直接比较，包括毒性方面的评估，支持AGS在TWW处理中的应用，考虑到其不规则排放中含有越来越多的AgNP等新兴污染物浓度。

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引用次数: 0

Migration characteristics of ARGs from pig manure in compost - soil - lettuce 猪粪中ARGs在堆肥-土壤-生菜中的迁移特性。

IF 6.1 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety

Pub Date : 2025-12-01 DOI: 10.1016/j.ecoenv.2025.119447

Yihao Huang , Ruyu Li , Yuzhen Dai , Zhuqing Ren , Jian Wu

This study aims to reveal the contamination patterns, persistence characteristics, and fate dynamics of ARGs during aerobic composting of swine manure with different carbon-nitrogen ratios (C/N = 15:1, 25:1, 35:1) and their subsequent dissemination in soil-plant systems following fertilization. The absolute abundances of 101 ARGs of six categories ranged from 10⁵ to 10¹⁴ copies/g during the composting process. The tetracyclines, macrolides and β-lactams ARGs were effectively reduced by the maturation phase. Among them, the β-lactam ARGs had the highest abatement efficiency (73–89 %). Quinolones, aminoglycosides and sulfonamides ARGs had relatively high residues during the maturation phase. Composting treatments with higher C/N (25:1 and 35:1) exhibited superior performance in ARGs reduction. Metagenomic analysis revealed the compost microbial community succession from Firmicutes to Proteobacteria and Actinobacteria. Luteimonas may be potential hosts for high-residual ARGs in compost, while Acinetobacter exhibited strong associations with β-lactam and macrolide ARGs that can be easily reduced. The ARGs in the fertilized soil increased significantly. ARGs such as floR, tetG-01, sul1 and sul2 have the highest abundance in the soil where lettuce is grown. The ARGs reduction is better in C/N 25:1 group, and the ARGs abundance of the soil is lower after fertilization with compost products. The sulfonamide sul1 and sul2 genes have always maintained a high abundance in compost, soil and lettuce. This study provides a theoretical basis for controlling the residue and spread of ARGs by regulating the C/N of compost to drive changes in microbial community.

本研究旨在揭示不同碳氮比（C/N = 15:1,25:1,35:1）猪粪好氧堆肥过程中ARGs的污染模式、持久性特征和命运动态，以及施肥后它们在土壤-植物系统中的传播。6类101种ARGs在堆肥过程中的绝对丰度在105 ~ 1014拷贝/g之间。四环素类、大环内酯类和β-内酰胺类ARGs在成熟阶段有效减少。其中，β-内酰胺类ARGs的减排效率最高（73-89 %）。喹诺酮类药物、氨基糖苷类药物和磺胺类药物在成熟阶段的残留相对较高。较高C/N（25:1和35:1）处理的ARGs减量效果较好。宏基因组分析揭示了堆肥微生物群落从厚壁菌门到变形菌门和放线菌门的演替过程。黄体单胞菌可能是堆肥中高残留ARGs的潜在宿主，而不动杆菌与β-内酰胺和大环内酯类ARGs有很强的关联，且易于还原。施肥后土壤ARGs显著增加。在种植生菜的土壤中，floR、tetG-01、sul1和sul2等ARGs的丰度最高。C/N为25:1时，土壤中ARGs的还原效果较好，堆肥产品施肥后土壤ARGs丰度较低。磺胺sul1和sul2基因在堆肥、土壤和生菜中一直保持较高的丰度。本研究为通过调节堆肥C/N驱动微生物群落变化来控制ARGs的残留和扩散提供了理论依据。

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引用次数: 0

The selection of reference substances for improving chemical persistence assessment in higher tier OECD 309 simulation tests 为改进OECD 309高级模拟试验中的化学持久性评估而选择参考物质。

IF 6.1 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety

Pub Date : 2025-12-01 DOI: 10.1016/j.ecoenv.2025.119499

H.K. Schofield , C.B. Hughes , D. Scheerbaum , C. Maeß , D.M. Brown , S. Hakvåg

The reliable assessment of chemical persistence is critical for environmental risk evaluation, yet variability in OECD 309 test guideline (TG) for surface water simulation tests can undermine confidence in results. Current reference substances, aniline and sodium benzoate, degrade rapidly and may not adequately reflect inoculum performance, limiting their value for test validation. This study applied a structured, multi-step process to identify and validate alternative reference substances that improve robustness in OECD 309 testing. From an initial list of 32 candidates, eight screened for physicochemical suitability and biodegradation behaviour using an adapted OECD 301D TG method. Two substances, caffeine and 2,4-dichlorophenoxyacetic acid (2,4-D), were selected for further evaluation under OECD 309 TG conditions at two temperatures (12 and 20°C) and two concentrations (1 and 10 µg L⁻¹). Caffeine demonstrated slower but consistent mineralisation compared to existing references, making it a suitable positive control for inoculum viability. 2,4-D exhibited limited degradation, particularly at 12°C, supporting its use as a negative benchmark for persistence. Adoption of these substances could strengthen OECD TG 309 validity criteria and improve regulatory persistence assessments under frameworks such as REACH. These findings provide a basis for an interlaboratory ring test to confirm their suitability and enhance comparability of persistence data.

对化学持久性的可靠评估对于环境风险评价至关重要，但经合组织309地表水模拟试验指南（TG）的差异可能会破坏对结果的信心。目前的标准物质苯胺和苯甲酸钠降解迅速，可能不能充分反映接种物的性能，限制了它们在试验验证中的价值。本研究采用了一个结构化的、多步骤的过程来识别和验证替代对照物质，以提高OECD 309测试的稳健性。从最初的32个候选名单中，有8个候选材料使用经调整的OECD 301D TG方法筛选了物理化学适用性和生物降解行为。选择两种物质，咖啡因和2,4-二氯苯氧乙酸（2,4- d），在OECD 309 TG条件下在两种温度（12和20°C）和两种浓度（1和10 µg L-1）下进行进一步评价。与现有的参考文献相比，咖啡因表现出较慢但一致的矿化作用，使其成为接种活力的合适阳性对照。2,4- d表现出有限的降解，特别是在12°C时，支持将其用作持久性的负基准。采用这些物质可以加强经合组织TG 309的有效性标准，并改善REACH等框架下的监管持久性评估。这些发现为实验室间环测试提供了基础，以确认其适用性并增强持久性数据的可比性。

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引用次数: 0

Sex-specific reproductive toxicity of polystyrene nanoplastics and DEHP in adult zebrafish (Danio rerio) 聚苯乙烯纳米塑料和DEHP对成年斑马鱼的性别特异性生殖毒性研究

IF 6.1 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety

Pub Date : 2025-12-01 DOI: 10.1016/j.ecoenv.2025.119488

Guanglong Chen , Min Zeng , Wanjing Liu , Hongping Liao , Jun Wang

Micro- and nanoplastics (MNPs) and di(2-ethylhexyl) phthalate (DEHP) are ubiquitous environmental contaminants; however, the risks of their combined exposure to aquatic reproductive health, particularly sex-specific differences, remain incompletely understood. This study investigated the effects of single and combined exposure to polystyrene nanoplastics (PS-NPs; 0.1 and 1 mg/L) and DEHP (10 μg/L) on the reproductive endocrine system of adult male and female zebrafish (Danio rerio) Results demonstrated that PS-NPs accumulated in the zebrafish intestine. High concentrations of PS-NP and DEHP and their combined exposures induced significant adverse effects in both sexes, including gonadal tissue damage and oxidative stress. A striking sexual dimorphism was observed in endocrine responses. Females exhibited a pronounced suppression of both 17β-estradiol (E2) and testosterone (T) levels, which correlated with inhibited ovarian cyp19a gene expression under co-exposure. Conversely, male E2 levels remained stable and T levels decreased only under co-exposure, increasing E2/T ratio. This distinct male endocrine profile was associated with differential regulation of testicular cyp19a and 17β-hsd expression. This study confirms that PS-NPs and DEHP exert profound sex-specific reproductive toxicity in zebrafish. These effects are mediated by disrupting the hypothalamic-pituitary-gonadal (HPG) axis, while inducing sex-specific alterations in brain and gonadal gene expression. Overall, this study highlights the critical importance of considering sex differences and pollutant mixture effects in environmental risk assessments.

微塑料和纳米塑料（MNPs）和邻苯二甲酸二（2-乙基己基）酯（DEHP）是普遍存在的环境污染物；然而，他们共同接触水生生殖健康的风险，特别是性别差异，仍然没有完全了解。本研究研究了聚苯乙烯纳米塑料（PS-NPs分别为0.1和1 mg/L）和DEHP（10 μg/L）对成年雌雄斑马鱼生殖内分泌系统的影响。结果表明，PS-NPs在斑马鱼肠道内积累。高浓度的PS-NP和DEHP及其联合暴露会对两性产生显著的不良影响，包括性腺组织损伤和氧化应激。在内分泌反应中观察到明显的两性二态性。雌性的17β-雌二醇（E2）和睾酮(T)水平均明显受到抑制，这与共暴露下卵巢cyp19a基因表达的抑制有关。相反，只有在共暴露条件下，男性E2水平保持稳定，T水平下降，E2/T比值升高。这种独特的男性内分泌特征与睾丸cyp19a和17β-hsd表达的差异调控有关。本研究证实了PS-NPs和DEHP对斑马鱼具有深刻的性别特异性生殖毒性。这些影响是通过破坏下丘脑-垂体-性腺（HPG）轴介导的，同时诱导脑和性腺基因表达的性别特异性改变。总体而言，本研究强调了在环境风险评估中考虑性别差异和污染物混合效应的重要性。

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引用次数: 0

Aflatoxin B1-induced lipid disturbance and neuroinflammation contribute to Alzheimer's disease-like neuropathology in C57BL/6J mice 黄曲霉毒素b1诱导的脂质紊乱和神经炎症有助于C57BL/6J小鼠阿尔茨海默病样神经病理。

IF 6.1 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety

Pub Date : 2025-12-01 DOI: 10.1016/j.ecoenv.2025.119495

Jinxian Lin , Jiayi Li , Zhengwei Liang , Haiyan Yu , Sicheng Liu , Qixue Zheng , Jinping Yu , Zhulin Du , Kun Luo , Xionghua Yang , Lingling Yang , Ping Deng , Huifeng Pi , Zhengping Yu , Zhou Zhou , Wei Yuan , Huihui Hong

Aflatoxin B₁ (AFB₁) is a ubiquitous foodborne mycotoxin that has been associated with cognitive decline. In this study, we investigated the neuropathology linked to Alzheimer's disease (AD) caused by AFB₁ and revealed the underlying mechanism. Here, C57BL/6 J mice received AFB₁ (1.5 mg/L in drinking water) for 8 weeks. Behavioral tests, including Morris water maze and Y-maze, were conducted alongside hippocampal histology and immunostaining to detect cognitive deficits and hippocampal neuronal impairment. Non-targeted lipidomics was also employed to dissect alterations in the hippocampal lipid profile. Furthermore, dysregulation of the lipid-driven inflammatory response was confirmed by gene and protein assays for lipid metabolism and inflammatory signaling, as well as serum cytokine measurements. Results showed that AFB₁ impaired spatial learning and memory, caused hippocampal neuronal loss and increased App and phosphorylated Tau. Non-targeted lipidomics revealed that the AFB₁ exposure led to derangements in glycerophospholipid metabolism and increased the abundance of pro-inflammatory phosphatidylcholine (PC) species. Concurrently, the Tlr4/NF-κB cascade contributed to the enhanced systemic and hippocampal pro-inflammatory cytokine responses. Taken together, these results indicate that exposure to a low dose of AFB₁ results in an increase in pro-inflammatory PC species and hippocampal neuroinflammation via the Tlr4/NF-κB axis and hence contribute to the development of AD-like neuropathology. This highlights the therapeutic significance of targeting dysregulated lipid metabolism to counteract AFB₁-induced neurotoxicity in relation to AD.

黄曲霉毒素B1 （AFB1）是一种普遍存在的食源性真菌毒素，与认知能力下降有关。在这项研究中，我们研究了与AFB1引起的阿尔茨海默病（AD）相关的神经病理学，并揭示了其潜在的机制。在这里，C57BL/6 J小鼠接受AFB1（1.5 mg/L饮水）治疗8周。行为学测试包括Morris水迷宫和y迷宫，同时进行海马组织学和免疫染色，以检测认知缺陷和海马神经元损伤。非靶向脂质组学也被用于解剖海马脂质谱的改变。此外，脂质代谢和炎症信号的基因和蛋白质检测以及血清细胞因子测量证实了脂质驱动的炎症反应失调。结果显示，AFB1使空间学习和记忆功能受损，导致海马神经元丢失，App和Tau磷酸化增加。非靶向脂质组学显示，AFB1暴露导致甘油磷脂代谢紊乱，并增加促炎磷脂酰胆碱（PC）物种的丰度。同时，Tlr4/NF-κB级联有助于增强全身和海马的促炎细胞因子反应。综上所述，这些结果表明，暴露于低剂量AFB1可通过Tlr4/NF-κB轴导致促炎PC物种和海马神经炎症增加，从而促进ad样神经病理的发展。这突出了靶向失调的脂质代谢来对抗afb1诱导的与AD相关的神经毒性的治疗意义。

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引用次数: 0

Environmental pollutant-induced cholinergic disruption: Advances and perspectives in mechanistic insights, target heterogeneity, and neurotoxic synergy 环境污染物引起的胆碱能破坏：机制见解、目标异质性和神经毒性协同作用的进展和观点。

IF 6.1 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety

Pub Date : 2025-12-01 DOI: 10.1016/j.ecoenv.2025.119470

Wei Li, Ke Gao, Liping Lu

The cholinergic system serves as a central regulatory network for neurotransmission and behavioral control, and its complex signaling architecture renders it highly vulnerable to mixed environmental pollutants. In real-world scenarios, pollutants typically exist as complex mixtures whose synergistic or antagonistic interactions increase toxicity uncertainty, thereby challenging the traditional single-pollutant, single-target paradigm in mixture risk prediction. Integrating evidence across pollutant categories to uncover shared mechanistic principles is therefore essential for building a predictive assessment framework. Through quantitative interactome analysis of twenty pollutant categories, we identify two unifying principles of cholinergic disruption: mechanistic convergence and target heterogeneity. Pollutant effects converge on a limited set of shared pathways, primarily acetylcholinesterase (AChE) inhibition and acetylcholine receptor (AChR) modulation, while molecular targets differ in sensitivity, forming an AChE and nicotinic AChRs (nAChRs) core attack module. We further propose a dual-axis model of damage facilitation and regulatory remodeling, delineating the transition from acute target-specific perturbations to chronic regulatory dysfunction. The model establishes chemical structure as a key determinant through a three-tier cascade encompassing molecular initiating events, distributional behavior, and metabolic fate. This framework supports a tiered risk-assessment strategy that integrates qualitative, quantitative, and computational approaches. By linking molecular perturbations to ecological outcomes, we establish an exposure-target-outcome paradigm that captures multilayered pollutant impacts. Finally, we identify key bottlenecks in predictive modeling, cross-species extrapolation, and regulatory translation, and propose a translational roadmap integrating multi-omics biomarkers, advanced in vitro models, and artificial intelligence to advance environmental neurotoxicology toward a mechanism-driven predictive science.

胆碱能系统是神经传递和行为控制的中枢调节网络，其复杂的信号结构使其极易受到混合环境污染物的影响。在现实世界中，污染物通常以复杂的混合物形式存在，其协同或拮抗相互作用增加了毒性的不确定性，从而挑战了混合物风险预测中传统的单一污染物、单一目标范式。因此，整合跨污染物类别的证据以揭示共享的机制原则对于建立预测评估框架至关重要。通过对20种污染物类别的定量相互作用分析，我们确定了胆碱能破坏的两个统一原则：机制收敛和目标异质性。污染物效应集中在有限的共享途径上，主要是乙酰胆碱酯酶（AChE）抑制和乙酰胆碱受体（AChR）调节，而分子靶点在敏感性上存在差异，形成了AChE和烟碱AChRs （nAChRs）核心攻击模块。我们进一步提出了损伤促进和调节重塑的双轴模型，描述了从急性靶特异性扰动到慢性调节功能障碍的转变。该模型通过包括分子起始事件、分布行为和代谢命运在内的三层级联，将化学结构建立为关键的决定因素。该框架支持集成定性、定量和计算方法的分层风险评估策略。通过将分子扰动与生态结果联系起来，我们建立了一个暴露-目标-结果范式，可以捕获多层次的污染物影响。最后，我们确定了预测建模、跨物种外推和调控翻译的关键瓶颈，并提出了整合多组学生物标志物、先进的体外模型和人工智能的翻译路线图，以推动环境神经毒理学向机制驱动的预测科学发展。

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引用次数: 0

Evaluation of physiological changes in Mytilus galloprovincialis exposed to an isothiazolinone-based compound: A multi-marker approach 暴露于以异噻唑啉酮为基础的化合物的紫贻贝的生理变化评价：一种多标记方法。

IF 6.1 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety

Pub Date : 2025-12-01 DOI: 10.1016/j.ecoenv.2025.119508

Cristiana Roberta Multisanti , Maria Giovanna Rizzo , Federica Impellitteri , Kateryna Yunko , Lesya Gnatyshyna , Monia Perugini , Oksana Stoliar , Caterina Faggio

The present study aims to assess, through a multi-marker analysis, the changes in physiological parameters in the Mediterranean mussel, Mytilus galloprovincialis, due to exposure to methylchloroisothiazolinone (CMIT). The CMIT is an isothiazolinone-based compound widely employed in the formulations of several commercial products as a biocidal agent. The increasing use of isothiazolinones, especially during the COVID-19 pandemic, has increased concerns about the health of the ecosystem. Therefore, in the present study, specimens of M. galloprovincialis were exposed to environmentally relevant sub-lethal concentrations of CMIT (0.01 and 0.1 mg L^-¹) for 14 days. Responses in target tissues such as haemolymph (H), digestive gland (DG), and gills (G) were assessed. Cytotoxicity and phagocytosis ability were analysed in haemocytes. Also, cytotoxicity was measured in DG cells along with cell ability to respond to osmotic shock via the Regulatory Volume Decrease (RVD) assay. In G, oxidative stress indexes (protein carbonylation, TBARS, and superoxide dismutase) were measured. Findings indicated alterations in cell physiological functionality and osmoregulatory response as well as high vulnerability of biochemical responses. These results demonstrate the potential toxicity of CMIT on key physiological and biochemical parameters. This basic research exploits potency and lays the groundwork for future studies that will fully elucidate the effects of isothiazolinones on model organisms and the wider ecosystem, and indirectly on human health.

本研究旨在通过多标记分析评估地中海贻贝（Mytilus galloprovincialis）暴露于甲基氯异噻唑啉酮（methylchloroisothiazolinone， CMIT）后生理参数的变化。CMIT是一种基于异噻唑啉酮的化合物，广泛用于几种商业产品的配方中作为杀菌剂。异噻唑啉类药物的使用越来越多，特别是在2019冠状病毒病大流行期间，这加剧了人们对生态系统健康的担忧。因此，本研究采用环境相关亚致死浓度CMIT（0.01和0.1 mg L-¹）对加洛省支原体进行了14天的暴露处理。评估靶组织如血淋巴(H)、消化腺（DG）和鳃(G)的反应。分析了血细胞的细胞毒性和吞噬能力。此外，通过调节体积减少（RVD）测定DG细胞的细胞毒性以及细胞对渗透休克的反应能力。G组测定氧化应激指标（蛋白质羰基化、TBARS和超氧化物歧化酶）。结果表明，细胞生理功能和渗透调节反应发生改变，生化反应高度易感性。这些结果证明了CMIT对关键生理生化参数的潜在毒性。这项基础研究利用了其效力，并为今后的研究奠定了基础，这些研究将充分阐明异噻唑啉酮对模式生物和更广泛的生态系统的影响，并间接对人类健康产生影响。

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引用次数: 0

Asiaticoside ameliorates pyrimethanil-induced autophagy-dependent liver injury by suppressing CRHR1 积雪草苷通过抑制CRHR1改善乙胺乙胺诱导的自噬依赖性肝损伤。

IF 6.1 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety

Pub Date : 2025-12-01 DOI: 10.1016/j.ecoenv.2025.119482

Risi Chen , Ying Zeng , Meixin Min , Ke Xu , Tingting Liu , Jinze Ma , Qiang Luo , Yunxia Yang , Dan Deng , Yan Liu , Xiaoping Xiao

Pyrimethanil is a widely used fungicide that accumulates in the food chain and poses potential health risks, yet the mechanisms underlying its chronic hepatotoxicity remain poorly understood. Here, we demonstrate that pyrimethanil induces liver injury in zebrafish and mouse models by directly binding to and activating corticotropin-releasing hormone receptor 1 (CRHR1), without altering its expression. CRHR1 activation triggers excessive autophagy—characterized by elevated LC3-II accumulation and upregulation of autophagy-related genes—leading to hepatocyte apoptosis and subsequent hepatic inflammation. In a compound screen, the natural triterpenoid Asiaticoside effectively mitigated pyrimethanil-induced liver injury. Mechanistically, Asiaticoside downregulated CRHR1 expression, thereby suppressing excessive autophagy and blocking the apoptosis–inflammation cascade. Our study reveals a novel CRHR1-dependent autophagy pathway in pyrimethanil-induced hepatotoxicity and identifies Asiaticoside as a promising therapeutic candidate for pesticide-related liver injury.

嘧霉胺是一种广泛使用的杀菌剂，在食物链中积累并构成潜在的健康风险，但其慢性肝毒性的机制仍然知之甚少。在这里，我们证明了乙胺甲乙胺通过直接结合并激活促肾上腺皮质激素释放激素受体1 （CRHR1）而不改变其表达，在斑马鱼和小鼠模型中诱导肝损伤。CRHR1激活引发过度自噬，其特征是LC3-II积累升高和自噬相关基因上调，导致肝细胞凋亡和随后的肝脏炎症。在化合物筛选中，天然三萜积雪草苷有效地减轻了乙胺乙胺引起的肝损伤。机制上，积雪草苷下调CRHR1表达，从而抑制过度自噬，阻断细胞凋亡-炎症级联反应。我们的研究揭示了一种新的依赖于crhr1的自噬途径在乙胺乙胺诱导的肝毒性中，并确定积雪草苷是一种有希望的治疗农药相关肝损伤的候选药物。

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引用次数: 0

Adrenal injury induced by real-ambient PM2.5: Mechanisms of disrupted Shh/Wnt signaling crosstalk 真实环境PM2.5诱导肾上腺损伤：Shh/Wnt信号串扰中断的机制。

IF 6.1 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety

Pub Date : 2025-12-01 DOI: 10.1016/j.ecoenv.2025.119497

Zhicheng Zhang , Siying Tang , Huanyu Hao , Hao Ding , Xiaoyin Guo , Daochuan Li , Wen Chen , Rong Zhang , Rui Chen , Jinmei Piao

Fine particulate matter (PM_2.5) exposure is known to induce systemic endocrine disruption, yet the specific mechanisms underlying adrenal injury remain elusive. This study investigates the hypothesis that PM_2.5 impairs adrenal homeostasis by disrupting key paracrine signaling pathways, Sonic hedgehog (Shh) and Wnt/β-catenin, which are vital for adrenal cortical differentiation and function. Utilizing a novel real-ambient exposure system that closely mimics human inhalation exposure, as opposed to traditional instillation models, we assessed the pathological and endocrine-disrupting effects of PM_2.5 on murine adrenal glands. Our results demonstrate that PM_2.5 exposure triggered hypothalamic-pituitary-adrenal (HPA) axis activation and caused significant adrenal structural damage, including cortical architecture disruption and enhanced inflammation. Crucially, we found that these effects were associated with the dysregulation of both Shh and Wnt signaling pathways. The data suggest that PM_2.5 may hinder adrenal self-renewal and repair by impairing these critical pathways. Collectively, our findings indicate that PM_2.5-induced adrenal dysfunction involves inflammatory responses and the disruption of Shh and Wnt signaling, highlighting their potential key role in preserving adrenal endocrine health.

众所周知，细颗粒物（PM2.5）暴露会导致全身内分泌紊乱，但肾上腺损伤的具体机制尚不清楚。本研究探讨了PM2.5通过破坏关键的旁分泌信号通路、Sonic hedgehog （Shh）和Wnt/β-catenin来损害肾上腺稳态的假设，这些信号通路对肾上腺皮质分化和功能至关重要。利用一种新型的真实环境暴露系统，该系统与传统的吸入模型相反，密切模仿人类吸入暴露，我们评估了PM2.5对小鼠肾上腺的病理和内分泌干扰作用。我们的研究结果表明，PM2.5暴露引发下丘脑-垂体-肾上腺（HPA）轴激活，并导致显著的肾上腺结构损伤，包括皮质结构破坏和炎症增强。至关重要的是，我们发现这些影响与Shh和Wnt信号通路的失调有关。这些数据表明，PM2.5可能通过损害这些关键途径来阻碍肾上腺的自我更新和修复。总之，我们的研究结果表明，pm2.5诱导的肾上腺功能障碍涉及炎症反应和Shh和Wnt信号的破坏，突出了它们在保持肾上腺内分泌健康方面的潜在关键作用。

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引用次数: 0

Activation of Wnt/β-catenin signaling pathway alleviates the toxic effects of cadmium acute exposure on Penaeus vannamei Wnt/β-catenin信号通路的激活可减轻镉急性暴露对凡纳滨对虾的毒性作用

IF 6.1 2区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Ecotoxicology and Environmental Safety

Pub Date : 2025-11-15 DOI: 10.1016/j.ecoenv.2025.119387

Yudong Zheng , Asare Derrick , Gongyu Li , Zhihao Xue , Xinghui Luo , Zhibin Fu , Lili Shi , Shuang Zhang

Penaeus vannamei has been studied as a bioindicator for monitoring heavy metal pollution. Heavy metals exposure can lead to disease by disrupting the Wnt/β-catenin pathway. Cadmium (Cd), a common contaminant in aquatic environments, has been investigated for its toxic effects on P. vannamei. To date, the underlying mechanisms by which Cd exposure exerts adverse effects remain unclear. In this study, the relation between Wnt/β-catenin signaling pathway and Cd acute exposure in P. vannamei were investigated from the aspects of Cd bioaccumulation, hepatopancreatic histology, antioxidant capacity, and intestinal microbiota, using P. vannamei exposed by Cd and injected by the Wnt/β-catenin pathway activator (TWS119) and inhibitor (IWR1). The results showed that Cd exposure heightened GSK3β activity and transcription of gsk3β and axin, while simultaneously dampening β-catenin, pangolin, and c-myc expression, collectively revealing marked attenuation of the Wnt/β-catenin signalling cascade. Consequently, Cd accumulated in shrimp muscle and the bioaccumulation factor rose after Cd exposure, which accumulated was further amplified when the Wnt/β-catenin pathway remained suppressed. TWS119 restoration reversed Cd-imposed signalling repression, curtailed reactive oxygen species, and alleviated hepatopancreatic injury, whereas IWR1 intensified these detrimental outcomes. Furthermore, Cd exposure significantly decreased the intestinal microbiota α-diversity (Sobs, Shannon, Simpson, pielou, and pd) of P. vannamei, while the simpson, pielou, and pd indices were elevated of P. vannamei by injecting TWS119. Otherwise, Cd exposure disturbing the endocrine system, while the modulating of Wnt/β-catenin pathway was associated with endocrine and metabolic disorders. The findings suggested that activating the Wnt/β-catenin pathway can reverse the oxidative stress, Wnt/β-catenin pathway suppression, and disruption of intestinal microbiota caused by Cd exposure in P. vannamei.

凡纳滨对虾（Penaeus vannamei）已被研究作为监测重金属污染的生物指标。重金属暴露可通过破坏Wnt/β-连环蛋白通路而导致疾病。镉（Cd）是水生环境中常见的污染物，研究了其对凡纳梅的毒性作用。迄今为止，Cd暴露产生不良影响的潜在机制仍不清楚。本研究利用Cd暴露后注射Wnt/β-catenin通路激活剂（TWS119）和抑制剂（IWR1），从Cd生物蓄积、肝胰腺组织学、抗氧化能力和肠道菌群等方面研究Wnt/β-catenin信号通路与Cd急性暴露的关系。结果表明，Cd暴露提高了GSK3β活性和GSK3β和轴蛋白的转录，同时抑制了β-catenin、穿山甲蛋白和c-myc的表达，共同揭示了Wnt/β-catenin信号级联的显著衰减。Cd暴露后，Cd在虾肌肉中的积累和生物积累因子升高，且在Wnt/β-catenin通路被抑制的情况下，积累进一步放大。TWS119恢复逆转了cd施加的信号抑制，减少了活性氧，减轻了肝胰腺损伤，而IWR1则加剧了这些有害结果。此外，Cd暴露显著降低了vannamei肠道微生物群α-多样性（Sobs、Shannon、Simpson、pielou和pd），注射TWS119可提高vannamei的Simpson、pielou和pd指数。否则，Cd暴露会干扰内分泌系统，而Wnt/β-catenin通路的调节与内分泌和代谢紊乱有关。上述结果提示，激活Wnt/β-catenin通路可逆转Cd暴露引起的凡纳米拟虫氧化应激、Wnt/β-catenin通路抑制和肠道菌群破坏。

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引用次数: 0