Pub Date : 2024-09-01Epub Date: 2024-06-08DOI: 10.1016/j.molmed.2024.05.010
Qiuyue Ma, Stefanie Steiger
Crystalline material can cause a multitude of acute and chronic inflammatory diseases, such as gouty arthritis, silicosis, kidney disease, and atherosclerosis. Crystals of various types are thought to cause similar inflammatory responses, including the release of proinflammatory mediators and formation of neutrophil extracellular traps (NETs), processes that further promote necroinflammation and tissue damage. It has become apparent that the intensity of inflammation and the related mechanisms of NET formation and neutrophil death in crystal-associated diseases can vary depending on the crystal type, amount, and site of deposition. This review details new mechanistic insights into crystal biology, highlights the differential effects of various crystals on neutrophils and extracellular trap (ET) formation, and discusses treatment strategies and potential future approaches for crystal-associated disorders.
晶体物质可引起多种急性和慢性炎症性疾病,如痛风性关节炎、矽肺、肾病和动脉粥样硬化。各种类型的晶体被认为会引起类似的炎症反应,包括释放促炎症介质和形成中性粒细胞胞外陷阱(NET),这些过程会进一步促进坏死性炎症和组织损伤。显而易见的是,晶体相关疾病的炎症强度以及 NET 形成和中性粒细胞死亡的相关机制会因晶体类型、数量和沉积部位的不同而不同。这篇综述详细介绍了晶体生物学的新机理,强调了各种晶体对中性粒细胞和细胞外陷阱(ET)形成的不同影响,并讨论了晶体相关疾病的治疗策略和未来的潜在方法。
{"title":"Neutrophils and extracellular traps in crystal-associated diseases.","authors":"Qiuyue Ma, Stefanie Steiger","doi":"10.1016/j.molmed.2024.05.010","DOIUrl":"10.1016/j.molmed.2024.05.010","url":null,"abstract":"<p><p>Crystalline material can cause a multitude of acute and chronic inflammatory diseases, such as gouty arthritis, silicosis, kidney disease, and atherosclerosis. Crystals of various types are thought to cause similar inflammatory responses, including the release of proinflammatory mediators and formation of neutrophil extracellular traps (NETs), processes that further promote necroinflammation and tissue damage. It has become apparent that the intensity of inflammation and the related mechanisms of NET formation and neutrophil death in crystal-associated diseases can vary depending on the crystal type, amount, and site of deposition. This review details new mechanistic insights into crystal biology, highlights the differential effects of various crystals on neutrophils and extracellular trap (ET) formation, and discusses treatment strategies and potential future approaches for crystal-associated disorders.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-08-14DOI: 10.1016/j.molmed.2024.06.001
Delfien Syx, Fransiska Malfait
The Ehlers-Danlos syndromes (EDS) are a group of rare heritable connective tissue disorders, common hallmarks of which are skin hyperextensibility, joint hypermobility, and generalized connective tissue fragility. Currently, 13 EDS types are recognized, caused by defects in 20 genes which consequently alter biosynthesis, organization, and/or supramolecular assembly of collagen fibrils in the extracellular matrix (ECM). Molecular analyses on patient samples (mostly dermal fibroblast cultures), combined with studies on animal models, have highlighted that part of EDS pathogenesis can be attributed to impaired cellular dynamics. Although our understanding of the full extent of (extra)cellular consequences is still limited, this narrative review aims to provide a comprehensive overview of our current knowledge on the extracellular, pericellular, and intracellular alterations implicated in EDS pathogenesis.
{"title":"Pathogenic mechanisms in genetically defined Ehlers-Danlos syndromes.","authors":"Delfien Syx, Fransiska Malfait","doi":"10.1016/j.molmed.2024.06.001","DOIUrl":"10.1016/j.molmed.2024.06.001","url":null,"abstract":"<p><p>The Ehlers-Danlos syndromes (EDS) are a group of rare heritable connective tissue disorders, common hallmarks of which are skin hyperextensibility, joint hypermobility, and generalized connective tissue fragility. Currently, 13 EDS types are recognized, caused by defects in 20 genes which consequently alter biosynthesis, organization, and/or supramolecular assembly of collagen fibrils in the extracellular matrix (ECM). Molecular analyses on patient samples (mostly dermal fibroblast cultures), combined with studies on animal models, have highlighted that part of EDS pathogenesis can be attributed to impaired cellular dynamics. Although our understanding of the full extent of (extra)cellular consequences is still limited, this narrative review aims to provide a comprehensive overview of our current knowledge on the extracellular, pericellular, and intracellular alterations implicated in EDS pathogenesis.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-01Epub Date: 2024-06-05DOI: 10.1016/j.molmed.2024.05.015
Jingjing Xu, Suowen Xu
As an endogenous immunometabolite, itaconate has excellent anti-inflammatory effects. However, it remains unknown whether itaconate protects against atherosclerosis. Two recent studies, by Song et al. and Cyr et al., revealed the emerging role of the aconitate decarboxylase 1/itaconate pathway in atherosclerosis.
{"title":"The emerging role of ACOD1/itaconate pathway in atherosclerosis.","authors":"Jingjing Xu, Suowen Xu","doi":"10.1016/j.molmed.2024.05.015","DOIUrl":"10.1016/j.molmed.2024.05.015","url":null,"abstract":"<p><p>As an endogenous immunometabolite, itaconate has excellent anti-inflammatory effects. However, it remains unknown whether itaconate protects against atherosclerosis. Two recent studies, by Song et al. and Cyr et al., revealed the emerging role of the aconitate decarboxylase 1/itaconate pathway in atherosclerosis.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141284855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-23DOI: 10.1016/j.molmed.2024.08.001
Karina Pereira-Lima, Srijan Sen
Resident physicians face intense stressors that significantly heighten their depression risk. This article discusses research findings on critical factors contributing to depression among resident physicians. Understanding these factors is essential to developing targeted interventions, fostering healthy work environments, and ultimately improving physician wellbeing and patient care.
{"title":"Resident physician depression: systemic challenges and possible solutions.","authors":"Karina Pereira-Lima, Srijan Sen","doi":"10.1016/j.molmed.2024.08.001","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.08.001","url":null,"abstract":"<p><p>Resident physicians face intense stressors that significantly heighten their depression risk. This article discusses research findings on critical factors contributing to depression among resident physicians. Understanding these factors is essential to developing targeted interventions, fostering healthy work environments, and ultimately improving physician wellbeing and patient care.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-23DOI: 10.1016/j.molmed.2024.07.013
Jiliang Xia, Hongyan Zhao, Jacob L Edmondson, Brian Koss, Fenghuang Zhan
Never in mitosis A (NIMA)-related kinase 2 (NEK2) is a serine/threonine kinase found in the nucleus and cytoplasm throughout the cell cycle. NEK2 is overexpressed in many cancers and is a biomarker of poor prognosis. Factors contributing to NEK2 elevation in cancer cells include oncogenic transcription factors, decreased ubiquitination, DNA methylation, and the circular RNA (circRNA)/long noncoding RNA (lncRNA)-miRNA axis. NEK2 overexpression produces chromosomal instability and aneuploidy, thereby enhancing cancer progression and suppressing antitumor immunity, which highlights the prominence of NEK2 in tumorigenesis and tumor progression. Small-molecule inhibitors targeting NEK2 have demonstrated promising therapeutic potential in vitro and in vivo across various cancer types. This review outlines the regulatory mechanisms of NEK2 expression, emphasizes its functional roles in cancer initiation and progression, and highlights the anticancer properties of NEK2 inhibitors.
{"title":"Role of NEK2 in tumorigenesis and tumor progression.","authors":"Jiliang Xia, Hongyan Zhao, Jacob L Edmondson, Brian Koss, Fenghuang Zhan","doi":"10.1016/j.molmed.2024.07.013","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.07.013","url":null,"abstract":"<p><p>Never in mitosis A (NIMA)-related kinase 2 (NEK2) is a serine/threonine kinase found in the nucleus and cytoplasm throughout the cell cycle. NEK2 is overexpressed in many cancers and is a biomarker of poor prognosis. Factors contributing to NEK2 elevation in cancer cells include oncogenic transcription factors, decreased ubiquitination, DNA methylation, and the circular RNA (circRNA)/long noncoding RNA (lncRNA)-miRNA axis. NEK2 overexpression produces chromosomal instability and aneuploidy, thereby enhancing cancer progression and suppressing antitumor immunity, which highlights the prominence of NEK2 in tumorigenesis and tumor progression. Small-molecule inhibitors targeting NEK2 have demonstrated promising therapeutic potential in vitro and in vivo across various cancer types. This review outlines the regulatory mechanisms of NEK2 expression, emphasizes its functional roles in cancer initiation and progression, and highlights the anticancer properties of NEK2 inhibitors.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-23DOI: 10.1016/j.molmed.2024.07.010
Katlyn C Richardson, Karen Jung, Joanne A Matsubara, Jonathan C Choy, David J Granville
Aging is a major risk factor for pathologies that manifest later in life. Much attention is devoted towards elucidating how prolonged environmental exposures and inflammation promote biological (accelerated) tissue aging. Granzymes, a family of serine proteases, are increasingly recognized for their emerging roles in biological aging and disease. Widely recognized as intracellular mediators of cell death, granzymes, particularly granzyme B (GzmB), also accumulate in the extracellular milieu of tissues with age, contributing to chronic tissue injury, inflammation, and impaired healing. Consequently, this has prompted the field to reconsider how GzmB regulation, accumulation, and proteolysis impact health and disease with age. While GzmB is observed in numerous age-related conditions, the current review focuses on mechanistic studies where proof-of-concept has been forwarded.
{"title":"Granzyme B in aging and age-related pathologies.","authors":"Katlyn C Richardson, Karen Jung, Joanne A Matsubara, Jonathan C Choy, David J Granville","doi":"10.1016/j.molmed.2024.07.010","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.07.010","url":null,"abstract":"<p><p>Aging is a major risk factor for pathologies that manifest later in life. Much attention is devoted towards elucidating how prolonged environmental exposures and inflammation promote biological (accelerated) tissue aging. Granzymes, a family of serine proteases, are increasingly recognized for their emerging roles in biological aging and disease. Widely recognized as intracellular mediators of cell death, granzymes, particularly granzyme B (GzmB), also accumulate in the extracellular milieu of tissues with age, contributing to chronic tissue injury, inflammation, and impaired healing. Consequently, this has prompted the field to reconsider how GzmB regulation, accumulation, and proteolysis impact health and disease with age. While GzmB is observed in numerous age-related conditions, the current review focuses on mechanistic studies where proof-of-concept has been forwarded.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-16DOI: 10.1016/j.molmed.2024.07.008
Mallory L S Eisel, Matthew Burns, Tetsuo Ashizawa, Barry Byrne, Manuela Corti, Sub H Subramony
Recent investigations have defined the pathophysiological basis of many hereditary ataxias (HAs), including loss-of-function as well as gain-of-function mechanisms at either the RNA or protein level. Preclinical studies have assessed gene editing, gene and protein replacement, gene enhancement, and gene knockdown strategies. Methodologies include viral vector delivery of genes, oligonucleotide therapies, cell-penetrating peptides, synthetic transcription factors, and technologies to deliver therapies to defined targets. In this review, we focus on Friedreich ataxia (FRDA) and the polyglutamine ataxias in which translational research is active. However, much remains to be done to identify safe and effective molecules, create ideal delivery methods, and perform innovative clinical trials to prove the safety and efficacy of treatments for these rare but devastating diseases.
{"title":"Emerging therapies in hereditary ataxias.","authors":"Mallory L S Eisel, Matthew Burns, Tetsuo Ashizawa, Barry Byrne, Manuela Corti, Sub H Subramony","doi":"10.1016/j.molmed.2024.07.008","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.07.008","url":null,"abstract":"<p><p>Recent investigations have defined the pathophysiological basis of many hereditary ataxias (HAs), including loss-of-function as well as gain-of-function mechanisms at either the RNA or protein level. Preclinical studies have assessed gene editing, gene and protein replacement, gene enhancement, and gene knockdown strategies. Methodologies include viral vector delivery of genes, oligonucleotide therapies, cell-penetrating peptides, synthetic transcription factors, and technologies to deliver therapies to defined targets. In this review, we focus on Friedreich ataxia (FRDA) and the polyglutamine ataxias in which translational research is active. However, much remains to be done to identify safe and effective molecules, create ideal delivery methods, and perform innovative clinical trials to prove the safety and efficacy of treatments for these rare but devastating diseases.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-16DOI: 10.1016/j.molmed.2024.07.003
Yulan Xiong, Jianzhong Yu
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common causes of Parkinson's disease (PD) to date. Dysfunction in LRRK2 enzymatic activities and elevated protein levels are associated with the disease. How is LRRK2 activated, and what downstream molecular and cellular processes does LRRK2 regulate? Addressing these questions is crucial to decipher the disease mechanisms. In this review we focus on the upstream regulations and briefly discuss downstream substrates of LRRK2 as well as the cellular consequences caused by these regulations. Building on these basic findings, we discuss therapeutic strategies targeting LRRK2 and highlight the challenges in clinical trials. We further highlight the important questions that remains to be answered in the LRRK2 field.
{"title":"LRRK2 in Parkinson's disease: upstream regulation and therapeutic targeting.","authors":"Yulan Xiong, Jianzhong Yu","doi":"10.1016/j.molmed.2024.07.003","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.07.003","url":null,"abstract":"<p><p>Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common causes of Parkinson's disease (PD) to date. Dysfunction in LRRK2 enzymatic activities and elevated protein levels are associated with the disease. How is LRRK2 activated, and what downstream molecular and cellular processes does LRRK2 regulate? Addressing these questions is crucial to decipher the disease mechanisms. In this review we focus on the upstream regulations and briefly discuss downstream substrates of LRRK2 as well as the cellular consequences caused by these regulations. Building on these basic findings, we discuss therapeutic strategies targeting LRRK2 and highlight the challenges in clinical trials. We further highlight the important questions that remains to be answered in the LRRK2 field.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-15DOI: 10.1016/j.molmed.2024.07.009
Soumyadeep Sarkar, Xueyun Zheng, Geremy C Clair, Yu Mi Kwon, Youngki You, Adam C Swensen, Bobbie-Jo M Webb-Robertson, Ernesto S Nakayasu, Wei-Jun Qian, Thomas O Metz
Type 1 diabetes (T1D) is a devastating autoimmune disease for which advanced mass spectrometry (MS) methods are increasingly used to identify new biomarkers and better understand underlying mechanisms. For example, integration of MS analysis and machine learning has identified multimolecular biomarker panels. In mechanistic studies, MS has contributed to the discovery of neoepitopes, and pathways involved in disease development and identifying therapeutic targets. However, challenges remain in understanding the role of tissue microenvironments, spatial heterogeneity, and environmental factors in disease pathogenesis. Recent advancements in MS, such as ultra-fast ion-mobility separations, and single-cell and spatial omics, can play a central role in addressing these challenges. Here, we review recent advancements in MS-based molecular measurements and their role in understanding T1D.
1 型糖尿病(T1D)是一种毁灭性的自身免疫性疾病,先进的质谱分析(MS)方法越来越多地用于确定新的生物标记物和更好地了解其潜在机制。例如,质谱分析与机器学习的整合已经确定了多分子生物标记物面板。在机理研究中,质谱法有助于发现新表位和疾病发展途径,并确定治疗靶点。然而,在了解组织微环境、空间异质性和环境因素在疾病发病机制中的作用方面仍存在挑战。MS 领域的最新进展,如超高速离子迁移分离、单细胞和空间全息技术,可在应对这些挑战方面发挥核心作用。在此,我们回顾了基于 MS 的分子测量的最新进展及其在了解 T1D 方面的作用。
{"title":"Exploring new frontiers in type 1 diabetes through advanced mass-spectrometry-based molecular measurements.","authors":"Soumyadeep Sarkar, Xueyun Zheng, Geremy C Clair, Yu Mi Kwon, Youngki You, Adam C Swensen, Bobbie-Jo M Webb-Robertson, Ernesto S Nakayasu, Wei-Jun Qian, Thomas O Metz","doi":"10.1016/j.molmed.2024.07.009","DOIUrl":"https://doi.org/10.1016/j.molmed.2024.07.009","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) is a devastating autoimmune disease for which advanced mass spectrometry (MS) methods are increasingly used to identify new biomarkers and better understand underlying mechanisms. For example, integration of MS analysis and machine learning has identified multimolecular biomarker panels. In mechanistic studies, MS has contributed to the discovery of neoepitopes, and pathways involved in disease development and identifying therapeutic targets. However, challenges remain in understanding the role of tissue microenvironments, spatial heterogeneity, and environmental factors in disease pathogenesis. Recent advancements in MS, such as ultra-fast ion-mobility separations, and single-cell and spatial omics, can play a central role in addressing these challenges. Here, we review recent advancements in MS-based molecular measurements and their role in understanding T1D.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":12.8,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-14DOI: 10.1016/s1471-4914(24)00201-6
No Abstract
无摘要
{"title":"Subscription and Copyright Information","authors":"","doi":"10.1016/s1471-4914(24)00201-6","DOIUrl":"https://doi.org/10.1016/s1471-4914(24)00201-6","url":null,"abstract":"No Abstract","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":null,"pages":null},"PeriodicalIF":13.6,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142220404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}