Stem cells and development最新文献

{"title":"Human Embryoid Body-Based Assays for Preclinical Screening of Potential Teratogenic Drugs: Antiviral Drugs for Hepatitis B Virus as Examples.","authors":"Renjun Yang, Nuoya Yin, Yang Zhang, Francesco Faiola","doi":"10.1177/15473287251377795","DOIUrl":"https://doi.org/10.1177/15473287251377795","url":null,"abstract":"<p><p>Ensuring the safety of drugs during pregnancy is a critical concern in clinical practice. Animal tests are not always reliable for accurately identifying human teratogens, as evidenced by the infamous thalidomide case. Therefore, there is an urgent need for rapid, dependable, and cost-effective human in vitro assays for potential teratogenic drugs. Here, we utilized human embryoid body (hEB)-based assays, both serum-free and supplemented with pregnant woman serum, along with RNA-sequencing analyses, to demonstrate the effectiveness of hEB transcriptomics as a powerful tool for identifying potential teratogenic drugs, in comparison with other cell systems. Additionally, we subjected our hEB systems to C_max doses of four nucleoside/nucleotide analogs (adefovir dipivoxil [ADV], entecavir [ETV], lamivudine [LAM], and tenofovir disoproxil fumarate [TDF]), which are used for anti-hepatitis B virus treatment and belong to different pregnancy-related risk categories. Transcriptomics after drug treatments were determined and analyzed for important changes in genes, gene categories, signaling pathways, and cell lineages. TDF and ADV appear to be safer options during the very early stages of embryonic development compared with LAM and ETV. Our findings indicate that EB transcriptomics-based analyses can accurately identify potent teratogens and aid in assessing the potential risk of commonly prescribed drugs during pregnancy.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145082086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Come Fly with Me: <i>Drosophila</i> Intestinal Stem Cells as a Model for Epithelial Homeostasis and Disease.","authors":"Fanila Shahzad, David P Doupé","doi":"10.1177/15473287251375493","DOIUrl":"https://doi.org/10.1177/15473287251375493","url":null,"abstract":"<p><p>Epithelial tissues rely on tightly regulated stem cell populations to sustain self-renewal and repair, with fundamental signaling pathways and molecular mechanisms playing conserved roles across species. While mammalian models, particularly mice, have been widely used to study these processes, the cost, complexity, and ethical considerations associated with these models necessitate complementary approaches. The <i>Drosophila</i> midgut has emerged as a powerful model system for studying epithelial stem cell biology, providing insights into homeostasis, aging, and cancer. The genetic tools, affordability, and rapid experimental timeline of <i>Drosophila</i> make it an ideal system for investigating fundamental principles of epithelial stem cell regulation. Complementary use of <i>Drosophila</i> alongside mammalian <i>in vivo</i> and advanced <i>in vitro</i> models such as organoids has the potential to accelerate discoveries in homeostasis, aging, and cancer biology.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"UC2288-Mediated Increased Osteogenic Expression in Mesenchymal Stem Cells.","authors":"Sina Jafari, Julie Sandria, Priyatha Premnath","doi":"10.1177/15473287251377796","DOIUrl":"https://doi.org/10.1177/15473287251377796","url":null,"abstract":"<p><p>p21 is a cell cycle regulator that has been implicated in regeneration of tissues and in development of certain tumors. p21 inhibition also enhances bone regeneration after injury in p21^-/- mice. To translate these findings to the clinic, we sought an FDA-approved p21 attenuator. UC2288, a derivative of sorafenib, selectively inhibits p21 independently of p53 and induces apoptosis in cancer cells. Given the central role of p21 in mesenchymal stem cell (MSC) proliferation and differentiation, its effects on MSCs merits investigation but remains unknown. Consequently, we hypothesized that UC2288 will improve the osteogenic potential of mesenchymal stem cells by suppressing p21. First, we examined the differential interaction of UC2288 with human bone marrow (BM) MSCs compared with breast cancer cells via viability assays. Increased cell death was observed in cancer cells, particularly at higher concentrations and with longer interaction times, whereas MSCs demonstrated lower cell death. Gene expression assay revealed upregulation of osteogenic genes, though the specific genes overexpressed varied depending on the culture medium. Interestingly, the culture medium also affected p21 expression, where p21 expression was upregulated in DMEM/F12 and downregulated in alpha-MEM as evidenced in gene and protein expression assays. Alizarin Red staining confirmed increased mineralization when UC2288 or UC2288+osteogenic factors were added. These findings indicate that UC2288 promotes osteogenesis in BM-MSCs in a concentration- and time-dependent manner. Further research is needed to optimize conditions for preclinical and clinical translation as an anabolic bone formation therapy.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145067108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravenous Allogeneic Mesenchymal Stem Cell Therapy for Canine Immune-Mediated Hemolytic Anemia: A Retrospective Clinical Evaluation.","authors":"Steven D Garner, Emily D Laughrun","doi":"10.1177/15473287251375491","DOIUrl":"10.1177/15473287251375491","url":null,"abstract":"<p><p>This study evaluates the clinical efficacy and safety of intravenous allogeneic mesenchymal stem cell (MSC) therapy as an adjunct to standard immunosuppressive treatment in dogs diagnosed with primary immune-mediated hemolytic anemia (IMHA), particularly in cases with inadequate response to conventional immunosuppressive protocols. A total of 157 client-owned dogs with IMHA received MSC therapy at Safari Veterinary Care Center or collaborating clinics. A core cohort of 43 dogs met strict inclusion criteria: confirmed primary IMHA, no significant comorbidities, and receipt of at least two MSC treatments. A retrospective analysis was performed on medical records of treated dogs. Packed cell volume (PCV) trends were used to assess treatment response, with success defined as sustained improvement to ≥30% PCV following MSC therapy. Safety was assessed by reviewing for adverse reactions postinfusion. In the core cohort, 76% (33/43) of dogs achieved successful hematological recovery. Across the broader cohort, clinical improvement was also observed, particularly in dogs with poor initial response to standard therapy. No serious adverse events were recorded following MSC infusion. Allogeneic MSC therapy appears to be a well-tolerated and potentially effective adjunctive treatment for canine IMHA, particularly in refractory cases. These findings support further investigation in controlled clinical trials.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":""},"PeriodicalIF":2.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145002313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of the Inflammatory Microenvironment on Odontogenic Differentiation of Dental Pulp Stem Cells.","authors":"Shangzhou Jiang, Youkai Lin, Dingming Huang, Xuelian Tan","doi":"10.1177/15473287251366979","DOIUrl":"10.1177/15473287251366979","url":null,"abstract":"<p><p>The dental pulp not only serves as the tooth's nutritional core but also creates a finely tuned microenvironment that is enriched with blood vessels, nerves, extracellular matrix components, and signaling molecules, all of which guide the fate of resident dental pulp stem cells (DPSCs). Trauma and microbial invasion disrupt this niche, leading to pulpitis and necrosis. Although conventional root canal treatment preserves the tooth's structure by removing infected pulp, it can increase tooth brittleness and impede root development in immature permanent teeth. Harnessing DPSCs' multipotency for pulp regeneration promises to restore the natural pulp-dentin complex in situ. Importantly, DPSCs encounter an inflammatory microenvironment composed of pathogen-associated molecular patterns, a spectrum of pro- and anti-inflammatory cytokines, diverse immune cell phenotypes, and altered matrix signals. While earlier work examined the isolated effects of mediators such as lipopolysaccharide, tumor necrosis factor-alpha, or macrophage-derived exosomes on odontogenic differentiation, this review focuses on how these mediators collectively interact in both synergistic and antagonistic ways within the inflammatory niche. We systematically delineate how these collective stimuli converge on wingless/integrated/beta-catenin, mitogen-activated protein kinase, nuclear factor kappa-B (NF-κB), and bone morphogenetic protein/Sma and Mad related protein pathways to modulate key odontogenic markers (runt-related transcription factor 2, dentin sialophosphoprotein, dentin matrix protein 1, alkaline phosphatase) and mineralization outcomes. By applying a microenvironment-centric lens, we reveal novel targets and strategies to recalibrate inflammation, steer DPSCs toward reparative odontogenesis, and ultimately enhance the efficacy of regenerative endodontic therapies.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"374-384"},"PeriodicalIF":2.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in Sickle Cell Disease Treatment: A Comparative Review of Hematopoietic Stem Cell Transplantation and Gene Therapy (Casgevy and Lyfgenia).","authors":"Omer Tarig Fathi Abdelazim, Abu-Baker Khalid Sharafeldin, Mohammed Kawari, Zahra Abdulla Isa Yusuf Hasan, Zainab Abdulmajeed Toorani","doi":"10.1177/15473287251362882","DOIUrl":"10.1177/15473287251362882","url":null,"abstract":"<p><p>Sickle cell disease (SCD), affecting approximately 2.1% of Bahrain's population, is a prevalent inherited disorder that necessitates effective treatments and long-term management. This review highlights two innovative gene therapies (Casgevy and Lyfgenia) and compares their efficacy and safety with hematopoietic stem cell transplantation (HSCT)-the only curative option currently available for SCD. While HSCT offers a 90% success rate with suitable donors, its limitations include donor scarcity and toxicity. Gene therapies like Casgevy and Lyfgenia show promising efficacy in reducing SCD complications while bypassing such limitations. In the Kingdom of Bahrain, the Bahrain Oncology Center approved Casgevy in December 2023 and completed its first patient treatment in mid-February 2025, making Bahrain an early adopter. This milestone marks a crucial moment in the history of both SCD and gene therapies and thus warrants exploring the considerations revolving around their implementation. Although these therapies seem to offer hope for patients ineligible for HSCT, their long-term outcomes remain unassessed-further studies with extended follow-up are needed to confirm their safety and durability.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"363-373"},"PeriodicalIF":2.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amelogenin Promotes Periodontal Bone Regeneration by Inducing Bone Marrow Mesenchymal Stem Cell Homing.","authors":"Haijuan Zhang, Yuxuan Yang, Yandong Han, Ziyi Hu, Limin Guan, Shuang Wang","doi":"10.1177/15473287251370722","DOIUrl":"10.1177/15473287251370722","url":null,"abstract":"<p><p>Amelogenin has been widely used in clinical practice for periodontal bone regeneration. However, the precise mechanism underlying its osteogenic effects remains incompletely understood. In this study, we hypothesized that amelogenin enhances periodontal bone regeneration by facilitating the migration and homing of bone marrow mesenchymal stem cells (BMMSCs). BMMSCs were used to evaluate the cell migration promoting ability of amelogenin by the Transwell test. Immunofluorescence was performed to assess the beta-catenin nuclear translocation following amelogenin treatment. To investigate amelogenin-induced cell homing in vivo, we established a green fluorescent protein (GFP)-labeled bone marrow transplantation model using BALB/c mice transgenic for GFP. The migratory effects of amelogenin were examined in this model, with Wnt3a, a Wnt/β-catenin pathway activator, serving as a positive control. Subsequently, cell homing and bone regeneration were evaluated through a fluorescence microscope, micro-CT, hematoxylin and eosin (H&E), and Masson staining. In vitro Transwell assays demonstrated that amelogenin significantly enhanced BMMSC migration, with effects comparable with Wnt3a, a canonical Wnt/β-catenin pathway activator. Immunofluorescence analysis revealed pronounced nuclear translocation of β-catenin in BMMSCs following a 24-h amelogenin treatment. Notably, these effects were abolished by a Wnt/β-catenin pathway inhibitor, confirming the pathway's involvement. In GFP-labeled bone marrow-transplanted mice, amelogenin treatment significantly increased GFP⁺ cell recruitment to the bone defect site, mirroring the effects of Wnt3a. Micro-CT and histological (H&E) analyses further demonstrated that both amelogenin and Wnt3a accelerated bone regeneration compared with untreated controls. Crucially, this regenerative effect was suppressed upon Wnt/β-catenin pathway inhibition, reinforcing the mechanistic link between amelogenin and β-catenin-mediated osteogenesis. Amelogenin and Wnt3a promoted periodontal bone regeneration both in vitro and in vivo by enhancing BMMSC migration through Wnt/β-catenin signaling activation.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"395-404"},"PeriodicalIF":2.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144984612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem Cells from Human Exfoliated Deciduous Teeth Improve Motor Function after Sciatic Nerve Injury Through Suppression of Inflammation.","authors":"Takahiro Oyama, Koji Osuka, Yusuke Nishimura, Chiharu Suzuki, Yusuke Ohmichi, Mika Ohmichi, Tomoya Nishii, Naoto Kawaguchi, Yoshitaka Nagashima, Yasuyuki Mitani, Ryuta Saito","doi":"10.1177/15473287251362888","DOIUrl":"10.1177/15473287251362888","url":null,"abstract":"<p><p>Stem cell therapy employing stem cells from human exfoliated deciduous teeth (SHED) has demonstrated efficacy in treating peripheral nerve injury; however, the precise underlying mechanisms remain largely undefined. In this study, we investigated the effects of SHED on signal transducer and activator of transcription 3 (STAT3), a key mediator of inflammation following sciatic nerve injury (SNI). The left sciatic nerve was transected (cut group), sutured and wrapped with cellulose (suture group), or sutured and enveloped with SHED-soaked cellulose (SHED group). The L4-5 segments of the spinal cord were harvested up to 7 days post-SNI, and tissues were separated into ipsilateral and contralateral regions for molecular and immunohistochemical analyses. In the SHED group, the sciatic functional index showed significant improvement compared with the suture group beginning at 4 weeks postinjury, and tibialis anterior muscle mass was markedly restored at 12 weeks. STAT3 phosphorylation at Tyr⁷⁰⁵ (<i>p</i>-STAT3) was prominently elevated between 12 and 48 h post-SNI on the ipsilateral side, but not contralaterally. This phosphorylation was localized to motor neurons in the anterior horn and was substantially attenuated by SHED administration between 24 and 48 h postinjury. Moreover, interleukin (IL)-6 expression was significantly reduced at 12 h, while <i>p</i>-STAT3 and importin β1 levels were notably decreased between 12 and 24 h. Erk signaling was significantly activated in S100β-positive Schwann cells (SCs) on day 4 at the site of SNI in the SHED group. These results suggest that SHED mitigate neuroinflammation by suppressing IL-6 expression and modulating STAT3 activation, while concurrently enhancing remyelination through Erk signaling activation in SCs at the injury site. Collectively, these findings underscore the therapeutic promise of SHED as a potent and innovative intervention for peripheral nerve avulsion injuries.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"385-394"},"PeriodicalIF":2.0,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144839575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intravenous Transplantation of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells and a Change in Chronic Pain.","authors":"Kosuke Mabuchi, Yoshie Takahashi, Mitsue Iketani, Yuka Okinaka, Sota Satani, Toshio Takesaka, Teppei Akita, Atsushi Ishibashi, Toshiyuki Goto, Yosky Kataoka, Akihiko Taguchi","doi":"10.1089/scd.2025.0065","DOIUrl":"10.1089/scd.2025.0065","url":null,"abstract":"<p><p>Globally, more than 300 million individuals experience chronic pain. Chronic inflammation with increased infiltration of activated inflammatory cells is a major cause of chronic pain. Mesenchymal stem cells (MSCs) are known to suppress excessive inflammation, and their mechanism of action has been shown to be a gap junction-mediated interaction with the endothelium and circulating white blood cells. In vitro-expanded autologous adipose tissue-derived MSC were transplanted intravenously into patients with chronic pain. The degree of pain was evaluated before and after treatment using the Faces Pain Scale and Pain Disability Assessment Scale. This study included 28 patients. The potential of MSCs for gap junction-mediated transfer of small water-soluble molecules was evaluated in vitro. Autologous adipose tissue-derived MSC significantly attenuated chronic pain compared with pain before cell transplantation. In vitro analysis confirmed that about 80% of transplanted MSC could transfer small molecules via gap junctions. Our results indicate that transplantation of in vitro-expanded adipose tissue-derived MSC, which can transfer small molecules via gap junctions, is safe and may suppress chronic pain. Further double-blinded clinical studies are required to confirm the effect.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"357-362"},"PeriodicalIF":2.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144532181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Vesicles from Mesenchymal Stromal Cells Modulate Inflammatory Responses on Feline Mixed Glia.","authors":"Nikolia Darzenta, Emily Davis, Anna Cochran, Matthew Murray, Olivia Moore, Maria C Naskou","doi":"10.1089/scd.2025.0042","DOIUrl":"10.1089/scd.2025.0042","url":null,"abstract":"<p><p>The extracellular vesicles (EVs) secreted by mesenchymal stromal cells (MSC-EVs) exhibit immunoregulatory functions dependent on their parent cells. MSC-EVs are promising candidates for treating neuroinflammation in neurological diseases due to their acellular nature and their ability to reach the central nervous system. However, the conditions of MSCs for producing EVs with the highest anti-inflammatory efficacy are still unknown. Therefore, the first objective was to study the characteristics of the EVs produced by MSCs cultured in different conditions. The second objective was to evaluate the <i>in vitro</i> anti-inflammatory properties of those EVs in feline stimulated mixed glia. Umbilical cord-derived MSCs were treated with serum-free (SF) media, inflammatory (IF) media, or media supplemented with 5% EV-depleted fetal bovine serum (FBS). The isolated MSC-EVs were characterized by particle size and yield, and their anti-inflammatory ability was evaluated in lipopolysaccharide (LPS) stimulated feline mixed glia. All EV isolates were <160 nm, and the primary mixed glia consisted of microglia, astrocytes, neurons, and endothelial cells. Our results indicate that IF-EVs statistically significantly decreased the production of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) and downregulated the transcription of the, nuclear factor kappa B p65 subunit in inflammatory mixed glia after 48 hours. In addition, SF- and FBS-EVs significantly reduced <i>in vitro</i> the secretion of IL-6 after 48 hours<i>,</i> but only SF-EVs achieved a significant effect on inhibiting the expression of p65 at 48 hours. Moreover, messenger RNA (mRNA) levels of inducible nitric oxide synthase (iNOS) were significantly decreased following treatment with SF-EV for 24 hours. This study demonstrates that MSC culture conditions affect the therapeutic potential of the secreted EVs in feline mixed glia.</p>","PeriodicalId":94214,"journal":{"name":"Stem cells and development","volume":" ","pages":"343-356"},"PeriodicalIF":2.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}