Tissue Barriers最新文献

{"title":"Inter-claudin antagonism of paracellular pore function: mechanism and beyond.","authors":"Wanapas Wachiradejkul, Pawin Pongkorpsakol","doi":"10.1080/21688370.2024.2330773","DOIUrl":"10.1080/21688370.2024.2330773","url":null,"abstract":"<p><p>Claudin-2-dependent pore function mediates paracellular cation permeability and can result in pathogenesis of many diseases. Although existing various types of claudins, including barrier-forming and pore-forming claudins, their heterodimeric interaction affecting barrier and pore functions has never been fully elucidated yet. Recently, Shashikanth and colleagues demonstrated that expression of claudin-4 was able to antagonize paracellular pore activity of claudin-2. This commentary will emphasize the mechanism underlying claudin-4-mediated claudin-2-dependent pore inhibition and discuss its potential therapeutic and prognostic applications.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2330773"},"PeriodicalIF":4.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140144150","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":"Spermine oxidase inhibitor, MDL 72527, reduced neovascularization, vascular permeability, and acrolein-conjugated proteins in a mouse model of ischemic retinopathy.","authors":"Abdullah Alhumaid, Fang Liu, Shengshuai Shan, Eissa Jafari, Nadia Nourin, Payaningal R Somanath, S Priya Narayanan","doi":"10.1080/21688370.2024.2347070","DOIUrl":"10.1080/21688370.2024.2347070","url":null,"abstract":"<p><p>Disruptions in polyamine metabolism have been identified as contributing factors to various central nervous system disorders. Our laboratory has previously highlighted the crucial role of polyamine oxidation in retinal disease models, specifically noting elevated levels of spermine oxidase (SMOX) in inner retinal neurons. Our prior research demonstrated that inhibiting SMOX with MDL 72527 protected against vascular injury and microglial activation induced by hyperoxia in the retina. However, the effects of SMOX inhibition on retinal neovascularization and vascular permeability, along with the underlying molecular mechanisms of vascular protection, remain incompletely understood. In this study, we utilized the oxygen-induced retinopathy (OIR) model to explore the impact of SMOX inhibition on retinal neovascularization, vascular permeability, and the molecular mechanisms underlying MDL 72527-mediated vasoprotection in the OIR retina. Our findings indicate that inhibiting SMOX with MDL 72527 mitigated vaso-obliteration and neovascularization in the OIR retina. Additionally, it reduced OIR-induced vascular permeability and Claudin-5 expression, suppressed acrolein-conjugated protein levels, and downregulated P38/ERK1/2/STAT3 signaling. Furthermore, our results revealed that treatment with BSA-Acrolein conjugates significantly decreased the viability of human retinal endothelial cells (HRECs) and activated P38 signaling. These observations contribute valuable insights into the potential therapeutic benefits of SMOX inhibition by MDL 72527 in ischemic retinopathy.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2347070"},"PeriodicalIF":4.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140851564","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":"Molecular alterations in claudin 18 suppressed and non-suppressed gastric adenocarcinomas to guide targeted therapies.","authors":"Ioannis A Voutsadakis","doi":"10.1080/21688370.2024.2348852","DOIUrl":"10.1080/21688370.2024.2348852","url":null,"abstract":"<p><strong>Background: </strong>Gastric adenocarcinoma represents an aggressive type of cancer and an important cause of cancer mortality. Progress in gastric cancer therapeutics has resulted from a better understanding of the molecular pathogenesis of the disease and introduction of targeted therapies, but most gastric cancer patients still rely on non-targeted chemotherapy as the mainstay of treatment for advanced disease.</p><p><strong>Methods: </strong>An analysis of publicly available series from The Cancer Genome Atlas (TCGA) gastric cancer cohort was undertaken to delineate the clinical and genomic landscape of gastric cancers with suppressed expression of claudin 18 compared with cancers with non-suppressed claudin 18. Claudin 18 suppressed cancers were defined as having an mRNA expression z-score relative to normal samples (log RNA Seq V2) of less than -1. Claudin 18 non-suppressed cancers were defined as having an mRNA expression z-score relative to normal samples (log RNA Seq V2) above 0.5.</p><p><strong>Results: </strong>Gastric cancers with claudin 18 mRNA suppression represented 7.7% of the gastric adenocarcinomas of TCGA cohort, while non-suppressed cancers represented 46.6% of the cases. The two groups did not differ in clinical and genomic characteristics, such as mean age, histology, grade, and stage. The mutation landscape of claudin 18 suppressed cases included high mutation rates of TP53, of genes of the WNT/β-catenin pathway and of ubiquitin ligase <i>FBXW7</i>. Moreover, a subset of both claudin 18 suppressed and non-suppressed cancers displayed mutations in Mismatch Repair (MMR) associated genes or a high tumor mutation burden (TMB). At the mRNA expression level, claudin 18 suppressed gastric cancers showed up-regulation of EMT core transcription factor Snail 2 and down-regulation of genes of HLA cluster. The survival of gastric cancer patients with claudin 18 mRNA suppression was not significantly different compared with patients with non-suppressed claudin 18.</p><p><strong>Conclusion: </strong>Sub-sets of gastric cancers with claudin 18 mRNA suppression displayed characteristics of potential therapeutic interest, such as mutations in WNT and PI3K pathways and MMR defects. These may guide the development of alternative targeted therapies, in this sub-set of gastric cancers which are not candidates for claudin 18 targeting therapies.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2348852"},"PeriodicalIF":4.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140872223","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":"HIV1-Nef perturbs the integrity of blood testis barrier in rat model.","authors":"Deependra Singh, Saurabh Kumar, Rajnikant Mishra, Anjali, R K Tripathi, Monika Sachdev","doi":"10.1080/21688370.2024.2357406","DOIUrl":"10.1080/21688370.2024.2357406","url":null,"abstract":"<p><p>The blood-testis barrier is a specialized feature within the mammalian testis, located in close proximity to the basement membrane of seminiferous tubules. This barrier serves to divide the seminiferous epithelium into distinct basal and adluminal (apical) compartments. The selectivity of the BTB to foreign particles makes it a safe haven for the virus, and the high affinity of HIV for testis might lead to the vertical transmission of the virus. In the present study, recombinant HIV1-Nef (rNef) protein was injected intravenously to examine the effect of rNef on BTB. SD male rats received 250 µg and 500 µg of rNef along with 2% Evans blue dye within 1 ml through the tail vein. After 1 hour of perfusion, the animals were sacrificed for analysis. The dye migration assay and ELISA confirmed a significant impairment in the blood-testis barrier (BTB) and the manifestation of rNef in testes tissues, respectively. Moreover, a decline in the expression of tight junction proteins, including ZO1 and Occludin, was observed during rNef-induced BTB disruption. Overall, our findings demonstrated that rNef induces BTB disruption through various signaling events. At the site of ectoplasmic specialization of the seminiferous epithelium, the localization of cadherins was found to be disrupted, making the testis a vulnerable site. In conclusion, rNef perturbs the integrity of the blood-testis barrier in rat models; hence, it can also serve as a suitable model for studying the dynamics of the blood-testis barrier.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2357406"},"PeriodicalIF":4.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082380","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":"Erk1/2 is not required for endothelial barrier establishment despite its requirement for cAMP-dependent Rac1 activation in heart endothelium.","authors":"Sina Moztarzadeh, Hilda Vargas-Robles, Michael Schnoor, Mariya Y Radeva, Jens Waschke, Alexander Garcia-Ponce","doi":"10.1080/21688370.2024.2398875","DOIUrl":"10.1080/21688370.2024.2398875","url":null,"abstract":"<p><p>The contribution of Erk1/2 to endothelial barrier regulation is convoluted and differs depending on the vascular bed. We explored the effects of Erk1/2 inhibition on endothelial barrier maintenance and its relationship with cAMP-dependent barrier strengthening. Thus, myocardial endothelial cells (MyEnd) were isolated and protein expression, localization and activity of structural and signaling molecules involved in maintenance of endothelial function were investigated by Western blot, immunostainings and G-LISA, respectively. The transendothelial electrical resistance (TEER) from confluent MyEnd monolayers was measured and used as a direct indicator of barrier integrity in vitro. Miles assay was performed to evaluate vascular permeability in vivo. Erk1/2 inhibition with U0126 affected neither the structural organization of adherens or tight junctions nor the protein level of their components, However, TEER drop significantly upon U0126 application, but the effect was transitory as the barrier function recovered 30 min after treatment. Erk1/2 inhibition delayed cAMP-mediated barrier strengthening but did not prevent barrier fortification despite diminishing Rac1 activation. Moreover, Erk1/2 inhibition, induced vascular leakage that could be prevented by local cAMP elevation in vivo. Our data demonstrate that Erk1/2 is required to prevent vascular permeability but is not critical for cAMP-mediated barrier enhancement.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2398875"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142126822","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":"Ephrin-Eph signaling: an important regulator of epithelial integrity and barrier function.","authors":"Mohan Liu, Joseph G Charek, Rodolfo D Vicetti Miguel, Thomas L Cherpes","doi":"10.1080/21688370.2025.2462855","DOIUrl":"10.1080/21688370.2025.2462855","url":null,"abstract":"<p><p>Eph receptor-interacting proteins (ephrin) ligands and their erythropoietin-producing human hepatocellular (Eph) receptors elicit bidirectional signals that regulate cell migration, angiogenesis, neuronal plasticity, and other developmental processes in the embryo. In adulthood, ephrin-Eph signaling regulates numerous homeostatic events, including epithelial cell proliferation and differentiation. Epithelial surfaces, including those of skin and vagina, are lined by layers of stratified squamous epithelium (SSE) that protect against mechanical stress and microbial pathogen invasion. Ephrin-Eph signaling is known to promote cutaneous epithelial barrier function by regulating the expression of specialized cell-cell adhesion junctions termed desmosomes, but the role of this signaling system in maintaining epithelial integrity and barrier function in the vagina is less explored. This review summarizes current understanding of ephrin-Eph signaling that regulates desmosome expression and barrier function in the skin and considers evidence that suggests ephrin-Eph signaling similarly regulates these processes in vaginal SSE.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2462855"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374859","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":"The application of explants, crypts, and organoids as models in intestinal barrier research.","authors":"Snezhanna Medvedeva, Kseniya Achasova, Lidiya Boldyreva, Anna Ogienko, Elena Kozhevnikova","doi":"10.1080/21688370.2024.2423137","DOIUrl":"10.1080/21688370.2024.2423137","url":null,"abstract":"<p><p><i>In vitro</i> models are of great importance in advancing our understanding of human diseases, especially complex disorders with unknown etiologies like inflammatory bowel diseases (IBD). One of the key IBD features is the increased intestinal permeability. The disruption of the intestinal barrier can occur due to a destructive inflammatory response involving intestinal cell death. Alternatively, proteins that form tight junctions (TJ) fail to form function complexes and promote epithelial barrier disruption. The mechanisms behind this process are not fully understood. Thus, <i>in vitro</i> models that facilitate studying the intestinal barrier and its molecular components are of particular importance in the context of IBD. There are <i>in vitro</i> and <i>ex vivo</i> models that can be used to recapitulate some aspects of IBD. Among these are intestinal explants, crypts, and epithelial 3D-organoids. Here we describe some practical limitations of isolated crypts, gut tissue explants, and intestinal organoids as models in epithelial barrier biology, and TJ in particular. Our findings demonstrate that only 3D intestinal organoids formed from single cells are suitable to study barrier permeability <i>in vitro</i>, as primary crypt-derived organoids do not retain epithelial integrity due to cell death. Importantly, 3D organoids raised in culture conditions may fail to recapitulate inflammatory and barrier phenotypes of the source mouse model. To study the features of the inflamed epithelium, <i>ex vivo</i> intestinal explants and crypts were employed. We show here that isolated crypts do not preserve native TJ structure in a long-term experimental setting and tend to disintegrate in the unsupported culture environment. However, intestinal explants were stable in culture conditions for about 24 hours and demonstrated their applicability for short-term living tissue imaging and fluorescence recovery after photobleaching (FRAP). Thus, a combination of 3D organoids and intestinal explants provides a more accurate experimental platform to understand the intestinal epithelial barrier.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2423137"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584404","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":"Potential of nutraceuticals in celiac disease.","authors":"Mahtab Jahdkaran, Nastaran Asri, Hadi Esmaily, Mohammad Rostami-Nejad","doi":"10.1080/21688370.2024.2374628","DOIUrl":"10.1080/21688370.2024.2374628","url":null,"abstract":"<p><p>Celiac Disease (CD) is the most common hereditarily-based food intolerance worldwide and a chronic inflammatory condition. The current standard treatment for CD involves strict observance and compliance with a gluten-free diet (GFD). However, maintaining a complete GFD poses challenges, necessitating the exploration of alternative therapeutic approaches. Nutraceuticals, bioactive products bridging nutrition and pharmaceuticals, have emerged as potential candidates to regulate pathways associated with CD and offer therapeutic benefits. Despite extensive research on nutraceuticals in various diseases, their role in CD has been relatively overlooked. This review proposes comprehensively assessing the potential of different nutraceuticals, including phytochemicals, fatty acids, vitamins, minerals, plant-based enzymes, and dietary amino acids, in managing CD. Nutraceuticals exhibit the ability to modulate crucial CD pathways, such as regulating gluten fragment accessibility and digestion, intestinal barrier function, downregulation of tissue transglutaminase (TG2), intestinal epithelial morphology, regulating innate and adaptive immune responses, inflammation, oxidative stress, and gut microbiota composition. However, further investigation is necessary to fully elucidate the underlying cellular and molecular mechanisms behind the therapeutic and prophylactic effects of nutraceuticals for CD. Emphasizing such research would contribute to future developments in CD therapies and interventions.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2374628"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471058","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":"Frataxin deficiency and the pathology of Friedreich's Ataxia across tissues.","authors":"Wesley S Ercanbrack, Mateo Ramirez, Austin Dungan, Ella Gaul, Sarah J Ercanbrack, Rebecca A Wingert","doi":"10.1080/21688370.2025.2462357","DOIUrl":"10.1080/21688370.2025.2462357","url":null,"abstract":"<p><p>Friedreich's Ataxia (FRDA) is a neurodegenerative disease that affects a variety of different organ systems. The disease is caused by GAA repeat expansions in intron 1 of the <i>Frataxin</i> gene (<i>FXN</i>), which results in a decrease in the expression of the FXN protein. FXN is needed for the biogenesis of iron-sulfur clusters (ISC) which are required by key metabolic processes in the mitochondria. Without ISCs those processes do not occur properly. As a result, reactive oxygen species accumulate, and the mitochondria cease to function. Iron is also thought to accumulate in the cells of certain tissue types. These processes are thought to be intimately related to the pathologies affecting a myriad of tissues in FRDA. Most FRDA patients suffer from loss of motor control, cardiomyopathy, scoliosis, foot deformities, and diabetes. In this review, we discuss the known features of FRDA pathology and the current understanding about the basis of these alterations.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2462357"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12667646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143469306","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":"Treatment with TNFα and lipolysis-stimulated lipoprotein receptor (LSR) antibody in the presence of HDAC inhibitors promotes apoptosis in human salivary duct adenocarcinoma.","authors":"Soshi Nishida, Takumi Konno, Takayuki Kohno, Masahiko Ohyanagi, Masaya Nakano, Kizuku Ohwada, Kazufumi Obata, Takuya Kakuki, Akito Kakiuchi, Makoto Kurose, Kenichi Takano, Takashi Kojima","doi":"10.1080/21688370.2024.2437215","DOIUrl":"10.1080/21688370.2024.2437215","url":null,"abstract":"<p><p>Lipolysis-stimulated lipoprotein receptor (LSR), a lipid metabolism-related factor localized in tricellular tight junctions (tTJs), plays an important role in maintaining the epithelial homeostasis. LSR is highly expressed in well-differentiated cancers, and its expression decreases during malignancy. The LSR antibody inhibits cell growth and promotes apoptosis in some cancers. Histone deacetylases (HDACs) are thought to play a crucial role in carcinogenesis, and HDAC inhibitors promote differentiation and prevent cell proliferation and migration in cancers. HDAC inhibitors together with TNFα also induce apoptosis via TNFα-related apoptosis-inducing ligand (TRAIL) in some cancers. In this study, we investigated the apoptosis signaling induced by an anti-LSR antibody in human salivary duct adenocarcinoma (SDC) cell line A253, compared to TRAIL-induced apoptosis. A253 cells were treated with human recombinant TNFα with or without HDAC inhibitor trichostatin A (TSA) and quisinostat (JNJ-26481585). Treatment using TNFα with HDAC inhibitors markedly induced apoptosis in A253 cells and the anti-TNFα antibody prevented the induced apoptosis. A253 cells were treated with an antibody against the extracellular N-terminal domain of human LSR (LSR-N-ab) with or without HDAC inhibitors. Treatment with HDAC inhibitors induced LSR expression in the membranes of A253 cells. Treatment using LSR-N-ab with HDAC inhibitors markedly promoted apoptosis in A253 cells. The tricellular signaling pathway JNK inhibitor SP600125 and Hippo pathway MST1/2 inhibitor XMU-MP-1 prevented the apoptosis induced by treatment using TNFα or LSR-N-ab with HDAC inhibitors. Our findings indicated that treatment with TNFα or LSR-N-ab with HDAC inhibitors might be useful in the therapy for human SDC by enhancing apoptosis.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2437215"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830086","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}