Environmental Epigenetics最新文献

{"title":"Developmental exposure to methylmercury and ADHD, a literature review of epigenetic studies.","authors":"Tao Ke,&nbsp;Alexey A Tinkov,&nbsp;Antoly V Skalny,&nbsp;Aaron B Bowman,&nbsp;Joao B T Rocha,&nbsp;Abel Santamaria,&nbsp;Michael Aschner","doi":"10.1093/eep/dvab014","DOIUrl":"https://doi.org/10.1093/eep/dvab014","url":null,"abstract":"<p><p>Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that affects the competence of academic performance and social wellness in children and adults. The causes of ADHD are unclear. Both genetic and environmental factors contribute to the development of ADHD. The behavioral impairments in ADHD are associated with epigenetic changes in genes that are important for neurodevelopment. Among environmental causes of ADHD, the neurotoxin methylmercury (MeHg) is associated with an increased risk for ADHD. Developing children are susceptible to neurotoxic effects of prenatal MeHg exposure. Human epidemiology studies have shown that prenatal MeHg exposure could invoke epigenetic changes in genes that are involved in ADHD. In addition, the pathogenesis of ADHD involves dopaminergic system, which is a target of developmental MeHg exposure. MeHg-induced alterations in the dopaminergic system have a profound impact on behavioral functions in adults. As a trace level of MeHg (around nM) can induce long-lasting behavioral alterations, potential mechanisms of MeHg-induced functional changes in the dopaminergic system may involve epigenetic mechanisms. Here, we review the relevant evidence on developmental MeHg exposures and the risk for ADHD. We also point out research gaps in understanding environmental causes of ADHD.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":" ","pages":"dvab014"},"PeriodicalIF":3.8,"publicationDate":"2021-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8648069/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39817100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of environmentally induced epigenetic transgenerational inheritance in evolutionary biology: Unified Evolution Theory.","authors":"Michael K Skinner,&nbsp;Eric E Nilsson","doi":"10.1093/eep/dvab012","DOIUrl":"https://doi.org/10.1093/eep/dvab012","url":null,"abstract":"<p><p>The current evolutionary biology theory primarily involves genetic alterations and random DNA sequence mutations to generate the phenotypic variation required for Darwinian natural selection to act. This neo-Darwinian evolution is termed the Modern Evolution Synthesis and has been the primary paradigm for nearly 100 years. Although environmental factors have a role in neo-Darwinian natural selection, Modern Evolution Synthesis does not consider environment to impact the basic molecular processes involved in evolution. An Extended Evolutionary Synthesis has recently developed that extends the modern synthesis to consider non-genetic processes. Over the past few decades, environmental epigenetics research has been demonstrated to regulate genetic processes and directly generate phenotypic variation independent of genetic sequence alterations. Therefore, the environment can on a molecular level through non-genetic (i.e. epigenetic) mechanisms directly influence phenotypic variation, genetic variation, inheritance and adaptation. This direct action of the environment to alter phenotype that is heritable is a neo-Lamarckian concept that can facilitate neo-Darwinian (i.e. Modern Synthesis) evolution. The integration of genetics, epigenetics, Darwinian theory, Lamarckian concepts, environment, and epigenetic inheritance provides a paradigm shift in evolution theory. The role of environmental-induced epigenetic transgenerational inheritance in evolution is presented to describe a more unified theory of evolutionary biology.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":" ","pages":"dvab012"},"PeriodicalIF":3.8,"publicationDate":"2021-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/15/9a/dvab012.PMC8557805.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39689907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation changes induced by prenatal toxic metal exposure: An overview of epidemiological evidence.","authors":"Alexander Vaiserman,&nbsp;Oleh Lushchak","doi":"10.1093/eep/dvab007","DOIUrl":"https://doi.org/10.1093/eep/dvab007","url":null,"abstract":"<p><p>Accumulating evidence suggests that exposure to unfavorable conditions early in life can substantially contribute to the risk of chronic disorders later in life ('developmental programming' phenomenon). The mechanistic basis for this phenomenon remains poorly understood so far, although epigenetic mechanisms such as DNA methylation, histone modifications and microRNA-mediated gene regulation apparently play a crucial role. The key role of epigenetic modifications triggered by unfavorable environmental cues during sensitive developmental periods in linking adverse early-life events to later-life health outcomes is evident from a large body of studies, including methylome-wide association studies and research of candidate genes. Toxic metals (TMs), such as heavy metals, including lead, chromium, cadmium, arsenic, mercury, etc., are among environmental contaminants currently most significantly impacting human health status. Since TMs can cross the placental barrier and accumulate in fetal tissues, exposure to high doses of these xenobiotics early in development is considered to be among important factors contributing to the developmental programming of adult-life diseases in modern societies. In this mini-review, we summarize epidemiological findings indicating that prenatal TM exposure can induce epigenetic dysregulation, thereby potentially affecting adult health outcomes.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":" ","pages":"dvab007"},"PeriodicalIF":3.8,"publicationDate":"2021-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/af/cc/dvab007.PMC8493661.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39505622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined exposure to polychlorinated biphenyls and high-fat diet modifies the global epitranscriptomic landscape in mouse liver.","authors":"Carolyn M Klinge, Kellianne M Piell, Belinda J Petri, Liqing He, Xiang Zhang, Jianmin Pan, Shesh N Rai, Kalina Andreeva, Eric C Rouchka, Banrida Wahlang, Juliane I Beier, Matthew C Cave","doi":"10.1093/eep/dvab008","DOIUrl":"10.1093/eep/dvab008","url":null,"abstract":"<p><p>Exposure to a single dose of polychlorinated biphenyls (PCBs) and a 12-week high-fat diet (HFD) results in nonalcoholic steatohepatitis (NASH) in mice by altering intracellular signaling and inhibiting epidermal growth factor receptor signaling. Post-transcriptional chemical modification (PTM) of RNA regulates biological processes, but the contribution of epitranscriptomics to PCB-induced steatosis remains unknown. This study tested the hypothesis that PCB and HFD exposure alters the global RNA epitranscriptome in male mouse liver. C57BL/6J male mice were fed a HFD for 12 weeks and exposed to a single dose of Aroclor 1260 (20 mg/kg), PCB 126 (20 µg/kg), both Aroclor 1260 and PCB 126 or vehicle control after 2 weeks on HFD. Chemical RNA modifications were identified at the nucleoside level by liquid chromatography-mass spectrometry. From 22 PTM global RNA modifications, we identified 10 significant changes in RNA modifications in liver with HFD and PCB 126 exposure. Only two modifications were significantly different from HFD control liver in all three PCB exposure groups: 2'-O-methyladenosine (Am) and N(6)-methyladenosine (m6A). Exposure to HFD + PCB 126 + Aroclor 1260 increased the abundance of N(6), O(2)-dimethyladenosine (m6Am), which is associated with the largest number of transcript changes. Increased m6Am and pseudouridine were associated with increased protein expression of the writers of these modifications: Phosphorylated CTD Interacting Factor 1 (PCIF1) and Pseudouridine Synthase 10 (PUS10), respectively, in HFD + PCB 126- + Aroclor 1260-exposed mouse liver. Increased N1-methyladenosine (m1A) and m6A were associated with increased transcript levels of the readers of these modifications: YTH N6-Methyladenosine RNA Binding Protein 2 (YTHDF2), YTH Domain Containing 2 (YTHDC2), and reader FMRP Translational Regulator 1 (FMR1) transcript and protein abundance. The results demonstrate that PCB exposure alters the global epitranscriptome in a mouse model of NASH; however, the mechanism for these changes requires further investigation.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"7 1","pages":"dvab008"},"PeriodicalIF":3.8,"publicationDate":"2021-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448424/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9731720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: Adolescent Epigenetic Profiles and Environmental Exposures from Early Life through Peri-Adolescence.","authors":"","doi":"10.1093/eep/dvab006","DOIUrl":"https://doi.org/10.1093/eep/dvab006","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/eep/dvw018.].</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":" ","pages":"dvab006"},"PeriodicalIF":3.8,"publicationDate":"2021-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/06/61/dvab006.PMC8496744.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39505621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation at birth potentially mediates the association between prenatal lead (Pb) exposure and infant neurodevelopmental outcomes.","authors":"Christine A Rygiel, Dana C Dolinoy, Kelly M Bakulski, Max T Aung, Wei Perng, Tamara R Jones, Maritsa Solano-González, Howard Hu, Martha M Tellez-Rojo, Lourdes Schnaas, Erika Marcela, Karen E Peterson, Jaclyn M Goodrich","doi":"10.1093/eep/dvab005","DOIUrl":"10.1093/eep/dvab005","url":null,"abstract":"<p><p>Early-life lead (Pb) exposure has been linked to adverse neurodevelopmental outcomes. Recent evidence has indicated a critical role of DNA methylation (DNAm) in cognition, and Pb exposure has also been shown to alter DNAm. However, it is unknown whether DNAm is part of the mechanism of Pb neurotoxicity. This longitudinal study investigated the associations between trimester-specific (T1, T2, and T3) maternal blood Pb concentrations, gene-specific DNAm in umbilical cord blood, and infant neurodevelopmental outcomes at 12 and 24 months of age (mental development index, psychomotor development index, and behavioral rating scale of orientation/engagement and emotional regulation) among 85 mother-infant pairs from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) study. In the mediation analysis for this pilot study, <i>P</i> < 0.1 was considered significant. DNAm at a locus in <i>CCSER1</i> (probe ID cg02901723) mediated the association between T2 Pb on 24-month orientation/engagement [indirect effect estimate 4.44, 95% confidence interval (-0.09, 10.68), <i>P</i> = 0.06] and emotional regulation [3.62 (-0.05, 8.69), <i>P</i> = 0.05]. Cg18515027 (<i>GCNT1</i>) DNAm mediated the association of T1 Pb [-4.94 (-10.6, -0.77), <i>P</i> = 0.01] and T2 Pb [-3.52 (-8.09, -0.36), <i>P</i> = 0.02] with 24-month EMOCI, but there was a positive indirect effect estimate between T2 Pb and 24-month psychomotor development index [1.25 (-0.11, 3.32), <i>P</i> = 0.09]. The indirect effect was significant for cg19703494 (<i>TRAPPC6A</i>) DNAm in the association between T2 Pb and 24-month mental development index [1.54 (0, 3.87), <i>P</i> = 0.05]. There was also an indirect effect of cg23280166 (<i>VPS11</i>) DNAm on T3 Pb and 24-month EMOCI [2.43 (-0.16, 6.38), <i>P</i> = 0.08]. These associations provide preliminary evidence for gene-specific DNAm as mediators between prenatal Pb and adverse cognitive outcomes in offspring.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"7 1","pages":"dvab005"},"PeriodicalIF":4.8,"publicationDate":"2021-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e2/35/dvab005.PMC8206046.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9177640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential DNA methylation in somatic and sperm cells of hatchery vs wild (natural-origin) steelhead trout populations.","authors":"Eric Nilsson,&nbsp;Ingrid Sadler-Riggleman,&nbsp;Daniel Beck,&nbsp;Michael K Skinner","doi":"10.1093/eep/dvab002","DOIUrl":"https://doi.org/10.1093/eep/dvab002","url":null,"abstract":"<p><p>Environmental factors such as nutrition, stress, and toxicants can influence epigenetic programming and phenotypes of a wide variety of species from plants to humans. The current study was designed to investigate the impacts of hatchery spawning and rearing on steelhead trout (<i>Oncorhynchus mykiss</i>) vs the wild fish on a molecular level. Additionally, epigenetic differences between feeding practices that allow slow growth (2 years) and fast growth (1 year) hatchery trout were investigated. The sperm and red blood cells (RBC) from adult male slow growth/maturation hatchery steelhead, fast growth/maturation hatchery steelhead, and wild (natural-origin) steelhead were collected for DNA preparation to investigate potential alterations in differential DNA methylation regions (DMRs) and genetic mutations, involving copy number variations (CNVs). The sperm and RBC DNA both had a large number of DMRs when comparing the hatchery vs wild steelhead trout populations. The DMRs were cell type specific with negligible overlap. Slow growth/maturation compared to fast growth/maturation steelhead also had a larger number of DMRs in the RBC samples. A number of the DMRs had associated genes that were correlated to various biological processes and pathologies. Observations demonstrate a major epigenetic programming difference between the hatchery and wild natural-origin fish populations, but negligible genetic differences. Therefore, hatchery conditions and growth/maturation rate can alter the epigenetic developmental programming of the steelhead trout. Interestingly, epigenetic alterations in the sperm allow for potential epigenetic transgenerational inheritance of phenotypic variation to future generations. The impacts of hatchery exposures are not only important to consider on the fish exposed, but also on future generations and evolutionary trajectory of fish in the river populations.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":" ","pages":"dvab002"},"PeriodicalIF":3.8,"publicationDate":"2021-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvab002","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38940899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Controlled human exposures to diesel exhaust: a human epigenome-wide experiment of target bronchial epithelial cells.","authors":"Andres Cardenas, Raj P Fadadu, Lars Van Der Laan, Cavin Ward-Caviness, Louis Granger, David Diaz-Sanchez, Robert B Devlin, Marie-Abèle Bind","doi":"10.1093/eep/dvab003","DOIUrl":"10.1093/eep/dvab003","url":null,"abstract":"<p><p>Diesel exhaust (DE) is a major contributor to ambient air pollution around the world. It is a known human carcinogen that targets the respiratory system and increases risk for many diseases, but there is limited research on the effects of DE exposure on the epigenome of human bronchial epithelial cells. Understanding the epigenetic impact of this environmental pollutant can elucidate biological mechanisms involved in the pathogenesis of harmful DE-related health effects. To estimate the causal effect of short-term DE exposure on the bronchial epithelial epigenome, we conducted a controlled single-blinded randomized crossover human experiment of exposure to DE and used bronchoscopy and Illumina 450K arrays for data collection and analysis, respectively. Of the 13 participants, 11 (85%) were male and 2 (15%) were female, and 12 (92%) were White and one (8%) was Hispanic; the mean age was 26 years (SD = 3.8 years). Eighty CpGs were differentially methylated, achieving the minimum possible exact <i>P</i>-value of <i>P </i>=<i> </i>2.44 × 10^-4 (<i>i.e.</i> 2/2¹³). In regional analyses, we found two differentially methylated regions (DMRs) annotated to the chromosome 5 open reading frame 63 genes (<i>C5orf63</i>; 7-CpGs) and unc-45 myosin chaperone A gene (<i>UNC45A</i>; 5-CpGs). Both DMRs showed increased DNA methylation after DE exposure. The average causal effects for the DMRs ranged from 1.5% to 6.0% increases in DNA methylation at individual CpGs. In conclusion, we found that short-term DE alters DNA methylation of genes in target bronchial epithelial cells, demonstrating epigenetic level effects of exposure that could be implicated in pulmonary pathologies.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":"7 1","pages":"dvab003"},"PeriodicalIF":4.8,"publicationDate":"2021-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/61/54/dvab003.PMC8035831.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10294144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Environmental Epigenetics</i> update.","authors":"Michael K Skinner","doi":"10.1093/eep/dvab001","DOIUrl":"https://doi.org/10.1093/eep/dvab001","url":null,"abstract":"Environmental Epigenetics, an Oxford University Press publication, just initiated its seventh year of operations with this Volume 7 Issue 1. We are a completely 100% Open Access journal listed in PMC and PubMed, along with numerous other access sites. Environmental Epigenetics initiated its review to obtain an impact factor in 2020 and hope to receive this over the next year. Special issues have occurred each year and we encourage requests for special issues in environmental epigenetics. Our Special Issue in 2020 was on Epigenetic Transgenerational Inheritance involving 21 manuscripts (https://academic.oup. com/eep/pages/special_issues). The amount and diversity of our published studies is increasing as the field of environmental epigenetics grows and expands. We are looking forward to another productive year and encourage you to consider submissions to Environmental Epigenetics.","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":" ","pages":"dvab001"},"PeriodicalIF":3.8,"publicationDate":"2021-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvab001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38811537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ancestral plastics exposure induces transgenerational disease-specific sperm epigenome-wide association biomarkers.","authors":"Jennifer L M Thorson,&nbsp;Daniel Beck,&nbsp;Millissia Ben Maamar,&nbsp;Eric E Nilsson,&nbsp;Michael K Skinner","doi":"10.1093/eep/dvaa023","DOIUrl":"https://doi.org/10.1093/eep/dvaa023","url":null,"abstract":"<p><p>Plastic-derived compounds are one of the most frequent daily worldwide exposures. Previously a mixture of plastic-derived toxicants composed of bisphenol A, bis(2-ethylhexyl) phthalate, and dibutyl phthalate at low-dose exposures of a gestating female rats was found to promote the epigenetic transgenerational inheritance of disease to the offspring (F1 generation), grand-offspring (F2 generation), and great-grand-offspring (F3 generation). Epigenetic analysis of the male sperm was found to result in differential DNA methylation regions (DMRs) in the transgenerational F3 generation male sperm. The current study is distinct and was designed to use an epigenome-wide association study to identify potential sperm DNA methylation biomarkers for specific transgenerational diseases. Observations indicate disease-specific DMRs called epimutations in the transgenerational F3 generation great-grand-offspring of rats ancestrally exposed to plastics. The epigenetic DMR biomarkers were identified for testis disease, kidney disease, and multiple (≥2) diseases. These disease sperm epimutation biomarkers were found to be predominantly disease-specific. The genomic locations and features of these DMRs were identified. Interestingly, the disease-specific DMR-associated genes were previously shown to be linked with each of the specific diseases. Therefore, the germline has ancestrally derived epimutations that potentially transmit transgenerational disease susceptibilities. Epigenetic biomarkers for specific diseases could be used as diagnostics to facilitate clinical management of disease and preventative medicine.</p>","PeriodicalId":11774,"journal":{"name":"Environmental Epigenetics","volume":" ","pages":"dvaa023"},"PeriodicalIF":3.8,"publicationDate":"2021-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/eep/dvaa023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25581214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}