Environmental and Molecular Mutagenesis最新文献_第9页

Oxidative DNA damage on the VEGF G-quadruplex forming promoter is repaired via long-patch BER VEGF G-四链体形成启动子上的氧化性DNA损伤通过长片BER修复。

IF 2.8 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2023-08-22 DOI: 10.1002/em.22570

Adil S. Hussen, Haley L. Kravitz, Bret D. Freudenthal, Amy M. Whitaker

{"title":"Oxidative DNA damage on the VEGF G-quadruplex forming promoter is repaired via long-patch BER","authors":"Adil S. Hussen, Haley L. Kravitz, Bret D. Freudenthal, Amy M. Whitaker","doi":"10.1002/em.22570","DOIUrl":"10.1002/em.22570","url":null,"abstract":"In response to oxidative damage, base excision repair (BER) enzymes perturb the structural equilibrium of the VEGF promoter between B-form and G4 DNA conformations, resulting in epigenetic-like modifications of gene expression. However, the mechanistic details remain enigmatic, including the activity and coordination of BER enzymes on the damaged G4 promoter. To address this, we investigated the ability of each BER factor to conduct its repair activity on VEGF promoter G4 DNA substrates by employing pre-steady-state kinetics assays and in vitro coupled BER assays. OGG1 was able to initiate BER on double-stranded VEGF promoter G4 DNA substrates. Moreover, pre-steady-state kinetics revealed that compared to B-form DNA, APE1 repair activity on the G4 was decreased ~two-fold and is the result of slower product release as opposed to inefficient strand cleavage. Interestingly, Pol β performs multiple insertions on G4 substrates via strand displacement DNA synthesis in contrast to a single insertion on B-form DNA. The multiple insertions inhibit ligation of the Pol β products, and hence BER is not completed on the VEGF G4 promoter substrates through canonical short-patch BER. Instead, repair requires the long-patch BER flap-endonuclease activity of FEN1 in response to the multiple insertions by Pol β prior to ligation. Because the BER proteins and their repair activities are a key part of the VEGF transcriptional enhancement in response to oxidative DNA damage of the G4 VEGF promoter, the new insights reported here on BER activity in the context of this promoter are relevant toward understanding the mechanism of transcriptional regulation.","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"65 S1","pages":"25-39"},"PeriodicalIF":2.8,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10984112/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10182876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genome-wide impact of cytosine methylation and DNA sequence context on UV-induced CPD formation 胞嘧啶甲基化和DNA序列背景对紫外线诱导CPD形成的全基因组影响。

IF 2.8 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2023-08-09 DOI: 10.1002/em.22569

Hannah E. Wilson, John J. Wyrick

{"title":"Genome-wide impact of cytosine methylation and DNA sequence context on UV-induced CPD formation","authors":"Hannah E. Wilson, John J. Wyrick","doi":"10.1002/em.22569","DOIUrl":"10.1002/em.22569","url":null,"abstract":"Exposure to ultraviolet (UV) light is the primary etiological agent for skin cancers because UV damages cellular DNA. The most frequent form of UV damage is the cyclobutane pyrimidine dimer (CPD), which consists of covalent linkages between neighboring pyrimidine bases in DNA. In human cells, the 5′ position of cytosine bases in CG dinucleotides is frequently methylated, and methylated cytosines in the TP53 tumor suppressor are often sites of mutation hotspots in skin cancers. It has been argued that this is because cytosine methylation promotes UV-induced CPD formation; however, the effects of cytosine methylation on CPD formation are controversial, with conflicting results from previous studies. Here, we use a genome-wide method known as CPD-seq to map UVB- and UVC-induced CPDs across the yeast genome in the presence or absence in vitro methylation by the CpG methyltransferase M.SssI. Our data indicate that cytosine methylation increases UVB-induced CPD formation nearly 2-fold relative to unmethylated DNA, but the magnitude of induction depends on the flanking sequence context. Sequence contexts with a 5′ guanine base (e.g., GCCG and GTCG) show the strongest induction due to cytosine methylation, potentially because these sequence contexts are less efficient at forming CPD lesions in the absence of methylation. We show that cytosine methylation also modulates UVC-induced CPD formation, albeit to a lesser extent than UVB. These findings can potentially reconcile previous studies, and define the impact of cytosine methylation on UV damage across a eukaryotic genome.","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"65 S1","pages":"14-24"},"PeriodicalIF":2.8,"publicationDate":"2023-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10853481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10121130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of Transcription Factor IIH complex in nucleotide excision repair 转录因子 IIH 复合物在核苷酸切除修复中的作用

IF 2.8 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2023-08-06 DOI: 10.1002/em.22568

Allyson Hoag, Mingrui Duan, Peng Mao

{"title":"The role of Transcription Factor IIH complex in nucleotide excision repair","authors":"Allyson Hoag, Mingrui Duan, Peng Mao","doi":"10.1002/em.22568","DOIUrl":"10.1002/em.22568","url":null,"abstract":"DNA damage occurs throughout life from a variety of sources, and it is imperative to repair damage in a timely manner to maintain genome stability. Thus, DNA repair mechanisms are a fundamental part of life. Nucleotide excision repair (NER) plays an important role in the removal of bulky DNA adducts, such as cyclobutane pyrimidine dimers from ultraviolet light or DNA crosslinking damage from platinum-based chemotherapeutics, such as cisplatin. A main component for the NER pathway is transcription factor IIH (TFIIH), a multifunctional, 10-subunit protein complex with crucial roles in both transcription and NER. In transcription, TFIIH is a component of the pre-initiation complex and is important for promoter opening and the phosphorylation of RNA Polymerase II (RNA Pol II). During repair, TFIIH is important for DNA unwinding, recruitment of downstream repair factors, and verification of the bulky lesion. Several different disease states can arise from mutations within subunits of the TFIIH complex. Most strikingly are xeroderma pigmentosum (XP), XP combined with Cockayne syndrome (CS), and trichothiodystrophy (TTD). Here, we summarize the recruitment and functions of TFIIH in the two NER subpathways, global genomic (GG-NER) and transcription-coupled NER (TC-NER). We will also discuss how TFIIH's roles in the two subpathways lead to different genetic disorders.","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"65 S1","pages":"72-81"},"PeriodicalIF":2.8,"publicationDate":"2023-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10903506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10102551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impact of individual factors on DNA methylation of drug metabolism genes: A systematic review 个体因素对药物代谢基因DNA甲基化的影响:系统综述

IF 2.8 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2023-07-31 DOI: 10.1002/em.22567

Jialu Bian, Jinxia Zhao, Yinyu Zhao, Xu Hao, Shiyu He, Yuanyuan Li, Lin Huang

引用次数: 0

Unbiased whole genome detection of ultrarare off-target mutations in genome-edited cell populations by HiFi sequencing 通过HiFi测序无偏全基因组检测基因组编辑细胞群体中的超罕见脱靶突变

IF 2.8 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2023-07-24 DOI: 10.1002/em.22566

Jaime A. Miranda, Kristina Fenner, Page B. McKinzie, Vasily N. Dobrovolsky, Javier R. Revollo

{"title":"Unbiased whole genome detection of ultrarare off-target mutations in genome-edited cell populations by HiFi sequencing","authors":"Jaime A. Miranda, Kristina Fenner, Page B. McKinzie, Vasily N. Dobrovolsky, Javier R. Revollo","doi":"10.1002/em.22566","DOIUrl":"10.1002/em.22566","url":null,"abstract":"DNA base editors (BEs) composed of a nuclease-deficient Cas9 fused to a DNA-modifying enzyme can achieve on-target mutagenesis without creating double-strand DNA breaks (DSBs). As a result, BEs generate far less DNA damage than traditional nuclease-proficient Cas9 systems, which do rely on the creation of DSBs to achieve on-target mutagenesis. The inability of BEs to create DSBs makes the detection of their undesired off-target effects very difficult. PacBio HiFi sequencing can efficiently detect ultrarare mutations resulting from chemical mutagenesis in whole genomes with a sensitivity ~1 × 10−8 mutations per base pair. In this proof-of-principle study, we evaluated whether this technique could also detect the on- and off-target mutations generated by a cytosine-to-thymine (C>T) BE targeting the LacZ gene in Escherichia coli (E. coli). HiFi sequencing detected on-target mutant allele fractions ranging from ~7% to ~63%, depending on the single-guide RNA (sgRNA) used, while no on-target mutations were detected in controls lacking the BE. The presence of the BE resulted in a ~3-fold increase in mutation frequencies compared to controls lacking the BE, irrespective of the sgRNA used. These increases were mostly composed of C:G>T:A substitutions distributed throughout the genome. Our results demonstrate that HiFi sequencing can efficiently identify on- and off-target mutations in cell populations that have undergone genome editing.","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 7","pages":"374-381"},"PeriodicalIF":2.8,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10092557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cadmium exposure induces necroptosis of porcine spleen via ROS-mediated activation of STAT1/RIPK3 signaling pathway 镉暴露通过ros介导的STAT1/RIPK3信号通路激活诱导猪脾脏坏死

IF 2.8 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2023-07-15 DOI: 10.1002/em.22565

Yu Xia, Yiming Zhang, Jintao Zhang, Yongzhen Du, Yixuan Wang, Anqi Xu, Shu Li

{"title":"Cadmium exposure induces necroptosis of porcine spleen via ROS-mediated activation of STAT1/RIPK3 signaling pathway","authors":"Yu Xia, Yiming Zhang, Jintao Zhang, Yongzhen Du, Yixuan Wang, Anqi Xu, Shu Li","doi":"10.1002/em.22565","DOIUrl":"10.1002/em.22565","url":null,"abstract":"Cadmium (Cd), a heavy metal, is used in a wide range of applications, such as plastics, electroplating process, electronics, and so forth. Due to its bioaccumulation ability, Cd can contaminate soil, water, air and food. To determine the effect of Cd exposure on the necroptosis in pig spleen and its mechanistic investigation, we constructed a model in pigs by feeding them food containing 20 mg/kg Cd. In this study, we analyzed the effects of Cd exposure on pig spleen through HE staining, Quantitative real-time PCR (qRT-PCR), Western blot (WB), and principal component analysis (PCA). Results show that Cd exposure can destroy the structure and function of pig spleen, which is closely related to necroptosis. Further results show that Cd exposure can induce necroptosis through ROS-mediated activation of Signal transducer and activator of transcription 1/Receptor-Interacting Serine/Threonine-Protein Kinase 3 (STAT1/RIPK3) signaling pathway in pig spleen. Additionally, Cd exposure also can affect the stability of mitochondrial-associated endoplasmic reticulum membrane (MAMs) structure, which also contributes to the process of necroptosis. Our study provides insights into the physiological toxicity caused by Cd exposure.","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 7","pages":"382-392"},"PeriodicalIF":2.8,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10214519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Templated insertions—DNA repair gets acrobatic 模板化插入--DNA 修复变得杂技化

IF 2.8 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2023-07-12 DOI: 10.1002/em.22564

Susanna Stroik, Adam J. Luthman, Dale A. Ramsden

{"title":"Templated insertions—DNA repair gets acrobatic","authors":"Susanna Stroik, Adam J. Luthman, Dale A. Ramsden","doi":"10.1002/em.22564","DOIUrl":"10.1002/em.22564","url":null,"abstract":"Deletions associated with the repair of DNA double-strand breaks is a source of genetic alternation and a recognized source of disease-causing mutagenesis. Theta-mediated end joining is a DNA repair mechanism, which guarantees deletions by its employment of microhomology (MH) alignment to facilitate end joining. A lesser-characterized templated insertion ability of this pathway, on the other hand, is associated with both deletion and insertion. This mechanism is characterized by at least one round of polymerase θ-mediated synthesis, which does not result in successful repair, followed by a subsequent round of polymerase engagement and synthesis that does lead to repair. Here we focus on the mechanisms by which polymerase θ introduces these insertions—direct, inverse, and a new class which we have termed strand switching. We observe this new class of templated insertions at multiple loci and across multiple species, often at a comparable frequency to those previously characterized. Templated insertion mutations are often enriched in cancer genomes and repeat expansion disorders. This repair mechanism thus contributes to disease-associated mutagenesis, and may plausibly even promote disease. Characterization of the types of polymerase θ-dependent insertions can provide new insight into these diseases and clinical promise for treatment.","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"65 S1","pages":"82-89"},"PeriodicalIF":2.8,"publicationDate":"2023-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10962320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10257790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Kinetics of the in vivo genotoxic and radioprotective effects of methyl gallate and epigallocatechin gallate 没食子儿茶素没食子酸甲酯和没食子儿茶素没食子酸甲酯的体内遗传毒性和放射防护作用动力学

IF 2.8 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2023-07-10 DOI: 10.1002/em.22563

Virginia Cruz-Vallejo, Anaís Zarco-Mendoza, Pedro Morales-Ramírez

{"title":"Kinetics of the in vivo genotoxic and radioprotective effects of methyl gallate and epigallocatechin gallate","authors":"Virginia Cruz-Vallejo, Anaís Zarco-Mendoza, Pedro Morales-Ramírez","doi":"10.1002/em.22563","DOIUrl":"10.1002/em.22563","url":null,"abstract":"The aim of this study was to compare the kinetics of the in vivo action of equimolar doses of methyl gallate (MG) and epigallocatechin gallate (EGCG) on their capacity to induce DNA damage and to protect against DNA damage induced by 60Co gamma rays. DNA-damaged cells were determined by single-cell gel electrophoresis (comets) in murine peripheral blood leukocytes. The maximum radioprotective effects of MG and EGCG (approximately 70%) occurred at 15 min after administration when their effect was determined 2 min following irradiation. MG and EGCG have similar radioprotective indexes, which due to their fast response indicate that they are involved in free radical scavenging. Due to the similar radioprotective activities of MG and EGCG, the in vivo radioprotective effects of these agents do not seem to be dependent on the number of hydroxyl groups present in their structures but instead on the presence of the galloyl radical. EGCG induces an early, significant, and persistent increase in the number of DNA-damaged cells and a later and more important increase in the number of damaged cells, suggesting that it has two mechanisms by which it can induce DNA damage. MG at the same molar dose as EGCG caused a significant and persistent increase in DNA damaged cells but to a much lesser extent to that induce by EGCG, suggesting that the galloyl radical is not involved in the mechanism of DNA breaks induction.","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 7","pages":"393-400"},"PeriodicalIF":2.8,"publicationDate":"2023-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10101950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chromosome damage in regions with different levels of air pollution 不同空气污染程度地区的染色体损伤

IF 2.8 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2023-07-08 DOI: 10.1002/em.22562

Petra Musilova, Dita Kadlcikova, Hana Hradska, Miluse Vozdova, Iveta Selingerova, Halina Cernohorska, Dusan Salat, Jiri Rubes

{"title":"Chromosome damage in regions with different levels of air pollution","authors":"Petra Musilova, Dita Kadlcikova, Hana Hradska, Miluse Vozdova, Iveta Selingerova, Halina Cernohorska, Dusan Salat, Jiri Rubes","doi":"10.1002/em.22562","DOIUrl":"10.1002/em.22562","url":null,"abstract":"Air pollution is an important environmental factor influencing human health. In this study, we compared chromosome damage in city policemen from three cities in the Czech Republic: industrial Ostrava characterized by high levels of benzo[a]pyrene, Prague with heavy traffic emitting nitrogen oxides, and relatively clean Ceske Budejovice located in an area with predominantly agricultural activity. Chromosomal aberrations in lymphocytes were evaluated by fluorescence in situ hybridization with painting probes for chromosomes 1, 2, 3, and 4 in spring and autumn. An increase in the frequency of unstable chromosome aberrations, that is, dicentric chromosomes and acentric fragments, was observed in spring samples from Ostrava (p = .014 and p = .044, respectively) and Prague (p = .002 and p = .006, respectively) in comparison with Ceske Budejovice. The difference was significant only for samples taken after the winter period, when the concentration of pollutants in the air increases due to poor dispersion conditions. An increased frequency of dicentric chromosomes was observed in spring compared to autumn in both Ostrava and Prague (p = .017 and p = .023, respectively), but not in Ceske Budejovice. More breakpoints were observed on chromosome 1 than on the other chromosomes examined (p < .001). The number of breakpoints in the heterochromatin region 1p11-q12 was lower than in other parts of chromosome 1 (p < .001), suggesting a protective function of heterochromatin against damage. Our study showed, that air pollution increased the frequency of unstable chromosome aberrations, especially dicentric chromosomes. However, we did not show an effect on stable chromosome rearrangements.","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 6","pages":"326-334"},"PeriodicalIF":2.8,"publicationDate":"2023-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/em.22562","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9884020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Toxicity and mutagenicity studies of 6PPD-quinone in a marine invertebrate species and bacteria 6ppd -醌对海洋无脊椎动物和细菌的毒性和致突变性研究

IF 2.8 4区医学

Environmental and Molecular Mutagenesis Pub Date : 2023-07-04 DOI: 10.1002/em.22560

Marina Tenório Botelho, Gabriely Groto Militão, Markus Brinkmann, Gisela de Aragão Umbuzeiro

{"title":"Toxicity and mutagenicity studies of 6PPD-quinone in a marine invertebrate species and bacteria","authors":"Marina Tenório Botelho, Gabriely Groto Militão, Markus Brinkmann, Gisela de Aragão Umbuzeiro","doi":"10.1002/em.22560","DOIUrl":"10.1002/em.22560","url":null,"abstract":"N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine-quinone (6PPD-quinone), an oxidation product of the tire additive, 6PPD, has been associated with high mortality of salmonids (0.1 μg/L). The objective of this study was to determine the acute toxicity using neonates and mutagenicity (micronuclei in hemolymph of exposed adults) of 6PPD-quinone in the marine amphipod Parhyale hawaiensis. Also, we studied its mutagenicity in the Salmonella/microsome assay using five strains of Salmonella with and without metabolic system (rat liver S9, 5%). 6PPD-quinone did not present acute toxicity to P. hawaiensis from 31.25 to 500 μg/L. Micronuclei frequency increased after 96 h-exposure to 6PPD-quinone (250 and 500 μg/L) when compared to the negative control. 6PPD-quinone also showed a weak mutagenic effect for TA100 only in the presence of S9. We conclude that 6PPD-quinone is mutagenic to P. hawaiensis and weakly mutagenic to bacteria. Our work provides information for future risk assessment of the presence of 6PPD-quinone in the aquatic environment.","PeriodicalId":11791,"journal":{"name":"Environmental and Molecular Mutagenesis","volume":"64 6","pages":"335-341"},"PeriodicalIF":2.8,"publicationDate":"2023-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10239502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1