Journal of signal transduction最新文献

{"title":"The Roles of Mitogen-Activated Protein Kinase Pathways in TGF-β-Induced Epithelial-Mesenchymal Transition.","authors":"Ting Gui,&nbsp;Yujing Sun,&nbsp;Aiko Shimokado,&nbsp;Yasuteru Muragaki","doi":"10.1155/2012/289243","DOIUrl":"https://doi.org/10.1155/2012/289243","url":null,"abstract":"<p><p>The mitogen-activated protein kinase (MAPK) pathway allows cells to interpret external signals and respond appropriately, especially during the epithelial-mesenchymal transition (EMT). EMT is an important process during embryonic development, fibrosis, and tumor progression in which epithelial cells acquire mesenchymal, fibroblast-like properties and show reduced intercellular adhesion and increased motility. TGF-β signaling is the first pathway to be described as an inducer of EMT, and its relationship with the Smad family is already well characterized. Studies of four members of the MAPK family in different biological systems have shown that the MAPK and TGF-β signaling pathways interact with each other and have a synergistic effect on the secretion of additional growth factors and cytokines that in turn promote EMT. In this paper, we present background on the regulation and function of MAPKs and their cascades, highlight the mechanisms of MAPK crosstalk with TGF-β signaling, and discuss the roles of MAPKs in EMT.</p>","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"289243"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/289243","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30484715","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}

{"title":"Contractile Activity Regulates Inducible Nitric Oxide Synthase Expression and NO(i) Production in Cardiomyocytes via a FAK-Dependent Signaling Pathway.","authors":"Miensheng Chu,&nbsp;Yevgeniya Koshman,&nbsp;Rekha Iyengar,&nbsp;Taehoon Kim,&nbsp;Brenda Russell,&nbsp;Allen M Samarel","doi":"10.1155/2012/473410","DOIUrl":"https://doi.org/10.1155/2012/473410","url":null,"abstract":"<p><p>Intracellular nitric oxide (NO(i)) is a physiological regulator of excitation-contraction coupling, but is also involved in the development of cardiac dysfunction during hypertrophy and heart failure. To determine whether contractile activity regulates nitric oxide synthase (NOS) expression, spontaneously contracting, neonatal rat ventricular myocytes (NRVM) were treat with L-type calcium channel blockers (nifedipine and verapamil) or myosin II ATPase inhibitors (butanedione monoxime (BDM) and blebbistatin) to produce contractile arrest. Both types of inhibitors significantly reduced iNOS but not eNOS expression, and also reduced NO(i) production. Inhibiting contractile activity also reduced focal adhesion kinase (FAK) and AKT phosphorylation. Contraction-induced iNOS expression required FAK and phosphatidylinositol 3-kinase (PI(3)K), as both PF573228 and LY294002 (10 μM, 24 h) eliminated contraction-induced iNOS expression. Similarly, shRNAs specific for FAK (shFAK) caused FAK knockdown, reduced AKT phosphorylation at T308 and S473, and reduced iNOS expression. In contrast, shRNA-mediated knockdown of PYK2, the other member of the FAK-family of protein tyrosine kinases, had much less of an effect. Conversely, overexpression of a constitutively active form of FAK (CD2-FAK) or AKT (Myr-AKT) reversed the inhibitory effect of BDM on iNOS expression and NO(i) production. Thus, contraction-induced iNOS expression and NO(i) production in NRVM are mediated via a FAK-PI(3)K-AKT signaling pathway.</p>","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"473410"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/473410","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30839012","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}

{"title":"Antiangiogenic therapy for glioma.","authors":"Valentina Cea,&nbsp;Carlo Sala,&nbsp;Chiara Verpelli","doi":"10.1155/2012/483040","DOIUrl":"https://doi.org/10.1155/2012/483040","url":null,"abstract":"<p><p>Currently, antiangiogenic agents are routinely used for the treatment of patients with glioma. However, despite advances in pharmacological and surgical therapy, glioma remains an incurable disease. Indeed, the formation of an abnormal tumor vasculature and the invasion of glioma cells along neuronal tracts are proposed to comprise the major factors that are attributed to the therapeutic resistance of these tumors. The development of curative therapeutic modalities for the treatment of glioma requires further investigation of the molecular mechanisms regulating angiogenesis and invasion. In this review, we discuss the molecular characteristics of angiogenesis and invasion in human malignant glioma, we present several available drugs that are used or can potentially be utilized for the inhibition of angiogenesis in glioma, and we focus our attention on the key mediators of the molecular mechanisms underlying the resistance of glioma to antiangiogenic therapy.</p>","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"483040"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/483040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30787667","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}

{"title":"Pathogenic role of store-operated and receptor-operated ca(2+) channels in pulmonary arterial hypertension.","authors":"Ruby A Fernandez,&nbsp;Premanand Sundivakkam,&nbsp;Kimberly A Smith,&nbsp;Amy S Zeifman,&nbsp;Abigail R Drennan,&nbsp;Jason X-J Yuan","doi":"10.1155/2012/951497","DOIUrl":"https://doi.org/10.1155/2012/951497","url":null,"abstract":"Pulmonary circulation is an important circulatory system in which the body brings in oxygen. Pulmonary arterial hypertension (PAH) is a progressive and fatal disease that predominantly affects women. Sustained pulmonary vasoconstriction, excessive pulmonary vascular remodeling, in situ thrombosis, and increased pulmonary vascular stiffness are the major causes for the elevated pulmonary vascular resistance (PVR) in patients with PAH. The elevated PVR causes an increase in afterload in the right ventricle, leading to right ventricular hypertrophy, right heart failure, and eventually death. Understanding the pathogenic mechanisms of PAH is important for developing more effective therapeutic approach for the disease. An increase in cytosolic free Ca2+ concentration ([Ca2+]cyt) in pulmonary arterial smooth muscle cells (PASMC) is a major trigger for pulmonary vasoconstriction and an important stimulus for PASMC migration and proliferation which lead to pulmonary vascular wall thickening and remodeling. It is thus pertinent to define the pathogenic role of Ca2+ signaling in pulmonary vasoconstriction and PASMC proliferation to develop new therapies for PAH. [Ca2+]cyt in PASMC is increased by Ca2+ influx through Ca2+ channels in the plasma membrane and by Ca2+ release or mobilization from the intracellular stores, such as sarcoplasmic reticulum (SR) or endoplasmic reticulum (ER). There are two Ca2+ entry pathways, voltage-dependent Ca2+ influx through voltage-dependent Ca2+ channels (VDCC) and voltage-independent Ca2+ influx through store-operated Ca2+ channels (SOC) and receptor-operated Ca2+ channels (ROC). This paper will focus on the potential role of VDCC, SOC, and ROC in the development and progression of sustained pulmonary vasoconstriction and excessive pulmonary vascular remodeling in PAH.","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"951497"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/951497","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30969660","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}

{"title":"Signals regulating adhesion dynamics.","authors":"Donna J Webb,&nbsp;Claire M Brown,&nbsp;Kris A DeMali","doi":"10.1155/2012/785196","DOIUrl":"https://doi.org/10.1155/2012/785196","url":null,"abstract":"Adhesions are sites of contact between cells (cell-cell) and between cells and the extracellular matrix (cell-ECM) that are essential for numerous biological processes such as embryogenesis, wound healing, and the immune response. They are composed of many different molecules including adhesion receptors, signaling proteins (e.g., kinases, phosphatases, and adaptor proteins), and structural proteins (e.g., actin-binding proteins) [1–3]. Adhesions are dynamic structures whose molecular composition and structure can undergo rapid changes to allow cells to respond to external signals [1, 4]. Indeed, this dynamic nature of adhesions within localized regions of cells is critical for many complex processes such as cell migration. \u0000 \u0000For cell-ECM adhesions, their assembly is initiated by the binding of integrin adhesion receptors to the ECM. These new adhesions can either disassemble, allowing cells to migrate, or continue to mature by recruiting signaling and structural proteins to these sites. The dynamics and composition of adhesions are controlled by signaling networks that function to integrate molecular signals from outside and within cells. This special issue focuses on the molecular signals that regulate adhesion dynamics with an emphasis on cell-ECM adhesions. \u0000 \u0000Integrins are transmembrane adhesion receptors that provide a functional link between the ECM and the actin cytoskeleton. Integrin engagement of the ECM serves to transduce signals to the interior of cells which regulate cell behavior. RGD-dependent integrins are a subgroup of adhesion receptors that specifically recognize the RGD motif, which is a three-amino-acid sequence (Arg-Gly-Asp) that is found in some ECM proteins. In this special issue, Y. D. Benoit et al. review recent findings regarding the importance of RGD-dependent integrins in epithelial cell homeostasis. Integrins also play important roles in blood clotting and wound healing by regulating platelet adhesion and aggregation. G. F. Guidetti and M. Torti discuss recent insights into the role of Rap1 in regulating platelet adhesion. Rap1 is a member of the Rap family of small GTPases and is a downstream effector of integrin signaling. A-Kinase-Anchoring Proteins (AKAP) are emerging as pivotal scaffolding proteins that bring together key signaling molecules to modulate cell migration. S. Akakura and I. H. Gelman provide insight into the regulation of AKAP12 and how it contributes to cell adhesion. Moreover, they discuss the scaffolding function of AKAP12 and its contribution to cell migration, maintenance of cytoskeletal architecture, cell proliferation, and cytokinesis. \u0000 \u0000While integrin-containing matrix contacts were first identified in classic focal adhesions, they have subsequently been shown to exist in other structures including podosomes and invadopodia. Podosomes and invadopodia do not have the typical elongated shape of focal adhesions but form circular adhesive structures. Podosomes are found in phagocytic cells, w","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"785196"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/785196","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31180590","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}

{"title":"Reactive oxygen species: friends and foes of signal transduction.","authors":"Saverio Francesco Retta,&nbsp;Paola Chiarugi,&nbsp;Lorenza Trabalzini,&nbsp;Paolo Pinton,&nbsp;Alexey M Belkin","doi":"10.1155/2012/534029","DOIUrl":"https://doi.org/10.1155/2012/534029","url":null,"abstract":"The maintenance of highly regulated mechanisms to control intracellular levels of reactive oxygen species (ROS) is essential for normal cellular homeostasis. Indeed, most ROS, including free radicals and peroxides, are produced at low level by normal aerobic metabolism and play an important role in the redox-dependent regulation of many signaling processes. In contrast, excessive accumulation of ROS, resulting from an imbalance between ROS production and scavenging, leads to a condition of oxidative stress that can cause extensive oxidative damage to most cellular components, including proteins, lipids, and DNA, and may have pathophysiological consequences. Remarkably, oxidative stress has been clearly implicated in aging and the pathogenesis of several human diseases, including cardiovascular, metabolic, inflammatory, and neurodegenerative diseases and cancer. Thus, ROS may function as friends or foes of signal transduction depending on specific threshold levels and cell context. \u0000 \u0000To highlight the important topics in this evolving field the Journal of Signal Transduction presents a special issue on the involvement of ROS in physiological and pathological signal transduction processes from prokaryotes to low and high eukaryotes. \u0000 \u0000In particular, the topics covered in this special issue include ROS-mediated signaling in bacteria (in the first paper), the mechanisms by which ROS affect Neurospora crassa light signal transduction (in the second paper), the interplay between ROS and mitochondria in the control of cell death and aging (in the third and fourth papers) and cancer progression (in the fifth and sixth papers), the role of ROS in nuclear transport (in the seventh paper), the interplay between ROS and Ras GTPases (in the eighth paper), the role of ROS in the crosstalk between integrins and cadherins (in the ninth paper), integrin signaling (in the tenth paper), and skeletal muscle signaling (in the eleventh paper). These articles describe our current understanding of this field. Furthermore, this special issue highlights the importance of gaining a greater understanding of the physiological and pathological role of ROS in the perspective of defining new therapeutic strategies based on redox regulation of signal transduction processes. \u0000 \u0000 \u0000Saverio Francesco Retta \u0000 \u0000Paola Chiarugi \u0000 \u0000Lorenza Trabalzini \u0000 \u0000Paolo Pinton \u0000 \u0000Alexey M. Belkin","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":" ","pages":"534029"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/534029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40172367","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}

{"title":"Commitment of Satellite Cells Expressing the Calcium Channel α2δ1 Subunit to the Muscle Lineage.","authors":"Tammy Tamayo,&nbsp;Liliana Grajales,&nbsp;Jesús García","doi":"10.1155/2012/460842","DOIUrl":"https://doi.org/10.1155/2012/460842","url":null,"abstract":"<p><p>Satellite cells can maintain or repair muscle because they possess stem cell properties, making them a valuable option for cell therapy. However, cell transplants into skeletal muscle of patients with muscular dystrophy are limited by donor cell attachment, migration, and survival in the host tissue. Cells used for therapy are selected based on specific markers present in the plasma membrane. Although many markers have been identified, there is a need to find a marker that is expressed at different states in satellite cells, activated, quiescent, or differentiated cell. Furthermore, the marker has to be present in human tissue. Recently we reported that the plasma membrane α2δ1 protein is involved in cell attachment and migration in myoblasts. The α2δ1 subunit forms a part of the L-type voltage-dependent calcium channel in adult skeletal muscle. We found that the α2δ1 subunit is expressed in the majority of newly isolated satellite cells and that it appears earlier than the α1 subunits and at higher levels than the β or γ subunits. We also found that those cells that expressed α2δ1 would differentiate into muscle cells. This evidence indicates that the α2δ1 may be used as a marker of satellite cells that will differentiate into muscle.</p>","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"460842"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/460842","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31129598","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}

{"title":"Reactive oxygen species in skeletal muscle signaling.","authors":"Elena Barbieri,&nbsp;Piero Sestili","doi":"10.1155/2012/982794","DOIUrl":"https://doi.org/10.1155/2012/982794","url":null,"abstract":"<p><p>Generation of reactive oxygen species (ROS) is a ubiquitous phenomenon in eukaryotic cells' life. Up to the 1990s of the past century, ROS have been solely considered as toxic species resulting in oxidative stress, pathogenesis and aging. However, there is now clear evidence that ROS are not merely toxic species but also-within certain concentrations-useful signaling molecules regulating physiological processes. During intense skeletal muscle contractile activity myotubes' mitochondria generate high ROS flows: this renders skeletal muscle a tissue where ROS hold a particular relevance. According to their hormetic nature, in muscles ROS may trigger different signaling pathways leading to diverging responses, from adaptation to cell death. Whether a \"positive\" or \"negative\" response will prevail depends on many variables such as, among others, the site of ROS production, the persistence of ROS flow or target cells' antioxidant status. In this light, a specific threshold of physiological ROS concentrations above which ROS exert negative, toxic effects is hard to determine, and the concept of \"physiologically compatible\" levels of ROS would better fit with such a dynamic scenario. In this review these concepts will be discussed along with the most relevant signaling pathways triggered and/or affected by ROS in skeletal muscle.</p>","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"982794"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/982794","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30330762","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}

{"title":"MAPK usage in periodontal disease progression.","authors":"Qiyan Li,&nbsp;Michael S Valerio,&nbsp;Keith L Kirkwood","doi":"10.1155/2012/308943","DOIUrl":"https://doi.org/10.1155/2012/308943","url":null,"abstract":"<p><p>In periodontal disease, host recognition of bacterial constituents, including lipopolysaccharide (LPS), induces p38 MAPK activation and subsequent inflammatory cytokine expression, favoring osteoclastogenesis and increased net bone resorption in the local periodontal environment. In this paper, we discuss evidence that the p38/MAPK-activated protein kinase-2 (MK2) signaling axis is needed for periodontal disease progression: an orally administered p38α inhibitor reduced the progression of experimental periodontal bone loss by reducing inflammation and cytokine expression. Subsequently, the significance of p38 signaling was confirmed with RNA interference to attenuate MK2-reduced cytokine expression and LPS-induced alveolar bone loss. MAPK phosphatase-1 (MKP-1), a negative regulator of MAPK activation, was also critical for periodontal disease progression. In MPK-1-deficient mice, p38-sustained activation increased osteoclast formation and bone loss, whereas MKP-1 overexpression dampened p38 signaling and subsequent cytokine expression. Finally, overexpression of the p38/MK2 target RNA-binding tristetraprolin (TTP) decreased mRNA stability of key inflammatory cytokines at the posttranscriptional level, thereby protecting against periodontal inflammation. Collectively, these studies highlight the importance of p38 MAPK signaling in immune cytokine production and periodontal disease progression.</p>","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"308943"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/308943","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30443961","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}

{"title":"Functional mechanisms and roles of adaptor proteins in abl-regulated cytoskeletal actin dynamics.","authors":"Mizuho Sato,&nbsp;Masahiro Maruoka,&nbsp;Tatsuo Takeya","doi":"10.1155/2012/414913","DOIUrl":"https://doi.org/10.1155/2012/414913","url":null,"abstract":"<p><p>Abl is a nonreceptor tyrosine kinase and plays an essential role in the modeling and remodeling of F-actin by transducing extracellular signals. Abl and its paralog, Arg, are unique among the tyrosine kinase family in that they contain an unusual extended C-terminal half consisting of multiple functional domains. This structural characteristic may underlie the role of Abl as a mediator of upstream signals to downstream signaling machineries involved in actin dynamics. Indeed, a group of SH3-containing accessory proteins, or adaptor proteins, have been identified that bind to a proline-rich domain of the C-terminal portion of Abl and modulate its kinase activity, substrate recognition, and intracellular localization. Moreover, the existence of signaling cascade and biological outcomes unique to each adaptor protein has been demonstrated. In this paper, we summarize functional roles and mechanisms of adaptor proteins in Abl-regulated actin dynamics, mainly focusing on a family of adaptor proteins, Abi. The mechanism of Abl's activation and downstream signaling mediated by Abi is described in comparison with those by another adaptor protein, Crk.</p>","PeriodicalId":89176,"journal":{"name":"Journal of signal transduction","volume":"2012 ","pages":"414913"},"PeriodicalIF":0.0,"publicationDate":"2012-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2012/414913","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30674631","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}