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Histopathological analysis of mussels Mytilus galloprovincialis after foodborne exposure to three sizes of polystyrene nanoplastics: Relevance of confounding factors 食源性暴露于三种尺寸聚苯乙烯纳米塑料后贻贝的组织病理学分析:混杂因素的相关性
IF 6.1 2区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2026-03-15 Epub Date: 2026-03-13 DOI: 10.1016/j.ecoenv.2026.119976
Tania Ramírez , Nagore González-Soto , Tamer Hafez , Marisa Sárria Pereira de Passos , Eider Bilbao , Amaia Orbea , Douglas Gilliland , Miguel-Ángel Serra-Beltrán , Miren P. Cajaraville
Given the widespread occurrence of polystyrene (PS) micro- and nanoplastics in the marine environment, it is important to determine their potential adverse effects on representative sentinel marine species as mussels. Foodborne exposure is more environmentally realistic than waterborne exposure in mussels, but it has received less attention. The aim of this work was to assess the histopathological effects of foodborne exposure to PS nanoplastics (NPs) of different sizes on marine mussels, focusing on inflammatory reactions involving hemocytes, since microplastics (MPs) and NPs have been reported to produce inflammatory responses. Mussels Mytilus galloprovincialis were dietarily exposed through algae Isochrysis galbana to PS NPs of 50, 200 and 1000 nm at nominal low (LD) (10^3 NPs/mL) and high concentrations (HD) (10^8 NPs/mL for 50 and 200 nm NPs and10^6 NPs/mL for 1000 nm NPs). Exposures took place for seven days in duplicate and two independent experiments were carried out per NP (E1 and E4 for 50 nm, E2 and E5 for 200 nm and E3 and E6 for 1000 nm PS NPs). All experiments were developed during three weeks in September-October (E1-E2, E3-E4 and E5-E6) to minimize the influence of confounding factors on studied parameters. High prevalences of hemocytic infiltration, fibrosis and atrophy and necrosis of the digestive tubule epithelium (DE) were detected in the marine mussels’ digestive glands. In the gonad, prevalences of the different alterations were generally lower than in the digestive gland. Overall, the GLMM showed that stage of gametogenic development and the presence of parasites were significant confounding factors that influenced atrophy and necrosis of DE, oocyte atresia and hemocytic infiltration in the connective tissue of the gonad. Thus, it does not appear that these responses can be used as biomarkers of NP exposure in mussels, at least at the nominal concentrations tested and in a short-term exposure, since other factors such as reproductive stage and parasitosis affect these responses too. It remains to be determined whether longer term exposures could result in more severe histopathological alterations, independent of the physiological condition of mussels. Further work is required on environmentally realistic NPs that might pose additional risks compared to pristine ones.
鉴于聚苯乙烯(PS)微塑料和纳米塑料在海洋环境中的广泛存在,确定它们对贻贝等代表性海洋哨兵物种的潜在不利影响非常重要。食源性暴露比水生暴露在贻贝中的环境更现实,但它受到的关注较少。这项工作的目的是评估食源性暴露于不同大小的PS纳米塑料(NPs)对海洋贻贝的组织病理学影响,重点关注涉及血细胞的炎症反应,因为有报道称微塑料(MPs)和NPs会产生炎症反应。通过galbana藻类等裂解法,将贻贝(Mytilus galloprovincialis)暴露于50、200和1000 nm的名义低浓度(LD) (10^3 NPs/mL)和高浓度(HD)(50和200 nm NPs为10^8 NPs/mL, 1000 nm NPs为10^6 NPs/mL)的PS NPs中。每个NP进行两次独立实验(E1和E4为50 nm, E2和E5为200 nm, E3和E6为1000 nm),重复暴露7天。所有试验均在9 - 10月(E1-E2、E3-E4和E5-E6)的3周内进行,以尽量减少混杂因素对研究参数的影响。在贻贝的消化腺中发现了大量的血细胞浸润、纤维化和消化小管上皮(DE)的萎缩和坏死。在性腺中,不同改变的患病率普遍低于消化腺。总体而言,GLMM显示配子体发育阶段和寄生虫的存在是影响DE萎缩和坏死、卵母细胞闭锁和性腺结缔组织血细胞浸润的重要混杂因素。因此,这些反应似乎不能作为贻贝NP暴露的生物标志物,至少在名义浓度测试和短期暴露下,因为生殖阶段和寄生虫病等其他因素也会影响这些反应。与贻贝的生理状况无关,长期暴露是否会导致更严重的组织病理学改变仍有待确定。需要进一步研究具有环境现实意义的核废料,因为与原始核废料相比,这些核废料可能构成额外的风险。
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引用次数: 0
Microplastic biodegradation and environmental safety: From microbial mechanisms to engineered systems and circular bio-based implementation 微塑料生物降解和环境安全:从微生物机制到工程系统和循环生物基实施
IF 6.1 2区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2026-03-15 Epub Date: 2026-03-14 DOI: 10.1016/j.ecoenv.2026.120016
Haixin Jiao , Rania Al-Tohamy , Min Xiong , Michael Schagerl , Thomas Reinthaler , Majid Al-Zahrani , Jianzhong Sun , Sameh S. Ali
Microplastics, defined as synthetic polymer particles smaller than 5 mm, have become pervasive environmental contaminants across aquatic, terrestrial, and atmospheric systems. Their chemical stability, hydrophobicity, and resistance to natural attenuation limit the effectiveness of conventional physical and chemical removal technologies. Microbial and enzymatic approaches have therefore emerged as promising strategies for microplastic transformation and controlled degradation, although complete mineralization is not consistently achieved. Degradation outcomes vary widely depending on polymer structure, environmental conditions, and microbial community dynamics, and incomplete depolymerization may generate intermediate products with distinct ecological implications. This review provides a mechanistically integrated analysis of microplastic biodegradation, explicitly distinguishing surface modification, depolymerization, biotransformation, and complete mineralization. Abiotic preconditioning processes, enzyme–polymer interactions, kinetic constraints in real environmental matrices, and the functional roles of single strains, microbial consortia, and genetically engineered systems are examined. Particular attention is given to environmental safety considerations, including degradation byproducts, additive release, horizontal gene transfer risks, and biosafety containment strategies. The feasibility of integrating microbial degradation into circular bio-based recycling frameworks is critically assessed through translational strategies, pilot-scale considerations, and life cycle perspectives. Although advances in enzyme engineering and synthetic biology have significantly improved depolymerization efficiency under controlled conditions, scalability, regulatory compliance, and ecosystem-level risk assessment remain central challenges. Bridging mechanistic insight with environmental realism and regulatory preparedness is essential to ensure that biodegradation strategies reduce environmental burden without redistributing ecological risk.
微塑料被定义为小于5 毫米的合成聚合物颗粒,已成为水生、陆地和大气系统中普遍存在的环境污染物。它们的化学稳定性、疏水性和抗自然衰减性限制了传统物理和化学去除技术的有效性。因此,微生物和酶的方法已经成为微塑性转化和控制降解的有希望的策略,尽管完全矿化并不一致。降解结果因聚合物结构、环境条件和微生物群落动态而有很大差异,不完全解聚可能产生具有不同生态意义的中间产物。本文综述了微塑料生物降解的机理综合分析,明确区分了表面改性、解聚、生物转化和完全矿化。非生物预处理过程,酶-聚合物的相互作用,在真实的环境基质动力学约束,和单一菌株的功能作用,微生物联合体,和基因工程系统进行了检查。特别注意环境安全方面的考虑,包括降解副产物、添加剂释放、水平基因转移风险和生物安全控制战略。将微生物降解整合到循环生物基回收框架的可行性通过转化策略、中试规模考虑和生命周期观点进行了严格评估。尽管酶工程和合成生物学的进步显著提高了受控条件下的解聚效率,但可扩展性、法规遵从性和生态系统级风险评估仍然是核心挑战。要确保生物降解战略在不重新分配生态风险的情况下减轻环境负担,就必须将机制洞察力与环境现实主义和监管准备联系起来。
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引用次数: 0
Role of humic acid in modulating the combined toxicity of polylactic acid microplastics and diflubenzuron: Impacts on mitochondrial genotoxicity in Daphnia magna 腐植酸在调节聚乳酸微塑料和二氟苯脲联合毒性中的作用:对大水蚤线粒体遗传毒性的影响。
IF 6.1 2区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2026-03-15 Epub Date: 2026-03-14 DOI: 10.1016/j.ecoenv.2026.120020
Gunay Karimova , Hanseong Kim , Kimleng Keang , Rovshan Abbasov , Jinho Jung , Joorim Na
The proliferation of biodegradable plastics like polylactic acid (PLA) necessitates a deeper understanding of their ecotoxicological impacts, particularly their interactions with co-existing pollutants in aquatic ecosystems. This study investigates the combined toxicity of PLA microplastics (MPs), the insecticide diflubenzuron (DFB), and the influence of natural organic matter (NOM) on the freshwater cladoceran Daphnia magna. Acute 48-hour exposures were conducted to assess mortality, while sublethal impacts were evaluated by measuring oxidative stress biomarkers (reactive oxygen species, malondialdehyde), mitochondrial DNA (mtDNA) copy number, and cellular ATP levels. The interaction between PLA MPs and humic acid (HA) led to the formation of bridge-like structures. The presence of HA generally alleviated the enhanced acute toxicity resulting from the combined exposure to PLA MPs and DFB. At sublethal concentrations, the combination of high DFB (50 ng L⁻¹), HA (5 mg L⁻¹), and PLA MPs (1 mg L⁻¹) resulted in a reduction in mtDNA copy number, which in turn triggered enhanced ATP content as a compensatory mechanism at the cellular and molecular levels. These findings indicate that NOM, acting as an environmental modifier, significantly influences the toxicity of biodegradable MPs and pesticides at various biological levels, emphasizing the need to integrate such natural factors into the risk assessment frameworks for these emerging contaminants.
聚乳酸(PLA)等可生物降解塑料的激增需要更深入地了解其生态毒理学影响,特别是它们与水生生态系统中共存污染物的相互作用。本研究探讨了聚乳酸微塑料(MPs)、杀虫剂氟虫脲(DFB)和天然有机物(NOM)对大水蚤(Daphnia magna)的联合毒性。急性48小时暴露以评估死亡率,而亚致死影响则通过测量氧化应激生物标志物(活性氧、丙二醛)、线粒体DNA (mtDNA)拷贝数和细胞ATP水平来评估。PLA MPs与腐植酸(HA)之间的相互作用导致桥状结构的形成。透明质酸的存在通常减轻了PLA MPs和DFB联合暴露引起的急性毒性增强。在亚致死浓度下,高DFB(50 ng L -毒血症)、HA(5 mg L -毒血症)和PLA MPs(1 mg L -毒血症)的结合导致mtDNA拷贝数的减少,进而引发ATP含量的增加,作为细胞和分子水平上的一种补偿机制。这些发现表明,作为一种环境调节剂,NOM在不同的生物水平上显著影响可生物降解的MPs和农药的毒性,强调需要将这些自然因素纳入这些新兴污染物的风险评估框架。
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引用次数: 0
Manganese thresholds govern antagonism–synergy switching in tetracycline phytotoxicity in Lemna minor 锰阈值控制小野菜中四环素植物毒性的拮抗-协同转换。
IF 6.1 2区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2026-03-01 Epub Date: 2026-02-25 DOI: 10.1016/j.ecoenv.2026.119930
Junfang Tu , Yue Tong , Yilong Xi
Tetracycline antibiotics frequently co-occur with manganese (Mn) in freshwater environments, yet how Mn background gradients reshape mixture phytotoxicity remains insufficiently resolved. The objective of this study was to systematically investigate how varying Mn background levels modulate the phytotoxicity and interaction patterns of tetracycline antibiotics. Using Lemna minor as a model species, we employed full-factorial Mn × tetracycline concentration matrices (tetracycline, TC; oxytetracycline, OTC; and chlortetracycline, CTC) to quantify Mn-dependent modulation of tetracycline toxicity and identified operational Mn regimes supported by breakpoint robustness analysis. Growth-rate responses delineated a low-Mn window (0.10–0.40 mg·L⁻¹), a transition interval (0.40–1.60 mg·L⁻¹), and a high-Mn domain (≥1.60 mg·L⁻¹). Under low Mn conditions, Mn generally promoted antagonistic interactions, with inhibition weaker than expected, a pattern consistently observed across growth, pigment, and antioxidant endpoints. In contrast, under high Mn conditions, synergistic interactions emerged at specific Mn × antibiotic combinations, characterized by stronger-than-expected inhibition, forming spatially heterogeneous interaction “islands” on the response surfaces. These regime-dependent patterns were concordant between integrated multi-endpoint ΔBliss interaction landscapes, which quantify deviations from Bliss independence, and potency-surface validation using δZIP, a zero-interaction potency (ZIP)–based deviation metric, based on chlorophyll a. Overall, the results support a threshold-based, operational reporting framework linking Mn regimes to mixture interaction landscapes and indicate that mixture outcomes cannot be inferred from antibiotic dose alone when background metal levels vary, underscoring the need to explicitly incorporate metal gradients in mixture risk assessment.
在淡水环境中,四环素类抗生素经常与锰(Mn)共存,但锰背景梯度如何重塑混合物的植物毒性仍未得到充分解决。本研究的目的是系统地研究不同锰背景水平如何调节四环素抗生素的植物毒性和相互作用模式。以小Lemna为模型物种,我们采用全因子Mn × 四环素浓度矩阵(四环素,TC;土霉素,OTC;和氯四环素,CTC)来量化四环素毒性的Mn依赖性调节,并通过断点鲁棒性分析确定了可操作的Mn制度。生长速率反应描绘了一个低锰窗口(0.10-0.40 mg·L⁻¹),一个过渡区间(0.40-1.60 mg·L⁻¹)和一个高锰域(≥1.60 mg·L⁻¹)。在低锰条件下,锰通常促进拮抗相互作用,抑制作用弱于预期,这一模式在生长、色素和抗氧化终点一致观察到。相反,在高Mn条件下,特定Mn × 抗生素组合出现协同相互作用,其抑制作用强于预期,在响应表面形成空间异质性相互作用“岛”。这些制度依赖模式在综合多端点ΔBliss相互作用景观(量化Bliss独立性的偏差)和基于叶绿素a的零相互作用效价(ZIP)偏差度量δZIP的效价表面验证之间是一致的。将锰制度与混合相互作用景观联系起来的操作报告框架表明,当背景金属水平变化时,不能仅从抗生素剂量推断混合结果,强调需要明确将金属梯度纳入混合风险评估。
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引用次数: 0
Evaluating machine learning models for predicting pesticide toxicity to honey bees 评估用于预测农药对蜜蜂毒性的机器学习模型。
IF 6.1 2区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2026-03-01 Epub Date: 2026-02-23 DOI: 10.1016/j.ecoenv.2026.119869
Jakub Adamczyk , Jakub Poziemski , Pawel Siedlecki
Small molecules play a critical role in the biomedical, environmental, and agrochemical domains, each with distinct physicochemical requirements and success criteria. Although biomedical research benefits from extensive datasets and established benchmarks, agrochemical data remain scarce, particularly with respect to species-specific toxicity. This work focuses on ApisTox, the most comprehensive dataset of experimentally validated chemical toxicity to the honey bee (Apis mellifera), an ecologically vital pollinator. The primary goal of this study was to determine the suitability of diverse machine learning approaches for modeling such toxicity, including molecular fingerprints, graph kernels, and graph neural networks, as well as pretrained models. Comparative analysis with medicinal datasets from the MoleculeNet benchmark reveals that ApisTox represents a distinct chemical space. Performance degradation on non-medicinal datasets, such as ApisTox, demonstrates their limited generalizability of current state-of-the-art algorithms trained solely on biomedical data. Our study highlights the need for more diverse datasets and for targeted model development geared towards the agrochemical domain.
小分子在生物医学、环境和农业化学领域发挥着关键作用,每个领域都有不同的物理化学要求和成功标准。尽管生物医学研究受益于广泛的数据集和既定的基准,但农用化学品的数据仍然很少,特别是关于特定物种毒性的数据。这项工作的重点是ApisTox,最全面的数据集,实验验证了化学毒性对蜜蜂(Apis mellifera),一个生态至关重要的传粉者。本研究的主要目标是确定各种机器学习方法对此类毒性建模的适用性,包括分子指纹、图核、图神经网络以及预训练模型。与来自MoleculeNet基准的药物数据集的比较分析表明,ApisTox代表了一个独特的化学空间。在ApisTox等非医疗数据集上的性能下降表明,目前仅在生物医学数据上训练的最先进算法的泛化能力有限。我们的研究强调需要更多样化的数据集和针对农化领域的有针对性的模型开发。
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引用次数: 0
Effect of deposition of Cr, Ba, Ni, Zn, and Cu on biomarker fatty acids as indirect indicators of peroxidation in Cepaea nemoralis (Helicidae) in situ and in vivo (in laboratory conditions) Cr, Ba, Ni, Zn和Cu沉积对生物标志物脂肪酸的影响,作为线虫属(Helicidae)体内和原位过氧化的间接指标。
IF 6.1 2区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2026-03-01 Epub Date: 2026-02-25 DOI: 10.1016/j.ecoenv.2026.119932
Aleksandra Garbacz , Weronika Kursa , Danuta Kowalczyk-Pecka
The study determined the effect of selected environmental variables (Cr, Ni, Ba, Zn and Cu) on the potential peroxidation of biomarker fatty acids (FAs) in snails Cepaea nemoralis, both in in situ and in vivo (in laboratory conditions). The following panel of biomarker FAs was used: C16:0; C18:0; C23:0; C18:1 n-9; C20:1 n-9; C18:2 n-6; C18:3 n-3; C20:2 n-6; C20:4 n-6; C20:5 n-3; C22:4 n-6; and C22:5 n-3. Field studies included samples obtained from a location potentially affected by anthropogenic sediment, containing a deposit of waste rock, and from a location without this influence. Waste rock, which is mining waste produced during extraction of bituminous coal, was treated as a potential source of metals. The study tested whether metals deposited in an anthropogenically contaminated environment whose main element is a waste rock deposit can be transferred to the body of land snails. In laboratory conditions, Cr³ ⁺, Ni²⁺, Zn²⁺ and Cu²⁺ ions were administered to snails separately, per os, using a pipette, in a volume of 10 µl per snail, in the form of independent solutions of prepared salts (CrCl3x6H2O; NiSO4x6H2O; ZnCl2; CuSO4). Separate experimental groups were created for each metal, in which three metal concentrations were used: 0.0005 mg Met/ml redistilled water; 0.00075 mg Met/ml redistilled water; and 0.001 mg Met/ml redistilled water. Due to the high toxicity of soluble barium compounds, poorly soluble BaSO4 was used as the source of this element, which in solid form, in an amount proportional to the other metals, was added to the agar constituting the base of the medium. Regardless of exposure to individual metals, three additional experimental groups were also created in which snails were supplemented with a mixture of the tested metal ions, administered together in equal proportions, corresponding to the three concentrations used. The results indicate that metals affect the physiological response in snails associated with changes in the composition of biomarker FAs, peroxidation (PI) and unsaturation (UI) indices, including potential lipid peroxidation. It is possible to identify a group of FAs which can be useful biomarkers of exposure of snails (Gastropoda, Pulmonata) to these variables, in both natural and laboratory conditions. The search for this type of biomarkers in invertebrates is important in ecotoxicology even in the case of subthreshold levels of environmental pollutants. When using snails as a source of biomarkers in situ, after determining the levels of the pollutants in their natural habitat, in order to determine the synergy or antagonism of these pollutants with elements of the environmental background, for example climate and soil factors, it is worth carrying out comparative testing in a laboratory using supplementation with the same substances in controlled conditions.
该研究确定了选定的环境变量(Cr, Ni, Ba, Zn和Cu)对蜗牛在原位和体内(实验室条件下)生物标志物脂肪酸(FAs)潜在过氧化的影响。使用的生物标志物FAs如下:C16:0;C18:0;C23:0;C18:1 n - 9;C20:1 n - 9;C18:2 n-6;C18:3 n - 3;C20:2 n-6;C20:4 n-6;C20:5 n - 3;C22:4 n-6;和C22:5 n-3。实地研究包括从可能受人为沉积物影响的地点、含有废石沉积物的地点和从没有这种影响的地点获得的样本。废石是烟煤开采过程中产生的采矿废物,被视为金属的潜在来源。该研究测试了在以废石沉积物为主要元素的人为污染环境中沉积的金属是否可以转移到蜗牛体内。在实验室条件下,Cr³ +、Ni 2 +、Zn 2 +和Cu 2 +离子分别用移液器滴入蜗牛体内,每只蜗牛的体积为10 µl,以制备盐(CrCl3x6H2O; NiSO4x6H2O; ZnCl2; CuSO4)的独立溶液形式滴入。每种金属分别建立实验组,使用三种金属浓度:0.0005 mg Met/ml再蒸馏水;0.00075 mg Met/ml蒸馏水;0.001 mg Met/ml蒸馏水。由于可溶性钡化合物的高毒性,难溶性BaSO4被用作这种元素的来源,它以固体形式,以与其他金属成比例的数量,被添加到构成培养基基础的琼脂中。除了接触到不同的金属外,研究人员还创建了另外三个实验组,在这些实验组中,蜗牛被补充了测试金属离子的混合物,并按照所使用的三种浓度,以相同的比例一起给药。结果表明,金属对蜗牛生理反应的影响与生物标志物FAs、过氧化(PI)和不饱和(UI)指数(包括潜在的脂质过氧化)组成的变化有关。在自然和实验室条件下,有可能鉴定出一组FAs,这些FAs可以作为蜗牛(腹足纲、肺门纲)暴露于这些变量的有用生物标志物。即使在环境污染物低于阈值水平的情况下,在无脊椎动物中寻找这种类型的生物标志物在生态毒理学中也是重要的。当使用蜗牛作为生物标志物的原位来源时,在确定其自然栖息地的污染物水平后,为了确定这些污染物与环境背景元素(例如气候和土壤因素)的协同作用或拮抗作用,值得在实验室中进行比较测试,在受控条件下补充相同的物质。
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引用次数: 0
Methyl-4-hydroxybenzoate induces osteoporosis via the AKT1/LC3B/Beclin1 autophagy signaling pathway: Integrating network toxicology and experimental validation 4-羟基苯甲酸甲酯通过AKT1/LC3B/Beclin1自噬信号通路诱导骨质疏松:整合网络毒理学和实验验证
IF 6.1 2区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2026-03-01 Epub Date: 2026-02-24 DOI: 10.1016/j.ecoenv.2026.119913
Furui Fu , Wenhao Wang , Yunqi Li , Senjie Shi , Jin Huang , Tianpeng Liu , Yi Shen , Mengting Yuan , Chuanglong Xu , Hongyu Wang , Haitao Zhang , Xiang Gao , Dezhi Tang

Background

As public awareness of environmental issues grows and research on ecological pollutants advances, mounting evidence indicates that Methyl-4-hydroxybenzoate (MEP) is associated with the development of various diseases. This study aims to uncover the key genes and underlying molecular mechanisms by which MEP influences osteoporosis (OP).

Methods

This study integrates network toxicology, molecular docking, and molecular dynamics simulation approaches. Potential targets of the environmental contaminant were identified using the Comparative Toxicogenomics Database (CTD). In contrast, osteoporosis-related targets were retrieved from the Gene Expression Omnibus (GEO), GeneCards, and Online Mendelian Inheritance in Man (OMIM) databases. The intersection between MEP and OP targets was subsequently analyzed using PPI networks and functional enrichment analyses to identify core targets and pathways. For experimental validation, Sprague-Dawley rats were administered MEP via gavage for three months. Bone tissues were then collected for Micro-CT analysis and Hematoxylin and eosin (H&E) staining to evaluate the impact of MEP on bone mass. Further mechanistic investigations were conducted using immunofluorescence staining, western blotting (WB), and real-time quantitative polymerase chain reaction (RT-qPCR).

Results

Bioinformatics analysis identified 379 overlapping genes between MEP and OP, with 31 core genes (e.g., AKT1, HSP90AA1) implicated in cell cycle regulation, oxidative stress, and DNA damage. Molecular docking confirmed stable binding of MEP to AKT1 (- 4.39 kcal/mol), Beclin1 (- 18.77 kcal/mol), and LC3B (- 3.55 kcal/mol). Molecular dynamics simulations revealed that the MEP-Beclin1 complex stabilized after 85 ns (RMSD ≈ 2.2 Å), with persistent hydrogen bond interactions. In vivo experiments confirmed that MEP disrupts bone microstructure in a dose-dependent manner. Both micro-computed tomography (Micro-CT) and H&E staining revealed trabecular fractures and enlarged bone marrow cavities. Immunofluorescence analysis demonstrated significantly reduced LC3B puncta (P < 0.0001). Further validation by WB and RT-qPCR showed significantly upregulated expression of the autophagy-related protein AKT1 (P < 0.01), whereas downregulated expression of autophagy-related proteins (LC3B, Beclin1) and osteogenic markers (RUNX2, BMP2) (P < 0.01).

Conclusions

Collectively, this study demonstrates that the environmental pollutant methylparaben (MEP) induces OP by suppressing AKT1-mediated autophagy signaling. Our findings provide novel mechanistic insights into how ecological contaminants may trigger OP pathogenesis, thereby establishing a theoretical foundation for the development of preventive and therapeutic strategies against pollutant-associated bone disorders.
背景:随着公众对环境问题认识的提高和对生态污染物研究的深入,越来越多的证据表明,甲基-4-羟基苯甲酸酯(MEP)与多种疾病的发生有关。本研究旨在揭示MEP影响骨质疏松症(OP)的关键基因及其分子机制。方法:结合网络毒理学、分子对接、分子动力学模拟等方法。利用比较毒物基因组学数据库(CTD)确定了环境污染物的潜在靶点。相反,骨质疏松相关的靶点是从基因表达综合(GEO)、GeneCards和在线孟德尔遗传(OMIM)数据库中检索的。随后使用PPI网络和功能富集分析分析了MEP和OP靶点之间的交集,以确定核心靶点和通路。为了实验验证,Sprague-Dawley大鼠灌胃给予MEP 3个月。然后收集骨组织进行Micro-CT分析和苏木精和伊红(H&E)染色,评估MEP对骨量的影响。采用免疫荧光染色、western blotting (WB)和实时定量聚合酶链反应(RT-qPCR)进行进一步的机制研究。结果:生物信息学分析发现,MEP和OP之间存在379个重叠基因,其中31个核心基因(如AKT1、HSP90AA1)与细胞周期调节、氧化应激和DNA损伤有关。分子对接证实MEP与AKT1(- 4.39 kcal/mol)、Beclin1(- 18.77 kcal/mol)和LC3B(- 3.55 kcal/mol)稳定结合。分子动力学模拟表明,MEP-Beclin1配合物在85 ns (RMSD≈2.2 Å)后稳定,并具有持续的氢键相互作用。体内实验证实,MEP以剂量依赖的方式破坏骨微观结构。显微计算机断层扫描(Micro-CT)和H&E染色均显示骨小梁骨折和骨髓腔增大。免疫荧光分析显示LC3B斑点明显减少(P )结论:本研究表明环境污染物对羟基苯甲酸甲酯(MEP)通过抑制akt1介导的自噬信号通路诱导OP。我们的研究结果为生态污染物如何触发OP发病机制提供了新的机制见解,从而为针对污染物相关骨骼疾病的预防和治疗策略的发展奠定了理论基础。
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引用次数: 0
Metabolomics‑driven, data‑augmented machine learning for predicting toxicity of microplastic mixtures 代谢组学驱动、数据增强的机器学习预测微塑料混合物的毒性。
IF 6.1 2区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2026-03-01 Epub Date: 2026-02-24 DOI: 10.1016/j.ecoenv.2026.119944
Beilei Yuan , Chengzhi Liu , Shuang Chen , Jiangliang Chu , Yifan Yang , Yong Pan , Huazhong Zhang
Microplastics (MPs) occur as heterogeneous mixtures in real‑world environments, making one‑by‑one toxicity testing impractical. This study aims to use predictive models to quickly and effectively evaluate the toxicity of MPs. We explored three model frameworks: a quantitative structure-activity relationship (QSAR) model based on physicochemical descriptors; a quantitative bioactivity relationship (QBAR) model with biodescriptors screened by metabolomics data; and a quantitative structure-bioactivity relationship (QSBAR) model combining both physicochemical and biodescriptors. Under a simplex centroid design, six machine learning algorithms were trained using data augmentation strategies to predict the cytotoxicity of microplastic mixtures. The results showed that the QBAR-based eXtreme Gradient Boosting (XGB-qbar) model performed best (R2tra = 0.9322, R2test = 0.8923), outperforming the QSAR and the QSBAR frameworks. The three descriptor importance methods consistently identified key biological descriptors helpful for toxicity prediction. Moreover, metabolomics analysis indicated that mixed exposure to MPs may mediate toxic responses by reprogramming cellular energy metabolism pathways. The metabolomics-driven and data-augmented machine learning approach proposed in this study can efficiently predict toxicity and provide mechanistic clues in small sample and complex mixture scenarios, providing a feasible path for environmental exposure risk assessment.
微塑料(MPs)在现实环境中以异质混合物的形式存在,使得逐一进行毒性测试变得不切实际。本研究旨在利用预测模型快速有效地评价MPs的毒性。我们探索了三种模型框架:基于物理化学描述符的定量构效关系(QSAR)模型;与代谢组学数据筛选的生物描述子建立定量生物活性关系(QBAR)模型;以及结合理化和生物描述符的定量结构-生物活性关系(QSBAR)模型。在单纯形质心设计下,使用数据增强策略训练六种机器学习算法来预测微塑料混合物的细胞毒性。结果表明,基于qbar的极限梯度增强(XGB-qbar)模型表现最佳(R2tra = 0.9322, R2test = 0.8923),优于QSAR和QSBAR框架。三种描述符重要性方法一致地确定了有助于毒性预测的关键生物描述符。此外,代谢组学分析表明,混合暴露于MPs可能通过重编程细胞能量代谢途径介导毒性反应。本研究提出的代谢组学驱动和数据增强的机器学习方法可以在小样本和复杂混合场景下有效预测毒性并提供机制线索,为环境暴露风险评估提供了可行途径。
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引用次数: 0
Role of the aluminium in situ bioaccumulation in the evolutive state of carotid atheromatous plaques 铝原位生物蓄积在颈动脉粥样斑块演变状态中的作用。
IF 6.1 2区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2026-03-01 Epub Date: 2026-02-24 DOI: 10.1016/j.ecoenv.2026.119933
Manuela Montanaro , Francesca Servadei , Valeria Palumbo , Renata Sisto , Stefano Casciardi , Fabio Massimo Oddi , Valentina Rovella , Alessandro Mauriello , Manuel Scimeca
Aluminium (Al), a widespread environmental contaminant, has been implicated in various human pathologies, yet its role in atherogenesis remains unexplored. In this study, we investigate Al bioaccumulation in human carotid atheromatous plaques and its possible association with plaque instability. Using ICP-MS, scanning and transmission electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM/TEM-EDX), we assessed the presence and localization of Al in 50 carotid endarterectomy specimens. Aluminium was detected in all of cases, with no preferential localization or significant association with plaque instability. Multivariate analyses demonstrated that Al presence did not influence the effect of major cardiovascular risk factors on plaque vulnerability. These findings suggest that Al bioaccumulation in the vascular wall is a diffuse and passive process, independent of acute thrombotic transformation. While not predictive of instability, Al may contribute to plaque growth or reflect cumulative environmental exposure.
铝(Al)是一种广泛存在的环境污染物,与各种人类疾病有关,但其在动脉粥样硬化中的作用仍未被探索。在这项研究中,我们研究了Al在人颈动脉粥样硬化斑块中的生物积累及其与斑块不稳定性的可能关联。利用ICP-MS、扫描和透射电子显微镜以及能量色散x射线能谱(SEM/TEM-EDX),我们评估了50例颈动脉内膜切除术标本中Al的存在和定位。在所有病例中都检测到铝,没有优先定位或与斑块不稳定的显著关联。多变量分析表明,Al的存在并不影响主要心血管危险因素对斑块易损性的影响。这些发现表明,铝在血管壁的生物积累是一个弥漫性和被动的过程,独立于急性血栓转化。虽然不能预测不稳定性,但人工智能可能有助于斑块的生长或反映累积的环境暴露。
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引用次数: 0
Gestational PFHxS exposure at environmentally relevant levels is associated with adult hepatic steatosis and PERK/SREBP1 pathway activation 妊娠期环境相关水平的PFHxS暴露与成人肝脏脂肪变性和PERK/SREBP1通路激活有关。
IF 6.1 2区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2026-03-01 Epub Date: 2026-03-03 DOI: 10.1016/j.ecoenv.2026.119970
Junyu Jiang , Muran He , Bo Li , Yanyan Xiong , Haotian Shi , Yichao Huang , Dexiang Xu , Jun Zhang
Perfluorohexane sulfonate (PFHxS), an increasingly detected environmental pollutant, poses potential metabolic health risks, yet its developmental toxicity at environmentally relevant doses remains poorly understood. Here, we investigated the long-term effects of PFHxS exposure on the hepatic development using a mouse model with oral administration of 0.03 and 0.3 μg/kg/day throughout pregnancy. Our findings demonstrated that gestational PFHxS exposure induced persistent hepatic oxidative stress and was associated with the activation of the endoplasmic reticulum stress response (PERK/eIF2α/ATF4 pathway) in adults. These molecular alterations were accompanied by the upregulation of sterol regulatory element-binding protein 1 (SREBP1) and the transcriptional activation of key lipogenic enzymes (ACC, FASN, SCD1), culminating in hepatic lipid accumulation, inflammation, and fibrosis. Notably, these pathological changes exhibited sex-specific characteristics. These findings revealed, for the first time, that gestational PFHxS exposure at environmental levels may contribute to adult hepatic steatosis, potentially through mechanisms involving PERK/SREBP1-mediated lipogenesis. This study provided critical insights into the emerging health risks of replacement PFAS compounds.
全氟己烷磺酸(PFHxS)是一种越来越多被发现的环境污染物,具有潜在的代谢健康风险,但其在环境相关剂量下的发育毒性仍知之甚少。本研究采用妊娠期口服0.03和0.3 μg/kg/d的小鼠模型,研究PFHxS暴露对肝脏发育的长期影响。我们的研究结果表明,妊娠期PFHxS暴露诱导了成人持续的肝脏氧化应激,并与内质网应激反应(PERK/eIF2α/ATF4途径)的激活有关。这些分子改变伴随着固醇调节元件结合蛋白1 (SREBP1)的上调和关键脂肪生成酶(ACC、FASN、SCD1)的转录激活,最终导致肝脏脂质积累、炎症和纤维化。值得注意的是,这些病理变化表现出性别特异性。这些发现首次揭示了妊娠期环境水平的PFHxS暴露可能通过PERK/ srebp1介导的脂肪生成机制导致成人肝脏脂肪变性。这项研究为新出现的PFAS替代化合物的健康风险提供了重要的见解。
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引用次数: 0
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Ecotoxicology and Environmental Safety
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