Stem Cell Reviews and Reports最新文献

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Patient-Derived Organoids: A Game-Changer in Personalized Cancer Medicine. 源自患者的器官组织:改变个性化癌症医学的游戏规则。
IF 4.5 3区 医学
Stem Cell Reviews and Reports Pub Date : 2024-10-21 DOI: 10.1007/s12015-024-10805-4
Mohammad Hadi Abbasian, Navid Sobhani, Mahsa Mollapour Sisakht, Alberto D'Angelo, Marianna Sirico, Raheleh Roudi
{"title":"Patient-Derived Organoids: A Game-Changer in Personalized Cancer Medicine.","authors":"Mohammad Hadi Abbasian, Navid Sobhani, Mahsa Mollapour Sisakht, Alberto D'Angelo, Marianna Sirico, Raheleh Roudi","doi":"10.1007/s12015-024-10805-4","DOIUrl":"https://doi.org/10.1007/s12015-024-10805-4","url":null,"abstract":"<p><p>Research on cancer therapies has benefited from predictive tools capable of simulating treatment response and other disease characteristics in a personalized manner, in particular three-dimensional cell culture models. Such models include tumor-derived spheroids, multicellular spheroids including organotypic multicellular spheroids, and tumor-derived organoids. Additionally, organoids can be grown from various cancer cell types, such as pluripotent stem cells and induced pluripotent stem cells, progenitor cells, and adult stem cells. Although patient-derived xenografts and genetically engineered mouse models replicate human disease in vivo, organoids are less expensive, less labor intensive, and less time-consuming, all-important aspects in high-throughput settings. Like in vivo models, organoids mimic the three-dimensional structure, cellular heterogeneity, and functions of primary tissues, with the advantage of representing the normal oxygen conditions of patient organs. In this review, we summarize the use of organoids in disease modeling, drug discovery, toxicity testing, and precision oncology. We also summarize the current clinical trials using organoids.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Correction: Current Landscape of iPSC Haplobanks. 更正:iPSC 单倍体库的现状。
IF 4.5 3区 医学
Stem Cell Reviews and Reports Pub Date : 2024-10-18 DOI: 10.1007/s12015-024-10804-5
Rubén Escribá, Meral Beksac, Annelise Bennaceur-Griscelli, Joel C Glover, Satu Koskela, Helen Latsoudis, Sergi Querol, Belén Alvarez-Palomo
{"title":"Correction: Current Landscape of iPSC Haplobanks.","authors":"Rubén Escribá, Meral Beksac, Annelise Bennaceur-Griscelli, Joel C Glover, Satu Koskela, Helen Latsoudis, Sergi Querol, Belén Alvarez-Palomo","doi":"10.1007/s12015-024-10804-5","DOIUrl":"10.1007/s12015-024-10804-5","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Mitochondria's Role in the Maintenance of Cancer Stem Cells in Hepatocellular Carcinoma. 线粒体在肝细胞癌中维持癌干细胞的作用
IF 4.5 3区 医学
Stem Cell Reviews and Reports Pub Date : 2024-10-18 DOI: 10.1007/s12015-024-10797-1
Manar A Elhinnawi, Michael Ibrahim Boushra, Donia Mohamed Hussien, Fatema Hesham Hussein, Islam Ahmed Abdelmawgood
{"title":"Mitochondria's Role in the Maintenance of Cancer Stem Cells in Hepatocellular Carcinoma.","authors":"Manar A Elhinnawi, Michael Ibrahim Boushra, Donia Mohamed Hussien, Fatema Hesham Hussein, Islam Ahmed Abdelmawgood","doi":"10.1007/s12015-024-10797-1","DOIUrl":"https://doi.org/10.1007/s12015-024-10797-1","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the predominant form of liver cancer and is recognized as a major contributor to cancer-related mortality worldwide. Cancer stem cells (CSCs) are a tiny group of cancer cells that possess a significant ability to regenerate themselves, form tumors, and undergo differentiation. CSCs have a pivotal role in the initiation, spread, recurrence, and resistance to treatment of cancer. As a result, they are very susceptible to being targeted for therapeutic intervention. The potential to cure HCC may be achieved by efficiently targeting drugs that eradicate cancer stem cells. Mitochondria have a crucial function in granting drug resistance to cancer stem cells by means of mitochondrial metabolism, biogenesis, and dynamics. Dysfunction in mitochondrial metabolic processes, such as mitochondrial oxidative phosphorylation (OXPHOS), calcium signaling, and reactive oxygen species (ROS) generation, contributes to the initiation and progression of human malignancies, including HCC. ROS have both beneficial and detrimental effects depending on their concentration. Consequently, ROS have become a prominent subject in the study of the fundamental mechanisms of HCC. Furthermore, an imbalance in the process of creating new mitochondria is a characteristic feature of CSCs, and an increase in mitochondrial biogenesis is associated with the heightened resistance observed in CSCs. This article provides a detailed examination of the involvement of mitochondria in the preservation of CSCs, as well as the spread of HCC. A deeper understanding of how mitochondria participate in tumorigenesis and drug resistance could result in the discovery of novel cancer treatments.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Retinal Organoids from Induced Pluripotent Stem Cells of Patients with Inherited Retinal Diseases: A Systematic Review. 遗传性视网膜疾病患者的诱导多能干细胞视网膜组织细胞:系统综述。
IF 4.5 3区 医学
Stem Cell Reviews and Reports Pub Date : 2024-10-18 DOI: 10.1007/s12015-024-10802-7
Yoo Jin Lee, Dong Hyun Jo
{"title":"Retinal Organoids from Induced Pluripotent Stem Cells of Patients with Inherited Retinal Diseases: A Systematic Review.","authors":"Yoo Jin Lee, Dong Hyun Jo","doi":"10.1007/s12015-024-10802-7","DOIUrl":"https://doi.org/10.1007/s12015-024-10802-7","url":null,"abstract":"<p><strong>Background: </strong>Currently, most inherited retinal diseases lack curative interventions, and available treatment modalities are constrained to symptomatic approaches. Retinal organoid technology has emerged as a method for treating inherited retinal diseases, with growing academic interest in recent years. The purpose of this review was to systematically organize the current protocols for generating retinal organoids using induced pluripotent stem cells from patients with inherited retinal disease and to investigate the application of retinal organoids in inherited retinal disease research.</p><p><strong>Methods: </strong>Data were collected from the PubMed, Scopus, and Web of Science databases using a keyword search. The main search term used was \"retinal organoid,\" accompanied by secondary keywords such as \"optic cup,\" \"three-dimensional,\" and \"self-organizing.\" The final search was conducted on October 2, 2024.</p><p><strong>Results: </strong>Of the 2,129 studies retrieved, 130 were included in the qualitative synthesis. The protocols for the generation of retinal organoids in inherited retinal disease research use five major approaches, categorized into 3D and a combination of 2D/3D approaches, implemented with modifications. Disease phenotypes have been successfully reproduced via the generation of retinal organoids from the induced pluripotent stem cells of individuals with inherited retinal diseases, facilitating the progression of research into novel therapeutic developments. Cells have been obtained from retinal organoids for cell therapy, and progress toward their potential integration into clinical practice is underway. Considering their potential applications, retinal organoid technology has shown promise across various domains.</p><p><strong>Conclusion: </strong>In this systematic review, we organized protocols for generating retinal organoids using induced pluripotent stem cells from patients with inherited retinal diseases. Retinal organoid technology has various applications including disease modeling, screening for novel therapies, and cell replacement therapy. Further advancements would make this technology a clinically significant tool for patients with inherited retinal diseases.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Influence of Microenvironmental Orchestration on Multicellular Lung Alveolar Organoid Development from Human Induced Pluripotent Stem Cells. 微环境协调对人类诱导多能干细胞多细胞肺泡类器官发育的影响
IF 4.5 3区 医学
Stem Cell Reviews and Reports Pub Date : 2024-10-17 DOI: 10.1007/s12015-024-10789-1
Vedat Burak Ozan, Huijuan Wang, Akshay Akshay, Deepika Anand, Youssef Hibaoui, Anis Feki, Janine Gote-Schniering, Ali Hashemi Gheinani, Manfred Heller, Anne-Christine Uldry, Sophie Braga Lagache, Amiq Gazdhar, Thomas Geiser
{"title":"Influence of Microenvironmental Orchestration on Multicellular Lung Alveolar Organoid Development from Human Induced Pluripotent Stem Cells.","authors":"Vedat Burak Ozan, Huijuan Wang, Akshay Akshay, Deepika Anand, Youssef Hibaoui, Anis Feki, Janine Gote-Schniering, Ali Hashemi Gheinani, Manfred Heller, Anne-Christine Uldry, Sophie Braga Lagache, Amiq Gazdhar, Thomas Geiser","doi":"10.1007/s12015-024-10789-1","DOIUrl":"https://doi.org/10.1007/s12015-024-10789-1","url":null,"abstract":"<p><p>Induced pluripotent stem cells (iPSCs) have emerged as promising in vitro tools, providing a robust system for disease modelling and facilitating drug screening. Human iPSCs have been successfully differentiated into lung cells and three-dimensional lung spheroids or organoids. The lung is a multicellular complex organ that develops under the symphonic influence of the microenvironment. Here, we hypothesize that the generation of lung organoids in a controlled microenvironment (cmO) (oxygen and pressure) yields multicellular organoids with architectural complexity resembling the lung alveoli. iPSCs were differentiated into mature lung organoids following a stepwise protocol in an oxygen and pressure-controlled microenvironment. The organoids developed in the controlled microenvironment displayed complex alveolar architecture and stained for SFTPC, PDPN, and KRT5, indicating the presence of alveolar epithelial type II and type I cells, as well as basal cells. Moreover, gene and protein expression levels were also increased in the cmO. Furthermore, pathway analysis of proteomics revealed upregulation of lung development-specific pathways in the cmO compared to those growing in normal culture conditions. In summary, by using a controlled microenvironment, we established a complex multicellular lung organoid derived from iPSCs as a novel cellular model to study lung alveolar biology in both lung health and disease.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Biological Scaffolds in 3D Cell Models: Driving Innovation in Drug Discovery. 三维细胞模型中的生物支架:推动药物发现的创新。
IF 4.5 3区 医学
Stem Cell Reviews and Reports Pub Date : 2024-10-10 DOI: 10.1007/s12015-024-10800-9
Raj Dave, Kshipra Pandey, Ritu Patel, Nidhi Gour, Dhiraj Bhatia
{"title":"Biological Scaffolds in 3D Cell Models: Driving Innovation in Drug Discovery.","authors":"Raj Dave, Kshipra Pandey, Ritu Patel, Nidhi Gour, Dhiraj Bhatia","doi":"10.1007/s12015-024-10800-9","DOIUrl":"https://doi.org/10.1007/s12015-024-10800-9","url":null,"abstract":"<p><p>The discipline of 3D cell modeling is currently undergoing a surge of captivating developments that are enhancing the realism and utility of tissue simulations. Using bioinks which represent cells, scaffolds, and growth factors scientists can construct intricate tissue architectures layer by layer using innovations like 3D bioprinting. Drug testing can be accelerated and organ functions more precisely replicated owing to the precise control that microfluidic technologies and organ-on-chip devices offer over the cellular environment. Tissue engineering is becoming more dynamic with materials that can modify their surroundings with the advent of hydrogels and smart biomaterials. Advances in spheroids and organoids are not only bringing us towards more effective and customized therapies, but they are also improving their ability to resemble actual human tissues. Confocal and two-photon microscopy are examples of advanced imaging methods that provide precise images of the functioning and interaction of cells. Artificial Intelligence models have applications for enhanced scaffold designs and for predicting the response of tissues to medications. Furthermore, via strengthening predictive models, optimizing data analysis, and simplifying 3D cell culture design, artificial intelligence is revolutionizing this field. When combined, these technologies are improving our ability to conduct research and moving us toward more individualized and effective medical interventions.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Advanced Therapeutic Strategies for Oral Submucous Fibrosis through Stem Cell Therapy. 通过干细胞疗法治疗口腔黏膜下纤维化的先进治疗策略。
IF 4.5 3区 医学
Stem Cell Reviews and Reports Pub Date : 2024-10-10 DOI: 10.1007/s12015-024-10801-8
Manoj Kumar Karuppan Perumal, Sava Nanda Gopal, Remya Rajan Renuka, Suresh Kumar Subbiah
{"title":"Advanced Therapeutic Strategies for Oral Submucous Fibrosis through Stem Cell Therapy.","authors":"Manoj Kumar Karuppan Perumal, Sava Nanda Gopal, Remya Rajan Renuka, Suresh Kumar Subbiah","doi":"10.1007/s12015-024-10801-8","DOIUrl":"https://doi.org/10.1007/s12015-024-10801-8","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Global Knowledge Map and Emerging Research Trends in Induced Pluripotent Stem Cells and Hereditary Diseases: A CiteSpace-based Visualization and Analysis. 诱导多能干细胞和遗传性疾病的全球知识地图和新兴研究趋势:基于 CiteSpace 的可视化和分析。
IF 4.5 3区 医学
Stem Cell Reviews and Reports Pub Date : 2024-10-08 DOI: 10.1007/s12015-024-10799-z
Jiajun Xu, Weiwei Gong, Chune Mo, Xianliang Hou, Minglin Ou
{"title":"Global Knowledge Map and Emerging Research Trends in Induced Pluripotent Stem Cells and Hereditary Diseases: A CiteSpace-based Visualization and Analysis.","authors":"Jiajun Xu, Weiwei Gong, Chune Mo, Xianliang Hou, Minglin Ou","doi":"10.1007/s12015-024-10799-z","DOIUrl":"https://doi.org/10.1007/s12015-024-10799-z","url":null,"abstract":"<p><p>The rise of induced pluripotent stem cells (iPSCs) technology has ushered in a landmark shift in the study of hereditary diseases. However, there is a scarcity of reports that offer a comprehensive and objective overview of the current state of research at the intersection of iPSCs and hereditary diseases. Therefore, this study endeavors to categorize and synthesize the publications in this field over the past decade through bibliometric methods and visual knowledge mapping, aiming to visually analyze their research focus and clinical trends. The English language literature on iPSCs and hereditary diseases, published from 2014 to 2023 in the Web of Science Core Collection (WoSCC), was examined. The CiteSpace (version 6.3.R1) software was utilized to visualize and analyze country/region, institution, scholar, co-cited authors, and co-cited journals. Additionally, the co-occurrence, clustering, and bursting of co-cited references were displayed. Analysis of 347 articles that met the inclusion criteria revealed a steady increase in the number of published articles and citation frequency in the field over the past decade. With regard to the countries/regions, institutions, scholars, and journals where the articles were published, the highest numbers were found in the USA, the University of California System, Suren M. Zakian, and Stem Cell Research, respectively. The current research is focused on the construction of disease models, both before and after correction, as well as drug target testing for single-gene hereditary diseases. Chromosome transplantation genomic therapy for hereditary diseases with abnormal chromosome structures may emerge as a future research hotspot in this field.</p>","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Cirrhotic Patients Exhibit Remarkable Vascular Regenerative Profile One Month after Liver Transplantation. 肝硬化患者在肝移植一个月后表现出明显的血管再生特征
IF 4.5 3区 医学
Stem Cell Reviews and Reports Pub Date : 2024-10-08 DOI: 10.1007/s12015-024-10796-2
Daniel Eyraud, Aurélien Philippe, Coralie Guerin, Ignacio Sarmiento, Ludovic Suner, Louis Puybasset, Sébastien Bertil, Jean-Christophe Vaillant, Dominique Helley, Benjamin Granger, David M Smadja, Pascale Gaussem
{"title":"Cirrhotic Patients Exhibit Remarkable Vascular Regenerative Profile One Month after Liver Transplantation.","authors":"Daniel Eyraud, Aurélien Philippe, Coralie Guerin, Ignacio Sarmiento, Ludovic Suner, Louis Puybasset, Sébastien Bertil, Jean-Christophe Vaillant, Dominique Helley, Benjamin Granger, David M Smadja, Pascale Gaussem","doi":"10.1007/s12015-024-10796-2","DOIUrl":"https://doi.org/10.1007/s12015-024-10796-2","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Atraric Acid Induces Hair Growth through the Stimulation of Sonic Hedgehog/GLI1 in Human Dermal Papilla Cells. 阿曲酸通过刺激人真皮乳头细胞中的Sonic Hedgehog/GLI1诱导毛发生长
IF 4.5 3区 医学
Stem Cell Reviews and Reports Pub Date : 2024-10-03 DOI: 10.1007/s12015-024-10798-0
Sultan Pulat, Wonyong Kim, Jee-Hyun Hwang, Rui Zhou, Chathurika D B Gamage, Mücahit Varlı, İsa Taş, Yi Yang, So-Yeon Park, Kyung-Min Lim, Jae-Seoun Hur, Hangun Kim
{"title":"Atraric Acid Induces Hair Growth through the Stimulation of Sonic Hedgehog/GLI1 in Human Dermal Papilla Cells.","authors":"Sultan Pulat, Wonyong Kim, Jee-Hyun Hwang, Rui Zhou, Chathurika D B Gamage, Mücahit Varlı, İsa Taş, Yi Yang, So-Yeon Park, Kyung-Min Lim, Jae-Seoun Hur, Hangun Kim","doi":"10.1007/s12015-024-10798-0","DOIUrl":"https://doi.org/10.1007/s12015-024-10798-0","url":null,"abstract":"","PeriodicalId":21955,"journal":{"name":"Stem Cell Reviews and Reports","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
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