Journal of Clinical Investigation最新文献

{"title":"Whole-exome sequencing association study reveals genetic effects on tumor microenvironment components in nasopharyngeal carcinoma.","authors":"Yanni Zeng, Chun-Ling Luo, Guo-Wang Lin, Fugui Li, Xiaomeng Bai, Josephine Mun-Yee Ko, Lei Xiong, Yang Liu, Shuai He, Jia-Xin Jiang, Wen-Xin Yan, Enya Hui Wen Ong, Zheng Li, Ya-Qing Zhou, Yun-He Zhou, An-Yi Xu, Shu-Qiang Liu, Yun-Miao Guo, Jie-Rong Chen, Xi-Xi Cheng, Yu-Lu Cao, Xia Yu, Biaohua Wu, Pan-Pan Wei, Zhao-Hui Ruan, Qiu-Yan Chen, Lin-Quan Tang, James D McKay, Wei-Hua Jia, Hai-Qiang Mai, Soon Thye Lim, Jian-Jun Liu, Dong-Xin Lin, Chiea Chuen Khor, Melvin Lee Kiang Chua, Mingfang Ji, Maria Li Lung, Yi-Xin Zeng, Jin-Xin Bei","doi":"10.1172/JCI182768","DOIUrl":"10.1172/JCI182768","url":null,"abstract":"<p><p>Nasopharyngeal carcinoma (NPC) presents a substantial clinical challenge due to the limited understanding of its genetic underpinnings. Here we conduct the largest scale whole-exome sequencing association study of NPC to date, encompassing 6,969 NPC cases and 7,100 controls. We unveil 3 germline genetic variants linked to NPC susceptibility: a common rs2276868 in RPL14, a rare rs5361 in SELE, and a common rs1050462 in HLA-B. We also underscore the critical impact of rare genetic variants on NPC heritability and introduce a refined composite polygenic risk score (rcPRS), which outperforms existing models in predicting NPC risk. Importantly, we reveal that the polygenic risk for NPC is mediated by EBV infection status. Utilizing a comprehensive multiomics approach that integrates both bulk-transcriptomic (n = 356) and single-cell RNA sequencing (n = 56) data with experimental validations, we demonstrate that the RPL14 variant modulates the EBV life cycle and NPC pathogenesis. Furthermore, our data indicate that the SELE variant contributes to modifying endothelial cell function, thereby facilitating NPC progression. Collectively, our study provides crucial insights into the intricate genetic architecture of NPC, spotlighting the vital interplay between genetic variations and tumor microenvironment components, including EBV and endothelial cells, in predisposing to NPC. This study opens new avenues for advancements in personalized risk assessments, early diagnosis, and targeted therapies for NPC.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clonal hematopoiesis JAKs up plaque formation.","authors":"Koral Campbell, Qing Li","doi":"10.1172/JCI187529","DOIUrl":"10.1172/JCI187529","url":null,"abstract":"<p><p>Clonal hematopoiesis (CH) is a condition in which hematopoietic stem cells (HSCs) acquire mutations seen in leukemia. While individuals with CH generally do not show signs of hematologic disease, the condition becomes more common with age and correlates with age-related diseases, especially cardiovascular disease (CVD). JAK2 mutations in HSCs can lead to CH and correlate with atherosclerosis, but the condition has been difficult to study because of challenges modeling the mutant cells at very low frequency. In this issue of the JCI, Liu et al. developed a low-allele-burden (LAB) mouse model in which a small number of bone marrow cells carrying the Jak2VF mutation were transplanted into mice predisposed to hyperlipidemia. Along with recapitulating features of plaque development, the authors identified the phagocytic receptors MERTK and TREM2 in WT cells as downstream of the inflammatory cytokine IL-1. These findings provide potential targets for preventing or treating patients at risk for CH-associated CVD.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684796/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neonatal T cells unleash innate powers to combat congenital cytomegalovirus infection.","authors":"Simon Grassmann","doi":"10.1172/JCI187789","DOIUrl":"10.1172/JCI187789","url":null,"abstract":"<p><p>Approximately 1 in 200 newborns worldwide are affected by congenital cytomegalovirus (CMV). Most of these cases are asymptomatic due to successful control of the infection by the newborn's immune system. In this issue of the JCI, Semmes et al. characterized the cellular immune response in cord blood of neonates with CMV infection. The authors found that conventional T cells with NK-like features expanded during congenital CMV infection. To exert their antiviral function, these cells relied on Fc receptors, recognizing virus-infected cells bound by IgG. Thereby, the fetal and maternal immune system can optimally cooperate to control CMV infection: maternal IgG crossing the placenta opsonizes virus-infected cells subsequently lysed by neonatal NK-like T cells. This finding suggests that innate-like programming of conventional T cells may have evolved to combat congenital CMV infection, offering insights that could inform the development of future therapies.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Type 2 immunity to the rescue: enhancing antitumor immunity for skin cancer prevention.","authors":"Matthew D Vesely, Sean R Christensen","doi":"10.1172/JCI188018","DOIUrl":"10.1172/JCI188018","url":null,"abstract":"<p><p>Cutaneous squamous cell carcinoma (cSCC) incidence and deaths continue to rise, underscoring the need for improved cSCC prevention. Elimination of actinic keratosis (AK) precursor lesions is a major strategy to prevent cSCC. Topical calcipotriol and 5-fluorouracil (5-FU) have been shown to eliminate AKs and reduce the risk of cSCC development, but the mechanism was undefined. In this issue of the JCI, Oka et al. demonstrate that type 2 immunity is necessary and sufficient for the elimination of premalignant keratinocytes and cSCC prevention. Paired biopsies from AK lesions and unaffected skin revealed that only keratinocytes from AKs produced thymic stromal lymphopoietin (TSLP) and damage-associated molecular patterns, resulting in selective recruitment of Th2 cells to the AK lesion. In mouse models of skin carcinogenesis, TSLP was necessary to recruit Th2 cells and trigger IL-24-mediated keratinocyte cell death. These findings suggest that the TSLP/Th2/IL-24 axis is a potential therapeutic target for SCC prevention.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATRX silences Cartpt expression in osteoblastic cells during skeletal development.","authors":"Yi-Ting Chen, Ming-Ming Jiang, Carolina Leynes, Mary Adeyeye, Camilla F Majano, Barakat Ibrahim, Urszula Polak, George Hung, Zixue Jin, Denise G Lanza, Lan Liao, Brian Dawson, Yuqing Chen-Evenson, Oscar E Ruiz, Richard J Gibbons, Jason D Heaney, Yangjin Bae, Brendan Lee","doi":"10.1172/JCI163587","DOIUrl":"10.1172/JCI163587","url":null,"abstract":"<p><p>ATP-dependent chromatin remodeling protein ATRX is an essential regulator involved in maintenance of DNA structure and chromatin state and regulation of gene expression during development. ATRX was originally identified as the monogenic cause of X-linked α-thalassemia mental retardation (ATR-X) syndrome. Affected individuals display a variety of developmental abnormalities and skeletal deformities. Studies from others investigated the role of ATRX in skeletal development by tissue-specific Atrx knockout. However, the impact of ATRX during early skeletal development has not been examined. Using preosteoblast-specific Atrx conditional knockout mice, we observed increased trabecular bone mass and decreased osteoclast number in bone. In vitro coculture of Atrx conditional knockout bone marrow stromal cells (BMSCs) with WT splenocytes showed impaired osteoclast differentiation. Additionally, Atrx deletion was associated with decreased receptor activator of nuclear factor κ-B ligand (Rankl)/ osteoprotegerin (Opg) expression ratio in BMSCs. Notably, Atrx-deficient osteolineage cells expressed high levels of the neuropeptide cocaine- and amphetamine-regulated transcript prepropeptide (Cartpt). Mechanistically, ATRX suppresses Cartpt transcription by binding to the promoter, which is otherwise poised for Cartpt expression by RUNX2 binding to the distal enhancer. Finally, Cartpt silencing in Atrx conditional knockout BMSCs rescued the molecular phenotype by increasing the Rankl/Opg expression ratio. Together, our data show a potent repressor function of ATRX in restricting Cartpt expression during skeletal development.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiac fibroblast BAG3 regulates TGFBR2 signaling and fibrosis in dilated cardiomyopathy.","authors":"Bryan Z Wang, Margaretha Aj Morsink, Seong Won Kim, Lori J Luo, Xiaokan Zhang, Rajesh Kumar Soni, Roberta I Lock, Jenny Rao, Youngbin Kim, Anran Zhang, Meraj Neyazi, Joshua M Gorham, Yuri Kim, Kemar Brown, Daniel M DeLaughter, Qi Zhang, Barbara McDonough, Josephine M Watkins, Katherine M Cunningham, Gavin Y Oudit, Barry M Fine, Christine E Seidman, Jonathan G Seidman, Gordana Vunjak-Novakovic","doi":"10.1172/JCI181630","DOIUrl":"10.1172/JCI181630","url":null,"abstract":"<p><p>Loss of Bcl2-associated athanogene 3 (BAG3) is associated with dilated cardiomyopathy (DCM). BAG3 regulates sarcomere protein turnover in cardiomyocytes; however, the function of BAG3 in other cardiac cell types is understudied. In this study, we used an isogenic pair of BAG3-knockout and wild-type human induced pluripotent stem cells (hiPSCs) to interrogate the role of BAG3 in hiPSC-derived cardiac fibroblasts (CFs). Analysis of cell type-specific conditional knockout engineered heart tissues revealed an essential contribution of CF BAG3 to contractility and cardiac fibrosis, recapitulating the phenotype of DCM. In BAG3-/- CFs, we observed an increased sensitivity to TGF-β signaling and activation of a fibrogenic response when cultured at physiological stiffness (8 kPa). Mechanistically, we showed that loss of BAG3 increased transforming growth factor-β receptor 2 (TGFBR2) levels by directly binding TGFBR2 and mediating its ubiquitination and proteasomal degradation. To further validate these results, we performed single-nucleus RNA sequencing of cardiac tissue from DCM patients carrying pathogenic BAG3 variants. BAG3 pathogenic variants increased fibrotic gene expression in CFs. Together, these results extend our understanding of the roles of BAG3 in heart disease beyond the cardiomyocyte-centric view and highlight the ability of tissue-engineered hiPSC models to elucidate cell type-specific aspects of cardiac disease.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A single-cell compendium of human cerebrospinal fluid identifies disease-associated immune cell populations.","authors":"Claudia Cantoni, Roman A Smirnov, Maria Firulyova, Prabhakar S Andhey, Tara R Bradstreet, Ekaterina Esaulova, Marina Terekhova, Elizabeth A Schwarzkopf, Nada M Abdalla, Maksim Kleverov, Joseph J Sabatino, Kang Liu, Nicholas Schwab, Gerd Meyer Zu Hörste, Anne H Cross, Maxim N Artyomov, Brian T Edelson, Gregory F Wu","doi":"10.1172/JCI177793","DOIUrl":"10.1172/JCI177793","url":null,"abstract":"<p><p>Single-cell transcriptomics applied to cerebrospinal fluid (CSF) for elucidating the pathophysiology of neurologic diseases has produced only a preliminary characterization of CSF immune cells. CSF derives from and borders central nervous system (CNS) tissue, allowing for comprehensive accounting of cell types along with their relative abundance and immunologic profiles relevant to CNS diseases. Using integration techniques applied to publicly available datasets in combination with our own studies, we generated a compendium with 139 subjects encompassing 135 CSF and 58 blood samples. Healthy subjects and individuals across a wide range of diseases, such as multiple sclerosis (MS), Alzheimer's disease, Parkinson's disease, COVID-19, and autoimmune encephalitis, were included. We found differences in lymphocyte and myeloid subset frequencies across different diseases as well as in their distribution between blood and CSF. We identified what we believe to be a new subset of AREG+ dendritic cells exclusive to the CSF that was more abundant in subjects with MS compared with healthy controls. Finally, transcriptional cell states in CSF microglia-like cells and lymphoid subsets were elucidated. Altogether, we have created a reference compendium for single-cell transcriptional profiling encompassing CSF immune cells useful to the scientific community for future studies on neurologic diseases.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human intraepithelial mast cell differentiation and effector function are directed by TGF-β signaling.","authors":"Tahereh Derakhshan, Eleanor Hollers, Alex Perniss, Tessa Ryan, Alanna McGill, Jonathan Hacker, Regan W Bergmark, Neil Bhattacharyya, Stella E Lee, Alice Z Maxfield, Rachel E Roditi, Lora Bankova, Kathleen M Buchheit, Tanya M Laidlaw, Joshua A Boyce, Daniel F Dwyer","doi":"10.1172/JCI174981","DOIUrl":"10.1172/JCI174981","url":null,"abstract":"<p><p>Mast cells (MCs) expressing a distinctive protease phenotype (MCTs) selectively expand within the epithelium of human mucosal tissues during type 2 (T2) inflammation. While MCTs are phenotypically distinct from subepithelial MCs (MCTCs), signals driving human MCT differentiation and this subset's contribution to inflammation remain unexplored. Here, we have identified TGF-β as a key driver of the MCT transcriptome in nasal polyps. We found that short-term TGF-β signaling alters MC cell surface receptor expression and partially recapitulated the in vivo MCT transcriptome, while TGF-β signaling during MC differentiation upregulated a larger number of MCT-associated transcripts. TGF-β inhibited the hallmark MCTC proteases chymase and cathepsin G at both the transcript and protein level, allowing selective in vitro differentiation of MCTs for functional study. We identified discrete differences in effector phenotype between in vitro-derived MCTs and MCTCs, with MCTs exhibiting enhanced proinflammatory lipid mediator generation and a distinct cytokine, chemokine, and growth factor production profile in response to both innate and adaptive stimuli, recapitulating functional features of their tissue-associated counterpart MC subsets. Thus, our findings support a role for TGF-β in promoting human MCT differentiation and identified a discrete contribution of this cell type to T2 inflammation.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MHC-related protein 1-restricted recognition of cancer via a semi-invariant TCR-α chain.","authors":"Garry Dolton, Hannah Thomas, Li Rong Tan, Cristina Rius Rafael, Stephanie Doetsch, Giulia-Andreea Ionescu, Lucia F Cardo, Michael D Crowther, Enas Behiry, Théo Morin, Marine E Caillaud, Devinder Srai, Lucia Parolini, Md Samiul Hasan, Anna Fuller, Katie Topley, Aaron Wall, Jade R Hopkins, Nader Omidvar, Caroline Alvares, Joanna Zabkiewicz, John Frater, Barbara Szomolay, Andrew K Sewell","doi":"10.1172/JCI181895","DOIUrl":"10.1172/JCI181895","url":null,"abstract":"<p><p>The T cell antigen presentation platform MR1 consists of 6 allomorphs in humans that differ by no more than 5 amino acids. The principal function of this highly conserved molecule involves presenting microbial metabolites to the abundant mucosal-associated invariant T (MAIT) cell subset. Recent developments suggest that the role of MR1 extends to presenting antigens from cancer cells, a function dependent on the K43 residue in the MR1 antigen binding cleft. Here, we successfully cultured cancer-activated, MR1-restricted T cells from multiple donors and confirmed that they recognized a wide range of cancer types expressing the most common MR1*01 and/or MR1*02 allomorphs (over 95% of the population), while remaining inert to healthy cells including healthy B cells and monocytes. Curiously, in all but one donor these T cells were found to incorporate a conserved TCR-α chain motif, CAXYGGSQGNLIF (where X represents 3-5 amino acids), because of pairing between 10 different TRAV genes and the TRAJ42 gene segment. This semi-invariance in the TCR-α chain is reminiscent of MAIT cells and suggests recognition of a conserved antigen bound to K43.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A vaccine against cytomegalovirus: how close are we?","authors":"Sallie R Permar, Mark R Schleiss, Stanley A Plotkin","doi":"10.1172/JCI182317","DOIUrl":"10.1172/JCI182317","url":null,"abstract":"<p><p>The pursuit of a vaccine against the human cytomegalovirus (HCMV) has been ongoing for more than 50 years. HCMV is the leading infectious cause of birth defects, including damage to the brain, and is a common cause of complications in organ transplantation. The complex biology of HCMV has made vaccine development difficult, but a recent meeting sponsored by the National Institute of Allergy and Infectious Diseases in September of 2023 brought together experts from academia, industry, and federal agencies to discuss progress in the field. The meeting reviewed the status of candidate HCMV vaccines under study and the challenges in clinical trial design in demonstrating efficacy against congenital CMV infection or the reduction of HCMV disease following solid organ transplantation or hematopoietic stem cell transplantation. Discussion in the meeting revealed that, with the numerous candidate vaccines that are under study, it is clear that a safe and effective HCMV vaccine is within reach. Meeting attendees achieved a consensus opinion that even a partially effective vaccine would have a major effect on the global health consequences of HCMV infection.</p>","PeriodicalId":15469,"journal":{"name":"Journal of Clinical Investigation","volume":"135 1","pages":""},"PeriodicalIF":13.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11684802/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}