42 results on '"Xiaowei Zhang"'
Search Results
2. Methodology for Effect-Based Identification of Bioconcentratable Endocrine Disrupting Chemicals (EDCs) in Water: Establishment, Validation, and Application
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Jing Guo, Keng Tu, Chengzhuo Zhou, Die Lin, Si Wei, Xiaowei Zhang, Hongxia Yu, and Wei Shi
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Environmental Chemistry ,General Chemistry - Published
- 2023
3. Bioaccumulation, Trophic Transfer, and Biotransformation of Polychlorinated Diphenyl Ethers in a Simulated Aquatic Food Chain
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Xuesheng Zhang, Wenli Xiong, Qiuxuan Wu, Kainan Nian, Xiaoxue Pan, Doug Crump, Xiaoxiang Wang, Yishan Lin, Xiaowei Zhang, and Rui Zhang
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Environmental Chemistry ,General Chemistry - Published
- 2023
4. Effect-Directed Analysis Based on the Reduced Human Transcriptome (RHT) to Identify Organic Contaminants in Source and Tap Waters along the Yangtze River
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Jing Guo, Yanhong Shen, Xiaowei Zhang, Die Lin, Pu Xia, Maoyong Song, Lu Yan, Wenjun Zhong, Xiao Gou, Chang Wang, Si Wei, Hongxia Yu, and Wei Shi
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China ,Estradiol ,Rivers ,Humans ,Water ,Environmental Chemistry ,Estrogens ,General Chemistry ,Transcriptome ,Water Pollutants, Chemical ,Environmental Monitoring - Abstract
Since a large number of contaminants are detected in source waters (SWs) and tap waters (TWs), it is important to perform a comprehensive effect evaluation and key contributor identification. A reduced human transcriptome (RHT)-based effect-directed analysis, which consisted of a concentration-dependent RHT to reveal the comprehensive effects and noteworthy pathways and systematic identification of key contributors based on the interactions between compounds and pathway effects, was developed and applied to typical SWs and TWs along the Yangtze River. By RHT, 42% more differentially expressed genes and 33% more pathways were identified in the middle and lower reaches, indicating heavier pollution. Hormone and immune pathways were prioritized based on the detection frequency, sensitivity, and removal efficiency, among which the estrogen receptor pathway was the most noteworthy. Consistent with RHT, estrogenic effects were widespread along the Yangtze River based on
- Published
- 2022
5. Using In Vitro and Machine Learning Approaches to Determine Species-Specific Dioxin-like Potency and Congener-Specific Relative Sensitivity among Birds for Brominated Dioxin Analogues
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Xuesheng Zhang, Ying Peng, Xiaowei Zhang, Xiaoxiang Wang, Rui Zhang, Doug Crump, Xiaoyi Qi, Chao Song, and Qiuxuan Wu
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biology ,Congener specific ,Chemistry ,business.industry ,Ecotoxicological risk ,General Chemistry ,Aryl hydrocarbon receptor ,Machine learning ,computer.software_genre ,World health ,In vitro ,Congener ,biology.protein ,Environmental Chemistry ,Potency ,Polybrominated Biphenyls ,Artificial intelligence ,business ,computer - Abstract
There is a paucity of experimental data regarding dioxin-like toxicity of polybrominated dibenzo-p-dioxins/dibenzofurans (PBDD/Fs) and non-ortho polybrominated biphenyls (PBBs). In this study, avian aryl hydrocarbon receptor 1 (AHR1)-luciferase reporter gene assays were used to determine their species-specific dioxin-like potencies (DLPs) and congener-specific interspecies relative sensitivities in birds. The results suggested that DLPs of the brominated congeners for chicken-like (Ile324_Ser380) species did not always follow World Health Organization toxicity equivalency factors of their chlorinated analogues. For ring-necked pheasant-like (Ile324_Ala380) and Japanese quail-like (Val324_Ala380) species, the difference in DLP for several congeners was 1 or even 2 orders of magnitude. Moreover, molecular docking and molecular dynamics simulation were performed to explore the interactions between the brominated congeners and AHR1-ligand-binding domain (LBD). The molecular mechanics energy (EMM) between each congener and each individual amino acid (AA) residue in AHR1-LBD was calculated. These EMM values could finely characterize the final conformation of species-specific AHR1-LBD for each brominated congener. Based on this, mechanism-driven generalized linear models were successfully built using machine learning algorithms and the spline approximation method, and these models could qualitatively predict the complex relationships between AHR1 conformations and DLPs or avian interspecies relative sensitivity to brominated dioxin-like compounds (DLCs). In addition, several AAs conserved among birds were found to potentially interact with species-specific AAs, thereby inducing species-specific interactions between AHR1 and brominated DLCs. The present study provides a novel strategy to facilitate the development of mechanism-driven computational prediction models for supporting safety assessment of DLCs, as well as a basis for the ecotoxicological risk assessment of brominated congeners in birds.
- Published
- 2021
6. Cross-Model Comparison of Transcriptomic Dose–Response of Short-Chain Chlorinated Paraffins
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Wendi Fang, Mingming Tian, Cong Ma, Jason M. O'Brien, Wei Shi, Doug Crump, Ying Peng, Yanhong Shen, Xiaowei Zhang, and Pu Xia
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China ,Pregnane X receptor ,biology ,Chemistry ,General Chemistry ,010501 environmental sciences ,biology.organism_classification ,01 natural sciences ,Cell biology ,Biological pathway ,Transcriptome ,Nicotinic acetylcholine receptor ,Chlorinated paraffins ,Paraffin ,Hydrocarbons, Chlorinated ,Animals ,Humans ,Environmental Chemistry ,Zebrafish ,Neural development ,Drug metabolism ,Environmental Monitoring ,0105 earth and related environmental sciences - Abstract
Short-chain chlorinated paraffins (SCCPs) have attracted attention because of their toxicological potential in humans and wildlife at environmentally relevant doses. However, limited information is available regarding mechanistic differences across species in terms of the biological pathways that are impacted by SCCP exposure. Here, a concentration-dependent reduced human transcriptome (RHT) approach was conducted to evaluate 15 SCCPs in HepG2 cells and compared with our previous results using a reduced zebrafish transcriptome (RZT) approach in zebrafish embryos (ZFEs). Generally, SCCPs induced a broader suite of biological pathways in ZFEs than HepG2 cells, and all of the 15 SCCPs were more potent in HepG2 cells compared to ZFEs. Despite these general differences, the transcriptional potency of SCCPs in both model systems showed a significant linear relationship (p = 0.0017, r2 = 0.57), and the average ratios of transcriptional potency for each SCCP in RZT to that in RHT were ∼100,000. C10H14Cl8 was the most potent SCCP, while C10H17Cl5 was the least potent in both ZFEs and HepG2 cells. An adverse outcome pathway network-based analysis demonstrated model-specific responses, such as xenobiotic metabolism that may be mediated by different nuclear receptor-mediated pathways between HepG2 cells (e.g., CAR and AhR activation) and ZFEs (e.g., PXR activation). Moreover, induced transcriptional changes in ZFEs associated with pathways and molecular initiating events (e.g., activation of nicotinic acetylcholine receptor) suggest that SCCPs may disrupt neural development processes. The cross-model comparison of concentration-dependent transcriptomics represents a promising approach to assess and prioritize SCCPs.
- Published
- 2021
7. Oral Exposure to 1,4-Dioxane Induces Hepatic Inflammation in Mice: The Potential Promoting Effect of the Gut Microbiome
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Xiaowei Zhang, Jingfan Qiu, Qing Zhou, Aimin Li, Robert V. Swanda, Peng Shi, Liujing Jiang, and Yang Pan
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Inflammation ,Male ,biology ,Lipopolysaccharide ,Chemistry ,Gastrointestinal Microbiome ,Porphyromonadaceae ,General Chemistry ,1,4-Dioxane ,010501 environmental sciences ,Pharmacology ,Gut flora ,biology.organism_classification ,01 natural sciences ,Dioxanes ,Transcriptome ,Mice ,chemistry.chemical_compound ,Liver ,In vivo ,Metabolome ,Animals ,Environmental Chemistry ,0105 earth and related environmental sciences - Abstract
1,4-Dioxane is a widely used industrial solvent that has been frequently detected in aquatic environments. However, the hepatotoxicity of long-term dioxane exposure at environmentally relevant concentrations and underlying mechanisms of liver damage remain unclear. In this study, male mice were exposed to dioxane at concentrations of 0.5, 5, 50, and 500 ppm for 12 weeks, followed by histopathological examination of liver sections and multiomics investigation of the hepatic transcriptome, serum metabolome, and gut microbiome. Results showed that dioxane exposure at environmentally relevant concentrations induced hepatic inflammation and caused changes in the hepatic transcriptome and serum metabolic profiles. However, no inflammatory response was observed after in vitro exposure to all concentrations of dioxane and its in vivo metabolites. The gut microbiome was considered to be contributing to this apparently contradictory response. Increased levels of lipopolysaccharide (LPS) may be produced by some gut microbiota, such as Porphyromonadaceae and Helicobacteraceae, after in vivo 500 ppm of dioxane exposure. LPS may enter the blood circulation through an impaired intestinal wall and aggravate hepatic inflammation in mice. This study provides novel insight into the underlying mechanisms of hepatic inflammation induced by dioxane and highlights the need for concerns about environmentally relevant concentrations of dioxane exposure.
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- 2020
8. A Tiered Approach for Screening and Assessment of Environmental Mixtures by Omics and In Vitro Assays
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Lu Yan, Ying Peng, Pu Xia, Xiaowei Zhang, and Wendi Fang
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In vitro toxicology ,General Chemistry ,Computational biology ,010501 environmental sciences ,Omics ,01 natural sciences ,In vitro ,Transcriptome ,Biological pathway ,chemistry.chemical_compound ,chemistry ,Environmental Chemistry ,Bioassay ,Solid phase extraction ,0105 earth and related environmental sciences ,Toxicant - Abstract
New methodology approaches with a broad coverage of the biological effects are urgently needed to evaluate the safety of the universe of environmentally relevant chemicals. Here, we propose a tiered approach incorporating transcriptomics and in vitro bioassays to assess environmental mixtures. The mixture samples and the perturbed biological pathways are prioritized by concentration-dependent transcriptome (CDT) and then used to guide the selection of in vitro bioassays for toxicant identification. To evaluate omics' screening capability, we first applied a CDT technique to test mixture samples by HepG2 and MCF7 cells. The effect recoveries of large-volume solid-phase extraction on the overall bioactivity of the mixture were 48.9% in HepG2 and 58.3% in MCF7. The overall bioactivity potencies obtained by transcriptomics were positively correlated with the panel of 8 bioassays among 14 mixture samples combined with the previous data. Transcriptomics could predict their activation status (AUC = 0.783) and the relative potency (p < 0.05) of bioassays for four of the eight receptors (AhR, ER, AR, and Nrf2). Furthermore, the CDT identified other biological pathways perturbated by mixture samples, such as the pathway related to TP53, CAR, FXR, HIF, THRA, etc. Overall, this study demonstrates the potential of concentration-dependent omics for effect-based water quality assessment.
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- 2020
9. Early Life Stage Bioactivity Assessment of Short-Chain Chlorinated Paraffins at Environmentally Relevant Concentrations by Concentration-Dependent Transcriptomic Analysis of Zebrafish Embryos
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Xiaowei Zhang, Wendi Fang, Zhihao Wang, Pingping Wang, Lu Yan, Jiaxin Yu, and Ying Peng
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Pollutant ,China ,biology ,Chemistry ,General Chemistry ,010501 environmental sciences ,biology.organism_classification ,01 natural sciences ,Early life ,Transcriptome ,Concentration dependent ,Biochemistry ,Chlorinated paraffins ,Paraffin ,Hydrocarbons, Chlorinated ,Zebrafish embryo ,Animals ,Environmental Chemistry ,Embryonic period ,Zebrafish ,Environmental Monitoring ,0105 earth and related environmental sciences - Abstract
Short-chain chlorinated paraffins (SCCPs), a class of ubiquitous pollutants, are considered to be embryotoxic and teratogenic. However, little is known regarding the bioactivity and mechanisms at environmentally relevant concentrations at the embryonic period. Here, a concentration-dependent reduced transcriptomic approach was used to evaluate the environmental dose ( 60%) (p = 0.038), and the chlorine content of SCCP congeners affected the bioactivity associated with genotoxic pathways. The concentration-dependent reduced transcriptomic approach significantly improved the understanding of the ecological risk of environmental contaminants at early life stages.
- Published
- 2019
10. Correction to Structures of Endocrine-Disrupting Chemicals Determine Binding to and Activation of the Estrogen Receptor α and Androgen Receptor
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Haoyue Tan, Xiaoxiang Wang, Huixiao Hong, Emilio Benfenati, John P. Giesy, Giuseppina C. Gini, Rebeca Kusko, Xiaowei Zhang, Hongxia Yu, and Wei Shi
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Environmental Chemistry ,General Chemistry - Published
- 2022
11. Environmental DNA Metabarcoding Supporting Community Assessment of Environmental Stressors in a Field-Based Sediment Microcosm Study
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Katherine J. Jeppe, Vincent Pettigrove, Jianghua Yang, and Xiaowei Zhang
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0301 basic medicine ,education.field_of_study ,Ecology ,Population ,Biodiversity ,Community structure ,DNA ,General Chemistry ,010501 environmental sciences ,Biology ,01 natural sciences ,03 medical and health sciences ,030104 developmental biology ,Benthic zone ,DNA Barcoding, Taxonomic ,Environmental Chemistry ,Ecotoxicology ,Environmental DNA ,Prospective Studies ,Microcosm ,education ,Relative species abundance ,Retrospective Studies ,0105 earth and related environmental sciences - Abstract
Conventional ecological risk assessment on toxic stressors in sediment is limited to a small and selected fraction of benthic communities. Ecogenomic approaches provide unprecedented capacity to monitor the changes of biodiversity and community composition in the field, but how to utilize it to assess ecological impact by contaminates remains largely unexplored. Here, an environmental DNA (eDNA) metabarcoding approach was used to assess the effect of copper on changes in biodiversity and community composition across the tree of life (including bacteria, protists, algae, fungi, and metazoa) in a field-based microcosm. Many microorganisms across a broad range of taxa groups changed their relative abundance in response to increased copper concentrations in sediments. Changes in community structure of microbiota appeared to be more sensitive to copper than survival of laboratory-bred organisms and indigenous macroinvertebrates. Copper caused a significant shift in prokaryotic community composition via substitution of dominant species. Network heterogeneity and Shannon diversity of the bacterial community decreased in the high copper treatments. eDNA metabarcoding assessed the effects of copper-contaminated sediment with less effort than manually processing samples. Our study highlighted the value of community profiling by an eDNA-based approach in prospective and retrospective risk assessment of environmental stressors.
- Published
- 2018
12. A Reduced Transcriptome Approach to Assess Environmental Toxicants Using Zebrafish Embryo Test
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Xiaowei Zhang, Jianghua Yang, Zhihao Wang, Pingping Wang, Hongxia Yu, Daniel L. Villeneuve, Wei Shi, Ying Peng, and Pu Xia
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0301 basic medicine ,Embryo, Nonmammalian ,biology ,Sequence Analysis, RNA ,Gene Expression Profiling ,General Chemistry ,Computational biology ,010501 environmental sciences ,biology.organism_classification ,01 natural sciences ,Article ,Transcriptome ,Biological pathway ,03 medical and health sciences ,030104 developmental biology ,Gene expression ,Zebrafish embryo ,Animals ,Environmental Chemistry ,Zebrafish ,Gene ,0105 earth and related environmental sciences - Abstract
Omics approaches can monitor responses of biological pathways at genome-scale, which are useful to predict potential adverse effects by environmental toxicants. However, high throughput application of transcriptomics in chemical assessment is limited due to the high cost and lack of matured dose response models. Here, a reduced zebrafish transcriptome (RZT) approach was developed to represent the whole transcriptome and to profile bioactivity of chemical and environmental mixtures in zebrafish embryo. Quantitative analysis of RZT gene expression by RNA-ampliseq technology was used to identify differentially expressed genes (DEGs) at 32 hpf following exposure to reference chemical, BPA, and four water samples ranging from wastewater to drinking water. Concentration-response modeling was used to calculate the effect concentrations (ECs) of DEGs and corresponding molecular pathways. RZT gene set of 1637 zebrafish Entrez genes was designed to cover a wide range of biological processes, and faithfully captured gene-level and pathway-level changes by toxicants compared with the whole transcriptome. The RZT-ampliseq-embryo approach was able to differentiate low dose response from a wide spectrum of biological activities for BPA. Finally, water quality was benchmarked based on the sensitivity distribution curve of biological pathways detected using RZT-ampliseq-embryo, and the most sensitive biological pathways were identified. RZT-ampliseq-embryo approach provides an efficient and cost-effective tool to derive pathway-based information of environmental toxicants.
- Published
- 2018
13. Benchmarking Water Quality from Wastewater to Drinking Waters Using Reduced Transcriptome of Human Cells
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Pu Xia, Pingping Wang, Xiaowei Zhang, Hongxia Yu, Mingming Tian, and Hanxin Zhang
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0301 basic medicine ,Wastewater ,010501 environmental sciences ,Biology ,01 natural sciences ,Transcriptome ,03 medical and health sciences ,Water Quality ,Environmental monitoring ,Humans ,Environmental Chemistry ,Bioassay ,0105 earth and related environmental sciences ,Pollutant ,business.industry ,Drinking Water ,General Chemistry ,Omics ,In vitro ,Biotechnology ,Benchmarking ,030104 developmental biology ,Water quality ,business ,Water Pollutants, Chemical ,Environmental Monitoring - Abstract
One of the major challenges in environmental science is monitoring and assessing the risk of complex environmental mixtures. In vitro bioassays with limited key toxicological end points have been shown to be suitable to evaluate mixtures of organic pollutants in wastewater and recycled water. Omics approaches such as transcriptomics can monitor biological effects at the genome scale. However, few studies have applied omics approach in the assessment of mixtures of organic micropollutants. Here, an omics approach was developed for profiling bioactivity of 10 water samples ranging from wastewater to drinking water in human cells by a reduced human transcriptome (RHT) approach and dose-response modeling. Transcriptional expression of 1200 selected genes were measured by an Ampliseq technology in two cell lines, HepG2 and MCF7, that were exposed to eight serial dilutions of each sample. Concentration-effect models were used to identify differentially expressed genes (DEGs) and to calculate effect concentrations (ECs) of DEGs, which could be ranked to investigate low dose response. Furthermore, molecular pathways disrupted by different samples were evaluated by Gene Ontology (GO) enrichment analysis. The ability of RHT for representing bioactivity utilizing both HepG2 and MCF7 was shown to be comparable to the results of previous in vitro bioassays. Finally, the relative potencies of the mixtures indicated by RHT analysis were consistent with the chemical profiles of the samples. RHT analysis with human cells provides an efficient and cost-effective approach to benchmarking mixture of micropollutants and may offer novel insight into the assessment of mixture toxicity in water.
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- 2017
14. Ecogenomics of Zooplankton Community Reveals Ecological Threshold of Ammonia Nitrogen
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Chao Song, Hongxia Yu, John P. Giesy, Yuwei Xie, Jianghua Yang, Jingying Sun, Xiaowei Zhang, and Yong Zhang
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0301 basic medicine ,Aquatic Organisms ,Nitrogen ,Fresh Water ,010501 environmental sciences ,01 natural sciences ,Zooplankton ,03 medical and health sciences ,Nutrient ,Ammonia ,parasitic diseases ,Animals ,Environmental Chemistry ,Ecosystem ,Water pollution ,0105 earth and related environmental sciences ,biology ,Ecology ,fungi ,General Chemistry ,Plankton ,biology.organism_classification ,030104 developmental biology ,Cladocera ,Water quality ,Eutrophication ,Water Pollutants, Chemical - Abstract
Communities of zooplankton can be adversely affected by contamination resulting from human activities. Yet understanding the influence of water quality on zooplankton under field-conditions is hindered by traditional labor-intensive approaches that are prone to incomplete or uncertain taxonomic determinations. Here, for the first time, an eco-genomic approach, based on genetic diversity in the mitochondrial cytochrome c oxidase I (COI) region of DNA of zooplankton was used to develop a site-specific, water quality criterion (WQC) for ammonia (NH3). Ammonia has been recognized as a primary stressor in the catchment of the large, eutrophic Tai Lake, China. Nutrients, especially NH3 and nitrite (NO3–) had more significant effects on structure of the zooplankton community than did other environmental factors. Abundances of rotifers increased along a gradient of increasing concentrations of total ammonia nitrogen (TAN), while abundances of copepods and cladocera decreased. A novel, rapid, species sensitivity d...
- Published
- 2017
15. Identification of Thyroid Hormone Disruptors among HO-PBDEs: In Vitro Investigations and Coregulator Involved Simulations
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Yu Hongxia, Wei Shi, Xiaoxiang Wang, Chen Qinchang, John P. Giesy, and Xiaowei Zhang
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0301 basic medicine ,Thyroid Hormones ,endocrine system ,medicine.medical_specialty ,In silico ,Endocrine Disruptors ,Molecular Dynamics Simulation ,010501 environmental sciences ,Biology ,01 natural sciences ,03 medical and health sciences ,Polybrominated diphenyl ethers ,Competitive binding ,Internal medicine ,Coactivator ,Halogenated Diphenyl Ethers ,medicine ,Humans ,Environmental Chemistry ,Receptor ,reproductive and urinary physiology ,0105 earth and related environmental sciences ,Binding Sites ,Receptors, Thyroid Hormone ,Thyroid ,General Chemistry ,In vitro ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Hormone - Abstract
Some hydroxylated polybrominated diphenyl ethers (HO-PBDEs), that have been widely detected in the environment and tissues of humans and wildlife, bind to thyroid hormone (TH) receptor (TR) and can disrupt functioning of systems modulated by the TR. However, mechanisms of TH disrupting effects are still equivocal. Here, disruption of functions of TH modulated pathways by HO-PBDEs was evaluated by assays of competitive binding, coactivator recruitment, and proliferation of GH3 cells. In silico simulations considering effects of coregulators were carried out to investigate molecular mechanisms and to predict potencies for disrupting functions of the TH. Some HO-PBDEs were able to bind to TR with moderate affinities but were not agonists. In GH3 proliferation assays, 13 out of 16 HO-PBDEs were antagonists for the TH. In silico simulations of molecular dynamics revealed that coregulators were essential for identification of TH disruptors. Among HO-PBDEs, binding of passive antagonists induced repositioning of H12, blocking AF-2 (transactivation function 2) and preventing recruitment of the coactivator. Binding of active antagonists exposed the coregulator binding site, which tended to bind to the corepressor rather than the coactivator. By considering both passive and active antagonisms, anti-TH potencies of HO-PBDEs could be predicted from free energy of binding.
- Published
- 2016
16. Application of Environmental DNA Metabarcoding for Predicting Anthropogenic Pollution in Rivers
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Ying Peng, Xiaowei Zhang, Wendi Fang, Florian Altermatt, Yuwei Xie, Jianghua Yang, Feilong Li, University of Zurich, and Zhang, Xiaowei
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0301 basic medicine ,Pollution ,media_common.quotation_subject ,1600 General Chemistry ,010501 environmental sciences ,01 natural sciences ,Freshwater ecosystem ,Environmental data ,10127 Institute of Evolutionary Biology and Environmental Studies ,03 medical and health sciences ,Rivers ,Environmental monitoring ,Animals ,DNA Barcoding, Taxonomic ,Environmental Chemistry ,Ecosystem ,Environmental DNA ,0105 earth and related environmental sciences ,media_common ,Ecology ,Community structure ,DNA ,General Chemistry ,15. Life on land ,030104 developmental biology ,13. Climate action ,2304 Environmental Chemistry ,Threatened species ,570 Life sciences ,biology ,590 Animals (Zoology) ,Environmental science ,Environmental Monitoring - Abstract
Rivers are among the most threatened freshwater ecosystems, and anthropogenic activities are affecting both river structures and water quality. While assessing the organisms can provide a comprehensive measure of a river's ecological status, it is limited by the traditional morphotaxonomy-based biomonitoring. Recent advances in environmental DNA (eDNA) metabarcoding allow to identify prokaryotes and eukaryotes in one sequencing run, and could thus allow unprecedented resolution. Whether such eDNA-based data can be used directly to predict the pollution status of rivers as a complementation of environmental data remains unknown. Here we used eDNA metabarcoding to explore the main stressors of rivers along which community structure changes, and to identify the method's potential for predicting pollution status based on eDNA data. We showed that a broad range of taxa in bacterial, protistan, and metazoan communities could be profiled with eDNA. Nutrients were the main driving stressor affecting communities' structure, alpha diversity, and the ecological network. We specifically observed that the relative abundance of indicative OTUs was significantly correlated with nutrient levels. These OTUs data could be used to predict the nutrient status up to 79% accuracy on testing data sets. Thus, our study gives a novel approach to predicting the pollution status of rivers by eDNA data.
- Published
- 2018
17. Bioaccumulation, Biotransformation, and Toxicity of BDE-47, 6-OH-BDE-47, and 6-MeO-BDE-47 in Early Life-Stages of Zebrafish (Danio rerio)
- Author
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Yuting Zhu, Chunsheng Liu, Hongling Liu, Xiaowei Zhang, Xinmei Zheng, John P. Giesy, Song Tang, Zhiyuan Ma, Hongxia Yu, David M.V. Saunders, and Markus Hecker
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Embryo, Nonmammalian ,Polybrominated Biphenyls ,Estrogen receptor ,Anisoles ,Endocrine Disruptors ,Biology ,Receptors, Glucocorticoid ,Glucocorticoid receptor ,Polybrominated diphenyl ethers ,Halogenated Diphenyl Ethers ,Animals ,Environmental Chemistry ,Receptor ,Biotransformation ,Zebrafish ,Flame Retardants ,Receptors, Thyroid Hormone ,Gene Expression Regulation, Developmental ,General Chemistry ,Aryl hydrocarbon receptor ,Receptors, Mineralocorticoid ,Receptors, Aryl Hydrocarbon ,Receptors, Estrogen ,Biochemistry ,Nuclear receptor ,Thyroid hormone receptor alpha ,Receptors, Androgen ,Larva ,Environmental chemistry ,biology.protein ,Water Pollutants, Chemical ,Hormone - Abstract
2,2',4,4'-Tetrabromodiphenyl ether (BDE-47), 6-hydroxy-tetrabromodiphenyl ether (6-OH-BDE-47), and 6-methoxy-tetrabromodiphenyl ether (6-MeO-BDE-47) are the most detected congeners of polybrominated diphenyl ethers (PBDEs), OH-BDEs, and MeO-BDEs, respectively, in aquatic organisms. Although it has been demonstrated that BDE-47 can interfere with certain endocrine functions that are mediated through several nuclear hormone receptors (NRs), most of these findings were from mammalian cell lines exposed in vitro. In the present study, embryos and larvae of zebrafish were exposed to BDE-47, 6-OH-BDE-47, and 6-MeO-BDE-47 to compare their accumulation, biotransformation, and bioconcentration factors (BCF) from 4 to 120 hpf. In addition, effects on expression of genes associated with eight different pathways regulated by NRs were investigated at 120 hpf. 6-MeO-BDE-47 was most bioaccumulated and 6-OH-BDE-47, which was the most potent BDE, was least bioaccumulated. Moreover, the amount of 6-MeO-BDE-47, but not BDE-47, transformed to 6-OH-BDE-47 increased in a time-dependent manner, approximately 0.01%, 0.04%, and 0.08% at 48, 96, and 120 hpf, respectively. Expression of genes regulated by the aryl hydrocarbon receptor (AhR), estrogen receptor (ER), and mineralocorticoid receptor (MR) was affected in larvae exposed to 6-OH-BDE-47, whereas genes regulated by AhR, ER, and the glucocorticoid receptor (GR) were altered in larvae exposed to BDE-47. The greatest effect on expression of genes was observed in larvae exposed to 6-MeO-BDE-47. Specifically, 6-MeO-BDE-47 affected the expression of genes regulated by AhR, ER, AR, GR, and thyroid hormone receptor alpha (TRα). These pathways were mostly down-regulated at 2.5 μM. Taken together, these results demonstrate the importance of usage of an internal dose to assess the toxic effects of PBDEs. BDE-47 and its analogs elicited distinct effects on expression of genes of different hormone receptor-mediated pathways, which have expanded the knowledge of different mechanisms of endocrine disrupting effects in aquatic vertebrates. Because some of these homologues are natural products, assessments of risks of anthropogenic PBDE need to be made against the background of concentrations from naturally occurring products. Even though PBDEs are being phased out as flame retardants, the natural products remain.
- Published
- 2015
18. Activation of Avian Aryl Hydrocarbon Receptor and Inter-species Sensitivity Variations by Polychlorinated Diphenylsulfides
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Junjiang Zhang, Rui Zhang, Ruijuan Qu, Xiaowei Zhang, Jiamin Zhang, Jun Chen, Zunyao Wang, Hongxia Yu, and Xing Liu
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Sulfides ,Biology ,Pheasant ,Species Specificity ,biology.animal ,Chlorocebus aethiops ,Animals ,Environmental Chemistry ,Bioassay ,Potency ,Galliformes ,Luciferases ,Receptor ,Gene ,Genetics ,Analysis of Variance ,Molecular Structure ,Ecology ,General Chemistry ,Aryl hydrocarbon receptor ,Polychlorinated Biphenyls ,Quail ,Receptors, Aryl Hydrocarbon ,COS Cells ,Toxicity ,biology.protein ,Biological Assay ,Environmental Pollutants - Abstract
It was hypothesized that polychlorinated diphenyl sulfides (PCDPSs) can potentially interact with an aryl hydrocarbon receptor (AHR) and thereby cause adverse effects in wildlife like birds. A recently developed avian AHR1-luciferase report gene (LRG) assay was used to assess the interaction between avian AHR1 and 18 PCDPSs and to compare the interspecies sensitivity among chicken, ring-necked pheasant, and Japanese quail by PCDPSs. Most of the tested PCDPSs could activate the AHR1-mediated pathways in avian species, and the relative potency (ReP) of the PCDPSs increased with the increasing number of substituted Cl atoms. The rank orders of PCDPSs potency were generally similar among birds, although the ReP varied. In addition, not all the sensitivity rank orders of avian AHR1 constructs for PCDPSs were consistent with that of TCDD. ReP values of PCDPSs suggested that some PCDPSs like 2,3,3',4,5,6-hexa-CDPS and 2,2',3,3',4,5,6-hepta-CDPS are higher than the avian WHO-TEFs of OctaCDD, OctaCDF, and most of the coplanar PCBs. Our results report for the first time the activation of an AHR1-mediated molecular toxicological mechanism by PCDPSs, and provide the ranking of ReP and relative sensitivity values of different congeners, which could guide the further toxicity test of this group of potential high priority environmental pollutants.
- Published
- 2014
19. Mechanisms of Toxicity of Hydroxylated Polybrominated Diphenyl Ethers (HO-PBDEs) Determined by Toxicogenomic Analysis with a Live Cell Array Coupled with Mutagenesis in Escherichia coli
- Author
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Guanyong Su, John P. Giesy, Xiaowei Zhang, Hongxia Yu, and Michael H.W. Lam
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endocrine system ,Hydroxylation ,Real-Time Polymerase Chain Reaction ,medicine.disease_cause ,Toxicogenetics ,chemistry.chemical_compound ,Polybrominated diphenyl ethers ,Escherichia coli ,Halogenated Diphenyl Ethers ,medicine ,Environmental Chemistry ,Organic chemistry ,Cytotoxic T cell ,Gene Regulatory Networks ,Cytotoxicity ,reproductive and urinary physiology ,EC50 ,Microbial Viability ,Gene Expression Profiling ,Mutagenesis ,Diphenyl ether ,Gene Expression Regulation, Bacterial ,General Chemistry ,Biochemistry ,chemistry ,Genes, Bacterial ,Mutation ,Toxicity ,Transcription Factors - Abstract
Results of previous studies have indicated that 6-HO-BDE-47, the addition of the hydroxyl (HO) group to the backbone of BDE-47, significantly increased the toxicity of the chemical compared to its postulated precursor analogues, BDE-47 and 6-MeO-BDE-47. However, whether such a result is conserved across polybrominated diphenyl ether (PBDE) congeners was unknown. Here, cytotoxicity of 32 PBDE analogues (17 HO-PBDEs and 15 MeO-PBDEs) was further tested and the underlying molecular mechanism was investigated. A total of 14 of the 17 HO-PBDEs inhibited growth of Escherichia coli during 4 or 24 h durations of exposure, but none of the MeO-PBDEs was cytotoxic at the concentrations tested. 6-HO-BDE-47 and 2-HO-BDE-28 were most potent with 4 h median effect concentrations (EC50) of 12.13 and 6.25 mg/L, respectively, which trended to be lesser with a longer exposure time (24 h). Expression of 30 modulated and validated genes by 6-HO-BDE-47 in a previous study was also observed after exposure to other HO-PBDE analogues. For instance, uhpT was upregulated by 13 HO-PBDEs, and three rRNA operons (rrnA, rrnB, and rrnC) were downregulated by 8 HO-PBDEs. These unanimous responses suggested a potential common molecular signaling modulated by HO-PBDEs. To explore new information on mechanisms of action, this work was extended by testing the increased susceptibility of 182 mutations of transcriptional factors (TFs) and 22 mutations as genes modulated by 6-HO-BDE-47 after exposure to 6-HO-BDE-47 at the 4 h IC50 concentration. Although a unanimous upregulation of uhpT was observed after exposure to HO-PBDEs, no significant shift in sensitivity was observed in uhpT-defective mutants. The 54 genes, selected by cut-offs of 0.35 and 0.65, were determined to be responsible for "organic acid/oxoacid/carboxylic acid metabolic process" pathways, which supported a previous finding.
- Published
- 2014
20. Occurrence of Perfluoroalkyl Acids Including Perfluorooctane Sulfonate Isomers in Huai River Basin and Taihu Lake in Jiangsu Province, China
- Author
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Xiaowei Zhang, Beibei Zhang, Jianfang Feng, Wei Shi, Guanyong Su, Hongxia Yu, Si Wei, and Nanyang Yu
- Subjects
China ,Fluorocarbons ,geography ,geography.geographical_feature_category ,Water pollutants ,Drainage basin ,General Chemistry ,Lakes ,chemistry.chemical_compound ,Perfluorooctane ,Sulfonate ,Alkanesulfonic Acids ,Isomerism ,Rivers ,chemistry ,Environmental chemistry ,Perfluorohexanoic acid ,Environmental Chemistry ,Perfluorooctanoic acid ,Surface water ,Water Pollutants, Chemical ,Environmental Monitoring - Abstract
The spatial distribution of 10 perfluoroalkyl acids including linear and branched (six monotrifluoromethyl isomers) perfluorooctane sulfonate (PFOS) in surface water was investigated in Huai River Basin and Taihu Lake in Jiangsu Province, China. In the water samples from Huai River Basin, perfluorooctanoic acid (PFOA) and PFOS were the predominant compounds (mean 18 ng/L and 4.7 ng/L, respectively), while in samples from Taihu Lake, PFOA, perfluorohexanoic acid (PFHxA), and PFOS were the predominant compounds (mean 56 ng/L, 19 ng/L, and 15 ng/L, respectively). Branched PFOS (Br-PFOS) isomers accounting for 48.1% to 62.5% of total PFOS were enriched in all samples from Taihu Lake, compared to technical electrochemical fluorination (ECF) PFOS (Br-PFOS ∼30.0%), while the similar phenomena were not found in samples from Huai River Basin (Br-PFOS 29.0-35.0%). Principal component analysis (PCA) on the percentages of the individual isomer showed that the first two components accounted for 78.4% and 15.3% of the overall observed data variance. Samples from Huai River Basin were grouped together with the ECF PFOS standard suggesting the profiles were similar, while samples from Taihu Lake were grouped by themselves, suggesting that isomer profiles in these samples were different from that of Huai River Basin. The obvious difference in isomer profiles probably results from the different environmental behaviors of PFOS isomers and/or unknown sources (PFOS or PFOS precursors).
- Published
- 2013
21. Occurrence of Thyroid Hormone Activities in Drinking Water from Eastern China: Contributions of Phthalate Esters
- Author
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Wei Shi, Guanjiu Hu, Xiaowei Zhang, Hongxia Yu, Hongling Liu, Xinxin Hu, John P. Giesy, Fengxian Zhang, Si Wei, Yingqun Hao, and Xinru Wang
- Subjects
China ,Dibutyl phthalate ,Tetrazolium Salts ,Endocrine Disruptors ,In Vitro Techniques ,Cell Line ,Water Purification ,chemistry.chemical_compound ,Tap water ,Chlorocebus aethiops ,medicine ,Animals ,Humans ,Environmental Chemistry ,Analysis of Variance ,Receptors, Thyroid Hormone ,Thyroid hormone receptor ,Drinking Water ,Thyroid ,Phthalate ,Esters ,General Chemistry ,Diisobutyl phthalate ,Biodegradation ,Dibutyl Phthalate ,Thiazoles ,medicine.anatomical_structure ,chemistry ,Environmental chemistry ,Toxicity ,Water Pollutants, Chemical - Abstract
Thyroid hormone is essential for the development of humans. However, some synthetic chemicals with thyroid disrupting potentials are detectable in drinking water. This study investigated the presence of thyroid active chemicals and their toxicity potential in drinking water from five cities in eastern China by use of an in vitro CV-1 cell-based reporter gene assay. Waters were examined from several phases of drinking water processing, including source water, finished water from waterworks, tap water, and boiled tap water. To identify the responsible compounds, concentrations and toxic equivalents of a list of phthalate esters were quantitatively determined. None of the extracts exhibited thyroid receptor (TR) agonist activity. Most of the water samples exhibited TR antagonistic activities. None of the boiled water displayed the TR antagonistic activity. Dibutyl phthalate accounted for 84.0-98.1% of the antagonist equivalents in water sources, while diisobutyl phthalate, di-n-octyl phthalate and di-2-ethylhexyl phthalate also contributed. Approximately 90% of phthalate esters and TR antagonistic activities were removable by waterworks treatment processes, including filtration, coagulation, aerobic biodegradation, chlorination, and ozonation. Boiling water effectively removed phthalate esters from tap water. Thus, this process was recommended to local residents to reduce certain potential thyroid related risks through drinking water.
- Published
- 2012
22. Toxicogenomic Mechanisms of 6-HO-BDE-47, 6-MeO-BDE-47, and BDE-47 in E. coli
- Author
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Hongling Liu, Guanyong Su, Michael H.W. Lam, Hongxia Yu, Xiaowei Zhang, John P. Giesy, Paul K.S. Lam, Javed Musarrat, Maqsood A. Siddiqui, and Abdulaziz A. Al-Khedhairy
- Subjects
Regulation of gene expression ,Reporter gene ,Molecular Structure ,Cell growth ,Gene Expression Profiling ,Polybrominated Biphenyls ,Gene Expression Regulation, Bacterial ,General Chemistry ,Anisoles ,Biology ,Molecular biology ,Fold change ,Green fluorescent protein ,Phenols ,Gene expression ,Escherichia coli ,Halogenated Diphenyl Ethers ,Environmental Chemistry ,Cytotoxicity ,Gene ,Flame Retardants - Abstract
Cytotoxicity of 6-HO-BDE-47 and its two analogues, BDE-47 and 6-MeO-BDE-47, and the associated molecular mechanisms were assessed by use of a live cell reporter assay system which contains a library of 1820 modified green fluorescent protein (GFP) expressing promoter reporter vectors constructed from E. coli K12 strains. 6-HO-BDE-47 inhibited growth of E. coli with a 4 h median effect concentration (EC50) of 22.52 ± 2.20 mg/L, but neither BDE-47 nor 6-MeO-BDE-47 were cytotoxic. Thus, 6-HO-BDE-47 might serve as an antibiotic in some living organisms. Exposure to 6-HO-BDE-47 resulted in 65 (fold change >2) or 129 (fold change >1.5) genes being differentially expressed. The no observed transcriptional effect concentration (NOTEC) and median transcriptional effect concentration (TEC50) based on transcriptional end points, of 6-HO-BDE-47 were 0.0438 and 0.580 mg/L, respectively. The transcriptional responses were 514- and 39-fold more sensitive than the acute EC50 to inhibit cell growth. Most of the genes that were differentially expressed in response to 6-HO-BDE-47 were not modulated by BDE-47 or 6-MeO-BDE-47. These results suggest that cytotoxicity of 6-HO-BDE-47 to E. coli was via a mechanism that was different from that of either BDE-47 or 6-MeO-BDE-47. Gene expression associated with metabolic pathways was more responsive to 6-HO-BDE-47, which suggests that this pathway might be the primary target of this compound.
- Published
- 2011
23. Effects of Prochloraz or Propylthiouracil on the Cross-Talk between the HPG, HPA, and HPT Axes in Zebrafish
- Author
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Jun Deng, Xiaowei Zhang, John P. Giesy, Markus Hecker, Abdulaziz A. Al-Khedhairy, Bingsheng Zhou, and Chunsheng Liu
- Subjects
endocrine system ,medicine.medical_specialty ,Corticotropin-Releasing Hormone ,Hypothalamus ,Thyroid Gland ,Biology ,Corticotropin-releasing hormone ,Follicle-stimulating hormone ,Internal medicine ,Adrenal Glands ,medicine ,Animals ,Environmental Chemistry ,Testosterone ,RNA, Messenger ,Gonads ,Zebrafish ,Triiodothyronine ,Estradiol ,Imidazoles ,Pituitary gonadal axis ,Receptor Cross-Talk ,General Chemistry ,Endocrinology ,Propylthiouracil ,Pituitary Gland ,Female ,Luteinizing hormone ,Water Pollutants, Chemical ,hormones, hormone substitutes, and hormone antagonists ,Hormone ,medicine.drug - Abstract
The objective of this study was to assess chemical-induced effects on cross-talk among the hypothalamic-pituitary-gonad (HPG), hypothalamic-pituitary-adrenal (HPA), and hypothalamic-pituitary-thyroid (HPT) axes of fish. Adult female zebrafish were exposed to 300 mu g/L prochloraz (PCZ) or 100 mg/L propylthiouracil (PTU), and the transcriptional profiles of the HPG, HPA, and HPT axes were examined. Exposure to PCZ decreased plasma testosterone (T) and 17 beta-estradiol (E2) concentrations and affected HPA and HPT axes by down-regulating corticotrophin-releasing hormone (CRH) after 12 and 48 h. By using correlation analyses, it was found that the decrease in E2 plasma concentrations caused by PCZ was correlated with the down-regulation of CRH mRNA expression. Exposure to PTU resulted in lesser concentrations of thyroxine (14) and triiodothyronine (T3), greater concentrations of follicle stimulating hormone (FSH) and luteinizing hormone (LH) peptides, and increase in steroidogenic gene expression after 12 and 48 h. Concentrations of FSH and LH were negatively correlated with concentrations of 14 and T3. These results are consistent with the hypothesis that increased steroidogenic gene expression after Pill exposure resulted from a reduction in T4 and 13 concentrations, which resulted in greater secretion of FSH and LH.
- Published
- 2010
24. Interconversion of Hydroxylated and Methoxylated Polybrominated Diphenyl Ethers in Japanese Medaka
- Author
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Paul D. Jones, Steve Wiseman, Michael H.W. Lam, Markus Hecker, Yi Wan, Xiaowei Zhang, Hong Chang, Fengyan Liu, and John P. Giesy
- Subjects
Male ,Eggs ,Oryzias ,Polybrominated Biphenyls ,Anisoles ,Hydroxylation ,chemistry.chemical_compound ,Polybrominated diphenyl ethers ,Biotransformation ,Halogenated Diphenyl Ethers ,Hydroxides ,Animals ,Environmental Chemistry ,reproductive and urinary physiology ,Demethylation ,biology ,Aquatic animal ,General Chemistry ,Japanese Medaka ,biology.organism_classification ,Diet ,chemistry ,Biochemistry ,Environmental chemistry ,Microsome ,Female ,Water Pollutants, Chemical - Abstract
Polybrominated diphenyl ethers (PBDEs), hydroxylated (OH) and methoxylated (MeO), have been widely detected in aquatic environments. However, relationships among these structurally related compounds in exposed organisms are unclear. To elucidate biotransformation relationships among BDE-47, 6-OH-BDE-47, and 6-MeO-BDE-47, dietary accumulation, maternal transfer, and tissue distribution of these compounds and their transformation products were investigated in sexually mature Japanese medaka (Oryzias latipes). In addition, transformation of each compound was determined in vitro using liver microsomes of medaka. OH-PBDEs and MeO-PBDEs were not detected in fish exposed to BDE-47. However, significant concentrations of 6-OH-BDE-47 were detected in medaka or microsomes exposed to 6-MeO-BDE-47. Significant concentrations of 6-MeO-BDE-47 were also measured in fish exposed to 6-OH-BDE-47, but 6-MeO-BDE-47 was not detected in microsomes exposed to 6-OH-BDE-47. Similar patterns of transformation products were observed in medaka eggs from adult fish during exposure. This study presents direct in vivo evidence of biotransformation of 6-MeO-BDE-47 to 6-OH-BDE-47. In addition, this is the first study to demonstrate biotransformation of 6-OH-BDE-47 to 6-MeO-BDE-47. Demethylation of 6-MeO-BDE-47 was the primary transformation pathway leading to formation of 6-OH-BDE-47 in medaka, while the previously hypothesized formation of OH-PBDEs from synthetic BDE-47 did not occur. Biotransformation products formed in adult female medaka were transferred to eggs.
- Published
- 2010
25. Quantitative RT-PCR Methods for Evaluating Toxicant-Induced Effects on Steroidogenesis Using the H295R Cell Line
- Author
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Markus Hecker, Tannia Gracia, Gabriel K. W. Lam, John P. Giesy, Richard Man Kit Yu, Paul D. Jones, Xiaowei Zhang, J. Thomas Sanderson, Rudolf S.S. Wu, John L. Newsted, and Klára Hilscherová
- Subjects
Regulation of gene expression ,Reverse Transcriptase Polymerase Chain Reaction ,Endocrine System ,General Chemistry ,Biology ,Phosphoproteins ,Bioinformatics ,Cell biology ,Gene expression profiling ,Reverse transcription polymerase chain reaction ,chemistry.chemical_compound ,Real-time polymerase chain reaction ,Gene Expression Regulation ,chemistry ,Cell culture ,Cell Line, Tumor ,Gene expression ,Humans ,RNA ,Environmental Chemistry ,Steroids ,Tomography, X-Ray Computed ,Gene ,Environmental Monitoring ,Toxicant - Abstract
Gene expression profiles show considerable promise for the evaluation of the toxic potential of environmental contaminants. For example, any alterations in the pathways of steroid synthesis or breakdown have the potential to Cause endocrine disruption. Therefore monitoring these pathways can provide information relative to a chemical's ability to impact endocrine function. One approach to monitoring these pathways has been to use a human adrenocortical carcinoma cell line (H295R) that expresses all the key enzymes necessary for steroidogenesis. In this study we have further developed these methods using accurate and specific quantification methods utilizing molecular beacon-based quantitative RT-PCR (Q-RT-PCR). The assay system was used to analyze the expression patterns of 11 steroidogenic genes in H295R cells. The expression of gene transcripts was measured using a real-time PCR system and quantified based on both a standard curve method using a dilution series of RNA standards and a comparative Ct method. To validate the optimized method, cells were exposed to specific and nonspecific model compounds (inducers and inhibitors of various steroidogenic enzymes) for gene expression profiling. Similar gene expression profiles were exhibited by cells treated with chemicals acting through common mechanisms of action. Overall, our findings demonstrated that the present assay can facilitate the development of compound-specific response profiles, and will provide a sensitive and integrative screen for the effects of chemicals on steroidogenesis.
- Published
- 2005
26. Effect-Directed Analysis of Aryl Hydrocarbon Receptor Agonists in Sediments from the Three Gorges Reservoir, China.
- Author
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Hongxia Xiao, Krauss, Martin, Floehr, Tilman, Yan Yan, Bahlmann, Arnold, Eichbaum, Kathrin, Brinkmann, Markus, Xiaowei Zhang, Xingzhong Yuan, Brack, Werner, and Hollert, Henner
- Published
- 2016
- Full Text
- View/download PDF
27. Functional Toxicogenomic Assessment of Triclosan in Human HepG2 Cells Using Genome-Wide CRISPR-Cas9 Screening.
- Author
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Pu Xia, Xiaowei Zhang, Yuwei Xie, Miao Guan, Villeneuve, Daniel L., and Hongxia Yu
- Subjects
- *
CRISPRS , *TOXICOGENOMICS , *TRICLOSAN , *CANCER cells , *LIVER cancer , *CELL survival , *MESSENGER RNA - Abstract
There are thousands of chemicals used by humans and detected in the environment for which limited or no toxicological data are available. Rapid and cost-effective approaches for assessing the toxicological properties of chemicals are needed. We used CRISPR-Cas9 functional genomic screening to identify the potential molecular mechanism of a widely used antimicrobial triclosan (TCS) in HepG2 cells. Resistant genes at IC50 (the concentration causing a 50% reduction in cell viability) were significantly enriched in the adherens junction pathway, MAPK signaling pathway, and PPAR signaling pathway, suggesting a potential role in the molecular mechanism of TCS-induced cytotoxicity. Evaluation of the top-ranked resistant genes, FTO (encoding an mRNA demethylase) and MAP2K3 (a MAP kinase kinase family gene), revealed that their loss conferred resistance to TCS. In contrast, sensitive genes at IC10 and IC20 were specifically enriched in pathways involved with immune responses, which was concordant with transcriptomic profiling of TCS at concentrations of
- Published
- 2016
- Full Text
- View/download PDF
28. Bioaccumulation, Biotransformation, and Toxicity of BDE-47, 6-OH-BDE-47, and 6-MeO-BDE-47 in Early Life-Stages of Zebrafish (Danio rerio).
- Author
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Hongling Liu, Song Tang, Xinmei Zheng, Yuting Zhu, Zhiyuan Ma, Chunsheng Liu, Hecker, Markus, Saunders, David M. V., Giesy, John P., Xiaowei Zhang, and Hongxia Yu
- Published
- 2015
- Full Text
- View/download PDF
29. Activation of Avian Aryl Hydrocarbon Receptor and Inter-species Sensitivity Variations by Polychlorinated Diphenylsulfides.
- Author
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Rui Zhang, Xiaowei Zhang, Junjiang Zhang, Ruijuan Qu, Jiamin Zhang, Xing Liu, Jun Chen, Zunyao Wang, and Hongxia Yu
- Subjects
- *
EFFECT of pollution on birds , *ARYL hydrocarbon receptors , *POLYCHLORINATED biphenyls , *POLLUTANTS , *MICROBIAL sensitivity tests - Abstract
It was hypothesized that polychlorinated diphenyl sulfides (PCDPSs) can potentially interact with an aryl hydrocarbon receptor (AHR) and thereby cause adverse effects in wildlife like birds. A recently developed avian AHRl-luciferase report gene (LRG) assay was used to assess the interaction between avian AHR1 and 18 PCDPSs and to compare the interspecies sensitivity among chicken, ring-necked pheasant, and Japanese quail by PCDPSs. Most of the tested PCDPSs could activate the AHR1-mediated pathways in avian species, and the relative potency (ReP) of the PCDPSs increased with the increasing number of substituted Cl atoms. The rank orders of PCDPSs potency were generally similar among birds, although the ReP varied. In addition, not all the sensitivity rank orders of avian AHR1 constructs for PCDPSs were consistent with that of TCDD. ReP values of PCDPSs suggested that some PCDPSs like 2,3,3',4,5,6-hexa-CDPS and 2,2',3,3',4,5,6-hepta-CDPS are higher than the avian WHO-TEFs of OctaCDD, OctaCDF, and most of the coplanar PCBs. Our results report for the first time the activation of an AHR1-mediated molecular toxicological mechanism by PCDPSs, and provide the ranking of ReP and relative sensitivity values of different congeners, which could guide the further toxicity test of this group of potential high priority environmental pollutants. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
30. Effects of HO-/MeO-PBDEs on Androgen Receptor: In Vitro Investigation and Helix 12-Involved MD Simulation.
- Author
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Xiaoxiang Wang, Huaiyu Yang, Xinxin Hu, Xiaowei Zhang, Qiansen Zhang, Hualiang Jiang, Wei Shi, and Hongxia Yu
- Published
- 2013
- Full Text
- View/download PDF
31. Occurrence and Potential Causes of Androgenic Activities in Source and Drinking Water in China.
- Author
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Xinxin Hu, Wei Shi, Si Wei, Xiaowei Zhang, Jianfang Feng, Guanjiu Hu, Sulan Chen, Giesy, John P., and Hongxia Yu
- Published
- 2013
- Full Text
- View/download PDF
32. Relative Potencies of Aroclor Mixtures Derived from Avian in Vitro Bioassays: Comparisons with Calculated Toxic Equivalents.
- Author
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Rui Zhang, Manning, Gillian E., Farmahin, Reza, Crump, Doug, Xiaowei Zhang, and Kennedy, Sean W.
- Published
- 2013
- Full Text
- View/download PDF
33. Occurrence of Perfluoroalkyl Acids Including Perfluorooctane Sulfonate Isomers in Huai River Basin and Taihu Lake in Jiangsu Province, China.
- Author
-
Nanyang Yu, Wei Shi, Beibei Zhang, Guanyong Su, Jianfang Feng, Xiaowei Zhang, Si Wei, and Hongxia Yu
- Published
- 2013
- Full Text
- View/download PDF
34. Dioxin-like Potency of HO- and MeO- Analogues of PBDEs' the Potential Risk through Consumption of Fish from Eastern China.
- Author
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Guanyong Su, Jie Xia, Hongling Liu, Michael H. W. Lam, Hongxia Yu, Giesy, John P., and Xiaowei Zhang
- Published
- 2012
- Full Text
- View/download PDF
35. Toxicogenomic Mechanisms of 6-HO-BDE-47, 6-MeO-BDE-47, and BDE-47 in E. coli.
- Author
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Guanyong Su, Xiaowei Zhang, Hongling Liu, Giesy, John P., Lam, Michael H. W., Lam, Paul K. S., Siddiqui, Maqsood A., Musarrat, Javed, Al-Khedhairy, Abdulaziz, and Hongxia Yu
- Subjects
- *
TOXICOGENOMICS , *INHIBITORY Concentration 50 , *CELL-mediated cytotoxicity , *POLYBROMINATED diphenyl ethers & the environment , *ESCHERICHIA coli , *GENE expression , *MOLECULAR toxicology - Abstract
Cytotoxicity of 6-HO-BDE-47 and its two analogues, BDE-47 and 6-MeO-BDE-47, and the associated molecular mechanisms were assessed by use of a live cell reporter assay system which contains a library of 1820 modified green fluorescent protein (GFP) expressing promoter reporter vectors constructed from E. coli K12 strains. 6-HO-BDE-47 inhibited growth of E. coli with a 4 h median effect concentration (EC50) of 22.52 ± 2.20 mg/L, but neither BDE-47 nor 6-MeO-BDE-47 were cytotoxic. Thus, 6-HO-BDE-47 might serve as an antibiotic in some living organisms. Exposure to 6-HO-BDE-47 resulted in 65 (fold change >2) or 129 (fold change >1.5) genes being differentially expressed. The no observed transcriptional effect concentration (NOTEC) and median transcriptional effect concentration (TEC50) based on transcriptional end points, of 6-HO-BDE-47 were 0.0438 and 0.580 mg/L, respectively. The transcriptional responses were 514- and 39-fold more sensitive than the acute EC50 to inhibit cell growth. Most of the genes that were differentially expressed in response to 6-HO-BDE-47 were not modulated by BDE-47 or 6-MeO-BDE-47. These results suggest that cytotoxicity of 6-HO-BDE-47 to E. coli was via a mechanism that was different from that of either BDE-47 or 6-MeO-BDE-47. Gene expression associated with metabolic pathways was more responsive to 6-HO-BDE-47, which suggests that this pathway might be the primary target of this compound. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
36. Assessing the Toxicity of Naphthenic Acids Using a Microbial Genome Wide Live Cell Reporter Array System.
- Author
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Xiaowei Zhang, Wiseman, Steve, Hongxia Yu, Hongling Liu, Giesy, John P., and Necker, Maskus
- Subjects
- *
NAPHTHENIC acids , *TOXICITY testing , *ENVIRONMENTAL toxicology research , *MICROBIAL genomes , *CELL receptors , *CARBOXYLIC acids , *OIL spills & the environment - Abstract
Mixtures of naphthenic acids (NAs), which include cyclopentyl and cyclohexyl carboxylic acids, have been suggested to be toxic components in oils spills, effluents from the petrochemical industry and in oil sands process waters (OSPW). The present study demonstrated, for the first time, an application of a high throughput live bacterial cell array in a genome-scale investigation of the toxic mechanisms of environmental chemicals, a commercial NAs technical mixture extracted from crude oil. Real time gene profiling of time- and concentration- dependent responses of live cells exposed to NAs for three hours was conducted using a library of 1800 fluorescent transcriptional reporters for Escherichia coli (E coli) growing in 384-well plates. The response patterns obtained after exposure to NAs suggested that the primary cellular responses were up-regulation of genes in the pentose phosphate pathway, involved in the molecular function of NADP or NADPH binding, and down-regulation of the ATP-binding cassette (ABC) transporter complex Transcriptional networks that were significantly modulated by NAs included those that were regulated by transcriptional factors such as CRP-, RecA-, and GadE. Down-regulation of the SOS response pathway suggested that DNA damage might not be the direct result of NAs within the first three hours of exposure. However, CRP-dependent genes modulated by exposure to NAs indicated that the cellular level of cyclic AMP was altered immediately upon exposure of cells to NAs. Furthermore, the linear range of the concentration-response curve of the selected gene reporters encompassed a range of concentrations between 10 and 1000 mg NAs/L, which covers concentrations typically observed in the environment and makes this assay system ideal for the detection of environmental NAs. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
37. Effects of Prochloraz or Propylthiouracil on the Cross-Talk between the HPG, HPA, and HPT Axes in Zebrafish.
- Author
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CHUNSHENG LIU, XIAOWEI ZHANG, JUN DENG, HECKER, MARKUS, AL-KHEDHAIRY, ABDULAZIZ, GIESY, JOHN P., and BINGSHENG ZHOU
- Subjects
- *
FISH research , *ZEBRA danio , *HYPOTHALAMIC-pituitary-adrenal axis , *STATISTICAL correlation , *TOXICITY testing , *LUTEINIZING hormone , *SOMATOSTATIN - Abstract
The objective of this study was to assess chemical-induced effects on cross-talk among the hypothalamic-pituitary-gonad (HPG), hypothalamic-pituitary-adrenal (HPA), and hypothalamic-pituitary-thyroid (HPT) axes of fish. Adult female zebrafish were exposed to 300 μg/L prochloraz (PCZ) or 100 mg/L propylthiouracil (PTU), and the transcriptional profiles of the HPG, HPA, and HPT axes were examined. Exposure to PCZ decreased plasma testosterone (T) and 17β-estradiol (E2) concentrations and affected HPA and HPT axes by down-regulating corticotrophin-releasing hormone (CRH) after 12 and 48 h. By using correlation analyses, it was found that the decrease in E2 plasma concentrations caused by PCZ was correlated with the down-regulation of CRH mRNA expression. Exposure to PTU resulted in lesser concentrations of thyroxine (T4) and triiodothyronine (T3), greater concentrations of follicle stimulating hormone (FSH) and luteinizing hormone (LH) peptides, and increase in steroidogenic gene expression after 12 and 48 h. Concentrations of FSH and LH were negatively correlated with concentrations of T4 and T3. These results are consistent with the hypothesis that increased steroidogenic gene expression after PTU exposure resulted from a reduction in T4 and T3 concentrations, which resulted in greater secretion of FSH and LH. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
38. Interconversion of Hydroxylated and Methoxylated Polybrominated Diphenyl Ethers in Japanese Medaka.
- Author
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YI WAN, FENGYAN LIU, WISEMAN, STEVE, XIAOWEI ZHANG, HONG CHANG, HECKER, MARKUS, JONES, PAUL D., LAM, MICHAEL H. W., and GIESY, JOHN P.
- Published
- 2010
- Full Text
- View/download PDF
39. Origin of Hydroxylated Brominated Diphenyl Ethers: Natural Compounds or Man-Made Flame Retardants?
- Author
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YI WAN, STEVE WISEMAN, HONG CHANG, XIAOWEI ZHANG, JONES, PAUL D., HECKER, MARKUS, KANNAN, KURUNTHACHALAM, TANABE, SHINSUKE, JIANYING HU, LAM, MICHAEL H. W., and GIESY, JOHN P.
- Published
- 2009
- Full Text
- View/download PDF
40. Classification of Chemicals Based on Concentration-Dependent Toxicological Data Using ToxClust.
- Author
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XIAOWEI ZHANG, NEWSTED, JOHN L., HECKER, MARKUS, HIGLEY, ERIC B., JONES, PAUL D., and GIESY, JOHN P.
- Subjects
- *
SYSTEMS biology , *HIGH throughput screening (Drug development) , *TOXICOLOGICAL interactions , *POISONS , *DOSE-response relationship in poisons , *TOXICOGENOMICS - Abstract
Concentration-dependent response relationships provide essential information on the characteristics of chemical-induced effects on toxicological end points, which include effect (inhibition or induction), potency, and efficacy of the chemical. Recent developments in systems biology and high through put technologies have allowed simultaneous examination of many chemicals at multiple end point levels. While this increase in the quantity of information generated offers great potential, it also poses a significant challenge to environmental scientists to efficiently manage and interpret these large data sets. Here we present a novel method, ToxClust, that allows clustering of chemicals on the basis of concentration-response data derived with single or multiple end points. This method utilizes a least distance-searching algorithm (LOSA) to measure the pattern dissimilarity of concentration-response curves between chemicals and their relative toxic potency. ToxCiust was tested using simulated data and chemical test data collected from the human H295R cell-based in vitro steroidogenesis assay. ToxClust effectively identified similar patterns of simulated data and responses to the exposure with the five model chemicals and separated them into different groups on the basis of their dissimilarities. These observations demonstrate that ToxClust not only provides an effective data analysis and visualization tool, but also has value in hypothesis generation and mechanism-based chemical classification. [ABSTRACT FROM AUTHOR]
- Published
- 2009
- Full Text
- View/download PDF
41. Responses of the Medaka HPG Axis PCR Array and Reproduction to Prochloraz and Ketoconazole.
- Author
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XIAOWEI ZHANG, HECKER, MARKUS, JONES, PAUL D., NEWSTED, JOHN, AU, DORIS, KONG, RICHARD, WU, RUDOLF S. S., and GIESY, JOHN P.
- Subjects
- *
IMIDAZOLES , *FUNGICIDES & the environment , *KETOCONAZOLE , *ORYZIAS latipes , *EFFECT of pollution on fishes , *FISH research , *DIAGNOSTIC use of polymerase chain reaction , *VITELLOGENINS , *CYTOCHROME P-450 , *CHOLESTEROL hydroxylase , *AROMATASE , *FERTILITY endocrinology - Abstract
Effects of two model imidazole-type fungicides, prochloraz (PCZ) and ketoconazole (KTC), on the hypothalamic-pituitary-gonadal (HPG) axis of the Japanese medaka (Oryzias latipe) were examined by use of real time PCR (RT-PCR) array. Fourteen-week-old Japanese medaka were exposed for seven days to concentrations of PCZ or KTC from 3.0 to 300 μg/L Exposure to KTC or PCZ caused significant reduction of fecundity of Japanese medaka and down-regulated expression of estrogen receptor (ER)-γ and egg precursors in livers of males and females. However, PCZ was more potent than KTC both in modulating transcription and causing lesser fecundity. Exposure to nominal 30 μg PCZ/L resulted in 50% less fecundity and significant down-regulation of vitellogenin // expression, but KTC did not cause such effects at this concentration. Exposure to PCZ caused a compensatory up-regulation in cytochrome P450 c17αhydroxylase, 17,20-lyase (CYP17) and aromatase (CYP19) expression in the ovary, while KTC did not Furthermore, the ecologically relevant end point, fecundity was log-log related to mRNA level of six genes in livers of females. [ABSTRACT FROM AUTHOR]
- Published
- 2008
- Full Text
- View/download PDF
42. Quantitative RT-PCR Methods for Evaluating Toxicant-Induced Effects on Steroidogenesis Using the H295R Cell Line.
- Author
-
Xiaowei Zhang, Richard M. K. Yu, Paul D. Jones, Gabriel K. W. Lam, John L. Newsted, Tannia Gracia, Markus Hecker, Klara Hilscherova, J. Thomas Sanderson, Rudolf S. S. Wu, and John P. Giesy
- Subjects
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GENE expression , *CELL lines , *ENZYMES , *CELL culture , *PROTEINS , *STEROIDS - Abstract
Gene expression profiles show considerable promise for the evaluation of the toxic potential of environmental contaminants. For example, any alterations in the pathways of steroid synthesis or breakdown have the potential to cause endocrine disruption. Therefore monitoring these pathways can provide information relative to a chemical's ability to impact endocrine function. One approach to monitoring these pathways has been to use a human adrenocortical carcinoma cell line (H295R) that expresses all the key enzymes necessary for steroidogenesis. In this study we have further developed these methods using accurate and specific quantification methods utilizing molecular beacon-based quantitative RT-PCR (Q-RT-PCR). The assay system was used to analyze the expression patterns of 11 steroidogenic genes in H295R cells. The expression of gene transcripts was measured using a real- time PCR system and quantified based on both a standard curve method using a dilution series of RNA standards and a comparative Ct method. To validate the optimized method, cells were exposed to specific and nonspecific model compounds (inducers and inhibitors of various steroidogenic enzymes) for gene expression profiling. Similar gene expression profiles were exhibited by cells treated with chemicals acting through common mechanisms of action. Overall, our findings demonstrated that the present assay can facilitate the development of compound- specific response profiles, and will provide a sensitive and integrative screen for the effects of chemicals on steroidogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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