Journal of Extracellular Vesicles最新文献

{"title":"Label-Free Clustering Analysis Platform Drives Cascaded Workflow for Scalable Production of Therapeutic Extracellular Vesicles.","authors":"Jing Zhou, Ping Chen, Xin Chen, Xu Xiao, Haonan Di, Yunyun Hu, Yarong Zhen, Xiaomei Yan","doi":"10.1002/jev2.70333","DOIUrl":"10.1002/jev2.70333","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) have emerged as highly promising natural nanomedicines and nanocarriers, holding transformative potential for the treatment of various diseases. However, the lack of rapid and comprehensive characterization techniques for EV preparation analysis, coupled with the absence of efficient quality control methods, significantly hinders process optimization and large-scale production. To address these challenges, we developed a label-free clustering analysis (LFCA) platform that integrates nano-flow cytometry for particle size distribution analysis with a clustering algorithm to deconvolute EV subpopulations and distinguish them from impurities. This platform enables the rapid quantification of EV component distribution and composition within 5 min using minimal sample input. Leveraging the high-throughput capabilities of LFCA, we established a cascaded workflow incorporating a microcarrier-based 3D culture system, a custom tangential flow filtration device, and multimodal size exclusion chromatography for EV preparation from adipose mesenchymal stem cells. This approach achieves a 4-fold increase in EV yield compared to ultracentrifugation while maintaining comparable purity and preserving EV integrity. Critically, the resulting EVs exhibited enhanced functional potency in pro-angiogenic and anti-inflammatory assays, confirming the clinical relevance of our optimized production system. These advancements provide a scalable solution for EV production, paving the way for clinical applications.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 6","pages":"e70333"},"PeriodicalIF":21.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13291197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Vesicles Released by Picornavirus-Infected Cells Modify Antiviral Immune Cell Responses.","authors":"Xinyi Pei, Janine T A T Stienstra, Margarida Viola, Renee G C Maas, Kyra A Y Defourny, Erik Mul, Saskia C A de Jager, Joost P G Sluijter, Frank J M van Kuppeveld, Esther N M Nolte-'t Hoen","doi":"10.1002/jev2.70305","DOIUrl":"10.1002/jev2.70305","url":null,"abstract":"<p><p>Naked viruses of the family Picornaviridae commonly spread via lysis of infected cells. Recent studies indicate that, prior to cell lysis, naked viruses are packaged and released inside extracellular vesicles (EVs). This has been considered a pro-viral mechanism because EV membranes protect enclosed virions from neutralizing antibodies. Here, we explored whether immune cells can respond to picornavirus-induced EVs. Using two different picornaviruses, we demonstrate that EVs from virus-infected cells stimulate human immune cells to produce the antiviral cytokine type I IFN and chemotactic cytokine IP-10. Virus-containing EVs trigger higher cytokine levels than similar amounts of naked virus. Monocytes are the predominant cell type to interact with and respond to virus-induced EVs. By blocking virion-receptor interactions we demonstrate that both EV-enclosed virions and additional host/virus components in EVs aid in immune cell stimulation. This EV-induced response may provide protection prior to lytic virus release and development of the humoral immune response. We further demonstrate that EV-enclosed viruses, in contrast to naked virus, cannot be opsonized by neutralizing antibodies. This prevents enhanced uptake of EV-enclosed virus and ensuing pro-inflammatory cytokine production by immune cells needed for viral clearance. This work underscores the role of virus-induced EVs in host antiviral responses to picornavirus infections.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 6","pages":"e70305"},"PeriodicalIF":21.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13291189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal Oleic Acid Promotes Lymphangiogenesis and Nodal Metastasis in Cervical Cancer via the AKT/mTOR Pathway.","authors":"Jinqiu Li, Xiaojing Huang, Guzhalinuer Abulizi, Ayshamgul Hasim","doi":"10.1002/jev2.70328","DOIUrl":"10.1002/jev2.70328","url":null,"abstract":"<p><p>Cervical cancer (CC) exhibits a pronounced tropism for regional lymphatic dissemination, a process driven by tumor-associated lymphangiogenesis. While metabolites within the metastatic niche are increasingly recognized as determinants of organotropic metastasis, the role of exosome-mediated metabolite transfer in tumor-lymphatic endothelial cell (LEC) crosstalk remains largely unexplored. Here, we demonstrate that oleic acid (OA) is significantly enriched in both CC lymph node metastases and the peritumoral lymphatic microenvironment. Exosomes derived from highly metastatic CC cells actively package OA in a manner dependent on stearoyl-CoA desaturase (SCD), the rate-limiting enzyme of de novo fatty acid synthesis. Upon internalization by LECs, exosomal OA triggers the AKT/mTOR signaling axis, eliciting robust LEC proliferation and endothelial-to-mesenchymal transition (EndMT), thereby fostering lymphangiogenesis and nodal colonization. Knockdown of SCD abolishes these pro-lymphangiogenic effects, a deficit fully reversed by the reconstitution of OA-loaded exosomes. In vivo, exosomes from SCD-silenced cells exhibit a severely compromised capacity to drive primary tumor growth, intratumoral lymphangiogenesis, and lymph node metastasis (LNM). Notably, free OA administration exerts substantially weaker effects than its exosomal counterpart, underscoring the superior efficiency of exosome-mediated metabolite trafficking. Clinically, FASN and SCD expression are significantly upregulated in lymph node-positive specimens and positively correlate with lymphatic vessel density and p-AKT levels. Furthermore, circulating exosomal OA levels are significantly elevated in patients with nodal involvement, suggesting its potential as a non-invasive diagnostic biomarker. Collectively, our findings establish a paradigm wherein tumor-derived exosomes function as specialized vehicles for intercellular OA transfer, activating the AKT/mTOR pathway to license lymphangiogenic reprogramming. This work identifies exosomal metabolite shuttling as a central node in tumor-lymphatic communication and proposes targeting OA synthesis or exosomal delivery as a promising therapeutic strategy against CC metastasis.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 6","pages":"e70328"},"PeriodicalIF":21.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13291205/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial Integrin-Linked Kinase (ILK) Deficiency Promotes Endothelial Activation and Cardiovascular Dysfunction via Receptor Interacting Protein Kinase-1 (RIPK1) Enriched-Extracellular Vesicle Signalling.","authors":"Alberto Cook-Calvete, María Delgado-Marín, Sara Jorquera Ortega, Silvia Moreta, Mercedes Castro-Pinto, José López-Menendez, Blanca Fernandez-Rodríguez, Julia García-García, Carlos Zaragoza, Marta Saura","doi":"10.1002/jev2.70335","DOIUrl":"10.1002/jev2.70335","url":null,"abstract":"<p><p>Integrin-linked kinase (ILK) maintains endothelial homeostasis by supporting endothelial nitric oxide synthase activity and restraining vascular inflammation. Although endothelial ILK loss is linked to vascular and cardiac disease, the mechanisms driving progression remain unclear. We hypothesized that extracellular vesicles (EVs) released by ILK-deficient endothelial cells propagate endothelial activation and cardiac dysfunction. In endothelial-specific ILK conditional knockout mice, ILK loss induced rapid endothelial activation, marked by increased iNOS, VCAM-1 and ICAM-1, followed by perivascular macrophage accumulation and chronic cardiac inflammation. In vitro, ILK-deficient endothelial cells exhibited barrier dysfunction, NF-κB activation and increased chemokine production. EVs derived from ILK deficient cells were enriched in pro-inflammatory cargo, including receptor-interacting protein kinase 1 (RIPK1), and transferred the activation phenotype to naïve endothelial cells. RIPK1 inhibition in recipient cells or RIPK1 silencing in donor cells abolished EV-induced activation, thereby confirming a necessary role for RIPK1. Endothelial ILK-deficient mice also exhibited increased circulating EVs enriched in endothelial activation markers and RIPK1. Transfer of these EVs to wild type mice induced coronary endothelial activation, macrophage recruitment, microvascular remodelling, cardiac fibrosis, and ventricular dysfunction mimicking the phenotype of the donor mice. RIPK1-dependent inflammatory effects were similarly observed with EVs from atherosclerotic ApoE^-/^- mice and patients with coronary artery disease. These findings reveal an ILK-RIPK1 EV signalling axis that propagates vascular inflammation and promotes cardiac dysfunction, establishing a conserved pathogenic mechanism operative in experimental models and in human coronary artery atherosclerosis.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 6","pages":"e70335"},"PeriodicalIF":21.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13291208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered Pericyte-Targeted Extracellular Vesicles Protect Against Hypoperfusion-Induced Cognitive Impairment and Vascular Demyelination","authors":"Weiwei Shen,&nbsp;Weishi Liu,&nbsp;Min Guo,&nbsp;Tongyao You,&nbsp;Yingzhe Wang,&nbsp;Tiansiyu Wen,&nbsp;Suzhen Liang,&nbsp;Xiaodi Xie,&nbsp;Yanfeng Jiang,&nbsp;Qiang Dong,&nbsp;Jin-Tai Yu,&nbsp;Mei Cui","doi":"10.1002/jev2.70319","DOIUrl":"10.1002/jev2.70319","url":null,"abstract":"<p>Pericyte dysfunction is an early hallmark of vascular cognitive impairment (VCI), yet targeted therapies remain limited. Here, we develop a bio-orthogonal approach to engineer extracellular vesicles (EVs) functionalized with cyclic NGR (cNGR) peptides for selective pericytes targeting. The resulting cNGR-EVs demonstrated efficient targeting of CD13-expressing brain pericytes both <i>in vitro</i> and <i>in vivo</i>. In a mouse model of chronic cerebral hypoperfusion (bilateral common carotid artery stenosis, BCAS), cNGR-EVs preserved pericyte contractility, protected against cerebral hypoperfusion, reduced blood-brain barrier leakage, and attenuated demyelination, leading to improved cognitive performance. Single-cell RNA sequencing further revealed that cNGR-EVs attenuated the majority of BCAS-induced transcriptional changes in pericytes, partially preserved pericyte-mediated intercellular communication, and normalized downstream neuronal and glial gene expression profiles. These findings underscore cNGR-EVs as a pericyte-targeted strategy capable of stabilizing the neurovascular unit, maintaining pericyte function, and preventing cognitive decline and myelin loss, highlighting pericytes as a promising therapeutic target in early VCI treatment.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 6","pages":""},"PeriodicalIF":14.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70319","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Dilution Paradox in Extracellular Vesicle Flow Cytometry.","authors":"Joyce Rops, Naomi Buntsma, Aleksandra Gąsecka, Leonie de Rond, Anne Yaël Nossent, Nyika D Kruyt, Rienk Nieuwland, Edwin van der Pol","doi":"10.1002/jev2.70312","DOIUrl":"10.1002/jev2.70312","url":null,"abstract":"<p><p>Concentrations of extracellular vesicles (EVs) can be measured by flow cytometry, which detects fluorescence and light scattering signals from single particles. To ensure single particle detection, plasma samples are diluted based on their particle concentration, which can differ 100-fold between samples. Here we studied how sample dilution affects EV detection by flow cytometry. EVs were measured in human plasma (i) with different concentrations of spiked-in purified lipoproteins, (ii) at different dilutions, and (iii) using either scatter-triggering or fluorescence-triggering. In addition, the reliability of two published clinical EV studies was evaluated using an analytical model. Our results show that the minimum dilution factor to prevent swarm detection by the light scattering detector can exceed the maximum dilution factor that ensures labelled EVs outnumber fluorescent background events. This 'dilution paradox' precludes reliable detection of both fluorescence and light scattering signals of EVs for some samples. In the two clinical studies, 30% and 65% of the measurements were unreliable, depending on the label used. Therefore, results from previous studies should be re-evaluated. The dilution paradox might be overcome by using fluorescence-triggering at a fixed sample dilution, removing non-EV particles from the sample, removing fluorescent particulates from staining reagents, and setting stricter inclusion criteria.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 6","pages":"e70312"},"PeriodicalIF":21.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13291209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Potency Assays for Therapeutic EVs: The Art of Congruence.","authors":"Mario Gimona, Marca H M Wauben, Sun Young Lee, Marta Monguió-Tortajada, Eva Rohde","doi":"10.1002/jev2.70336","DOIUrl":"10.1002/jev2.70336","url":null,"abstract":"","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 6","pages":"e70336"},"PeriodicalIF":21.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13291194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumour-Derived Extracellular Vesicles Reprogramme Tumour-Associated Macrophages Into Immunosuppressive Phenotype via NOD1 Signalling in Clear Cell Renal Cell Carcinoma","authors":"Xiu-wu Pan,&nbsp;Mu-chen Li,&nbsp;Tian-yue Yang,&nbsp;Yi-fan Liu,&nbsp;Jia-lin Zhou,&nbsp;Yi-fan Tang,&nbsp;Hong-feng Zheng,&nbsp;Jian-gui Liu,&nbsp;Zi-chang Liu,&nbsp;Wen-jie Ma,&nbsp;Wen-yan Li,&nbsp;Zi-xuan Gong,&nbsp;Shun Zhang,&nbsp;Hang-biao Zhang,&nbsp;Bing-nan Lu,&nbsp;Yun-tao Yao,&nbsp;Dong-hao Lyu,&nbsp;Guan-yu Zhu,&nbsp;Yuan-bo Zong,&nbsp;Han-lin Yao,&nbsp;Ai-ping Zhang,&nbsp;Jin Zeng,&nbsp;Si-tu Xiong,&nbsp;Ke-qin Dong,&nbsp;Wang Zhou,&nbsp;Bin Fu,&nbsp;Xin-gang Cui","doi":"10.1002/jev2.70317","DOIUrl":"10.1002/jev2.70317","url":null,"abstract":"<p>Clear cell renal cell carcinoma (ccRCC)-derived extracellular vesicles (EVs) play a pivotal role in myeloid cell differentiation toward immunosuppressive phenotypes, yet the underlying mechanisms remain poorly understood. Through integrated single-nucleus RNA sequencing, EV proteomics, and phenotype validation, we identified NOD1, a pattern recognition receptor (PRR), as a critical mediator of EV-driven macrophage differentiation. Clinically, NOD1 overexpression in ccRCC tissues correlated with increased immunosuppressive macrophage infiltration, immune checkpoint inhibitors (ICIs) therapy resistance, and poor prognosis. Mechanistically, ccRCC-EVs enriched with SCRIB, a Rho GTPase activator, triggered sustained NOD1 activation in macrophages via Rho GTPase signalling. Crucially, NOD1 signalling converged on interferon regulatory factor 4 (IRF4), whose expression might be dynamically regulated through NF-κB activation and MITF suppression. Furthermore, inhibition of NOD1 promotes the therapeutic effect of ICIs in vivo. Our findings unveil a novel EV-mediated immune evasion mechanism in ccRCC and propose the SCRIB-NOD1-IRF4 axis as a therapeutic target to restore anti-tumour immunity.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 6","pages":""},"PeriodicalIF":14.5,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jev2.70317","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148143498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial Extracellular Vesicles (BEVs) Derived from Chryseobacterium Inhibit Dengue Virus Infection by Disrupting Its Structural Integrity.","authors":"Yaqi Gao, Lijian Zhang, Tianci Zhang, Qiufeng Yao, Ruifang Gao, Yue Wang, Yunpeng Zhao, Tingting Zhou, Jikuai Chen, Xing Zhang, Hao Ren, Yongzhe Zhu, Ping Zhao, Zhongtian Qi, Li Luo, Zhaoling Qin","doi":"10.1002/jev2.70302","DOIUrl":"10.1002/jev2.70302","url":null,"abstract":"<p><p>Dengue virus (DENV) infection poses a significant global health threat, and current prevention and treatment strategies are limited by challenges of lacking effective mosquito control measures and antibody-dependent enhancement. This study reports that bacterial extracellular vesicles (BEVs) secreted by a soil bacterium Chryseobacterium aquifrigidense M24 exhibit potent anti-DENV activity by triggering the structural disintegration of DENV particles prior to cellular entry in a dose-dependent manner. Mechanistic investigations revealed that BEVs interact with the viral envelope, inducing premature membrane fusion. This process is characterized by reduced membrane fluidity and irreversible lipid rearrangement, leading to a significant increase in particle density, as shown by iodixanol gradient ultracentrifugation. The proposed 'fusion-triggered structural disruption' is further supported by the induction of aberrant E protein oligomerization and morphological changes observed via transmission electron microscopy. This mechanism is specific to enveloped viruses, as BEVs showed no effect on non-enveloped Enterovirus 71. Crucially, this BEV-mediated inactivation extends to other enveloped viruses, including HCV, WNV and YFV, indicating broad-spectrum potential. Our findings reveal a previously unexplored function of BEVs as virucidal agents, proposing a new 'virus-destructor' strategy that contrasts with conventional fusion inhibitors and offering promising avenues for developing broad-spectrum antiviral drugs.</p>","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 6","pages":"e70302"},"PeriodicalIF":21.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13291215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148308266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to 'Endothelial cell-derived extracellular vesicles alter vascular smooth muscle cell phenotype through high-mobility group box proteins'.","authors":"","doi":"10.1002/jev2.70326","DOIUrl":"10.1002/jev2.70326","url":null,"abstract":"","PeriodicalId":15811,"journal":{"name":"Journal of Extracellular Vesicles","volume":"15 6","pages":"e70326"},"PeriodicalIF":21.7,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13275987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}