STEM CELLS最新文献

{"title":"Lineage tracing of alpha-to-beta cell transition after injection of Wnt pathway-stimulated human multipotent stromal cell-secreted proteins.","authors":"Ajaya Sharma, Gillian I Bell, Nouran N Al-Banaa, Kushvir Saini, Caleb Podgers, Anargyros Xenocostas, David A Hess","doi":"10.1093/stmcls/sxag061","DOIUrl":"https://doi.org/10.1093/stmcls/sxag061","url":null,"abstract":"<p><p>Diabetes is projected to affect >600 million people by 2045. Although life-saving insulin therapy can manage hyperglycemia, exogenous insulin is not a cure for diabetes, and life-expectancy for those affected is reduced by 10-15 years. Regenerative therapies aimed at replenishing functional beta cell mass have gained interest. However, the cellular mechanisms that mediate islet regeneration remain unclear. We have shown that human bone marrow-derived multipotent stromal cells (MSC), licenced by WNT-pathway activation using CHIR99021 (CHIR), secrete factors (CHIR CdM) that promote beta-cell recovery in streptozotocin (STZ)-treated immunodeficient NOD/SCID mice. Here, we investigated whether this regeneration involved alpha-to-beta cell conversion, using a Glucagon-iCre;Rosa26-TdTomato (GcgXTdT) lineage-tracing model. Following hyperglycemia induction with STZ and intrapancreatic injection of CHIR CdM, TdTomato+/insulin+ cells were transiently increased within 4 days of injection, indicating alpha cell plasticity and acquisition of insulin expression. CHIR CdM injection also increased the abundance and proliferation of insulin+ cells at day 28. Additionally, CHIR CdM injection altered infiltrating pancreatic immune cell composition, including increased CD4+ and CD68+ cells. Together, these findings demonstrate that intrapancreatic administration of a single injection of CHIR CdM initiates a regenerative response characterized by alpha-to-beta cell plasticity, insulin+ cell-proliferation, and immune remodeling in immune competent GcgxTdT mice. While additional regenerative stimuli may be required for beta cell maturation to restore glycemic control, understanding the mechanisms by which pancreatic beta cell regeneration is initiated in the presence of immune cells may help inform therapies for the treatment of diabetes.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149340079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TAS1R3 biases bone marrow stromal cell fate toward adipogenesis through PLCβ4-p38 signaling.","authors":"Anna Yoshimura, Takuma Matsubara, William N Addison, Sen Higashi, Moyuri Inoue, Osamu Kaminuma, Hiroshi Takeuchi, Shoichiro Kokabu","doi":"10.1093/stmcls/sxag059","DOIUrl":"https://doi.org/10.1093/stmcls/sxag059","url":null,"abstract":"<p><p>How mesenchymal lineage allocation is regulated by nutrients remains poorly understood. Here, we identify TAS1R3, which has been recognized as a component of taste receptors in the taste buds, as being expressed in bone marrow stromal cells (BMSCs) and as a regulator of BMSC fate. Genetic deletion or pharmacological inhibition of TAS1R3 impaired adipogenic differentiation in primary BMSCs, whereas TAS1R3 overexpression enhanced adipogenesis in a BMSC-derived cell line. Consistent results were observed in a human MSC model, in which TAS1R3 promoted adipogenic differentiation and suppressed osteogenic differentiation. Transcriptomic, pharmacological, and knockdown analyses showed that TAS1R3 promotes adipogenesis through phospholipase C beta 4 (PLCβ4)-dependent p38 mitogen-activated protein kinase (MAPK) activation. In contrast, under osteogenic conditions, TAS1R3 attenuated p38 phosphorylation, reduced alkaline phosphatase activity, and restrained osteogenic differentiation. Together, these findings identify TAS1R3 as a context-dependent regulator of p38 signaling and show that extraoral TAS1R3 signaling directs mesenchymal lineage allocation toward adipogenesis at the expense of osteogenesis.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149340080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A role for SUMO activating enzyme-2 in human cancer transformation models reveals regulation of self-renewal and induced differentiation.","authors":"Ekta Manocha, Mohammad Reza Karimi, Amy Qiao, Meghan Statchuk, Cyrielle Richard, Allison L Boyd, Mickie Bhatia","doi":"10.1093/stmcls/sxag060","DOIUrl":"https://doi.org/10.1093/stmcls/sxag060","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) are a rare subset of tumor cells that initiate and sustain tumor regrowth and are associated with chemotherapy resistance leading to patient relapse. The molecular processes that endow CSCs with these unique behavioral characteristics are not fully understood. Post-translational modifications (PTMs), such as Small Ubiquitin-like Modifier (SUMO)-ylation, have emerged as one of several shared mechanisms across cancer subtypes also implicated in human CSC biology. Here, we investigated the role of SUMOylation by studying the E1-activating enzyme subunit, SUMO activating enzyme-2 (SAE2), in human models of CSCs and leukemia. Using loss- and gain-of-function strategies, we demonstrate that SAE2 is required and sufficient to sustain CSC self-renewal while its loss promotes differentiation. SAE2 overexpression enhances SUMOylation and stabilizes the central CSC mediator, OCT4 in the transformed-human pluripotent stem cell (t-hPSC) model, potentially by maintaining SAE2/OCT4/β-catenin axis. Knockdown of SAE2 in non-CSC lines such as OCI-AML3 leukemia cells activates AKT/ERK-mediated differentiation signaling leading to suppressed cell proliferation and reduced leukemic engraftment upon xenotransplantation. Our results indicate SAE2 as an important regulator of CSC biology in vitro and in vivo, with dissimilar roles in non-transformed human stem cells. These detailed observations suggest that targeting SAE2 and SUMOylated proteins may offer an attractive line of investigation into CSC regulation and understanding human cancer.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149340078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Msl3-mediated H4K16ac suppresses 2C-like reprogramming by sustaining LINE1 expression in mouse embryonic stem cells.","authors":"Yuqing Zhu, Shuo Cao, Qingying Wang, Jingjing Sun, Qian Song, Shoudong Ye","doi":"10.1093/stmcls/sxag056","DOIUrl":"10.1093/stmcls/sxag056","url":null,"abstract":"<p><strong>Background: </strong>Two-cell-like cells (2CLCs), a rare totipotent-like population within mouse embryonic stem cell (mESC) cultures, serve as a valuable model for studying early embryonic events like zygotic genome activation. However, the molecular mechanisms restraining their spontaneous emergence remain elusive.</p><p><strong>Methods: </strong>Here, we identify Msl3, an essential component of the male-specific lethal complex that is required for H4K16ac deposition, as a key suppressor of 2C-like reprogramming. Msl3-mediated H4K16ac promotes the expression of LINE1 retrotransposons, which act as upstream repressors of the 2C-lineage master regulator Dux.</p><p><strong>Results: </strong>Consequently, Msl3 depletion reduces LINE1 expression, derepresses Dux, and robustly activates 2C-specific genes. Furthermore, LINE1 inhibition leads to heterochromatin dispersal and fragmented nucleoli.</p><p><strong>Conclusions: </strong>Our findings unveil a novel MSL3-H4K16ac-LINE1-Dux axis that actively safeguards mESC pluripotency by suppressing a latent 2C-like program.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149056667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune cell development from human pluripotent stem cells.","authors":"Luisjesus S Cruz, Alejandro R Castañeda, Jakkrapatra Srisantitham, Dan S Kaufman","doi":"10.1093/stmcls/sxag048","DOIUrl":"10.1093/stmcls/sxag048","url":null,"abstract":"<p><p>The landmark derivation of induced pluripotent stem cells (iPSCs) sparked an enormous range of research on development of diverse cell populations. Perhaps no aspect of this work has been as productive as studies on blood and immune cell production. Indeed, essentially all human blood cell populations can be derived from human iPSCs. While derivation of transplantable hematopoietic stem cells (HSCs) from iPSCs has been relatively challenging, clinical translation of iPSC-derived immune cells has been particularly productive. Notably, more patients have been treated with iPSC-derived natural killer (NK) cells than any other iPSC-derived cell type. Use of iPSCs provides a key platform to incorporate multiplexed gene edits before differentiation, enabling NK cells to be engineered with tumor-targeting CARs, cytokine support for improved persistence, enhanced tumor trafficking, and resistance to host immune rejection, modifications uniformly expressed across the entire cellular product. While T cells, macrophages and other immune cells can be produced from human iPSCs, iPSC-derived NK cells have been the most widely used in clinical trials for treatment of refractory malignancies, as well as autoimmune disease. This review summarizes research with a focus on clinical translation of iPSC-derived immune cells, as well as highlights continued challenges and prospects of this field.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13708013/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148816928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paracrine bone-derived senescent secretome is associated with spatially patterned extracellular matrix remodeling and altered biomechanics in human brain organoids.","authors":"Chanul Kim, Luke D Ofria, Hossein Shaygani, Anannya Kshirsagar, Sai Kulkarni, Alan Y Liu, James L Kirkland, Annie Kathuria, Maryam Tilton","doi":"10.1093/stmcls/sxag057","DOIUrl":"10.1093/stmcls/sxag057","url":null,"abstract":"<p><p>Aging is increasingly recognized as a systemic process, yet the mechanisms by which signals from senescent peripheral cells accelerate brain aging remain poorly defined. Here, we used chronic exposure of human cerebral organoids to the secretome of senescent osteocytes to investigate how peripheral aging signals from bone reshape brain tissue architecture. We combined spatially resolved optical fiber-based interferometry nanoindentation with transcriptomic and immunofluorescence profiling, revealing distinct mechanical features across complementary measurements, including lower apparent modulus in intact organoids and spatially localized regions of elevated modulus in cryosectioned specimens. This spatially heterogeneous biomechanical remodeling was accompanied by upregulation of extracellular matrix (ECM), inflammatory, and senescence pathways, and suppression of neurodevelopmental and synaptic gene networks. Our results suggest that chronic paracrine exposure to senescent osteocyte-derived secretome is associated with localized extracellular matrix-related remodeling and mechanical vulnerability in human brain tissue, providing insight into how peripheral cellular senescence may contribute to regional brain fragility during aging. These pilot-scale findings were obtained using a single induced pluripotent stem cell line and a single conditioned-medium batch, with 1-6 experimental replicates per condition across assays; the mechanical analyses were exploratory.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13715799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149163614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging the Translational Gap in Sex-Specific Alzheimer's Disease Using Human iPSC-Based Neural Cell Models.","authors":"Sopak Supakul, Romruedee Phisalaphong, Makalin Changchai, Hideyuki Okano","doi":"10.1093/stmcls/sxag058","DOIUrl":"https://doi.org/10.1093/stmcls/sxag058","url":null,"abstract":"<p><p>Alzheimer's disease (AD) exhibits marked sex differences in disease prevalence, progression, and therapeutic responsiveness, with women disproportionately affected by both cognitive decline and neuropathological burden. Although sex hormones such as estrogen, progesterone, and testosterone have demonstrated neuroprotective effects in experimental systems, clinical outcomes of hormone-based interventions remain inconsistent. Emerging evidence further indicates that sex-specific molecular programs extend beyond endocrine signaling alone and include cell type-specific transcriptional architectures established across the lifespan. Recent single-cell transcriptomic studies have suggested that biological sex fundamentally shapes multicellular brain vulnerability. However, prevailing preclinical systems incompletely model human endocrine aging, sex chromosome biology, and patient-specific genetic heterogeneity, thereby limiting translational relevance. Human induced pluripotent stem cell (iPSC)-derived neural systems provide a new platform for mechanistically interrogating sex-specific pathways within human genetic backgrounds. By preserving donor-specific genetic backgrounds and sex chromosome complement, iPSC-derived neurons, astrocytes, microglia, and multicellular systems enable controlled investigation of hormone-responsive phenotypes, APOE-associated mechanisms, and cell type-specific transcriptional programs. However, their developmental immaturity and incomplete representation of systemic aging, vascular, immune, and endocrine physiology limit direct extrapolation to patients. Integration of these cellular systems with human omics datasets, neuropathological observations, and clinical studies may therefore help address specific components of the translational gap in AD.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149178354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Australian Public Attitudes Toward Organoid Research and Use: A Cross-Sectional Study.","authors":"Eden G Robertson, Kate Hetherington, Maeve McGillycuddy, Megan Munsie, Anai Gonzalez-Cordero","doi":"10.1093/stmcls/sxag054","DOIUrl":"https://doi.org/10.1093/stmcls/sxag054","url":null,"abstract":"<p><p>Organoid technologies offer promising new ways to study human biology and develop innovative therapies. While their scientific potential is clear, public awareness and acceptability remain largely unexplored - critical factors for ethical and equitable implementation. We conducted the first national survey of Australians (N = 502) to assess awareness, knowledge, attitudes, and acceptability of organoid technology. Awareness of stem cells was high, but organoids were largely unfamiliar. After a brief explanatory video, participants appeared to have more accurate conceptual framing (e.g., organoids as \"research tools\" and \"mini-organs\"), though objective knowledge remained limited. There was strong support for organoids, and more people expressed willingness to donate cells for stem cell or organoid research than have previously done so. Acceptability was correlated with attitudes toward animal research, knowledge, and some sociodemographic factors. Overall, public endorsement of organoid technology appears high but conditional, underscoring the need for transparent governance, clear consent, and inclusive communication.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of carcinogenesis resistance in Anatolian blind mole-rat mesenchymal stem cells and assessment of transcriptomic signatures.","authors":"Nese Unver, Ece Tavukcuoglu, Betul Budak, Onurcan Sezginer, Suleyman Can Ozturk, Saniye Elvan Ozturk, Ekim Z Taskiran, Teoman Kankilic, Kazim Yalcin Arga, Gunes Esendagli","doi":"10.1093/stmcls/sxag051","DOIUrl":"10.1093/stmcls/sxag051","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSCs) exhibit dual roles in tumor progression and therapy resistance. However, the blind mole-rat (BMR, Nannospalax xanthodon) exhibits extraordinary natural resistance to spontaneous and induced carcinogenesis, making its MSCs a subject of significant therapeutic interest. This study investigates BMR MSCs' and fibroblasts' resistance to the carcinogen N-methyl-N-nitrosourea (MNU).</p><p><strong>Methods: </strong>We examined the cellular behavior and transcriptomic expression differences of bone marrow-derived MSCs and also fibroblasts isolated and characterized from blind mole-rats after exposure to the chemical carcinogen MNU. Similar analyses were also performed on mouse, rat, and human-derived MSCs, and expression disparities between species were evaluated.</p><p><strong>Results: </strong>While MNU treatment significantly induced apoptosis and reduced cell viability in human and mouse MSCs, BMR MSCs maintained stable proliferation kinetics, viability, and multilineage differentiation potential. Transcriptomic profiling revealed species-specific gene expression patterns, highlighting unique adaptive responses in the BMR. In BMR fibroblasts, MNU treatment suppressed PI3K/Akt signaling and modulated mitochondrial oxidative phosphorylation, whereas BMR MSCs demonstrated a flexible signaling architecture that preserved cellular programming and p53-mediated transcriptional regulation. Cross-species analysis integrated with TCGA datasets identified LAMTOR3 as a critical p53-dependent tumor-protective node.</p><p><strong>Conclusion: </strong>The ability of BMR MSCs to maintain the p53-LAMTOR3 axis following MNU treatment, alongside the suppression of pro-tumoral SMAD signaling, suggests a robust evolutionary strategy to inhibit malignant transformation. These findings provide novel insights into the genomic integrity of the BMR and identify potential biomarkers and therapeutic targets for enhancing cancer resistance.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13641824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149035892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal stem cell therapy for ischemic stroke: bridging clinical evidence and translational challenges.","authors":"Samson Selvaraj","doi":"10.1093/stmcls/sxag052","DOIUrl":"10.1093/stmcls/sxag052","url":null,"abstract":"<p><p>Ischemic stroke remains a major cause of long-term disability worldwide. Despite advances in acute reperfusion therapies, many survivors experience persistent neurological deficits due to irreversible neuronal loss and limited endogenous repair, highlighting the need for effective regenerative strategies. Mesenchymal stem cells (MSCs) have emerged as promising candidates for cell-based therapy because of their multimodal paracrine effects, including immunomodulation, promotion of angiogenesis and neurogenesis, attenuation of neuroinflammation, and enhancement of endogenous neuroplasticity. This Concise Review synthesizes the current clinical evidence supporting MSC therapy for ischemic stroke, critically examines the biological and translational determinants of therapeutic efficacy, and discusses emerging strategies, including engineered MSCs, extracellular vesicle (EV)-based therapies, and integration with neurorehabilitation. A structured literature search of PubMed/MEDLINE, Embase, Web of Science, and the Cochrane Library through June 2026 prioritized randomized controlled trials, systematic reviews, and meta-analyses. The largest contemporary meta-analysis, encompassing 30 clinical studies and 1217 participants, confirmed the favorable safety profile of MSC therapy while emphasizing the need for larger, standardized randomized trials to establish definitive clinical efficacy. Available evidence indicates that MSC therapy is generally safe, with serious treatment-related adverse events being uncommon, and may improve neurological impairment and functional recovery. However, heterogeneity in cell source, manufacturing protocols, administration route, treatment timing, dosing strategies, and patient selection continues to limit definitive conclusions regarding efficacy. Future progress will depend on standardized Good Manufacturing Practice-compliant manufacturing, validated potency assays, optimized patient selection, identification of the optimal therapeutic window, and integration of engineered MSCs, EV-based therapies, and combination approaches with neuromodulation.</p>","PeriodicalId":231,"journal":{"name":"STEM CELLS","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}