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Meeting report - Alpine desmosome disease meeting 2024: advances and emerging topics in desmosomes and related diseases. 会议报告-高山桥粒病会议2024:桥粒和相关疾病的进展和新主题。
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2025-01-15 Epub Date: 2025-01-22 DOI: 10.1242/jcs.263796
Jens Waschke, Masayuki Amagai, Christoph Becker, Mario Delmar, Firat Duru, David R Garrod, Brenda Gerull, Kathleen J Green, Michael Hertl, Andrew P Kowalczyk, Carien M Niessen, Asma Nusrat, Camilla Schinner, Nicolas Schlegel, Sanjeevi Sivasankar, Franziska Vielmuth, Volker Spindler
{"title":"Meeting report - Alpine desmosome disease meeting 2024: advances and emerging topics in desmosomes and related diseases.","authors":"Jens Waschke, Masayuki Amagai, Christoph Becker, Mario Delmar, Firat Duru, David R Garrod, Brenda Gerull, Kathleen J Green, Michael Hertl, Andrew P Kowalczyk, Carien M Niessen, Asma Nusrat, Camilla Schinner, Nicolas Schlegel, Sanjeevi Sivasankar, Franziska Vielmuth, Volker Spindler","doi":"10.1242/jcs.263796","DOIUrl":"https://doi.org/10.1242/jcs.263796","url":null,"abstract":"<p><p>Desmosomes are adhesive cell contacts abundant in tissues exposed to mechanical strain, such as the stratified and simple epithelia of the epidermis and mucous membranes, as well as the myocardium. Besides their role in mechanical cell cohesion, desmosomes also modulate pathways important for tissue differentiation, wound healing and immune responses. Dysfunctional desmosomes, resulting from pathogenic variants in genes encoding desmosomal components, autoantibodies targeting desmosomal adhesion molecules or inflammation, cause the life-threatening diseases arrhythmogenic cardiomyopathy and pemphigus and contribute to the pathogenesis of inflammatory bowel diseases. The Alpine Desmosome Disease Meeting 2024 (ADDM 2024), held in Grainau, Germany in October 2024, connected international researchers from basic sciences with clinical experts from dermatology, cardiology, gastroenterology and surgery. The participants discussed recent advances, identified hot topics in desmosome biology and disease and provided new concepts for pathogenesis and treatment approaches.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rabin8 phosphorylated by NDR2, the canine early retinal degeneration gene product, directs rhodopsin Golgi-to-cilia trafficking. 犬早期视网膜变性(erd)基因产物NDR2/STK38L磷酸化的Rabin8调控视紫红质高尔基到纤毛的运输。
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2025-01-15 Epub Date: 2025-01-23 DOI: 10.1242/jcs.263401
Theresa Fresquez, Beatrice M Tam, Shannon C Eshelman, Orson L Moritz, Michael A Robichaux, Dusanka Deretic
{"title":"Rabin8 phosphorylated by NDR2, the canine early retinal degeneration gene product, directs rhodopsin Golgi-to-cilia trafficking.","authors":"Theresa Fresquez, Beatrice M Tam, Shannon C Eshelman, Orson L Moritz, Michael A Robichaux, Dusanka Deretic","doi":"10.1242/jcs.263401","DOIUrl":"10.1242/jcs.263401","url":null,"abstract":"<p><p>The Rab11-Rabin8-Rab8 ciliogenesis complex regulates the expansion of cilia-derived light-sensing organelles, the rod outer segments, via post-Golgi rhodopsin transport carriers (RTCs). Rabin8 (also known as RAB3IP), an effector of Rab11 proteins and a nucleotide exchange factor (GEF) for Rab8 proteins, is phosphorylated at S272 by NDR2 kinase (also known as STK38L), the canine early retinal degeneration (erd) gene product linked to the human ciliopathy Leber congenital amaurosis (LCA). Here, we define the step at which NDR2 phosphorylates Rabin8 and regulates Rab11-to-Rab8 succession in Xenopus laevis transgenic rod photoreceptors expressing human GFP-Rabin8 and its mutants. GFP-Rabin8 accumulated with endogenous Rabin8 at the Golgi-apposed exit sites (GESs), also known as the trans-Golgi network (TGN). Rabin8 mutants deficient in Rab11 binding prevented membrane association of GFP-Rabin8. GFP-Rabin8 and NDR2 kinase both interacted with the RTC-associated R-SNARE VAMP7 at the trans-Golgi and the GESs. Here, GFP-Rabin8 and the phosphomimetic GFP-Rabin8-S272E integrated into RTCs, which were subsequently functionalized by Rabin8 Rab8 GEF activity. Non-phosphorylatable GFP-Rabin8-S272A caused significant GES enlargement and deformation, possibly leading to unconventional membrane advancement toward the cilium, bypassing RTCs. Rabin8 phosphorylation loss due to an NDR2 gene disruption thereby likely causes dysfunctional rhodopsin Golgi-to-cilia trafficking underlying retinal degeneration and early-onset blindness.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11828469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cell migration signaling through the EGFR-VAV2-Rac1 pathway is sustained in endosomes. 通过EGFR-VAV2-Rac1途径的细胞迁移信号在内体中持续存在。
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2025-01-15 Epub Date: 2025-01-24 DOI: 10.1242/jcs.263541
Itziar Pinilla-Macua, Sachin Surve, Alexander Sorkin
{"title":"Cell migration signaling through the EGFR-VAV2-Rac1 pathway is sustained in endosomes.","authors":"Itziar Pinilla-Macua, Sachin Surve, Alexander Sorkin","doi":"10.1242/jcs.263541","DOIUrl":"10.1242/jcs.263541","url":null,"abstract":"<p><p>Ligand binding to EGFR activates Rho family GTPases, triggering actin cytoskeleton reorganization, cell migration and invasion. Activated EGFR is also rapidly endocytosed but the role of EGFR endocytosis in cell motility is poorly understood. Hence, we used live-cell microscopy imaging to demonstrate that endogenous fluorescently labeled VAV2, a guanine nucleotide exchange factor for Rho GTPases, is co-endocytosed with EGFR in genome-edited human oral squamous cell carcinoma (HSC3) cells, an in vitro model for head-and-neck cancer where VAV2 is known to promote metastasis and is associated with poor prognosis. Chemotactic migration of HSC3 cells toward an EGF gradient is found to require both VAV2 and clathrin-mediated endocytosis. Moreover, sustained activation of Rac1, a Rho family GTPase promoting cell migration and a major substrate of VAV2, also depends on clathrin. Endogenous fluorescently labeled Rac1 localizes to EGFR-containing endosomes. Altogether, our findings suggest that signaling through the EGFR-VAV2-Rac1 pathway persists in endosomes and that this endosomal signaling is required for EGFR-driven cell migration.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11828472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142914947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mitochondrial phosphatase PPTC7 promotes EGFR recycling by facilitating VPS4A endosomal localization. 线粒体磷酸酶PPTC7通过促进VPS4A内体定位促进EGFR再循环。
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2025-01-15 Epub Date: 2025-01-31 DOI: 10.1242/jcs.263676
Rahul Baroi, Hilal Ahmad Reshi, SubbaReddy Maddika
{"title":"Mitochondrial phosphatase PPTC7 promotes EGFR recycling by facilitating VPS4A endosomal localization.","authors":"Rahul Baroi, Hilal Ahmad Reshi, SubbaReddy Maddika","doi":"10.1242/jcs.263676","DOIUrl":"10.1242/jcs.263676","url":null,"abstract":"<p><p>PPTC7 is a mitochondrial phosphatase that is essential for mitochondrial biogenesis, metabolism, protein content maintenance and transport. Although the mitochondrial roles of PPTC7 are well characterized, its roles outside the mitochondria are unclear. Here we identified a non-mitochondrial role for PPTC7 in regulating epidermal growth factor receptor (EGFR) trafficking. PPTC7 interacts with and dephosphorylates VPS4A, a crucial ESCRT and multivesicular body-associated protein. We found that PPTC7-mediated dephosphorylation of VPS4A at serine 335 is required for VPS4A stability and its early endosomal localization. Either loss of PPTC7 or presence of constitutively phosphorylated VPS4A led to defective recycling of EGFR, thus leading to EGFR re-routing to lysosomes for degradation. Further, we demonstrate that PPTC7-VPS4A-dependent EGFR recycling promotes the AKT signaling pathway, thus enhancing cell proliferation and migration. Overall, our studies unveil an important mechanism where the PPTC7-VPS4A complex orchestrates an endosomal switch to promote EGFR recycling.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The novel ECM protein SNED1 mediates cell adhesion via the RGD-binding integrins α5β1 and αvβ3. 新的ECM蛋白SNED1通过rgd结合的整合素α5β1和αvβ3介导细胞粘附。
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2025-01-15 Epub Date: 2025-01-22 DOI: 10.1242/jcs.263479
Dharma Pally, Nandini Kapoor, Alexandra Naba
{"title":"The novel ECM protein SNED1 mediates cell adhesion via the RGD-binding integrins α5β1 and αvβ3.","authors":"Dharma Pally, Nandini Kapoor, Alexandra Naba","doi":"10.1242/jcs.263479","DOIUrl":"10.1242/jcs.263479","url":null,"abstract":"<p><p>The extracellular matrix (ECM) is a complex meshwork comprising over 100 proteins. It serves as an adhesive substrate for cells and, hence, plays crucial roles in health and disease. We have recently identified a novel ECM protein, SNED1, and have found that it is required for neural crest cell migration and craniofacial morphogenesis during development and in breast cancer, where it is necessary for the metastatic dissemination of tumor cells. Interestingly, both processes involve the dynamic remodeling of cell-ECM adhesions via cell surface receptors. Sequence analysis revealed that SNED1 contains two amino acid motifs, RGD and LDV, known to bind integrins, the largest class of ECM receptors. We thus sought to investigate the role of SNED1 in cell adhesion. Here, we report that SNED1 mediates breast cancer and neural crest cell adhesion via its RGD motif. We further demonstrate that cell adhesion to SNED1 is mediated by the RGD integrins α5β1 and αvβ3. These findings are a first step toward identifying the signaling pathways activated downstream of the SNED1-integrin interactions guiding craniofacial morphogenesis and breast cancer metastasis.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11828466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Expanding our support for the wider cell biology community.
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2025-01-15 Epub Date: 2025-01-27 DOI: 10.1242/jcs.263832
Michael Way
{"title":"Expanding our support for the wider cell biology community.","authors":"Michael Way","doi":"10.1242/jcs.263832","DOIUrl":"https://doi.org/10.1242/jcs.263832","url":null,"abstract":"","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143046961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Fibre type differences in the organisation of mononuclear cells and myonuclei at the tips of human myofibres. 人肌纤维顶端单个核细胞和肌核组织的纤维类型差异。
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2025-01-15 Epub Date: 2025-01-22 DOI: 10.1242/jcs.263660
Christian Hoegsbjerg, Ask Møbjerg, Ching-Yan Chloé Yeung, Peter Schjerling, Michael R Krogsgaard, Manuel Koch, Michael Kjaer, Arvind G von Keudell, Abigail L Mackey
{"title":"Fibre type differences in the organisation of mononuclear cells and myonuclei at the tips of human myofibres.","authors":"Christian Hoegsbjerg, Ask Møbjerg, Ching-Yan Chloé Yeung, Peter Schjerling, Michael R Krogsgaard, Manuel Koch, Michael Kjaer, Arvind G von Keudell, Abigail L Mackey","doi":"10.1242/jcs.263660","DOIUrl":"10.1242/jcs.263660","url":null,"abstract":"<p><p>The myotendinous junction (MTJ) is a weak link in the musculoskeletal system. Here, we isolated the tips of single myofibres from healthy (non-injured) human hamstring muscles for confocal microscopy (n=6) and undertook RNAscope in situ hybridisation (n=6) to gain insight into the profiles of cells and myonuclei in this region, in a fibre type manner. A marked presence of mononuclear cells was observed coating the myofibre tips (confirmed by serial block face scanning electron microscopy and cryosection immunofluorescence), with higher numbers for type I (median 29; range 16-63) than type II (16; 9-23) myofibres (P<0.05). The number of these cells expressing COL22A1 was comparable between fibre types. Myonuclear number and density gradually increased from the myofibre proper towards the tip for both fibre types (P<0.05). COL22A1 was expressed by similar proportions of myonuclei in type I (median 26%; range 13-56) and type II (19%; 3-67) myofibre tips. 70% of the COL22A1-positive nuclei in the MTJ region were myonuclei, and the remaining 30% were MTJ cells. This insight refines our fundamental understanding of the human MTJ at the cell and structural levels.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864229","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Point contact-restricted cAMP signaling controls ephrin-A5-induced axon repulsion. 点接触限制性cAMP信号控制ephrin- a5诱导的轴突排斥。
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2025-01-15 Epub Date: 2025-01-22 DOI: 10.1242/jcs.263480
Johann Bécret, Claudia Gomez-Bravo, Camille Michaud, Ahlem Assali, Naïg A L Chenais, Izeta Kankadze, Fiona Roche, Sandrine Couvet, Coralie Fassier, Xavier Nicol
{"title":"Point contact-restricted cAMP signaling controls ephrin-A5-induced axon repulsion.","authors":"Johann Bécret, Claudia Gomez-Bravo, Camille Michaud, Ahlem Assali, Naïg A L Chenais, Izeta Kankadze, Fiona Roche, Sandrine Couvet, Coralie Fassier, Xavier Nicol","doi":"10.1242/jcs.263480","DOIUrl":"10.1242/jcs.263480","url":null,"abstract":"<p><p>Signal transduction downstream of axon guidance molecules is essential for steering developing axons. Second messengers including cAMP are key molecules shared by a multitude of signaling pathways and are required for a wide range of cellular processes including axon pathfinding. Yet, how these signaling molecules achieve specificity for each of their downstream pathways remains elusive. Subcellular compartmentation has emerged as a flexible strategy to reach such a specificity. Here, we show that point contact-restricted cAMP signals control ephrin-A5-evoked axon repulsion in vitro by modulating focal adhesion kinase (FAK; also known as PTK2) phosphorylation and the assembly and disassembly rate of point contacts. Consistent with this, preventing point contact-specific cAMP signals in developing retinal ganglion cells in vivo alters the refinement of their terminal axonal arbor in the brain. Altogether, our study identifies point contacts as a compartment containing a local cAMP signal required for ephrin-A5-dependent axon guidance and highlights the crucial role of such subcellularly restricted second messenger signals in the wiring of neuronal circuits.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142949462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Company of Biologists: celebrating 100 years. 生物学家公司:庆祝100周年。
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2025-01-01 Epub Date: 2025-01-06 DOI: 10.1242/jcs.263761
Sarah J Bray, Stephen J Royle, Holly A Shiels, Daniel St Johnston
{"title":"The Company of Biologists: celebrating 100 years.","authors":"Sarah J Bray, Stephen J Royle, Holly A Shiels, Daniel St Johnston","doi":"10.1242/jcs.263761","DOIUrl":"https://doi.org/10.1242/jcs.263761","url":null,"abstract":"","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":"138 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Stem cell expression of CXCR4 regulates tissue composition in the vomeronasal organ. 干细胞表达的CXCR4调节犁鼻器官的组织组成。
IF 3.3 3区 生物学
Journal of cell science Pub Date : 2025-01-01 Epub Date: 2025-01-09 DOI: 10.1242/jcs.263451
André Dietz, Katja Senf, Eva M Neuhaus
{"title":"Stem cell expression of CXCR4 regulates tissue composition in the vomeronasal organ.","authors":"André Dietz, Katja Senf, Eva M Neuhaus","doi":"10.1242/jcs.263451","DOIUrl":"10.1242/jcs.263451","url":null,"abstract":"<p><p>The vomeronasal organ (VNO) detects signaling molecules that often prompt innate behaviors, such as aggression and reproduction. Vomeronasal sensory neurons, classified into apical and basal lineages based on receptor expression, have a limited lifespan and are continuously replaced from a common stem cell niche. Using a combination of single-cell RNA sequencing data, immunofluorescence staining and lineage tracing, we identified CXCR4 expression in proliferative stem cells and the basal neuronal lineage. Mice with a conditional knockout of Cxcr4 showed an increased number of SOX2-positive proliferative stem cells and enhanced basal neuronal lineage maturation. In addition, computational gene perturbation analysis revealed 87 transcription factors that might contribute to neurogenesis, among which was SOX2. Conditional knockout of Cxcr4 did not only disturb neuronal maturation, but also affected non-neuronal cell types, resulting in a decrease of basal lamina lining quiescent stem cells and an increase in sustentacular support cells. Together, these findings enhance our understanding how a common pool of stem cells can give rise to different cell types of the VNO, highlighting the distinct role of CXCR4 in this process.</p>","PeriodicalId":15227,"journal":{"name":"Journal of cell science","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11828470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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