Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis最新文献

{"title":"In Memoriam - Krishnaswami Sankaranarayanan (1933–2022)","authors":"Hooshang Nikjoo , George Hoffmann , Keith Baverstock","doi":"10.1016/j.mrfmmm.2022.111789","DOIUrl":"10.1016/j.mrfmmm.2022.111789","url":null,"abstract":"","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"825 ","pages":"Article 111789"},"PeriodicalIF":2.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40406972","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}

{"title":"Treatment with the anti-CD20 monoclonal antibody rituximab mitigates gonadal disruptions in the collagen-induced arthritis in male DBA/1 J mouse model","authors":"Mohammed A. Al-Hamamah,&nbsp;Moureq R. Alotaibi,&nbsp;Sheikh F. Ahmad,&nbsp;Ahmed Nadeem,&nbsp;Mohamed S.M. Attia,&nbsp;Mushtaq A. Ansari,&nbsp;Saleh A. Bakheet,&nbsp;Mohammed M. Alanazi,&nbsp;Sabry M. Attia","doi":"10.1016/j.mrfmmm.2022.111799","DOIUrl":"10.1016/j.mrfmmm.2022.111799","url":null,"abstract":"<div><p><span><span>Rheumatoid arthritis<span><span> (RA), which is driven by persistent activation of the immune system, primarily affects the joints. Several reports have estimated the risk of gonadal disruptions in arthritic patients, with potential attributable risk factors such as treatments with the disease-modifying antirheumatic drugs and the influence of the disease itself. The FDA approved rituximab, a therapy for non-Hodgkin's lymphoma, for management of RA in February 2006. However, the influence of repeated treatment with rituximab on </span>gonadal function<span><span> in RA has not been reported yet. Thus, the aim of the presents study is to evaluate whether repeated treatment with the clinically relevant dose of rituximab may change the gonadal disruptions in collagen-induced arthritis in male DBA/1 J mouse, a model of RA. Testicular disruptions, as determined by the sperm DNA strand breaks, </span>spermatocyte chromosomal analysis and spermiogram examination have been conducted by the use of standard techniques. Additionally, we aimed to test whether the anti-rheumatic effect of rituximab also decreases the cellular oxidant-antioxidant imbalance in arthritic male DBA/1 J mice. Repeated treatment of naïve control DBA/1 J mice with rituximab did not exhibit any significant deleterious effects. Moreover, </span></span></span>repeated administration<span><span> of rituximab to the arthritic DBA/1 J mice suppressed disease severity and decreased testicular disruptions. Rituximab treatment also diminished gonadal oxidative stress, through decreasing </span>reactive oxygen species generation and restoring the </span></span>reduced glutathione level in arthritic DBA/1 J mice. In conclusion, rituximab is a safe therapeutic agent and can mitigate gonadal disruptions induced by arthritis, which insinuates the importance for arthritic patients especially at reproductive age.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"825 ","pages":"Article 111799"},"PeriodicalIF":2.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10351756","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}

{"title":"Biased distribution of action-at-a-distance mutations by 8-oxo-7,8-dihydroguanine","authors":"Ruriko Fukushima ,&nbsp;Tetsuya Suzuki ,&nbsp;Yasuo Komatsu ,&nbsp;Hiroyuki Kamiya","doi":"10.1016/j.mrfmmm.2022.111794","DOIUrl":"10.1016/j.mrfmmm.2022.111794","url":null,"abstract":"<div><p><span>8-Oxo-7,8-dihydroguanine (8-hydroxyguanine, G°) is a major oxidized base that is considered to play pivotal roles in the pathogenesis of various diseases, including cancer. G° induces G:C → T:A transversions<span> at the damage site and untargeted (action-at-a-distance) mutations of G bases at 5′-GpA sequences. In this study, we examined the distribution of the action-at-a-distance mutations and the effects of the replication origin<span> position relative to G° on the untargeted mutagenesis. The G° base was introduced into two shuttle plasmids, each with the SV40 replication origin at a different position with respect to the </span></span></span><em>supF</em> gene. The oxidized base was located at an upstream or downstream site (outside of the gene), or the center of the region encoding the pre-tRNA sequence of the gene, in the sense strand. These shuttle plasmids were introduced into human U2OS cells. The action-at-a-distance mutations were more frequently induced when the G° base was located downstream of the <em>supF</em> gene than upstream of the gene. In addition, more action-at-a-distance mutations were observed when the SV40 origin was present on the 5′-side of the G° base. These results indicated that the action-at-a-distance mutations are predominantly induced on the 5′-side of the lesion and occurred more frequently when the damaged base was located on the lagging strand template.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"825 ","pages":"Article 111794"},"PeriodicalIF":2.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10359531","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}

{"title":"Whole genome analysis of UV-induced mutagenesis in Caulobacter crescentus","authors":"Ingrid R. Alves ,&nbsp;Ricardo Z. Vêncio ,&nbsp;Rodrigo S. Galhardo","doi":"10.1016/j.mrfmmm.2022.111787","DOIUrl":"10.1016/j.mrfmmm.2022.111787","url":null,"abstract":"<div><p><span>UV-induced mutagenesis is, to greater extent, a phenomenon dependent on translesion synthesis (TLS) and regulated by the SOS response in bacteria. </span><span><em>Caulobacter crescentus</em></span>, like many bacterial species, employs the ImuABC (ImuAB DnaE2) pathway in TLS. To have a better understanding of the characteristics of UV-induced mutagenesis in this organism, we performed a whole genome analysis of mutations present in survivors after an acute UVC exposure (300 J/m²<span>). We found an average of 3.2 mutations/genome in irradiated samples, distributed in a mutational spectrum consisting exclusively of base substitutions, including tandem mutations. Although limited in conclusions by the small number of mutations identified, our study points to the feasibility of using whole-genome sequencing to study mutagenesis occurring in experiments involving a single acute exposure to genotoxic agents.</span></p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"825 ","pages":"Article 111787"},"PeriodicalIF":2.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10709479","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}

{"title":"Lamin A and telomere maintenance in aging: Two to Tango","authors":"Duhita Sengupta ,&nbsp;Kaushik Sengupta","doi":"10.1016/j.mrfmmm.2022.111788","DOIUrl":"10.1016/j.mrfmmm.2022.111788","url":null,"abstract":"<div><p><span><span><span>Lamin<span><span> proteins which constitute the nuclear lamina<span><span> in almost all higher eukaryotes, are mainly of two types A &amp; B encoded by LMNA and LMNB1/B2 genes respectively. While lamin A remains the principal product of LMNA gene, variants like lamin C, C2 and A∆10 are also formed as alternate splice products. Role of lamin A in aging has been highlighted in recent times due to its association with progeroid or </span>premature aging<span> syndromes which is classified as a type of laminopathy. </span></span></span>Progeria caused by accelerated accumulation of lamin A Δ50 or </span></span>progerin<span> occurs due to a mutation in this LMNA gene leading to defects in post translational modification of lamin A. One of the most common and severe symptoms of progeroid laminopathy is accelerated cellular senescence or aging along with </span></span>bone resorption, muscle weakness, </span>lipodystrophy<span><span> and cardiovascular disorders. On the other hand, progerin accumulation and telomere<span><span> dysfunction merge as common traits in the process of chronological aging. Two major hallmarks of physiological aging in humans include loss of genomic integrity and telomere attrition which can result from defective laminar organization leading to deformed nuclear architecture and culminates into replicative senescence. This also adversely affects epigenetic landscape, mitochondrial dysfunction and several </span>signalling pathways like DNA repair, </span></span>mTOR<span>, MAPK, TGFβ. In this review, we discuss the telomere-lamina interplay in the context of physiological aging and progeria.</span></span></p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"825 ","pages":"Article 111788"},"PeriodicalIF":2.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10728301","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}

{"title":"MiRNA-144–5p down-modulates CDCA3 to regulate proliferation and apoptosis of lung adenocarcinoma cells","authors":"Jing Luo,&nbsp;Lilong Xia,&nbsp;Lei Zhang,&nbsp;Kaixiang Zhao,&nbsp;Chuanchuan Li","doi":"10.1016/j.mrfmmm.2022.111798","DOIUrl":"10.1016/j.mrfmmm.2022.111798","url":null,"abstract":"<div><h3>Background</h3><p>Lung adenocarcinoma<span> (LUAD) belongs to non-small cell lung cancer. In addition to surgical resection, chemotherapy and radiotherapy cause great side effects and low 5-year survival rates. MiRNAs are closely related to cancer development. This study aimed to analyze the molecular mechanism of miRNA-144–5p targeting CDCA3 to inhibit LUAD proliferation.</span></p></div><div><h3>Methods</h3><p><span>MiRNA and mRNA data were downloaded from TCGA-LUAD dataset for differential expression analysis. TargetScan and miRTarBase databases were adopted to predict the target genes of miRNA, and the </span>signaling pathways<span><span> involved were analyzed by gene set enrichment analysis. The functions of LUAD cells were analyzed by CCK-8, colony formation assay, stem cell spheroidization assay, and flow cytometry. The expression levels of CDCA3, p53, and cell cycle-associated proteins were evaluated by </span>Western blot.</span></p></div><div><h3>Results</h3><p>The expression of miRNA-144–5p was significantly down-regulated in LUAD, but overexpression of it repressed proliferation and spheroidization, and promoted apoptosis of LUAD cells. By bioinformatics prediction and dual-luciferase reporter assay, miRNA-144–5p was validated to target CDCA3, thereby regulating proliferation of LUAD cells. Besides, the results of cell experiments showed that miRNA-144–5p targeting CDCA3 affected cell proliferation and apoptosis in LUAD by regulating cell cycles, and miRNA-144–5p/CDCA3 mediated the p53 signaling pathway to affect the growth of LUAD cells.</p></div><div><h3>Significance</h3><p>Through the study of the pathogenesis of miRNA-144–5p regulating LUAD, we can better understand the molecular mechanism underlying LUAD development.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"825 ","pages":"Article 111798"},"PeriodicalIF":2.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10728355","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}

{"title":"The kidney-expressed transcription factor ZKSCAN3 is dispensable for autophagy transcriptional regulation and AKI progression in mouse","authors":"Zejian Liu ,&nbsp;Xiaoyu Li ,&nbsp;Xingyu Li ,&nbsp;Zixian Li ,&nbsp;Huixia Chen ,&nbsp;Siqiao Gong ,&nbsp;Minjie Zhang ,&nbsp;Yaozhi Zhang ,&nbsp;Zhihang Li ,&nbsp;Lin Yang ,&nbsp;Huafeng Liu","doi":"10.1016/j.mrfmmm.2022.111790","DOIUrl":"10.1016/j.mrfmmm.2022.111790","url":null,"abstract":"<div><p>Acute kidney injury (AKI) is a common clinical disease that can cause serious harm to the kidneys, but it has no effective treatment till now. The modulation of autophagy pathway regulation is considered a potentially effective therapeutic approach in AKI prevention and treatment. ZKSCAN3 has been shown to be an important transcription factor that negatively regulates autophagy activity in cancer tissues. In order to determine whether autophagy could be activated by knocking out ZKSCAN3 to exert the renal protective effect of autophagy, we constructed AKI models with <em>Zkscan3</em> knockout (KO) mice and detected renal pathological changes and renal function changes as well as autophagy-related indicators. We found that <em>Zkscan3</em> KO had no significant effect on kidney development. Besides, no significant changes in autophagy activity were observed under normal physiological or AKI conditions. In non-tumor tissues, ZKSCAN3 did not mediate transcriptional regulation of autophagy-related genes. These findings suggest that because ZKSCAN3 may not function in the transcriptional regulation of autophagy-related genes in non-tumor tissues, it may not be used as a therapeutic target for AKI.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"825 ","pages":"Article 111790"},"PeriodicalIF":2.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10358135","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}

{"title":"Both phosphorylation and phosphatase activity of PTEN are required to prevent replication fork progression during stress by inducing heterochromatin","authors":"Sandip Misra ,&nbsp;Sougata Ghosh Chowdhury ,&nbsp;Ginia Ghosh ,&nbsp;Ananda Mukherjee ,&nbsp;Parimal Karmakar","doi":"10.1016/j.mrfmmm.2022.111800","DOIUrl":"10.1016/j.mrfmmm.2022.111800","url":null,"abstract":"<div><p><span><span><span>PTEN is a tumor suppressor protein frequently altered in various cancers. PTEN-null cells have a characteristic of rapid proliferation with an unstable genome. Replication stress is one of the causes of the accumulation of </span>genomic instability if not sensed by the </span>cellular signaling<span>. Though PTEN-null cells have shown to be impaired in replication progression and stalled fork recovery, the association between the catalytic function of PTEN regulated by posttranslational modulation and cellular response to replication stress has not been studied explicitly. To understand molecular mechanism, we find that PTEN-null cells display unrestrained replication fork progression with accumulation of damaged DNA after treatment with </span></span>aphidicolin<span> which can be rescued by ectopic expression<span><span> of full-length PTEN, as evident from DNA fiber assay. Moreover, the C-terminal phosphorylation (Ser 380, Thr 382/383) of PTEN is essential for its chromatin association and sensing replication stress that, in response, induce cell cycle arrest. Further, we observed that PTEN induces HP1α expression and H3K9me3 foci formation in a C-terminal phosphorylation-dependent manner. However, </span>phosphatase<span><span> dead PTEN cannot sense replication stress though it can be associated with chromatin. Together, our results suggest that DNA replication perturbation by aphidicolin enables chromatin association of PTEN through C-terminal phosphorylation, induces heterochromatin formation by stabilizing and up-regulating H3K9me3 foci and augments CHK1 activation. Thereby, PTEN prevents DNA replication fork elongation and simultaneously causes G1-S </span>phase cell cycle arrest<span> to limit cell proliferation in stress conditions. Thus PTEN act as stress sensing protein during replication arrest to maintain genomic stability.</span></span></span></span></p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"825 ","pages":"Article 111800"},"PeriodicalIF":2.3,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10421124","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}

{"title":"Impact of glutathione S transferases P1 (Ile105Val) variants on the risk of GSTp, phosphorylated c-Jun kinase, and P53 phenotypic expression and their implications on overall survival outcomes in non-small cell lung cancer patients treated with chemotherapy","authors":"Anumesh K. Pathak ,&nbsp;Nuzhat Husain ,&nbsp;Saumya Shukla ,&nbsp;Rahul Kumar Pandey ,&nbsp;Surya Kant ,&nbsp;Lakshmi Bala","doi":"10.1016/j.mrfmmm.2022.111775","DOIUrl":"10.1016/j.mrfmmm.2022.111775","url":null,"abstract":"<div><h3>Aim</h3><p>This study focused on GST-M1, T1 null, and P1 Ile105Val variant genotypes associated with the risk of altered expression of GSTp, pJNK, and P53 in NSCLC patients. These markers and overall survival (OS) were correlated with a key set of clinicopathological characteristics.</p></div><div><h3>Methods</h3><p>Genotyping of GST- M1, T1 (+/−), and P1 (Ile105Val) was performed using PCR-RFLP.The expression of GSTp, pJNK, and P53 phenotypes was assessed by immunohistochemistry. The Spearman test was used to examine the correlation between GSTp, pJNK, and P53. Kaplan-Meier test was used for OS analysis.</p></div><div><h3>Results</h3><p><span>GSTP1<span> Val/Val and Ile/Val genotypes notably increased GSTp expression by 1.8 and 1.7 fold, respectively (p = 0.04,p = 0.06). GSTP1 Val/Val and Ile/Val genotypes considerably reduced P53 expression by 0.61 and 0.57 fold, respectively (p = 0.03&amp; p = 0.05), respectively. GSTp, pJNK, and P53 were significantly co-expressed (p &lt; 0.001). GSTp and pJNK expression showed a moderate negative correlation (ρ = −0.32, p = 0.046). In contrast, GSTp and P53 expression exhibited a strong negative correlation (ρ = −0.53, p &lt; 0.0001). There was no correlation between P53 and pJNK expression(ρ = 0.07, p = 0.54). The patient’s median OS was 8.9 months, and it was significantly related to pack-years, stage, metastasis, and GSTM1(-/-) genotypes (p &gt; 0.05). SQCLC showed poor OS than ADC (5.7 months vs.9.1 months, p = 0.2). Stage IV and metastasis significantly reduced the OS (p = 0.001). The tumour size and lymph nodes<span> reflected poor OS (p = 0.07&amp;p = 0.06). Gemcitabine+Cisplatin and Gefitinib showed a slightly higher rate of survival (9.3 months and 8.1 months) than Pemtrexe+Cisplatin treatment (7.0 months,p = 0.8). </span></span></span>Multivariate analysis revealed that pack-years and GSTp were independent predictors for OS (p = 0.03).</p></div><div><h3>Conclusion</h3><p>GSTp, pJNK, and P53 showed interconnected cascading. Age, pack-year, stage, and GSTp were found to be significant predictive factors for OS.Pack-years, GSTp independent OS predictor.</p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"824 ","pages":"Article 111775"},"PeriodicalIF":2.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39754435","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}

{"title":"Neutrophils and micronuclei: An emerging link between genomic instability and cancer-driven inflammation","authors":"Triet M. Bui,&nbsp;Ronen Sumagin","doi":"10.1016/j.mrfmmm.2022.111778","DOIUrl":"10.1016/j.mrfmmm.2022.111778","url":null,"abstract":"<div><p><span><span>Two recent studies by Bui and Butin-Israeli et al. have established the novel contribution of neutrophils to </span>genomic instability<span> induction and aberrant shaping of the DNA repair landscape, particularly observed in patients with inflammatory bowel diseases (IBD) and/or progressive </span></span>colorectal cancer<span><span> (CRC). In addition, these back-to-back studies uncovered a sharp increase in the numbers of micronuclei and lagging chromosomes in pre-cancerous and cancerous epithelium in response to prolonged PMN exposure. Given the emerging link between neutrophils and micronuclei as well as the established role of micronuclei in cGAS/STING activation, this special commentary aims to elaborate on the mechanisms by which CRC cells may adapt to neutrophil-driven genomic instability while concurrently sustain an inflamed tumor niche. We postulate that such tumor microenvironment with constant </span>immune cell presence, inflammatory milieu, and cumulative DNA damage can drive tumor adaptation and resistance to therapeutic interventions. Finally, we discuss potential novel therapeutic approaches that can be leveraged to target this emerging neutrophil-micronuclei pathological axis, thereby preventing perpetual CRC inflammation and unwanted tumor adaptation.</span></p></div>","PeriodicalId":49790,"journal":{"name":"Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis","volume":"824 ","pages":"Article 111778"},"PeriodicalIF":2.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10379545","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}