Novartis Foundation Symposium最新文献_第7页

Unusual cellular disposition of the mitochondrial molecular chaperones Hsp60, Hsp70 and Hsp10. 线粒体分子伴侣Hsp60, Hsp70和Hsp10的异常细胞配置。

Novartis Foundation Symposium Pub Date : 2008-01-01 DOI: 10.1002/9780470754030.ch5

Radhey S Gupta, Nallur B Ramachandra, Timothy Bowes, Bhag Singh

{"title":"Unusual cellular disposition of the mitochondrial molecular chaperones Hsp60, Hsp70 and Hsp10.","authors":"Radhey S Gupta, Nallur B Ramachandra, Timothy Bowes, Bhag Singh","doi":"10.1002/9780470754030.ch5","DOIUrl":"https://doi.org/10.1002/9780470754030.ch5","url":null,"abstract":"A number of molecular chaperones in mammalian cells are localized in mitochondria and they are presumed to function mainly within this organelle. However, there is now compelling evidence that these chaperones are also localized at a variety of other sites/compartments in cells where they perform important functions. These proteins include: (i) the major chaperonin Hsp60 (or P1), which was identified in mammalian cells as a protein altered in mutants resistant to microtubule inhibitors and is involved in numerous functions at the cell surface and in other compartments; (ii) the Hspl0 or Cpn10 protein, which is a co-chaperone for Hsp60 in protein folding but also serves as an early pregnancy factor in maternal serum; and (iii) the mHsp70 protein, which plays a central role in mitochondrial protein import but is also important for cellular senescence (mortalin) and antigen presentation processes. The presence of these mitochondrial chaperones at specific extramitochondrial locations greatly broadens the range of functions that they can carry out in cells. However, these observations also raise important questions regarding the mechanisms by which these proteins reach these extramitochondrial locations. My paper will review some work in this area and discuss the significance of these results.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"291 ","pages":"59-68; discussion 69-73, 137-40"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/9780470754030.ch5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27520028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 41

Cell stress proteins in extracellular fluids: friend or foe? 细胞外液中的细胞应激蛋白:是敌是友?

Novartis Foundation Symposium Pub Date : 2008-01-01 DOI: 10.1002/9780470754030.ch7

A Graham Pockley, Gabriele Multhoff

{"title":"Cell stress proteins in extracellular fluids: friend or foe?","authors":"A Graham Pockley, Gabriele Multhoff","doi":"10.1002/9780470754030.ch7","DOIUrl":"https://doi.org/10.1002/9780470754030.ch7","url":null,"abstract":"For many years the perception has been that mammalian stress proteins are intracellular molecules that are only present in the extracellular environment as a consequence of pathological situations such as necrotic cell death. However, many investigators have now shown that these proteins can be released from a variety of viable (non-necrotic) cell types in vitro, by a mechanism which has yet to be fully established. Moreover, we and a number of others have reported Hsp60 and/or Hsp70 to be present in the peripheral circulation of normal individuals. These observations have profound implications for the perceived role of these proteins as universal pro-inflammatory intercellular 'danger' signalling molecules, and the functional significance and role(s) of these ubiquitously expressed and highly conserved families of molecules must therefore be critically re-evaluated. This paper reviews the evolving evidence which indicates that stress proteins such as Hsp60 and Hsp70 are present in, and can be released into the extracellular compartment under normal physiological conditions, and puts into context their pro- and anti-inflammatory potential.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"291 ","pages":"86-95; discussion 96-100, 137-40"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/9780470754030.ch7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27520030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 46

HSP60 speaks to the immune system in many voices. HSP60通过多种声音与免疫系统对话。

Novartis Foundation Symposium Pub Date : 2008-01-01 DOI: 10.1002/9780470754030.ch8

Francisco J Quintana, Irun R Cohen

{"title":"HSP60 speaks to the immune system in many voices.","authors":"Francisco J Quintana, Irun R Cohen","doi":"10.1002/9780470754030.ch8","DOIUrl":"https://doi.org/10.1002/9780470754030.ch8","url":null,"abstract":"Heat shock proteins (HSP) were initially identified as a family of stress-induced proteins characterized by their chaperone activity. HSP, however, are also important players in the control of the immune response: HSP are targeted by HSP-specific T cells and antibodies in healthy subjects and also during the course of autoimmune disorders and, conversely, HSP influence the activity of several immune cell types via innate receptor signalling pathways. In addition, the immune response to HSP can be mined for information on the state of the immune system. Newborns carry autoantibodies to HSP. However, this natural autoreactivity to HSP is modified by inflammation, and these changes can be monitored as biomarkers during postnatal life. Using antigen microarrays, we have shown that autoantibody patterns identify individuals prone to develop autoimmune diabetes before disease onset. Moreover, changes in the inflammatory process in multiple sclerosis are also reflected in the antibody response to self-HSP. Herein, we discuss the relevance of HSP and their immune activities for the regulation and monitoring of inflammation and autoimmune disease.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"291 ","pages":"101-11; discussion 111-4, 137-40"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/9780470754030.ch8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27520031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 16

Re-establishing immune tolerance in type 1 diabetes via regulatory T cells. 通过调节性T细胞重建1型糖尿病的免疫耐受。

Novartis Foundation Symposium Pub Date : 2008-01-01 DOI: 10.1002/9780470697405.ch16

Silvia Gregori, Manuela Battaglia, Maria-Grazia Roncarolo

{"title":"Re-establishing immune tolerance in type 1 diabetes via regulatory T cells.","authors":"Silvia Gregori, Manuela Battaglia, Maria-Grazia Roncarolo","doi":"10.1002/9780470697405.ch16","DOIUrl":"https://doi.org/10.1002/9780470697405.ch16","url":null,"abstract":"Type 1 diabetes (T1D) is a disease in which tolerance to self-antigens, such as insulin, is broken leading to expansion of autoreactive T cells that attack pancreatic beta cells with consequent loss of insulin production. Regulatory T cells (Tregs) represent a specific T cell subset that plays a key role in inducing and maintaining immunological tolerance to self and non-self antigens. The naturally occurring CD4+CD25+ Tregs (nTregs) originate from the thymus, constitutively express the transcription factor FOXP3, and suppress immune responses mainly via cell-cell contact. Depletion of nTregs results in systemic autoimmune diseases in mice and, vice versa, transfer of nTregs prevents development of autoimmune diseases. Regulatory T type 1 (Tr1) cells are inducible Tregs generated in the periphery by chronic exposure to antigens in the presence of interleukin (IL)10. Tr1 cells are defined by their unique cytokine production profile (i.e. IL10++, IL5+, TGFbeta+, IL4-, IL2(low), IFNgamma(low). Tr1 cells are induced by a specialized subset of tolerogenic dendritic cells and suppress undesired immune responses mainly through production of IL10 and TGFbeta. Interestingly,Trl cells modulate responses to self-antigens such as insulin- and islet-derived peptides. In vitro expansion/induction of Tregs can be therefore envisaged as a therapeutic tool for re-establishing self-tolerance in T1D subjects.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"292 ","pages":"174-83; discussion 183-6, 202-3"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/9780470697405.ch16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27974155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13

Trajectories of anatomic brain development as a phenotype. 作为表型的大脑解剖发育轨迹。

Novartis Foundation Symposium Pub Date : 2008-01-01 DOI: 10.1002/9780470751251.ch9

Jay N Giedd, Rhoshel K Lenroot, Philip Shaw, Francois Lalonde, Mark Celano, Samantha White, Julia Tossell, Anjene Addington, Nitin Gogtay

{"title":"Trajectories of anatomic brain development as a phenotype.","authors":"Jay N Giedd, Rhoshel K Lenroot, Philip Shaw, Francois Lalonde, Mark Celano, Samantha White, Julia Tossell, Anjene Addington, Nitin Gogtay","doi":"10.1002/9780470751251.ch9","DOIUrl":"10.1002/9780470751251.ch9","url":null,"abstract":"Many cognitive, emotional and behavioural traits, as well as psychiatric disorders are highly heritable. However, identifying the specific genes and mechanisms by which this heritability manifests has been elusive. One approach to make this problem more tractable has been to attempt to identify and quantify biological markers that are intermediate steps along the gene-to-behaviour path. The field of neuroimaging offers several anatomic and physiologic possibilities to quantify. Stability over time has been proposed as a desired feature for these intermediate phenotypes. However, in this paper we discuss the value of looking at trajectories of anatomic brain development (i.e. morphometric changes over time), as opposed to static measures, as a phenotype. Examples drawn from longitudinal anatomic magnetic resonance imaging studies of typical development, attention deficit/hyperactivity disorder, and childhood-onset schizophrenia are used to demonstrate the utility of trajectories of brain development as a phenotypic bridge between genes and behaviour in health and in illness.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"289 ","pages":"101-12; discussion 112-8, 193-5"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024856/pdf/nihms207308.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27455933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neurotrophins and cytokines in neuronal plasticity. 神经元可塑性中的神经营养因子和细胞因子。

Novartis Foundation Symposium Pub Date : 2008-01-01 DOI: 10.1002/9780470751251.ch18

Michael Spedding, Pierre Gressens

{"title":"Neurotrophins and cytokines in neuronal plasticity.","authors":"Michael Spedding, Pierre Gressens","doi":"10.1002/9780470751251.ch18","DOIUrl":"https://doi.org/10.1002/9780470751251.ch18","url":null,"abstract":"Nerve growth factor (NGF) binds to TrkA receptors (neurotrophic) and P75(NTR) (apoptosis or other pathways depending on the coupled adaptor proteins). Brain derived growth factor (BDNF) can bind to TrkB (neurotrophic) and P75(NTR) receptors. BDNF is the main, activity-dependent, neurotrophin and sculpts neuronal organisation dependent on activity, thereby coupling and balancing effects on excitatory (glutamate) and inhibitory (GABA) transmission--in a synapse-specific manner. Some drugs can interact in a specific way. Positive modulators of AMPA receptors induce BDNF and favour long term potentiation (LTP) and memory processes. Some antidepressants such as tianeptine reverse stress-induced inhibition of LTP and restore neuronal plasticity in brain areas at risk. Inflammatory cytokines are produced in sickness behaviour mimicking depression. Interleukin (IL)1beta can exacerbate the immediate effects of stressors, and enhance and prolong the overall effects, which may be protective in preventing overuse or by increasing conservation-withdrawal: in some synapses IL1beta induces long term depression (LTD) or blocks LTP. The interactions with neurotrophins are complex and frequently reciprocal. However, NGF also contributes to inflammatory situations and mediates pain responses. This interplay is poorly understood but may be critical in cerebral palsy, neurodegenerative disorders such as amyotrophic lateral sclerosis and multiple sclerosis, and even Alzheimer's disease.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"289 ","pages":"222-33; discussion 233-40"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27458052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 66

BiP, an anti-inflammatory ER protein, is a potential new therapy for the treatment of rheumatoid arthritis. BiP是一种抗炎内质网蛋白，是治疗类风湿性关节炎的潜在新疗法。

Novartis Foundation Symposium Pub Date : 2008-01-01 DOI: 10.1002/9780470754030.ch16

Gabriel S Panayi, Valerie M Corrigall

{"title":"BiP, an anti-inflammatory ER protein, is a potential new therapy for the treatment of rheumatoid arthritis.","authors":"Gabriel S Panayi, Valerie M Corrigall","doi":"10.1002/9780470754030.ch16","DOIUrl":"https://doi.org/10.1002/9780470754030.ch16","url":null,"abstract":"The endoplasmic reticulum chaperone and stress protein BiP has hitherto been considered as having only crucial intracellular cell protective functions. However, we have shown that BiP can be present in the extracellular environment and that it binds to a putative but as yet uncloned cell surface receptor. It will stimulate human monocytes via this receptor to express a gene profile that is anti-inflammatory. It will generate T cells with a regulatory function from human peripheral blood most likely by altering dendritic cell development. Intravenous BiP will both prevent and treat ongoing collagen induced arthritis in the DBA/1 mouse. Part of the suppression of arthritis is linked to interleukin (IL)4 as BiP-specific lymph node and spleen cells from these mice secrete IL4, and BiP has no suppressive effect on collagen induced arthritis in IL4 knockout mice. Lymph node and spleen cells isolated from mice administered intravenous BiP will suppress arthritis when transferred intravenously into recipient arthritic mice without any further BiP having to be given. Thus, both in vitro work with human peripheral blood mononuclear cells and in vivo work in the collagen arthritis model lead to the conclusion that BiP induces regulatory cells. Finally, intravenous BiP will ablate the inflammatory cell infiltrate and inflammatory cytokine expression in rheumatoid synovial membrane tissue transplanted subcutaneously into SCID mice. The conclusion from all this experimental work is that BiP may be a novel therapy for the treatment of patients with rheumatoid arthritis.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"291 ","pages":"212-6; discussion 216-24"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/9780470754030.ch16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27517650","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 18

Longitudinal studies of gene-environment interaction in common diseases--good value for money? 常见病中基因-环境相互作用的纵向研究——物有所值？

Novartis Foundation Symposium Pub Date : 2008-01-01 DOI: 10.1002/9780470696781.ch10

Stephen P Robertson, Richie Poulton

{"title":"Longitudinal studies of gene-environment interaction in common diseases--good value for money?","authors":"Stephen P Robertson, Richie Poulton","doi":"10.1002/9780470696781.ch10","DOIUrl":"10.1002/9780470696781.ch10","url":null,"abstract":"Prospective cohort studies are costly and time consuming yet appear to be the best means for understanding how genes interact with environmental risk factors to cause disease. This information is a necessary prerequisite for evidenced-based disease prevention, yet not all researchers agree about the importance of studying the interplay between genes and environments. They argue that we already know enough about which environmental 'exposures' can prevent most common diseases, for example, wholesome diet, adequate housing/income and access to good healthcare. Implicit is the notion that current disease categories (i.e. phenotypes) are 'real' and represent homogenous entities, and that identifying environmentally mediated risk is relatively straightforward. Other concerns relate to scientific basis, utility and ethics. These arguments are critically examined for a range of disorders, from diabetes, cancer and inflammatory bowel disease to depression. We refute the contention that incorporating the measurement of genotype into longitudinal-epidemiological studies is wasteful or unlikely to yield significant benefits.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"46 1","pages":"128-37; discussion 138-42, 181-3"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50673750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Functions and mechanisms of BDNF mRNA trafficking. BDNF mRNA转运的功能和机制。

Novartis Foundation Symposium Pub Date : 2008-01-01 DOI: 10.1002/9780470751251.ch11

Enrico Tongiorgi, Gabriele Baj

{"title":"Functions and mechanisms of BDNF mRNA trafficking.","authors":"Enrico Tongiorgi, Gabriele Baj","doi":"10.1002/9780470751251.ch11","DOIUrl":"https://doi.org/10.1002/9780470751251.ch11","url":null,"abstract":"Long-lasting changes in the basis of memory storage require delivery of newly synthesized proteins to the affected synapses. While most of these proteins are generated in the cell body, several key molecules for plasticity can be delivered in the form of silent mRNAs at synapses in extra-somatic compartments where they are locally translated in response to specific stimuli. One such mRNA encodes brain derived neurotrophic factor (BDNF), a key molecule in neuronal development that plays a critical role in learning and memory, and which displays abnormal levels in several neuropsychiatric disorders. BDNF mRNA accumulates in distal dendrites in response to stimuli that trigger activation of NMDAR and TrkB receptors. A single BDNF protein is produced from several splice variants having different 5'UTRs. We have shown that these mRNA variants have a different subcellular localization (soma, proximal or distal dendritic compartment) and that the protein is co-localized with the transcript from which it originated. As these splice variants are also differentially expressed in response to various stimuli and antidepressants, we propose that they represent a spatial and temporal code to regulate BDNF protein expression locally.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"289 ","pages":"136-47; discussion 147-51, 193-5"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/9780470751251.ch11","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27455935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 30

Cell stress proteins: novel immunotherapeutics. 细胞应激蛋白:新型免疫疗法。

Novartis Foundation Symposium Pub Date : 2008-01-01 DOI: 10.1002/9780470754030.ch9

Stuart K Calderwood, Jianlin Gong, Jimmy R Theriault, Salamatu S Mambula, Philip J Gray

{"title":"Cell stress proteins: novel immunotherapeutics.","authors":"Stuart K Calderwood, Jianlin Gong, Jimmy R Theriault, Salamatu S Mambula, Philip J Gray","doi":"10.1002/9780470754030.ch9","DOIUrl":"https://doi.org/10.1002/9780470754030.ch9","url":null,"abstract":"Heat shock proteins (HSPs) play important roles in the immune system as carriers of tumour antigens and inflammatory agents. The HSPs are abundantly expressed stress proteins intrinsic to all cellular life, permitting proteins to carry out essential enzymic, signalling and structural functions within the tightly crowded milieu of the cell. To carry out these tasks, HSPs are equipped with a domain that binds unstructured sequences in polypeptides and a N-terminal ATPase domain that controls the opening and closing of the peptide-binding domain. HSPs can, using these domains, capture antigens processed by partial proteolysis in the cytoplasm of cancer cells. HSP/peptide complexes formed in the cytoplasm can then be secreted to take part in immune surveillance. Extracellular Hsp70 interacts with receptors on antigen presenting cells (APCs) either during episodes of cell death and lysis in vivo or during vaccination. A number of candidate receptors for Hsp70 on APCs have been proposed to take part in the antitumour immune function including the alpha2 macroglobulin receptor CD91, Toll-like receptors, the signalling receptor CD40 and a number of scavenger receptors. Finally, Hsp70 complexes are able to deliver antigens to MHC class I and II molecules on the APC cell surface and lead to the presentation of tumour antigens to T lymphocytes. HSP-antigen complexes have proven effective in the treatment of rodent tumours in preclinical studies and are now undergoing clinical trials for treatment of human cancer.","PeriodicalId":19323,"journal":{"name":"Novartis Foundation Symposium","volume":"291 ","pages":"115-31; discussion 131-40"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/9780470754030.ch9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27520032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17