Translational Research最新文献

{"title":"Editorial Advisory Board","authors":"","doi":"10.1016/S1931-5244(24)00040-9","DOIUrl":"https://doi.org/10.1016/S1931-5244(24)00040-9","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"266 ","pages":"Page A2"},"PeriodicalIF":7.8,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1931524424000409/pdfft?md5=1092111404692a7d2f2952440f15049e&pid=1-s2.0-S1931524424000409-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140067041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Information for Readers","authors":"","doi":"10.1016/S1931-5244(24)00042-2","DOIUrl":"https://doi.org/10.1016/S1931-5244(24)00042-2","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"266 ","pages":"Page IBC"},"PeriodicalIF":7.8,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140067214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Arginine methylation and respiratory disease","authors":"Binbin Zhang ,&nbsp;Youhong Guan ,&nbsp;Daxiong Zeng ,&nbsp;Ran Wang","doi":"10.1016/j.trsl.2024.03.002","DOIUrl":"10.1016/j.trsl.2024.03.002","url":null,"abstract":"<div><p>Arginine methylation, a vital post-translational modification, plays a pivotal role in numerous cellular functions such as signal transduction, DNA damage response and repair, regulation of gene transcription, mRNA splicing, and protein interactions. Central to this modification is the role of protein arginine methyltransferases (PRMTs), which have been increasingly recognized for their involvement in the pathogenesis of various respiratory diseases. This review begins with an exploration of the biochemical underpinnings of arginine methylation, shedding light on the intricate molecular regulatory mechanisms governed by PRMTs. It then delves into the impact of arginine methylation and the dysregulation of arginine methyltransferases in diverse pulmonary disorders. Concluding with a focus on the therapeutic potential and recent advancements in PRMT inhibitors, this article aims to offer novel perspectives and therapeutic avenues for the management and treatment of respiratory diseases.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"272 ","pages":"Pages 140-150"},"PeriodicalIF":6.4,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140061708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RAS protein activator-like 2 (RASAL2) initiates peritubular capillary rarefaction in hypoxic renal interstitial fibrosis","authors":"Yu Zhang ,&nbsp;Yiqiong Yang ,&nbsp;Xiuxiu Hu ,&nbsp;Bizhen Wei ,&nbsp;Qian Shen ,&nbsp;Chuanbing Shi ,&nbsp;Pingsheng Chen","doi":"10.1016/j.trsl.2024.03.003","DOIUrl":"10.1016/j.trsl.2024.03.003","url":null,"abstract":"<div><p>The progression of chronic kidney disease (CKD) often involves renal interstitial fibrosis (RIF) and subsequent loss of peritubular capillaries (PTCs), which enhances disease severity. Despite advancements in our understanding of fibrosis, effective interventions for reversing capillary loss remain elusive. Notably, RIF exhibits reduced capillary density, whereas renal cell carcinoma (RCC) shows robust angiogenesis under hypoxic conditions. Using RNA sequencing and bioinformatics, we identified differentially expressed genes (DEGs) in hypoxic human renal tubular epithelial cells (HK-2) and renal cancer cells (786-0). Analysis of altered Ras and PI3K/Akt pathways coupled with hub gene investigation revealed RAS protein activator-like 2 (RASAL2) as a key candidate. Subsequent <em>in vitro</em> and in vivo studies confirmed RASAL2′s early-stage response in RIF, which reduced with fibrosis progression. RASAL2 suppression in HK-2 cells enhanced angiogenesis, as evidenced by increased proliferation, migration, and branching of human umbilical vein endothelial cells (HUVECs) co-cultured with HK-2 cells. In mice, RASAL2 knockdown improved Vascular endothelial growth factor A (VEGFA) and Proliferating cell nuclear antigen (PCNA) levels in unilateral ureteral occlusion (UUO)-induced fibrosis (compared to wild type). Hypoxia-inducible factor 1 alpha (HIF-1α) emerged as a pivotal mediator, substantiated by chromatin immunoprecipitation (ChIP) sequencing, with its induction linked to activation. Hypoxia increased the production of RASAL2-enriched extracellular vesicles (EVs) derived from tubular cells, which were internalized by endothelial cells, contributing to the exacerbation of PTC loss. These findings underscore RASAL2′s role in mediating reduced angiogenesis in RIF and reveal a novel EV-mediated communication between hypoxic tubular- and endothelial cells, demonstrating a complex interplay between angiogenesis and fibrosis in CKD pathogenesis.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"269 ","pages":"Pages 14-30"},"PeriodicalIF":7.8,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140061709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of G protein-coupled receptor 68 using homoharringtonine attenuates chronic kidney disease-associated cardiac impairment","authors":"Yuya Yoshida ,&nbsp;Kohei Fukuoka ,&nbsp;Miyu Sakugawa ,&nbsp;Masayuki Kurogi ,&nbsp;Kengo Hamamura ,&nbsp;Keika Hamasaki ,&nbsp;Fumiaki Tsurusaki ,&nbsp;Kurumi Sotono ,&nbsp;Takumi Nishi ,&nbsp;Taiki Fukuda ,&nbsp;Taisei Kumamoto ,&nbsp;Kosuke Oyama ,&nbsp;Takashi Ogino ,&nbsp;Akito Tsuruta ,&nbsp;Kouta Mayanagi ,&nbsp;Tomohiro Yamashita ,&nbsp;Hiroyuki Fuchino ,&nbsp;Nobuo Kawahara ,&nbsp;Kayo Yoshimatsu ,&nbsp;Hitomi Kawakami ,&nbsp;Shigehiro Ohdo","doi":"10.1016/j.trsl.2024.02.004","DOIUrl":"10.1016/j.trsl.2024.02.004","url":null,"abstract":"<div><p>Chronic kidney disease (CKD) induces cardiac inflammation and fibrosis and reduces survival. We previously demonstrated that G protein-coupled receptor 68 (GPR68) promotes cardiac inflammation and fibrosis in mice with 5/6 nephrectomy (5/6Nx) and patients with CKD. However, no method of GPR68 inhibition has been found that has potential for therapeutic application. Here, we report that <em>Cephalotaxus harringtonia var. nana</em> extract and homoharringtonine ameliorate cardiac inflammation and fibrosis under CKD by suppressing GPR68 function. Reagents that inhibit the function of GPR68 were explored by high-throughput screening using a medicinal plant extract library (8,008 species), and we identified an extract from <em>Cephalotaxus harringtonia</em> var. <em>nana</em> as a GPR68 inhibitor that suppresses inflammatory cytokine production in a GPR68 expression-dependent manner. Consumption of the extract inhibited inflammatory cytokine expression and cardiac fibrosis and improved the decreased survival attributable to 5/6Nx. Additionally, homoharringtonine, a cephalotaxane compound characteristic of <em>C. harringtonia</em>, inhibited inflammatory cytokine production. Homoharringtonine administration in drinking water alleviated cardiac fibrosis and improved heart failure and survival in 5/6Nx mice. A previously unknown effect of <em>C. harringtonia</em> extract and homoharringtonine was revealed in which GPR68-dependent inflammation and cardiac dysfunction were suppressed. Utilizing these compounds could represent a new strategy for treating GPR68-associated diseases, including CKD.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"269 ","pages":"Pages 31-46"},"PeriodicalIF":7.8,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139944798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elevated expression of complement factor I in lung cancer cells associates with shorter survival–Potentially via non-canonical mechanism","authors":"Anna Felberg ,&nbsp;Michał Bieńkowski ,&nbsp;Tomasz Stokowy ,&nbsp;Kamil Myszczyński ,&nbsp;Zuzanna Polakiewicz ,&nbsp;Kamila Kitowska ,&nbsp;Rafał Sądej ,&nbsp;Frida Mohlin ,&nbsp;Alicja Kuźniewska ,&nbsp;Daria Kowalska ,&nbsp;Grzegorz Stasiłojć ,&nbsp;Ilse Jongerius ,&nbsp;Robbert Spaapen ,&nbsp;Miguel Mesa-Guzman ,&nbsp;Luis M. Montuenga ,&nbsp;Anna M. Blom ,&nbsp;Ruben Pio ,&nbsp;Marcin Okrój","doi":"10.1016/j.trsl.2024.02.003","DOIUrl":"10.1016/j.trsl.2024.02.003","url":null,"abstract":"<div><p>While numerous membrane-bound complement inhibitors protect the body's cells from innate immunity's autoaggression, soluble inhibitors like complement factor I (FI) are rarely produced outside the liver. Previously, we reported the expression of FI in non-small cell lung cancer (NSCLC) cell lines. Now, we assessed the content of FI in cancer biopsies from lung cancer patients and associated the results with clinicopathological characteristics and clinical outcomes. Immunohistochemical staining intensity did not correlate with age, smoking status, tumor size, stage, differentiation grade, and T cell infiltrates, but was associated with progression-free survival (PFS), overall survival (OS) and disease-specific survival (DSS). Multivariate Cox analysis of low vs. high FI content revealed HR 0.55, 95 % CI 0.32-0.95, p=0.031 for PFS, HR 0.51, 95 % CI 0.25-1.02, p=0.055 for OS, and HR 0.32, 95 % CI 0.12-0.84, p=0.021 for DSS. Unfavorable prognosis might stem from the non-canonical role of FI, as the staining pattern did not correlate with C4d - the product of FI-supported degradation of active complement component C4b. To elucidate that, we engineered three human NSCLC cell lines naturally expressing FI with CRISPR/Cas9 technology, and compared the transcriptome of FI-deficient and FI-sufficient clones in each cell line. RNA sequencing revealed differentially expressed genes engaged in intracellular signaling pathways controlling proliferation, apoptosis, and responsiveness to growth factors. Moreover, in vitro colony-formation assays showed that FI-deficient cells formed smaller foci than FI-sufficient NSCLC cells, but their size increased when purified FI protein was added to the medium. We postulate that a non-canonical activity of FI influences cellular physiology and contributes to the poor prognosis of lung cancer patients.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"269 ","pages":"Pages 1-13"},"PeriodicalIF":7.8,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139941452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ntsr1 contributes to pulmonary hypertension by enhancing endoplasmic reticulum stress via JAK2-STAT3-Thbs1 signaling","authors":"Zhi-Xing Wei ,&nbsp;Xing-Xing Cai ,&nbsp;Yu-Dong Fei ,&nbsp;Qian Wang ,&nbsp;Xiao-Liang Hu ,&nbsp;Cheng Li ,&nbsp;Jian-Wen Hou ,&nbsp;Yu-Li Yang ,&nbsp;Yue-Peng Wang ,&nbsp;Yi-Gang Li","doi":"10.1016/j.trsl.2024.02.002","DOIUrl":"10.1016/j.trsl.2024.02.002","url":null,"abstract":"<div><p>Pulmonary hypertension (PH) is a severe clinical syndrome with pulmonary vascular remodeling and poor long-term prognosis. Neurotensin receptor 1 (Ntsr1), serve as one of the G protein-coupled receptors (GPCRs), implicates in various biological processes, but the potential effects of Ntsr1 in PH development are unclear. The Sugen/Hypoxia (SuHx) or monocrotaline (MCT) induced rat PH model was used in our study and the PH rats showed aggravated pulmonary artery remodeling and increased right ventricular systolic pressure (RVSP). Our results revealed that Ntsr1 induced endoplasmic reticulum (ER) stress response via ATF6 activation contributed to the development of PH. Moreover, RNA-sequencing (RNA-seq) and phosphoproteomics were performed and the Ntsr1-JAK2-STAT3-thrombospondin 1 (Thbs1)-ATF6 signaling was distinguished as the key pathway. <em>In vitro</em>, pulmonary artery smooth muscle cells (PASMCs) under hypoxia condition showed enhanced proliferation and migration properties, which could be inhibited by Ntsr1 knockdown, JAK2 inhibitor (Fedratinib) treatment, STAT3 inhibitior (Stattic) treatment, Thbs1 knockdown or ATF6 knockdown. In addition, adeno-associated virus 1 (AAV1) were used to knockdown the expression of Ntsr1, Thbs1 or ATF6 in rats and reversed the phenotype of PH. In summary, our results reveal that Ntsr1-JAK2-STAT3-Thbs1 pathway can induce enhanced ER stress via ATF6 activation and increased PASMC proliferation and migration capacities, which can be mechanism of the pulmonary artery remodeling and PH. Targeting Ntsr1 might be a novel therapeutic strategy to ameliorate PH.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"269 ","pages":"Pages 64-75"},"PeriodicalIF":7.8,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1931524424000318/pdfft?md5=9541c40ba070e40a5cfaed1921c4b73d&pid=1-s2.0-S1931524424000318-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139921868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the plasma proteomic profile of Fabry disease: Potential sex- and clinical phenotype-specific biomarkers","authors":"Laura López-Valverde ,&nbsp;María E. Vázquez-Mosquera ,&nbsp;Cristóbal Colón-Mejeras ,&nbsp;Susana B. Bravo ,&nbsp;Sofía Barbosa-Gouveia ,&nbsp;J. Víctor Álvarez ,&nbsp;Rosario Sánchez-Martínez ,&nbsp;Manuel López-Mendoza ,&nbsp;Mónica López-Rodríguez ,&nbsp;Eduardo Villacorta-Argüelles ,&nbsp;María A. Goicoechea-Diezhandino ,&nbsp;Francisco J. Guerrero-Márquez ,&nbsp;Saida Ortolano ,&nbsp;Elisa Leao-Teles ,&nbsp;Álvaro Hermida-Ameijeiras ,&nbsp;María L. Couce","doi":"10.1016/j.trsl.2024.02.006","DOIUrl":"10.1016/j.trsl.2024.02.006","url":null,"abstract":"<div><p>Fabry disease (FD) is a X-linked rare lysosomal storage disorder caused by deficient α-galactosidase A (α-GalA) activity. Early diagnosis and the prediction of disease course are complicated by the clinical heterogeneity of FD, as well as by the frequently inconclusive biochemical and genetic test results that do not correlate with clinical course. We sought to identify potential biomarkers of FD to better understand the underlying pathophysiology and clinical phenotypes. We compared the plasma proteomes of 50 FD patients and 50 matched healthy controls using DDA and SWATH-MS. The &gt;30 proteins that were differentially expressed between the 2 groups included proteins implicated in processes such as inflammation, heme and haemoglobin metabolism, oxidative stress, coagulation, complement cascade, glucose and lipid metabolism, and glycocalyx formation. Stratification by sex revealed that certain proteins were differentially expressed in a sex-dependent manner. Apolipoprotein A-IV was upregulated in FD patients with complications, especially those with chronic kidney disease, and apolipoprotein C-III and fetuin-A were identified as possible markers of FD with left ventricular hypertrophy. All these proteins had a greater capacity to identify the presence of complications in FD patients than lyso-GB3, with apolipoprotein A-IV standing out as being more sensitive and effective in differentiating the presence and absence of chronic kidney disease in FD patients than renal markers such as creatinine, glomerular filtration rate and microalbuminuria. Identification of these potential biomarkers can help further our understanding of the pathophysiological processes that underlie the heterogeneous clinical manifestations associated with FD.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"269 ","pages":"Pages 47-63"},"PeriodicalIF":7.8,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1931524424000355/pdfft?md5=4c1c56c43c568fdd3271b34a5dc691dd&pid=1-s2.0-S1931524424000355-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139921869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Guidelines","authors":"","doi":"10.1016/S1931-5244(24)00024-0","DOIUrl":"https://doi.org/10.1016/S1931-5244(24)00024-0","url":null,"abstract":"","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"265 ","pages":"Pages A3-A4"},"PeriodicalIF":7.8,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139700386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nebulized platelet-derived extracellular vesicles attenuate chronic cigarette smoke-induced murine emphysema","authors":"Weixia Xuan ,&nbsp;Shaohua Wang ,&nbsp;Amarilys Alarcon-Calderon ,&nbsp;Monique Simone Bagwell ,&nbsp;Rachel Para ,&nbsp;Faping Wang ,&nbsp;Chujie Zhang ,&nbsp;Xue Tian ,&nbsp;Paul Stalboerger ,&nbsp;Timothy Peterson ,&nbsp;Michael S. Sabbah ,&nbsp;Zeji Du ,&nbsp;Tiffany Sarrafian ,&nbsp;Ryan Mahlberg ,&nbsp;Matthew L. Hillestad ,&nbsp;Skylar A. Rizzo ,&nbsp;Christopher R. Paradise ,&nbsp;Atta Behfar ,&nbsp;Robert Vassallo","doi":"10.1016/j.trsl.2024.02.001","DOIUrl":"10.1016/j.trsl.2024.02.001","url":null,"abstract":"<div><p>Chronic obstructive pulmonary disease (COPD) is a prevalent lung disease usually resulting from cigarette smoking (CS). Cigarette smoking induces oxidative stress, which causes inflammation and alveolar epithelial cell apoptosis and represents a compelling therapeutic target for COPD. Purified human platelet-derived exosome product (PEP) is endowed with antioxidant enzymes and immunomodulatory molecules that mediate tissue repair. In this study, a murine model of CS-induced emphysema was used to determine whether nebulized PEP can influence the development of CS-induced emphysema through the mitigation of oxidative stress and inflammation in the lung. Nebulization of PEP effectively delivered the PEP vesicles into the alveolar region, with evidence of their uptake by type I and type II alveolar epithelial cells and macrophages. Lung function testing and morphometric assessment showed a significant attenuation of CS-induced emphysema in mice treated with nebulized PEP thrice weekly for 4 weeks. Whole lung immuno-oncology RNA sequencing analysis revealed that PEP suppressed several CS-induced cell injuries and inflammatory pathways. Validation of inflammatory cytokines and apoptotic protein expression on the lung tissue revealed that mice treated with PEP had significantly lower levels of S100A8/A9 expressing macrophages, higher levels of CD4+/FOXP3+ Treg cells, and reduced NF-κB activation, inflammatory cytokine production, and apoptotic proteins expression. Further validation using <em>in vitro</em> cell culture showed that pretreatment of alveolar epithelial cells with PEP significantly attenuated CS extract-induced apoptotic cell death. These data show that nebulization of exosomes like PEP can effectively deliver exosome cargo into the lung, mitigate CS-induced emphysema in mice, and suppress oxidative lung injury, inflammation, and apoptotic alveolar epithelial cell death.</p></div>","PeriodicalId":23226,"journal":{"name":"Translational Research","volume":"269 ","pages":"Pages 76-93"},"PeriodicalIF":7.8,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139704323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}