Tissue Barriers最新文献

{"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":"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":"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":"Fistula in Crohn's disease: classification, pathogenesis, and treatment options.","authors":"Kimia Basiji, Nesa Kazemifard, Maryam Farmani, Kasra Jahankhani, Shaghayegh Baradaran Ghavami, Amir Fallahnia, Hesameddin Eghlimi, Adil Mir","doi":"10.1080/21688370.2025.2458784","DOIUrl":"10.1080/21688370.2025.2458784","url":null,"abstract":"<p><p>Crohn's disease is a form of inflammation that affects the gastrointestinal (GI) tract. It is characterized by persistent inflammation in the gut, which can lead to the formation of abnormal connections called fistulas. These fistulas can occur between the GI tract and the abdominal cavity, adjacent organs, or the skin. The most prevalent type of fistula in Crohn's disease patients is the perianal fistula, which forms between the rectum and the skin near the anus. Although the exact cause of fistula formation is not fully understood, research suggests that factors such as epithelial to mesenchymal transition, matrix metalloproteinase, immune system dysregulation, and microbiota may contribute to their development. There is currently no definitive treatment for fistula closure, but options include surgery, endoscopic procedures, antibiotics, biologic agents, and immunosuppressive drugs. These treatments can be used alone or in combination. However, recurrence is a significant challenge that needs to be addressed in the case of fistula treatment. This review provides an overview of the common types of fistulas, their characteristics, the main factors and mechanisms of fistula formation, and available therapeutic options.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2458784"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477869/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068209","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}

{"title":"Size-selective permeation-enhancing modulation of the tight junction by receptor-binding domains of <i>Clostridium perfringens</i> enterotoxin and <i>Clostridium perfringens</i> iota-toxin.","authors":"Keisuke Tachibana, Sayaka Sugimura, Shuko Sakimura, Lin Bai, Hiroshi Aoyama, Hiroyuki Takeda, Yuki Niwa, Masahiro Nagahama, Masuo Kondoh","doi":"10.1080/21688370.2025.2459963","DOIUrl":"10.1080/21688370.2025.2459963","url":null,"abstract":"<p><p>Modulation of claudin-based bicellular tight junction (TJ) and angulin-based tricellular TJ seals has been shown to enhance mucosal permeation of macromolecules, by using the receptor-binding fragments of <i>Clostridium perfringens</i> enterotoxin (C-CPE194, C-CPEmt, and C-CPEm19) and <i>Clostridium perfringens</i> iota-toxin (angubindin-1) as claudin modulators and an angulin modulator, respectively. Here, we compared the activity of these modulators on the TJ in human intestinal Caco-2 cells. All the claudin modulators loosened TJ integrity more potently compared to angubindin-1 with the order of potency being C-CPEm19 > C-CPE194 > C-CPEmt, and results for permeation enhancement were similar. Treatment with C-CPEmt and C-CPE194 at 100 µg/mL for 48 h enhanced the permeation of dextran sized 20 kDa and 70 kDa, respectively. Treatment with C-CPEm19 at 30 µg/mL for 48 h enhanced permeation of dextran with a molecular mass of up to 150 kDa. Furthermore, co-treatment of bicellular TJ modulators, such as C-CPEmt, C-CPE194, and C-CPEm19, and tricellular TJ modulators, such as angubindin-1, showed additive TJ-loosening and permeation-enhancing activities compared with individual treatments; specifically, C-CPEm19 and angubindin-1 co-treatment increased permeation of large molecules (70 kDa and 150 kDa). These findings indicate that TJ modulators may be used as size-selective permeation enhancers.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2459963"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256837","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":"Oncostatin M promotes epithelial barrier dysfunction in patients with eosinophilic chronic rhinosinusitis with nasal polyps.","authors":"Bao-Feng Wang, Ying-Ying Wang, Hai Lin, Yun-Lan Yi","doi":"10.1080/21688370.2024.2399235","DOIUrl":"10.1080/21688370.2024.2399235","url":null,"abstract":"<p><strong>Background: </strong>Oncostatin M (OSM) may be involved in the promotion of mucosal epithelial barrier dysfunction in patients with eosinophilic chronic rhinosinusitis with nasal polyps (Eos CRSwNP) by inducing matrix metalloproteinase (MMP) -1 and -7. The aim was to evaluate the roles and mechanisms of action of OSM on MMP-1 and -7 synthesis from nasal epithelial cells (NECs).</p><p><strong>Methods: </strong>OSM, OSM receptor (OSMR), MMP-1 and -7 expression was evaluated in nasal mucosa or primary NECs from scrapings by quantitative polymerase chain reaction (qPCR), immunofluorescence and immunohistochemistry. OSM and other cytokines were used to stimulate air-liquid interface (ALI) cultured NECs. qPCR, enzyme-linked immunosorbent assay (ELISA) and immunofluorescence were used to evaluate the expression of OSMR, MMP-1, -7 and occludin in NECs.</p><p><strong>Results: </strong>Elevated levels of OSMRβ, MMP-1 and -7 were found in the tissues and scraped NECs of Eos CRSwNP in comparison to them obtained from the inferior turbinate (IT) and control subjects. The levels of OSM and OSMRβ mRNA in tissues were positively correlated with the levels of MMP-1 and -7. OSM stimulation of NECs increased the expression of MMP-1 and -7, and the responses were suppressed by a STAT3 inhibitor, and a PI3K inhibitor respectively. In parallel studies, we found that stimulation with OSM disrupted the localization of occludin, a tight junction protein in NECs. The response was suppressed by a pan-MMP inhibitor.</p><p><strong>Conclusion: </strong>OSM induces the synthesis and release of MMP-1 and -7 in NECs. Furthermore, MMP-1 and -7 promote mucosal epithelial barrier dysfunction in patients with Eos CRSwNP.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2399235"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120751","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":"Dengue virus NS1 hits hard at the barrier integrity of human cerebral microvascular endothelial cells via cellular microRNA dysregulations.","authors":"Apoorva, Atul Kumar, Sunit K Singh","doi":"10.1080/21688370.2024.2424628","DOIUrl":"10.1080/21688370.2024.2424628","url":null,"abstract":"<p><p>Dengue virus (DENV) infections are commonly reported in the tropical and subtropical regions of the world. DENV is reported to exploit various strategies to cross the blood-brain barrier. The NS1 protein of DENV plays an important role in viral neuropathogenesis, resulting in endothelial hyperpermeability and cytokine-induced vascular leak. miRNAs are short non-coding RNAs that play an important role in post-transcriptional gene regulations. However, no comprehensive information about the involvement of miRNAs in DENV-NS1-mediated neuropathogenesis has been explored to date. We observed that DENV-NS1 significantly alters the cellular miRNome of human cerebral microvascular endothelial cells in a bystander fashion. Subsequent target prediction and pathway enrichment analysis indicated that these microRNAs and their corresponding target genes are involved in pathways associated with blood-brain barrier dysfunction such as \"Adherens junction\" and \"Tight junction\". Additionally, several miRNA-mRNA pairs were also found to be involved in cellular signaling pathways related to cytokine production, for instance, \"Jak-STAT signaling pathway\", \"Chemokine signaling pathway\", \"IL-17 signaling pathway\", \"NF-κB signaling pathway\", and \"Viral protein interaction with cytokine and cytokine receptor\". The dysregulated production of inflammatory cytokines is reported to compromise BBB permeability. This study is the first report to demonstrate that DENV-NS1-mediated miRNA perturbations are crucial in compromising endothelial barrier integrity. It also offers insights into potential therapeutic targets to mitigate DENV-NS1-induced vascular permeability and inflammation.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2424628"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142606629","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":"Cell-cell crosstalk in the pathogenesis of acute lung injury and acute respiratory distress syndrome.","authors":"Zhenzhen Zhu, Ying Zhang, Huan Chen, Huali Zhang","doi":"10.1080/21688370.2025.2452082","DOIUrl":"10.1080/21688370.2025.2452082","url":null,"abstract":"<p><p>Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the result of an exaggerated inflammatory response triggered by a variety of pulmonary and systemic insults. The lung tissues are comprised of a variety of cell types, including alveolar epithelial cells, pulmonary vascular endothelial cells, macrophages, neutrophils, and others. There is mounting evidence that these diverse cell populations within the lung interact to regulate lung inflammation in response to both direct and indirect stimuli. The aim of this review is to provide a summary and discussion of recent advances in the understanding of the importance of cell-cell crosstalk in the pathogenesis of ALI/ARDS, with a specific focus on the cell-cell interactions that may offer prospective therapeutic avenues for ALI/ARDS.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2452082"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12506906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967066","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":"Claudin-12: guardian of the tissue barrier or friend of tumor cells.","authors":"Desislava Apostolova, Georgi Apostolov, Dzhemal Moten, Tsvetelina Batsalova, Balik Dzhambazov","doi":"10.1080/21688370.2024.2387408","DOIUrl":"10.1080/21688370.2024.2387408","url":null,"abstract":"<p><p>Tight junctions (TJs) are an important component of cellular connectivity. Claudin family proteins, as a constituent of TJs, determine their barrier properties, cell polarity and paracellular permeability. Claudin-12 is an atypical member of the claudin family, as it belongs to the group of non-classical claudins that lack a PDZ-binding domain. It has been shown that claudin-12 is involved in paracellular Ca²⁺ transients and it is present in normal and hyperplastic tissues in addition to neoplastic tissues. Dysregulation of claudin-12 expression has been reported in various cancers, suggesting that this protein may play an important role in cancer cell migration, invasion, and metastasis. Some studies have shown that claudin-12 gene functions as a tumor suppressor, but others have reported that overexpression of claudin-12 significantly increases the metastatic properties of various tumor cells. Investigating this dual role of claudin-12 is of utmost importance and should therefore be studied in detail. The aim of this review is to provide an overview of the information available to date on claudin-12, including its structure, expression in various tissues and substances that may affect it, with a final focus on its role in cancer.</p>","PeriodicalId":23469,"journal":{"name":"Tissue Barriers","volume":" ","pages":"2387408"},"PeriodicalIF":4.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12363534/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861026","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}