Chemical Research in Toxicology最新文献

{"title":"In Vitro Screening for ToxCast Chemicals Binding to Thyroxine-Binding Globulin","authors":"Stephanie A. Eytcheson*,&nbsp;Alexander D. Zosel,&nbsp;Jennifer H. Olker,&nbsp;Michael W. Hornung and Sigmund J. Degitz*,&nbsp;","doi":"10.1021/acs.chemrestox.4c0018310.1021/acs.chemrestox.4c00183","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00183https://doi.org/10.1021/acs.chemrestox.4c00183","url":null,"abstract":"<p >Thyroid hormone (TH) carrier proteins play an important role in distributing TH to target tissue as well as maintaining the balance of free versus bound TH in the blood. Interference with the TH carrier proteins has been identified as a potential mechanism of thyroid system disruption. To address the lack of data regarding chemicals binding to these carrier proteins and displacing TH, a fluorescence-based <i>in vitro</i> screening assay was utilized to screen over 1,400 chemicals from the U.S. EPA’s ToxCast phase1_v2, phase 2, and e1k libraries for competitive binding to one of the carrier proteins, thyroxine-binding globulin. Initial screening at a single high concentration of 100 μM identified 714 chemicals that decreased signal of the bound fluorescent ligand by 20% or higher. Of these, 297 produced 50% or greater reduction in fluorescence and were further tested in concentration–response (0.004 to 150 μM) to determine relative potency. Ten chemicals were found to have EC50 values &lt;1 μM, 63 &lt; 10 μM, and 141 chemicals between 10 and 100 μM. Utilization of this assay contributes to expanding the number of <i>in vitro</i> assays available for identifying chemicals with the potential to disrupt TH homeostasis. These results support ranking and prioritization of chemicals to be tested <i>in vivo</i> to aid in the development of a framework for predicting <i>in vivo</i> effects from <i>in vitro</i> high-throughput data.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142517490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Vitro Screening for ToxCast Chemicals Binding to Thyroxine-Binding Globulin","authors":"Stephanie A. Eytcheson, Alexander D. Zosel, Jennifer H. Olker, Michael W. Hornung, Sigmund J. Degitz","doi":"10.1021/acs.chemrestox.4c00183","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00183","url":null,"abstract":"Thyroid hormone (TH) carrier proteins play an important role in distributing TH to target tissue as well as maintaining the balance of free versus bound TH in the blood. Interference with the TH carrier proteins has been identified as a potential mechanism of thyroid system disruption. To address the lack of data regarding chemicals binding to these carrier proteins and displacing TH, a fluorescence-based <i>in vitro</i> screening assay was utilized to screen over 1,400 chemicals from the U.S. EPA’s ToxCast phase1_v2, phase 2, and e1k libraries for competitive binding to one of the carrier proteins, thyroxine-binding globulin. Initial screening at a single high concentration of 100 μM identified 714 chemicals that decreased signal of the bound fluorescent ligand by 20% or higher. Of these, 297 produced 50% or greater reduction in fluorescence and were further tested in concentration–response (0.004 to 150 μM) to determine relative potency. Ten chemicals were found to have EC50 values &lt;1 μM, 63 &lt; 10 μM, and 141 chemicals between 10 and 100 μM. Utilization of this assay contributes to expanding the number of <i>in vitro</i> assays available for identifying chemicals with the potential to disrupt TH homeostasis. These results support ranking and prioritization of chemicals to be tested <i>in vivo</i> to aid in the development of a framework for predicting <i>in vivo</i> effects from <i>in vitro</i> high-throughput data.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260485","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Berberine Inhibits KLF4 Promoter Methylation and Ferroptosis to Ameliorate Diabetic Nephropathy in Mice","authors":"Shengyu Cai, Huizheng Zhu, Lingling Chen, Congcong Yu, Liyuan Su, Kaihua Chen, Yousheng Li","doi":"10.1021/acs.chemrestox.4c00263","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00263","url":null,"abstract":"Inflammation, oxidative stress, fibrosis, and ferroptosis play important roles in diabetic nephropathy development. Krüppel-like factor 4 (KLF4) is a transcriptional factor, which regulates multiple cell processes and is involved in diabetic nephropathy. Berberine has various biological activities, including anti-inflammation, antioxidative stress, and antiferroptosis. Berberine has been shown to inhibit diabetic nephropathy, but whether it involves KLF4 and ferroptosis remains unknown. We established a diabetic nephropathy mice model and administered berberine to the mice. The kidney function, renal structure and fibrosis, expression of KLF4 and DNA methylation enzymes, DNA methylation of the KLF4 promoter, mitochondria structure, and expression of oxidative stress and ferroptosis markers were analyzed. Berberine rescued kidney function and renal structure and prevented renal fibrosis in diabetic nephropathy mice. Berberine suppressed the expression of DNMT1 and DNMT2 and upregulated KLF4 expression by preventing KLF4 promoter methylation. Berberine inhibited the expression of oxidative stress and ferroptosis markers, maintained mitochondria structure, and prevented ferroptosis. Berberine ameliorates diabetic nephropathy by inhibiting Klf4 promoter methylation and ferroptosis.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmentally Sustainable Detection of Arsenic using Convolutional Neural Networks and Imidazole-Based Organic Probes: Application in Food Samples and Arsenic Album","authors":"Ramakrishnan AbhijnaKrishna, Adarsh Valoor, Sivan Velmathi","doi":"10.1021/acs.chemrestox.4c00200","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00200","url":null,"abstract":"Arsenic contamination poses a significant health risk, particularly when it infiltrates water supplies. While current detection methods offer precise analysis, they often involve complex instrumentation not suitable for field use. This study presents a novel approach by developing two probes, A1 and A2, based on 4-diethylaminosalicyladehyde, 2-hydroxy-1-naphthaldehyde, and 1,2-diaminoanthraquinone. These probes are highly sensitive and selective for detecting arsenite (As(III)) and arsenate (As(V)) in water, food samples, and homeopathic medicine with limits of detection in the nanomolar range. To elaborate our contribution to on-site arsenic detection, we introduce a convolutional neural network-based image recognition system. This system interprets images of the probes’ colorimetric response, effectively categorizing different ranges of arsenic concentrations in parts per million (ppm). Our approach offers a real-time, cost-effective, and user-friendly solution for arsenic detection, extending its applicability from scientific laboratories to in-field conditions and even household monitoring. The findings fill critical research gaps in real-time detection methods, potentially revolutionizing the way we monitor environmental contaminants like arsenic.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Berberine Inhibits KLF4 Promoter Methylation and Ferroptosis to Ameliorate Diabetic Nephropathy in Mice","authors":"Shengyu Cai*,&nbsp;Huizheng Zhu,&nbsp;Lingling Chen,&nbsp;Congcong Yu,&nbsp;Liyuan Su,&nbsp;Kaihua Chen and Yousheng Li*,&nbsp;","doi":"10.1021/acs.chemrestox.4c0026310.1021/acs.chemrestox.4c00263","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00263https://doi.org/10.1021/acs.chemrestox.4c00263","url":null,"abstract":"<p >Inflammation, oxidative stress, fibrosis, and ferroptosis play important roles in diabetic nephropathy development. Krüppel-like factor 4 (KLF4) is a transcriptional factor, which regulates multiple cell processes and is involved in diabetic nephropathy. Berberine has various biological activities, including anti-inflammation, antioxidative stress, and antiferroptosis. Berberine has been shown to inhibit diabetic nephropathy, but whether it involves KLF4 and ferroptosis remains unknown. We established a diabetic nephropathy mice model and administered berberine to the mice. The kidney function, renal structure and fibrosis, expression of KLF4 and DNA methylation enzymes, DNA methylation of the KLF4 promoter, mitochondria structure, and expression of oxidative stress and ferroptosis markers were analyzed. Berberine rescued kidney function and renal structure and prevented renal fibrosis in diabetic nephropathy mice. Berberine suppressed the expression of DNMT1 and DNMT2 and upregulated KLF4 expression by preventing KLF4 promoter methylation. Berberine inhibited the expression of oxidative stress and ferroptosis markers, maintained mitochondria structure, and prevented ferroptosis. Berberine ameliorates diabetic nephropathy by inhibiting Klf4 promoter methylation and ferroptosis.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-Term Exposure to Foodborne Xenoestrogens Affects Breast Cancer Cell Morphology and Motility Relevant for Metastatic Behavior In Vitro.","authors":"Giorgia Del Favero,Janice Bergen,Lena Palm,Christian Fellinger,Maria Matlaeva,András Szabadi,Ana Sofia Fernandes,Nuno Saraiva,Christian Schröder,Doris Marko","doi":"10.1021/acs.chemrestox.4c00061","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00061","url":null,"abstract":"Breast cancer is highly susceptible to metastasis formation. During the time of disease progression, tumor pathophysiology can be impacted by endogenous factors, like hormonal status, as well as by environmental exposures, such as those related to diet and lifestyle. New lines of evidence point toward a potential role for foodborne endocrine disruptive chemicals in this respect; however, mechanistic understanding remains limited. At the molecular level, crucial steps toward metastasis formation include cell structural changes, alteration of adhesion, and reorganization of cytoskeletal proteins involved in motility. Hence, this study investigates the potential of dietary xenoestrogens to impact selected aspects of breast cancer cell mechanotransduction. Taking the onset of the metastatic cascade as a model, experiments focused on cell-matrix adhesion, single-cell migration, and adaptation of cell morphology. Dietary mycoestrogens alternariol (AOH, 1 μM) and α-zearalenol (α-ZEL, 10 nM), soy isoflavone genistein (GEN, 1 μM), and food packaging plasticizer bisphenol A (BPA, 10 nM) were applied as single compounds or in mixtures. Pursuing the hypothesis that endocrine active molecules could affect cell functions beyond the estrogen receptor-dependent cascade, experiments were performed comparing the MCF-7 cell line to the triple negative breast cancer cells MDA MB-231. Indeed, the four compounds functionally affected the motility and the adhesion of both cell types. These responses were coherent with rearrangements of the actin cytoskeleton and with the modulation of the expression of integrin β1 and cathepsin D. Mechanistically, molecular dynamics simulations confirmed a potential interaction with fragments of the α1 and β1 integrin subunits. In sum, dietary xenoestrogens proved effective in modifying the motility and adhesion of breast cancer cells, as predictive end points for metastatic behavior in vitro. These effects were measurable after short incubation times (1 or 8 h) and contribute to shed novel light on the activity of compounds with hormonal mimicry potential in breast cancer progression.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening the ToxCast Chemical Libraries for Binding to Transthyretin","authors":"Stephanie A. Eytcheson*,&nbsp;Alexander D. Zosel,&nbsp;Jennifer H. Olker,&nbsp;Michael W. Hornung and Sigmund J. Degitz*,&nbsp;","doi":"10.1021/acs.chemrestox.4c0021510.1021/acs.chemrestox.4c00215","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00215https://doi.org/10.1021/acs.chemrestox.4c00215","url":null,"abstract":"<p >Transthyretin (TTR) is one of the serum binding proteins responsible for transport of thyroid hormones (TH) to target tissue and for maintaining the balance of available TH. Chemical binding to TTR and subsequent displacement of TH has been identified as an end point in screening chemicals for potential disruption of the thyroid system. To address the lack of data regarding chemicals binding to TTR, we optimized an <i>in vitro</i> assay utilizing the fluorescent probe 8-anilino-1-napthalenesulfonic acid (ANSA) and the human protein TTR to screen over 1500 chemicals from the U.S. EPA’s ToxCast ph1_v2, ph2, and e1k libraries utilizing a tiered approach. Testing of a single high concentration (target 100 μM) resulted in 888 chemicals with 20% or greater activity based on displacement of ANSA from TTR. Of these, 282 chemicals had activity of 85% or greater and were further tested in 12-point concentration–response with target concentrations ranging from 0.015 to 100 μM. An EC50 was obtained for 276 of these 301 chemicals. To date, this is the largest set of chemicals screened for binding to TTR. Utilization of this assay is a significant contribution toward expanding the suite of <i>in vitro</i> assays used to identify chemicals with the potential to disrupt thyroid hormone homeostasis.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142550380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Updating Reaction Mechanistic Domains for Skin Sensitization: 1. Nucleophilic Skin Sensitizers","authors":"David W. Roberts, Anne Marie Api, Aynur Aptula, Isabelle Lee, Holger Moustakas","doi":"10.1021/acs.chemrestox.4c00207","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00207","url":null,"abstract":"It has long been recognized that skin sensitizers either are electrophilic or can be activated to electrophilic species. Several nonanimal assays for skin sensitization are based on this premise. In the course of a project to update dermal sensitization thresholds (DST), we found a substantial number of sensitizers, with no electrophilic or pro-electrophilic alerts, that could be simply explained in terms of the sensitizer acting as a nucleophile. In some cases, the nucleophilic center is a sulfur or phosphorus atom, while in others, it is an aromatic carbon atom. For carbon-centered nucleophiles, a quantitative mechanistic model based on a combination of Hammett σ⁺ and logP values has been derived. This has been applied to rationalize several groups of known sensitizers with no electrophilic or pro-electrophilic alerts, including anacardic acids and cardols, which are known human sensitizers associated with, inter alia, cashew nut oil, mango, and <i>Ginkgo biloba</i>. The possibility of nucleophilic sensitization needs to be considered when evaluating new chemicals for skin sensitization potential and potency by nonanimal assays, particularly those based on the premise that skin sensitization is dependent upon reactions of electrophiles with skin protein-based nucleophiles.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening the ToxCast Chemical Libraries for Binding to Transthyretin","authors":"Stephanie A. Eytcheson, Alexander D. Zosel, Jennifer H. Olker, Michael W. Hornung, Sigmund J. Degitz","doi":"10.1021/acs.chemrestox.4c00215","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00215","url":null,"abstract":"Transthyretin (TTR) is one of the serum binding proteins responsible for transport of thyroid hormones (TH) to target tissue and for maintaining the balance of available TH. Chemical binding to TTR and subsequent displacement of TH has been identified as an end point in screening chemicals for potential disruption of the thyroid system. To address the lack of data regarding chemicals binding to TTR, we optimized an <i>in vitro</i> assay utilizing the fluorescent probe 8-anilino-1-napthalenesulfonic acid (ANSA) and the human protein TTR to screen over 1500 chemicals from the U.S. EPA’s ToxCast ph1_v2, ph2, and e1k libraries utilizing a tiered approach. Testing of a single high concentration (target 100 μM) resulted in 888 chemicals with 20% or greater activity based on displacement of ANSA from TTR. Of these, 282 chemicals had activity of 85% or greater and were further tested in 12-point concentration–response with target concentrations ranging from 0.015 to 100 μM. An EC50 was obtained for 276 of these 301 chemicals. To date, this is the largest set of chemicals screened for binding to TTR. Utilization of this assay is a significant contribution toward expanding the suite of <i>in vitro</i> assays used to identify chemicals with the potential to disrupt thyroid hormone homeostasis.","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142181680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-Term Exposure to Foodborne Xenoestrogens Affects Breast Cancer Cell Morphology and Motility Relevant for Metastatic Behavior In Vitro","authors":"Giorgia Del Favero*,&nbsp;Janice Bergen,&nbsp;Lena Palm,&nbsp;Christian Fellinger,&nbsp;Maria Matlaeva,&nbsp;András Szabadi,&nbsp;Ana Sofia Fernandes,&nbsp;Nuno Saraiva,&nbsp;Christian Schröder and Doris Marko,&nbsp;","doi":"10.1021/acs.chemrestox.4c0006110.1021/acs.chemrestox.4c00061","DOIUrl":"https://doi.org/10.1021/acs.chemrestox.4c00061https://doi.org/10.1021/acs.chemrestox.4c00061","url":null,"abstract":"<p >Breast cancer is highly susceptible to metastasis formation. During the time of disease progression, tumor pathophysiology can be impacted by endogenous factors, like hormonal status, as well as by environmental exposures, such as those related to diet and lifestyle. New lines of evidence point toward a potential role for foodborne endocrine disruptive chemicals in this respect; however, mechanistic understanding remains limited. At the molecular level, crucial steps toward metastasis formation include cell structural changes, alteration of adhesion, and reorganization of cytoskeletal proteins involved in motility. Hence, this study investigates the potential of dietary xenoestrogens to impact selected aspects of breast cancer cell mechanotransduction. Taking the onset of the metastatic cascade as a model, experiments focused on cell-matrix adhesion, single-cell migration, and adaptation of cell morphology. Dietary mycoestrogens alternariol (AOH, 1 μM) and α-zearalenol (α-ZEL, 10 nM), soy isoflavone genistein (GEN, 1 μM), and food packaging plasticizer bisphenol A (BPA, 10 nM) were applied as single compounds or in mixtures. Pursuing the hypothesis that endocrine active molecules could affect cell functions beyond the estrogen receptor-dependent cascade, experiments were performed comparing the MCF-7 cell line to the triple negative breast cancer cells MDA MB-231. Indeed, the four compounds functionally affected the motility and the adhesion of both cell types. These responses were coherent with rearrangements of the actin cytoskeleton and with the modulation of the expression of integrin β1 and cathepsin D. Mechanistically, molecular dynamics simulations confirmed a potential interaction with fragments of the α1 and β1 integrin subunits. In sum, dietary xenoestrogens proved effective in modifying the motility and adhesion of breast cancer cells, as predictive end points for metastatic behavior <i>in vitro</i>. These effects were measurable after short incubation times (1 or 8 h) and contribute to shed novel light on the activity of compounds with hormonal mimicry potential in breast cancer progression.</p>","PeriodicalId":31,"journal":{"name":"Chemical Research in Toxicology","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/epdf/10.1021/acs.chemrestox.4c00061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142517603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}