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Effects of Naphtho[2,1-a]pyrene Exposure on CYP1A1 Expression: An in Vivo and in Vitro Mechanistic Study Exploring the Role of m6A Posttranscriptional Modification. 萘并[2,1-a]芘暴露对 CYP1A1 表达的影响:探索 m6A 转录后修饰作用的体内和体外机理研究。
IF 10.1 1区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2024-08-01 Epub Date: 2024-08-12 DOI: 10.1289/EHP14055
Jiemiao Shen, Li Wang, Wen Zhang, Xing Gong, Sheng Li, Xuyan Zou, Chao Chen, Rong Xia, Di Zhang, Shuyu Xu, Jiayi Xu, Shaozhuo Wang, Yinyue Jiang, Hong Sun, Chao Wang, Shou-Lin Wang
<p><strong>Background: </strong>Currently, many emerging polycyclic aromatic hydrocarbons (PAHs) have been found to be widely present in the environment. However, little has been reported about their toxicity, particularly in relation to CYP1A1.</p><p><strong>Objectives: </strong>This study aimed to explore the toxicity of naphtho[2,1-<i>a</i>]pyrene (N21aP) and elucidate the mechanism underlying N21aP-induced expression of CYP1A1.</p><p><strong>Methods: </strong>The concentration and sources of N21aP were detected and analyzed by gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) and diagnostic ratio analysis. Then the effects of CYP1A1 on the toxicity of N21aP were conducted in male wild-type (WT) and <i>Cyp1a1</i> knockout mice exposed to N21aP (0.02, 0.2, and <math><mrow><mn>2</mn><mspace></mspace><mi>mg</mi><mo>/</mo><mi>kg</mi></mrow></math>) through intratracheal instillation. Further, the aryl hydrocarbon receptor (AhR) pathway was examined through luciferase and chromatin immunoprecipitation (ChIP) assays. <math><mrow><mrow><msup><mrow><mi>N</mi></mrow><mrow><mn>6</mn></mrow></msup></mrow></mrow></math>-methyladenosine (<math><mrow><mrow><msup><mrow><mi>m</mi></mrow><mrow><mn>6</mn></mrow></msup></mrow><mi>A</mi></mrow></math>) modification levels were measured on global RNA and specifically on <i>CYP1A1</i> mRNA using dot blotting and methylated RNA immunoprecipitation-quantitative real-time polymerase chain reaction (MeRIP qRT-PCR), with validation by <math><mrow><mrow><msup><mrow><mi>m</mi></mrow><mrow><mn>6</mn></mrow></msup></mrow><mi>A</mi></mrow></math> inhibitors, DAA and SAH. <math><mrow><mrow><msup><mrow><mi>m</mi></mrow><mrow><mn>6</mn></mrow></msup></mrow><mi>A</mi></mrow></math> sites on <i>CYP1A1</i> were identified by bioinformatics and luciferase assays, and <i>CYP1A1</i> mRNA's interaction with IGF2BP3 was confirmed by RNA pull-down, luciferase, and RNA binding protein immunoprecipitation (RIP) assays.</p><p><strong>Results: </strong>N21aP was of the same environmental origin as benzo[<i>a</i>]pyrene (BaP) but was more stably present in the environment. N21aP could be metabolically activated by CYP1A1 to produce epoxides, causing DNA damage and further leading to lung inflammation. Importantly, in addition to the classical AhR pathway (i.e., BaP), N21aP also induced CYP1A1 expression with a posttranscriptional modification of <math><mrow><mrow><msup><mrow><mi>m</mi></mrow><mrow><mn>6</mn></mrow></msup></mrow><mi>A</mi></mrow></math> in <i>CYP1A1</i> mRNA via the METTL14-IGF2BP3-CYP1A1 axis. Specifically, in the two recognition sites of METTL14 on the <i>CYP1A1</i> mRNA transcript (position at 2700 and 5218), a methylation site (position at 5218) in the 3'-untranslated region (UTR) was recognized by IGF2BP3, enhanced the stability of <i>CYP1A1</i> mRNA, and finally resulted in an increase in CYP1A1 expression.</p><p><strong>Discussion: </strong>This study systematically demonstrated that in addition to AhR-
背景:目前,许多新出现的多环芳烃(PAHs)被发现广泛存在于环境中。然而,关于它们的毒性,尤其是与 CYP1A1 的关系,却鲜有报道:本研究旨在探讨萘并[2,1-a]芘(N21aP)的毒性,并阐明 N21aP 诱导 CYP1A1 表达的机制:方法:采用气相色谱-三重四极杆质谱法(GC-MS/MS)和诊断比分析法检测和分析N21aP的浓度和来源。然后,在雄性野生型(WT)小鼠和 Cyp1a1 基因敲除小鼠中通过气管内灌注的方式暴露于 N21aP(0.02、0.2 和 2 毫克/千克),研究了 CYP1A1 对 N21aP 毒性的影响。此外,还通过荧光素酶和染色质免疫沉淀(ChIP)检测了芳基烃受体(AhR)通路。利用点印迹法和甲基化 RNA 免疫沉淀-定量实时聚合酶链反应(MeRIP qRT-PCR)测量了全 RNA 和 CYP1A1 mRNA 上的 N6-甲基腺苷(m6A)修饰水平,并通过 m6A 抑制剂 DAA 和 SAH 进行了验证。通过生物信息学和荧光素酶测定确定了 CYP1A1 上的 m6A 位点,并通过 RNA 拉取、荧光素酶和 RNA 结合蛋白免疫沉淀(RIP)测定证实了 CYP1A1 mRNA 与 IGF2BP3 的相互作用:结果:N21aP 与苯并[a]芘(BaP)的环境来源相同,但在环境中的存在更为稳定。N21aP 可通过 CYP1A1 代谢活化产生环氧化物,造成 DNA 损伤并进一步导致肺部炎症。重要的是,除了经典的 AhR 途径(即 BaP)外,N21aP 还能通过 METTL14-IGF2BP3-CYP1A1 轴对 CYP1A1 mRNA 中的 m6A 进行转录后修饰,从而诱导 CYP1A1 的表达。具体来说,在CYP1A1 mRNA转录本上METTL14的两个识别位点(2700位和5218位)中,3'-非翻译区(UTR)中的一个甲基化位点(5218位)被IGF2BP3识别,增强了CYP1A1 mRNA的稳定性,最终导致CYP1A1表达量的增加:本研究系统地证明了除 AhR 介导的转录调控外,N21aP 还具有 m6A 介导的转录后修饰新机制,共同促进了 CYP1A1 的表达。鉴于多环芳烃是 CYP1A1 的代谢底物,这项研究不仅有助于理解环境-遗传相互作用对多环芳烃毒性的意义,而且有助于更好地理解新出现的多环芳烃在环境暴露水平下的健康风险。https://doi.org/10.1289/EHP14055。
{"title":"<ArticleTitle xmlns:ns0=\"http://www.w3.org/1998/Math/MathML\">Effects of Naphtho[2,1-<i>a</i>]pyrene Exposure on CYP1A1 Expression: An <i>in Vivo</i> and <i>in Vitro</i> Mechanistic Study Exploring the Role of <ns0:math><ns0:mrow><ns0:mrow><ns0:msup><ns0:mrow><ns0:mi>m</ns0:mi></ns0:mrow><ns0:mrow><ns0:mi>6</ns0:mi></ns0:mrow></ns0:msup></ns0:mrow><ns0:mi>A</ns0:mi></ns0:mrow></ns0:math> Posttranscriptional Modification.","authors":"Jiemiao Shen, Li Wang, Wen Zhang, Xing Gong, Sheng Li, Xuyan Zou, Chao Chen, Rong Xia, Di Zhang, Shuyu Xu, Jiayi Xu, Shaozhuo Wang, Yinyue Jiang, Hong Sun, Chao Wang, Shou-Lin Wang","doi":"10.1289/EHP14055","DOIUrl":"10.1289/EHP14055","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Currently, many emerging polycyclic aromatic hydrocarbons (PAHs) have been found to be widely present in the environment. However, little has been reported about their toxicity, particularly in relation to CYP1A1.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;This study aimed to explore the toxicity of naphtho[2,1-&lt;i&gt;a&lt;/i&gt;]pyrene (N21aP) and elucidate the mechanism underlying N21aP-induced expression of CYP1A1.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The concentration and sources of N21aP were detected and analyzed by gas chromatography-triple quadrupole mass spectrometry (GC-MS/MS) and diagnostic ratio analysis. Then the effects of CYP1A1 on the toxicity of N21aP were conducted in male wild-type (WT) and &lt;i&gt;Cyp1a1&lt;/i&gt; knockout mice exposed to N21aP (0.02, 0.2, and &lt;math&gt;&lt;mrow&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mi&gt;mg&lt;/mi&gt;&lt;mo&gt;/&lt;/mo&gt;&lt;mi&gt;kg&lt;/mi&gt;&lt;/mrow&gt;&lt;/math&gt;) through intratracheal instillation. Further, the aryl hydrocarbon receptor (AhR) pathway was examined through luciferase and chromatin immunoprecipitation (ChIP) assays. &lt;math&gt;&lt;mrow&gt;&lt;mrow&gt;&lt;msup&gt;&lt;mrow&gt;&lt;mi&gt;N&lt;/mi&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mn&gt;6&lt;/mn&gt;&lt;/mrow&gt;&lt;/msup&gt;&lt;/mrow&gt;&lt;/mrow&gt;&lt;/math&gt;-methyladenosine (&lt;math&gt;&lt;mrow&gt;&lt;mrow&gt;&lt;msup&gt;&lt;mrow&gt;&lt;mi&gt;m&lt;/mi&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mn&gt;6&lt;/mn&gt;&lt;/mrow&gt;&lt;/msup&gt;&lt;/mrow&gt;&lt;mi&gt;A&lt;/mi&gt;&lt;/mrow&gt;&lt;/math&gt;) modification levels were measured on global RNA and specifically on &lt;i&gt;CYP1A1&lt;/i&gt; mRNA using dot blotting and methylated RNA immunoprecipitation-quantitative real-time polymerase chain reaction (MeRIP qRT-PCR), with validation by &lt;math&gt;&lt;mrow&gt;&lt;mrow&gt;&lt;msup&gt;&lt;mrow&gt;&lt;mi&gt;m&lt;/mi&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mn&gt;6&lt;/mn&gt;&lt;/mrow&gt;&lt;/msup&gt;&lt;/mrow&gt;&lt;mi&gt;A&lt;/mi&gt;&lt;/mrow&gt;&lt;/math&gt; inhibitors, DAA and SAH. &lt;math&gt;&lt;mrow&gt;&lt;mrow&gt;&lt;msup&gt;&lt;mrow&gt;&lt;mi&gt;m&lt;/mi&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mn&gt;6&lt;/mn&gt;&lt;/mrow&gt;&lt;/msup&gt;&lt;/mrow&gt;&lt;mi&gt;A&lt;/mi&gt;&lt;/mrow&gt;&lt;/math&gt; sites on &lt;i&gt;CYP1A1&lt;/i&gt; were identified by bioinformatics and luciferase assays, and &lt;i&gt;CYP1A1&lt;/i&gt; mRNA's interaction with IGF2BP3 was confirmed by RNA pull-down, luciferase, and RNA binding protein immunoprecipitation (RIP) assays.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;N21aP was of the same environmental origin as benzo[&lt;i&gt;a&lt;/i&gt;]pyrene (BaP) but was more stably present in the environment. N21aP could be metabolically activated by CYP1A1 to produce epoxides, causing DNA damage and further leading to lung inflammation. Importantly, in addition to the classical AhR pathway (i.e., BaP), N21aP also induced CYP1A1 expression with a posttranscriptional modification of &lt;math&gt;&lt;mrow&gt;&lt;mrow&gt;&lt;msup&gt;&lt;mrow&gt;&lt;mi&gt;m&lt;/mi&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mn&gt;6&lt;/mn&gt;&lt;/mrow&gt;&lt;/msup&gt;&lt;/mrow&gt;&lt;mi&gt;A&lt;/mi&gt;&lt;/mrow&gt;&lt;/math&gt; in &lt;i&gt;CYP1A1&lt;/i&gt; mRNA via the METTL14-IGF2BP3-CYP1A1 axis. Specifically, in the two recognition sites of METTL14 on the &lt;i&gt;CYP1A1&lt;/i&gt; mRNA transcript (position at 2700 and 5218), a methylation site (position at 5218) in the 3'-untranslated region (UTR) was recognized by IGF2BP3, enhanced the stability of &lt;i&gt;CYP1A1&lt;/i&gt; mRNA, and finally resulted in an increase in CYP1A1 expression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;This study systematically demonstrated that in addition to AhR-","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"132 8","pages":"87003"},"PeriodicalIF":10.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11318572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141916399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Effects of Early Life Exposures to the Aryl Hydrocarbon Receptor Ligand TCDF on Gut Microbiota and Host Metabolic Homeostasis in C57BL/6J Mice. 生命早期暴露于芳基烃受体配体 TCDF 对 C57BL/6J 小鼠肠道微生物群和宿主代谢稳态的影响
IF 10.1 1区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2024-08-01 Epub Date: 2024-08-14 DOI: 10.1289/EHP13356
Yuan Tian, Bipin Rimal, Jordan E Bisanz, Wei Gui, Trenton M Wolfe, Imhoi Koo, Iain A Murray, Shaneice K Nettleford, Shigetoshi Yokoyama, Fangcong Dong, Sergei Koshkin, K Sandeep Prabhu, Peter J Turnbaugh, Seth T Walk, Gary H Perdew, Andrew D Patterson

Background: Exposure to persistent organic pollutants (POPs) and disruptions in the gastrointestinal microbiota have been positively correlated with a predisposition to factors such as obesity, metabolic syndrome, and type 2 diabetes; however, it is unclear how the microbiome contributes to this relationship.

Objective: This study aimed to explore the association between early life exposure to a potent aryl hydrocarbon receptor (AHR) agonist and persistent disruptions in the microbiota, leading to impaired metabolic homeostasis later in life.

Methods: This study used metagenomics, nuclear magnetic resonance (NMR)- and mass spectrometry (MS)-based metabolomics, and biochemical assays to analyze the gut microbiome composition and function, as well as the physiological and metabolic effects of early life exposure to 2,3,7,8-tetrachlorodibenzofuran (TCDF) in conventional, germ-free (GF), and Ahr-null mice. The impact of TCDF on Akkermansia muciniphila (A. muciniphila) in vitro was assessed using optical density (OD 600), flow cytometry, transcriptomics, and MS-based metabolomics.

Results: TCDF-exposed mice exhibited lower abundances of A. muciniphila, lower levels of cecal short-chain fatty acids (SCFAs) and indole-3-lactic acid (ILA), as well as lower levels of the gut hormones glucagon-like peptide 1 (GLP-1) and peptide YY (PYY), findings suggestive of disruption in the gut microbiome community structure and function. Importantly, microbial and metabolic phenotypes associated with early life POP exposure were transferable to GF recipients in the absence of POP carry-over. In addition, AHR-independent interactions between POPs and the microbiota were observed, and they were significantly associated with growth, physiology, gene expression, and metabolic activity outcomes of A. muciniphila, supporting suppressed activity along the ILA pathway.

Conclusions: These data obtained in a mouse model point to the complex effects of POPs on the host and microbiota, providing strong evidence that early life, short-term, and self-limiting POP exposure can adversely impact the microbiome, with effects persisting into later life with associated health implications. https://doi.org/10.1289/EHP13356.

背景:暴露于持久性有机污染物(POPs)和胃肠道微生物群的紊乱与肥胖、代谢综合征和 2 型糖尿病等疾病的易感性呈正相关;然而,目前还不清楚微生物群是如何促成这种关系的:本研究旨在探讨生命早期暴露于强效芳烃受体(AHR)激动剂与微生物群持续紊乱之间的关系,这种紊乱会导致生命后期代谢平衡受损:本研究利用元基因组学、基于核磁共振(NMR)和质谱(MS)的代谢组学以及生化检测方法,分析了常规小鼠、无菌小鼠(GF)和Ahr-null小鼠的肠道微生物组组成和功能,以及早期暴露于2,3,7,8-四氯二苯并呋喃(TCDF)对其生理和代谢的影响。使用光密度(OD 600)、流式细胞仪、转录组学和基于质谱的代谢组学评估了TCDF对体外Akkermansia muciniphila(A. muciniphila)的影响:结果:暴露于 TCDF 的小鼠表现出较低的粘蛋白噬菌体丰度、较低水平的盲肠短链脂肪酸 (SCFA) 和吲哚-3-乳酸 (ILA),以及较低水平的肠道激素胰高血糖素样肽 1 (GLP-1) 和肽 YY (PYY),这些结果表明肠道微生物群落结构和功能受到了破坏。重要的是,与生命早期接触持久性有机污染物有关的微生物和代谢表型可转移到 GF 受体,而不存在持久性有机污染物携带。此外,还观察到了持久性有机污染物与微生物群之间不依赖于 AHR 的相互作用,这些相互作用与 A. muciniphila 的生长、生理、基因表达和代谢活动结果显著相关,支持 ILA 通路的活动受到抑制:在小鼠模型中获得的这些数据表明了持久性有机污染物对宿主和微生物群的复杂影响,有力地证明了生命早期、短期和自我限制的持久性有机污染物暴露会对微生物群产生不利影响,这种影响会持续到生命后期,并对健康产生相关影响。https://doi.org/10.1289/EHP13356。
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引用次数: 0
Neurotox Screen? Zebrafish Study Points to PFOS Early-Life Exposure Effects. 神经毒性筛选?斑马鱼研究表明全氟辛烷磺酸的早期生活接触会产生影响。
IF 10.1 1区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2024-08-01 Epub Date: 2024-08-23 DOI: 10.1289/EHP15467
Nate Seltenrich
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引用次数: 0
Invited Perspective: Leveraging Research and Resources to Mitigate Health Impacts of Environmental Disasters-Insights from a South Korean Tire Factory Fire. 特邀观点:利用研究和资源减轻环境灾难对健康的影响--来自韩国轮胎厂火灾的启示。
IF 10.1 1区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2024-08-01 Epub Date: 2024-08-28 DOI: 10.1289/EHP15463
Richard K Kwok, Aubrey K Miller
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引用次数: 0
Unlocking the Potential of Clustering and Classification Approaches: Navigating Supervised and Unsupervised Chemical Similarity. 释放聚类和分类方法的潜力:探索有监督和无监督的化学相似性。
IF 10.1 1区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2024-08-01 Epub Date: 2024-08-06 DOI: 10.1289/EHP14001
Kamel Mansouri, Kyla Taylor, Scott Auerbach, Stephen Ferguson, Rachel Frawley, Jui-Hua Hsieh, Gloria Jahnke, Nicole Kleinstreuer, Suril Mehta, José T Moreira-Filho, Fred Parham, Cynthia Rider, Andrew A Rooney, Amy Wang, Vicki Sutherland

Background: The field of toxicology has witnessed substantial advancements in recent years, particularly with the adoption of new approach methodologies (NAMs) to understand and predict chemical toxicity. Class-based methods such as clustering and classification are key to NAMs development and application, aiding the understanding of hazard and risk concerns associated with groups of chemicals without additional laboratory work. Advances in computational chemistry, data generation and availability, and machine learning algorithms represent important opportunities for continued improvement of these techniques to optimize their utility for specific regulatory and research purposes. However, due to their intricacy, deep understanding and careful selection are imperative to align the adequate methods with their intended applications.

Objectives: This commentary aims to deepen the understanding of class-based approaches by elucidating the pivotal role of chemical similarity (structural and biological) in clustering and classification approaches (CCAs). It addresses the dichotomy between general end point-agnostic similarity, often entailing unsupervised analysis, and end point-specific similarity necessitating supervised learning. The goal is to highlight the nuances of these approaches, their applications, and common misuses.

Discussion: Understanding similarity is pivotal in toxicological research involving CCAs. The effectiveness of these approaches depends on the right definition and measure of similarity, which varies based on context and objectives of the study. This choice is influenced by how chemical structures are represented and the respective labels indicating biological activity, if applicable. The distinction between unsupervised clustering and supervised classification methods is vital, requiring the use of end point-agnostic vs. end point-specific similarity definition. Separate use or combination of these methods requires careful consideration to prevent bias and ensure relevance for the goal of the study. Unsupervised methods use end point-agnostic similarity measures to uncover general structural patterns and relationships, aiding hypothesis generation and facilitating exploration of datasets without the need for predefined labels or explicit guidance. Conversely, supervised techniques demand end point-specific similarity to group chemicals into predefined classes or to train classification models, allowing accurate predictions for new chemicals. Misuse can arise when unsupervised methods are applied to end point-specific contexts, like analog selection in read-across, leading to erroneous conclusions. This commentary provides insights into the significance of similarity and its role in supervised classification and unsupervised clustering approaches. https://doi.org/10.1289/EHP14001.

背景:近年来,毒理学领域取得了长足的进步,尤其是采用新方法(NAMs)来了解和预测化学毒性。基于类别的方法(如聚类和分类)是新方法开发和应用的关键,有助于了解与化学品组相关的危害和风险问题,而无需额外的实验室工作。计算化学、数据生成和可用性以及机器学习算法方面的进步为这些技术的持续改进提供了重要机会,从而优化了它们在特定监管和研究目的中的实用性。然而,由于这些技术错综复杂,因此必须深入了解并谨慎选择,才能使适当的方法与其预期应用相匹配:本评论旨在通过阐明化学相似性(结构和生物)在聚类和分类方法(CCAs)中的关键作用,加深对基于类别的方法的理解。文章探讨了通常需要进行无监督分析的一般终点不可知相似性与需要进行监督学习的特定终点相似性之间的二分法。目的是强调这些方法的细微差别、应用和常见误用:讨论:了解相似性在涉及 CCA 的毒理学研究中至关重要。这些方法的有效性取决于对相似性的正确定义和衡量标准,而定义和衡量标准因研究的背景和目标而异。这种选择会受到化学结构的表示方法和相应的生物活性标签(如果适用)的影响。无监督聚类和有监督分类方法之间的区别至关重要,这要求使用与终点无关的相似性定义和与特定终点有关的相似性定义。单独使用或结合使用这些方法需要慎重考虑,以防止出现偏差,并确保与研究目标相关。无监督方法使用与端点无关的相似性度量来发现一般的结构模式和关系,有助于假设的生成,并促进数据集的探索,而无需预定义的标签或明确的指导。相反,有监督技术则需要特定端点的相似性,以便将化学品归入预定义类别或训练分类模型,从而对新化学品进行准确预测。如果将无监督方法应用于特定端点环境(如读取交叉中的类似物选择),则可能出现误用,导致错误结论。本评论深入探讨了相似性的意义及其在有监督分类和无监督聚类方法中的作用。https://doi.org/10.1289/EHP14001。
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引用次数: 0
Dioxins vs. PFAS: Science and Policy Challenges. 二恶英与全氟辛烷磺酸:科学与政策挑战》。
IF 10.1 1区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2024-08-01 Epub Date: 2024-08-12 DOI: 10.1289/EHP14449
Alex J George, Linda S Birnbaum

Background: Dioxin-like chemicals are a group of ubiquitous environmental toxicants that received intense attention in the last two decades of the 20th century. Through extensive mechanistic research and validation, the global community has agreed upon a regulatory strategy for these chemicals that centers on their common additive activation of a single receptor. Applying these regulations has led to decreased exposure in most populations studied. As dioxin-like chemicals moved out of the limelight, research and media attention has turned to other concerning contaminants, including per- and polyfluoroalkyl substances (PFAS). During the 20th century, PFAS were also being quietly emitted into the environment, but only in the last 20 years have we realized the serious threat they pose to health. There is active debate about how to appropriately classify and regulate the thousands of known PFAS and finding a solution for these "forever chemicals" is of the utmost urgency.

Objectives: Here, we compare important features of dioxin-like chemicals and PFAS, including the history, mechanism of action, and effective upstream regulatory strategies, with the objective of gleaning insight from the past to improve strategies for addressing PFAS.

Discussion: The differences between these two chemical classes means that regulatory strategies for dioxin-like chemicals will not be appropriate for PFAS. PFAS exert toxicity by both receptor-based and nonreceptor-based mechanisms, which complicates mixtures evaluation and stymies efforts to develop inexpensive assays that accurately capture toxicity. Furthermore, dioxin-like chemicals were unwanted byproducts, but PFAS are useful and valuable, which has led to intense resistance against efforts to restrict their production. Nonetheless, useful lessons can be drawn from dioxin-like chemicals and applied to PFAS, including eliminating nonessential production of new PFAS and proactive investment in environmental remediation to address their extraordinarily long environmental persistence. https://doi.org/10.1289/EHP14449.

背景:二恶英类化学品是一类无处不在的环境毒物,在 20 世纪的最后 20 年里受到了广泛关注。通过广泛的机理研究和验证,国际社会已就这些化学品的监管策略达成一致,其核心是这些化学品对单一受体的共同叠加激活作用。实施这些法规后,大多数被研究人群的接触量都有所下降。随着二恶英类化学物质逐渐淡出人们的视线,研究和媒体的注意力转向了其他令人担忧的污染物,包括全氟和多氟烷基物质 (PFAS)。20 世纪,PFAS 也悄悄地排放到环境中,但直到最近 20 年,我们才意识到它们对健康的严重威胁。目前,关于如何对数千种已知的全氟辛烷磺酸进行适当分类和监管的争论十分激烈,当务之急是为这些 "永远的化学品 "找到解决方案:在此,我们比较了二恶英类化学品和全氟辛烷磺酸的重要特征,包括历史、作用机理和有效的上游监管策略,目的是从过去的经验中吸取教训,改进应对全氟辛烷磺酸的策略:这两类化学品之间的差异意味着针对二恶英类化学品的监管策略并不适用于全氟辛烷磺酸。全氟辛烷磺酸通过基于受体和非基于受体的机制产生毒性,这使得混合物评估变得复杂,并阻碍了开发可准确捕捉毒性的廉价检测方法的工作。此外,二恶英类化学品是不受欢迎的副产品,而全氟辛烷磺酸却是有用和有价值的,这导致限制其生产的努力受到强烈抵制。尽管如此,我们仍可从二恶英类化学品中汲取有益的经验,并将其应用于全氟辛烷磺酸,包括消除新的全氟辛烷磺酸的非必要生产,并积极投资于环境修复,以解决其超长的环境持久性问题。https://doi.org/10.1289/EHP14449。
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引用次数: 0
Association of Phenols, Parabens, and Their Mixture with Maternal Blood Pressure Measurements in the PROTECT Cohort. PROTECT 群体中酚类、苯甲酸酯类及其混合物与产妇血压测量值的关系。
IF 10.1 1区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2024-08-01 Epub Date: 2024-08-14 DOI: 10.1289/EHP14008
Julia R Varshavsky, John D Meeker, Emily Zimmerman, Megan L Woodbury, Max T Aung, Zaira Y Rosario-Pabon, Amber L Cathey, Carmen M Vélez-Vega, José Cordero, Akram Alshawabkeh, Stephanie M Eick

Background: Phenols and parabens are two classes of high production volume chemicals that are used widely in consumer and personal care products and have been associated with reproductive harm and pregnancy complications, such as preeclampsia and gestational diabetes. However, studies examining their influence on maternal blood pressure and gestational hypertension are limited.

Objectives: We investigated associations between individual phenols, parabens, and their mixture on maternal blood pressure measurements, including systolic and diastolic blood pressure (SBP and DBP) and hypertension during pregnancy (defined as stage 1 or 2 hypertension), among N=1,433 Puerto Rico PROTECT study participants.

Methods: We examined these relationships cross-sectionally at two time points during pregnancy (16-20 and 24-28 wks gestation) and longitudinally using linear mixed models (LMMs). Finally, we used quantile g-computation to examine the mixture effect on continuous (SBP, DBP) and binary (hypertension during pregnancy) blood pressure outcomes.

Results: We observed a trend of higher odds of hypertension during pregnancy with exposure to multiple analytes and the overall mixture [including bisphenol A (BPA), bisphenol S (BPS), triclocarbon (TCC), triclosan (TCS), benzophenone-3 (BP-3), 2,4-dichlorophenol (2,4-DCP), 2,5-dichlorophenol (2,5-DCP), methyl paraben (M-PB), propyl paraben (P-PB), butyl paraben (B-PB), and ethyl paraben (E-PB)], especially at 24-28 wk gestation, with an adjusted mixture odds ratio(OR)=1.57 (95% CI: 1.03, 2.38). Lower SBP and higher DBP were also associated with individual analytes, with results from LMMs most consistent for methyl paraben (M-PB) or propyl paraben (P-PB) and increased DBP across pregnancy [adjusted M-PB β=0.78 (95% CI: 0.17, 1.38) and adjusted P-PB β=0.85 (95% CI: 0.19, 1.51)] and for BPA, which was associated with decreased SBP (adjusted β=-0.57; 95% CI: -1.09, -0.05). Consistent with other literature, we also found evidence of effect modification by fetal sex, with a strong inverse association observed between the overall exposure mixture and SBP at visit 1 among participants carrying female fetuses only.

Conclusions: Our findings indicate that phenol and paraben exposure may collectively increase the risk of stage 1 or 2 hypertension during pregnancy, which has important implications for fetal and maternal health. https://doi.org/10.1289/EHP14008.

背景:酚类和对羟基苯甲酸酯类是两类高产量化学品,它们被广泛用于消费品和个人护理产品中,并与生殖危害和妊娠并发症(如先兆子痫和妊娠糖尿病)有关。然而,有关它们对孕妇血压和妊娠高血压影响的研究却很有限:我们调查了波多黎各 PROTECT 研究的 1433 名参与者中,单个苯酚、对羟基苯甲酸酯及其混合物与孕妇血压测量值(包括收缩压和舒张压(SBP 和 DBP))和妊娠期高血压(定义为 1 期或 2 期高血压)之间的关系:我们在孕期的两个时间点(妊娠 16-20 周和 24-28 周)横向研究了这些关系,并使用线性混合模型 (LMM) 纵向研究了这些关系。最后,我们使用量子 g 计算方法研究了连续血压(SBP、DBP)和二元血压(孕期高血压)结果的混合效应:2,4-二氯苯酚 (2,4-DCP)、2,5-二氯苯酚 (2,5-DCP)、对羟基苯甲酸甲酯 (M-PB)、对羟基苯甲酸丙酯 (P-PB)、对羟基苯甲酸丁酯 (B-PB) 和对羟基苯甲酸乙酯 (E-PB)],尤其是在妊娠 24-28 周时,调整后的混合物几率比(OR)=1.57(95% CI:1.03,2.38)。SBP的降低和DBP的升高也与单个分析物有关,LMMs的结果与对羟基苯甲酸甲酯(M-PB)或对羟基苯甲酸丙酯(P-PB)以及整个孕期DBP的升高最为一致[调整后的M-PB β=0.78(95% CI:0.17,1.38),调整后的P-PB β=0.85(95% CI:0.19,1.51)],而双酚A则与SBP的降低有关(调整后的β=-0.57;95% CI:-1.09,-0.05)。与其他文献一致,我们还发现了胎儿性别对影响的修饰作用,仅在怀有雌性胎儿的参与者中观察到总体暴露混合物与第 1 次就诊时的 SBP 之间存在强烈的反向关联:我们的研究结果表明,苯酚和对羟基苯甲酸酯的暴露可能会共同增加孕期1期或2期高血压的风险,这对胎儿和孕产妇的健康具有重要影响。https://doi.org/10.1289/EHP14008。
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引用次数: 0
Estimating the Acute Health Effects of Smoke Exposure from an Urban Factory Fire Accident: A Case Study of a Tire Factory Fire in Korea. 估算城市工厂火灾事故烟雾暴露对健康的急性影响:韩国轮胎厂火灾案例研究》。
IF 10.1 1区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2024-08-01 Epub Date: 2024-08-28 DOI: 10.1289/EHP14115
Changwoo Han, Marnpyung Jang, Jaeyoung Yoon, Bolim Lee, Jaiyong Kim, Hoyeon Jang, Tarik Benmarhnia
<p><strong>Background: </strong>A major industrial fire accident occurred in a tire manufacturing factory in Daejeon, Korea, on 12 March 2023 and lasted for 3 d, generating air pollutant emissions. Although evidence regarding the health effects of urban fires is limited, residents near tire factory may have experienced health hazards due to smoke exposure from fire plumes.</p><p><strong>Objectives: </strong>Capitalizing on the timing of this fire incident as a natural experiment, we estimated the attributable excess air pollution exposure and associated disease development among residents living near the tire factory.</p><p><strong>Methods: </strong>We used the generalized synthetic control method to estimate air pollution exposure and health burden attributable to the accident among residents living in smoke-exposed districts. Based on satellite images and air pollution monitoring results, three administrative districts (within <math><mrow><mn>1.2</mn><mspace></mspace><mi>km</mi></mrow></math> from the factory) were defined as smoke-exposed, and the other 79 districts of Daejeon were defined as controls. Among the 11 monitoring stations in Daejeon, the station located <math><mrow><mn>500</mn><mspace></mspace><mi>m</mi></mrow></math> from the factory was used to estimate excess air pollution exposure (<math><mrow><mrow><msub><mrow><mrow><mi>PM</mi></mrow></mrow><mrow><mrow><mn>10</mn></mrow></mrow></msub></mrow></mrow></math>, <math><mrow><mrow><msub><mrow><mrow><mi>PM</mi></mrow></mrow><mrow><mrow><mn>2.5</mn></mrow></mrow></msub></mrow></mrow></math>, <math><mrow><mrow><msub><mrow><mi>NO</mi></mrow><mrow><mn>2</mn></mrow></msub></mrow></mrow></math>, <math><mrow><mrow><msub><mrow><mi>O</mi></mrow><mrow><mn>3</mn></mrow></msub></mrow></mrow></math>, <math><mrow><mrow><msub><mrow><mi>SO</mi></mrow><mrow><mn>2</mn></mrow></msub></mrow></mrow></math>, and CO) for residents in the exposed districts. The number of daily district-level disease-specific incidence cases were acquired from the National Health Insurance Database and used to estimate excess health burden resulting from the fire.</p><p><strong>Results: </strong>During the first week following the factory fire, residents of exposed districts had an estimated excess exposure to 125.2 [95% confidence interval (CI): 44.9, 156.7] <math><mrow><mrow><msup><mrow><mi>μ</mi><mi>g</mi><mo>/</mo><mi>m</mi></mrow><mrow><mn>3</mn></mrow></msup></mrow></mrow></math> of <math><mrow><mrow><msub><mrow><mrow><mi>PM</mi></mrow></mrow><mrow><mrow><mn>10</mn></mrow></mrow></msub></mrow></mrow></math>, 50.4 (95% CI: 12.7, 99.8) ppb of <math><mrow><mrow><msub><mrow><mi>NO</mi></mrow><mrow><mn>2</mn></mrow></msub></mrow></mrow></math>, and 32.0 (95% CI: 21.0, 35.9) ppb of <math><mrow><mrow><msub><mrow><mi>SO</mi></mrow><mrow><mn>2</mn></mrow></msub></mrow></mrow></math>. We also found an average increase in the incidence cases of other diseases of upper respiratory tract [20.6 persons (95% CI: 6.2, 37.4)], lung dis
背景:2023 年 3 月 12 日,韩国大田的一家轮胎制造厂发生了一起重大工业火灾事故,火灾持续了 3 天,产生了空气污染物排放。虽然有关城市火灾对健康影响的证据有限,但轮胎厂附近的居民可能会因暴露在火灾烟羽中而受到健康危害:目的:利用这次火灾事件的时间作为自然实验,我们估算了轮胎厂附近居民可归因的过量空气污染暴露和相关疾病的发生:方法:我们采用广义合成控制法估算了烟雾暴露区居民的空气污染暴露量和健康负担。根据卫星图像和空气污染监测结果,将大田市的三个行政区(距离轮胎厂 1.2km 范围内)定义为烟雾暴露区,其他 79 个行政区定义为对照区。在大田市的 11 个监测站中,距离工厂 500 米的监测站被用来估算烟雾暴露区居民的超标空气污染暴露量(PM10、PM2.5、二氧化氮、臭氧、二氧化硫和一氧化碳)。从国民健康保险数据库中获取了每日区级特定疾病发病病例数,用于估算火灾造成的超额健康负担:结果:在工厂火灾后的第一周,受影响地区的居民估计过量暴露于 125.2 [95% 置信区间 (CI):44.9, 156.7] 微克/立方米的 PM10、50.4 (95% CI:12.7, 99.8) ppb 的二氧化氮和 32.0 (95% CI:21.0, 35.9) ppb 的二氧化硫。我们还发现,在暴露于空气污染的地区,上呼吸道其他疾病[20.6 人(95% CI:6.2,37.4)]、外来因素引起的肺部疾病[2.5 人(95% CI:2.1,3.3)]、荨麻疹和红斑[5.9 人(95% CI:-0.6,11.2)]以及阵发性和发作性疾病[8.5 人(95% CI:3.7,13.4)]的发病率平均有所上升:讨论:在轮胎厂附近的居民中发现了过多的空气污染暴露和疾病发病率。采取预防措施(如预警系统)以避免吸入与火灾有关的污染对人们的健康造成影响,可能对受此类事件影响的社区有益。https://doi.org/10.1289/EHP14115。
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Although evidence regarding the health effects of urban fires is limited, residents near tire factory may have experienced health hazards due to smoke exposure from fire plumes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;Capitalizing on the timing of this fire incident as a natural experiment, we estimated the attributable excess air pollution exposure and associated disease development among residents living near the tire factory.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We used the generalized synthetic control method to estimate air pollution exposure and health burden attributable to the accident among residents living in smoke-exposed districts. Based on satellite images and air pollution monitoring results, three administrative districts (within &lt;math&gt;&lt;mrow&gt;&lt;mn&gt;1.2&lt;/mn&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mi&gt;km&lt;/mi&gt;&lt;/mrow&gt;&lt;/math&gt; from the factory) were defined as smoke-exposed, and the other 79 districts of Daejeon were defined as controls. Among the 11 monitoring stations in Daejeon, the station located &lt;math&gt;&lt;mrow&gt;&lt;mn&gt;500&lt;/mn&gt;&lt;mspace&gt;&lt;/mspace&gt;&lt;mi&gt;m&lt;/mi&gt;&lt;/mrow&gt;&lt;/math&gt; from the factory was used to estimate excess air pollution exposure (&lt;math&gt;&lt;mrow&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mrow&gt;&lt;mi&gt;PM&lt;/mi&gt;&lt;/mrow&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mrow&gt;&lt;mn&gt;10&lt;/mn&gt;&lt;/mrow&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;/mrow&gt;&lt;/mrow&gt;&lt;/math&gt;, &lt;math&gt;&lt;mrow&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mrow&gt;&lt;mi&gt;PM&lt;/mi&gt;&lt;/mrow&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mrow&gt;&lt;mn&gt;2.5&lt;/mn&gt;&lt;/mrow&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;/mrow&gt;&lt;/mrow&gt;&lt;/math&gt;, &lt;math&gt;&lt;mrow&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;NO&lt;/mi&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;/mrow&gt;&lt;/mrow&gt;&lt;/math&gt;, &lt;math&gt;&lt;mrow&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;O&lt;/mi&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mn&gt;3&lt;/mn&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;/mrow&gt;&lt;/mrow&gt;&lt;/math&gt;, &lt;math&gt;&lt;mrow&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;SO&lt;/mi&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;/mrow&gt;&lt;/mrow&gt;&lt;/math&gt;, and CO) for residents in the exposed districts. The number of daily district-level disease-specific incidence cases were acquired from the National Health Insurance Database and used to estimate excess health burden resulting from the fire.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;During the first week following the factory fire, residents of exposed districts had an estimated excess exposure to 125.2 [95% confidence interval (CI): 44.9, 156.7] &lt;math&gt;&lt;mrow&gt;&lt;mrow&gt;&lt;msup&gt;&lt;mrow&gt;&lt;mi&gt;μ&lt;/mi&gt;&lt;mi&gt;g&lt;/mi&gt;&lt;mo&gt;/&lt;/mo&gt;&lt;mi&gt;m&lt;/mi&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mn&gt;3&lt;/mn&gt;&lt;/mrow&gt;&lt;/msup&gt;&lt;/mrow&gt;&lt;/mrow&gt;&lt;/math&gt; of &lt;math&gt;&lt;mrow&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mrow&gt;&lt;mi&gt;PM&lt;/mi&gt;&lt;/mrow&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mrow&gt;&lt;mn&gt;10&lt;/mn&gt;&lt;/mrow&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;/mrow&gt;&lt;/mrow&gt;&lt;/math&gt;, 50.4 (95% CI: 12.7, 99.8) ppb of &lt;math&gt;&lt;mrow&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;NO&lt;/mi&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;/mrow&gt;&lt;/mrow&gt;&lt;/math&gt;, and 32.0 (95% CI: 21.0, 35.9) ppb of &lt;math&gt;&lt;mrow&gt;&lt;mrow&gt;&lt;msub&gt;&lt;mrow&gt;&lt;mi&gt;SO&lt;/mi&gt;&lt;/mrow&gt;&lt;mrow&gt;&lt;mn&gt;2&lt;/mn&gt;&lt;/mrow&gt;&lt;/msub&gt;&lt;/mrow&gt;&lt;/mrow&gt;&lt;/math&gt;. We also found an average increase in the incidence cases of other diseases of upper respiratory tract [20.6 persons (95% CI: 6.2, 37.4)], lung dis","PeriodicalId":11862,"journal":{"name":"Environmental Health Perspectives","volume":"132 8","pages":"87008"},"PeriodicalIF":10.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11353213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Response to "Comment on 'Evidence Synthesis of Observational Studies in Environmental Health: Lessons Learned from a Systematic Review on Traffic-Related Air Pollution'". 对 "关于'环境健康观察研究的证据综合'的评论:与交通有关的空气污染系统综述的经验教训 "的评论。
IF 10.1 1区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2024-08-01 Epub Date: 2024-08-13 DOI: 10.1289/EHP15822
Hanna Boogaard, Richard W Atkinson, Jeffrey R Brook, Howard H Chang, Gerard Hoek, Barbara Hoffmann, Sharon K Sagiv, Evangelia Samoli, Audrey Smargiassi, Adam A Szpiro, Danielle Vienneau, Jennifer Weuve, Frederick W Lurmann, Francesco Forastiere
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引用次数: 0
Invited Perspective: The All About Arsenic Program-A Blueprint for Leveraging Youth Engagement to Advance Water Justice. 特邀观点:关于砷的一切计划--利用青年参与推进水正义的蓝图。
IF 10.1 1区 环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES Pub Date : 2024-08-01 Epub Date: 2024-08-21 DOI: 10.1289/EHP15068
Yoshira Ornelas Van Horne, Anne E Nigra
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引用次数: 0
期刊
Environmental Health Perspectives
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