Journal of dental research最新文献

{"title":"Factors Involved in Enamel Knot Establishment and Cap Formation.","authors":"K Steklikova, L Dalecka, J Kubovciak, C Corneloup, S Pantalacci, M Hovorakova","doi":"10.1177/00220345251316834","DOIUrl":"10.1177/00220345251316834","url":null,"abstract":"<p><p>Development of dentition is a commonly studied process as a representative of the development of ectodermal derivates. A key step is the formation of a signaling center called the enamel knot (EK), which organizes tooth crown formation. In the mouse lower jaw, the anterior part of the tooth-forming region undergoes a series of complex events before the first molar primary EK can form more posteriorly and the tooth can progress through the cap stage. Although much is known about the molecular factors involved in tooth development, disentangling their specific roles is difficult. In this study, we circumvented this problem by isolating the posterior part of the tooth-forming region at embryonic day 13.5 and cultivating it in vitro. By treating them with molecules activating or inhibiting Sonic hedgehog (Shh) and fibroblast growth factor (Fgf) pathways, we demonstrate that Shh plays the role of an inhibitor of EK formation, and we suggest that the FGF pathways may have both positive and negative roles, as seen in hair. By RNA-sequencing of the cultivated isolates after 0, 16, or 24 h in vitro, respectively, we screened for genes whose expression varies with EK and cap formation and pointed to <i>Cdkn2b</i> and <i>Sema3b</i> as 2 promising candidates in this process.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"784-794"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660144","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":"IL6-Dependent PIEZO1 Activation Promotes M1-Mediated Orthodontic Root Resorption via CXCL12/CXCR4.","authors":"Z H Zhang, R Zhu, Y Liu, F F Wang, A Y Jiang, R C Dan, Y H Liu, Y X Tang, J Liu, J Wang","doi":"10.1177/00220345251316472","DOIUrl":"10.1177/00220345251316472","url":null,"abstract":"<p><p>Orthodontic root resorption (ORR) is a common yet significant complication of orthodontic treatment, largely driven by interactions between periodontal ligament cells (PDLCs) and M1 macrophages. Despite the clinical relevance of ORR, the role of mechanosensitive ion channels in PDLC-mediated ORR and the underlying mechanisms regulating inflammatory cell recruitment remain poorly understood. Here, we identified PIEZO1 as a critical mechanosensitive ion channel that modulates monocyte recruitment and ORR. Using in vivo models treated with the PIEZO1 activator Yoda1 and inhibitor AAV-sh<i>Piezo1</i>, we demonstrated that PIEZO1 activation promoted the recruitment of Ly6C^hi inflammatory monocytes and exacerbated ORR. In contrast, PIEZO1 inhibition attenuated ORR and the accumulation of M1 macrophages. Mechanistically, PIEZO1 positively regulated the C-X-C motif chemokine 12 (CXCL12) and its receptor, C-X-C chemokine receptor type 4 (CXCR4). Blocking the CXCL12/CXCR4 axis using the CXCR4 antagonist AMD3100 significantly alleviated ORR, reversed M1 macrophage accumulation, and mitigated the recruitment of CD11b⁺Ly6C^hi monocytes. Transwell migration assays with application of the PIEZO1 activator Yoda1 and PIEZO1 inhibitor GsMTX4 consistently confirmed the PIEZO1/CXCL12/CXCR4 axis as a key driver of PDLC-monocyte interactions. Notably, PIEZO1 overactivation was linked to excessive IL-6 production, and IL-6 deficiency inhibited the activation of PIEZO1 induced by Yoda1, leading to attenuation of ORR, M1 macrophage accumulation, and CXCL12/CXCR4 axis activation. Collectively, these findings reveal PIEZO1 in PDLCs as a pivotal modulator of inflammatory monocyte recruitment via the CXCL12/CXCR4 axis in ORR, with IL-6 playing an essential role in PIEZO1 activation. This study provides new insights into the molecular crosstalk between PDLCs and macrophages, offering potential therapeutic targets for mitigating ORR in orthodontic patients.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"763-773"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617996","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":"Real-Time Photocatalytic Measurement of Dental Materials in an Open System.","authors":"M-Y Lee, H-W Yoon, H Cai, S-J Shin, J-S Kwon","doi":"10.1177/00220345251319320","DOIUrl":"10.1177/00220345251319320","url":null,"abstract":"<p><p>It is common to encounter discrepancies between in vitro and in vivo studies, particularly when assessing the antibiofilm efficacy of dental materials. Typically, dental materials are tested in a closed system where fresh nutrients are not replenished, the test conditions are static, and the same planktonic bacteria persist. However, real environments are characterized by the continuous supply of fresh nutrients, dynamic saliva flow, and the periodic removal of planktonic bacteria through swallowing. To address these differences, we used an open system approach using microfluidic chips that simulate the nutrient and fluid flow conditions of the mouth. This setup enables the spatiotemporal development of biofilms, facilitates real-time observation, and provides deeper insights into the biofilm formation and removal processes. Photocatalytic dental materials are particularly suitable for use with microfluidic chips, as these devices allow real-time tracking of biofilm dynamics, both with and without light exposure. Nitrogen-doped titanium dioxide effectively produces reactive oxygen species (ROS) under visible light conditions, even when embedded in a resin matrix. These ROS have been shown to inhibit <i>Enterococcus faecalis</i> biofilms. The evaluation of the photocatalytic effects of dental materials using microfluidic chips showed that both new and established biofilms were disrupted by ROS production. ROS weakens the interface between the biofilm and dental material, allowing the biofilm mass to be removed by fluid flow. Furthermore, the open system provided by microfluidic chips demonstrated higher accuracy in evaluating antibiofilm efficiency than the conventional system did. Thus, the developed microfluidic chip is a novel and promising tool for assessing antibiofilm properties, with potential applications in various fields.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"870-880"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618000","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 Roles and Molecular Mechanisms of HIF-1α in Pulpitis.","authors":"L Shao, Q Wang, B Chen, Y Zheng","doi":"10.1177/00220345251320970","DOIUrl":"10.1177/00220345251320970","url":null,"abstract":"<p><p>Pulpitis is characterized by inflammation within dental pulp tissue, primarily triggered by bacterial infection. Hypoxia-inducible factor-1α (HIF-1α), a key transcriptional regulator, is stabilized under the hypoxic conditions associated with pulpitis. This review examines the roles and molecular mechanisms of HIF-1α in the pathogenesis and progression of pulpitis. Hypoxia in pulpitis prevents the degradation of HIF-1α, leading to its elevated expression. Furthermore, lipopolysaccharide from invading bacteria upregulates HIF-1α transcription through nuclear factor kappa B and mitogen-activated protein kinase pathways. HIF-1α regulates immunity and pulp remodeling in a stage-dependent manner by controlling various cytokines. During the inflammation stage, HIF-1α promotes recruitment of neutrophils and enhances their bactericidal effects by facilitating neutrophil extracellular trap release and M1 macrophage polarization. Concurrently, HIF-1α contributes to programmed cell death by increasing mitophagy. In the proliferation stage, HIF-1α stimulates immune responses involving T cells and dendritic cells. In the remodeling stage, HIF-1α supports angiogenesis and pulp-dentin regeneration. However, excessive pulpitis-induced hypoxia may disrupt vascular dynamics within the pulp chamber. This disruption highlights a critical threshold for HIF-1α, beyond which its effects might accelerate pulp necrosis. Overall, HIF-1α plays a central role in regulating immunity and tissue remodeling during pulpitis. A comprehensive understanding of the physiological and pathological roles of HIF-1α is essential for the advancement of effective strategies to manage irreversible pulpitis.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"715-724"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660150","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":"Mechanisms Tackling Salivary Gland Diseases with Extracellular Vesicle Therapies.","authors":"P Sawutdeechaikul, S Hwang, J Klangprapan, T V Phan, C Buu Lam, Y-J Yoon, S Seo, S Hong, J-Y Lim, J N Ferreira","doi":"10.1177/00220345251319295","DOIUrl":"10.1177/00220345251319295","url":null,"abstract":"<p><p>Extracellular vesicles (EVs) are lipid-enclosed particles released from cells, containing lipids, DNA, RNA, metabolites, and cytosolic and cell surface proteins. EVs support intercellular communication and orchestrate organogenesis by transferring bioactive molecules in between cells. Mesenchymal stem cells are known to produce EVs, which exhibit immunomodulatory and regenerative capabilities in many target organs, including the salivary glands (SGs). Since cell-based therapies still pose challenges (e.g., donor variability, limited hemocompatibility, and safety), specific EVs may constitute a therapeutic alternative for SG diseases. New EV guidelines (MISEV2023) have recently been updated and reported by our consortium to consolidate the principles of EV biology and expand the boundaries toward innovative therapies. These guidelines provide valuable guidance for researchers to consistently assess the effectiveness of mesenchymal stem cell-derived EV cargo cues, such as microRNA, proteins, and other molecules, to target SG diseases. This review provides a narrative synthesis of preclinical studies on EVs by highlighting EV mechanisms and their potential therapeutic applications for SG diseases, such as radiotherapy-induced SG hypofunction and Sjögren's syndrome, as well as inflammatory and aging-related SG conditions. Additionally, we highlight key areas of the MISEV2023 guidelines that will support future EV-based therapies in SG research. This review adhered to PRESS guidelines (Peer Review of Electronic Search Strategies) and utilized established databases, including Medline/PubMed, Embase, Web of Science, and Scopus, alongside machine learning tools for sorting the most impactful EV studies for SG diseases.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"704-714"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143712479","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 Z-DNA Enhances Cariogenicity of Biofilm.","authors":"S L Han, J Wang, H S Wang, P Yu, L Y Wang, Y L Ou, L J Ding, J Washio, N Takahashi, L L Zhang","doi":"10.1177/00220345251316822","DOIUrl":"10.1177/00220345251316822","url":null,"abstract":"<p><p>Extracellular DNA (eDNA) is one of the core components of the extracellular matrix (ECM) in biofilms and provides attachment sites for microbes and other ECM components. However, little is known about the functions and underlying mechanisms of eDNA in the cariogenicity of dental plaque biofilms. A recent study demonstrated that conformational diversity of eDNA exists in biofilms, and the transition of eDNA from right-handed (B-DNA) to left-handed (Z-DNA) is associated with the structural stability and pathogenicity of biofilms. Caries-related biofilm is a complex multispecies microenvironment. The presence and biological function of the conformational transition of eDNA within this biofilm have not been previously reported. In this study, we found that extracellular Z-DNA is widely present in carious tissues and cariogenic biofilm, especially <i>Streptococcus mutans</i>, indicating its possible role in the occurrence and activity of dental caries. The content of extracellular Z-DNA showed species heterogeneity. The modulation of Z-DNA formation affected the level of extracellular polysaccharide. Increased formation of Z-DNA substantially strengthened the cariogenicity of the biofilm by increasing DNase resistance, structural density, and acid production. These insights provide a new perspective to understand the underlying function of the conformation transition of eDNA in promoting carious lesions, as well as a possible anti-biofilm strategy targeting extracellular Z-DNA.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"774-783"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618062","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":"Role of Pink1 in Regulating Osteoclast Differentiation during Periodontitis.","authors":"H Gou, T Wang, Y Chen, Y Zhou, J Li, Y Xu","doi":"10.1177/00220345251315723","DOIUrl":"10.1177/00220345251315723","url":null,"abstract":"<p><p>Periodontitis has recently been recognized as an inflammatory disease caused by oxidative stress, with mitochondrial dysfunction being a key factor leading to oxidative stress. PTEN-induced kinase 1 (PINK1) is an essential protein for mitochondrial quality control, which protects cells from oxidative stress by inducing mitophagy to degrade damaged mitochondria, but its role in periodontitis has not been elucidated. This study aimed to explore the contribution and underlying mechanisms of Pink1 in regulating the differentiation and function of osteoclasts during periodontitis. Here we observed a significant downregulation of PINK1 expression in periodontitis-affected tissues. Then we constructed a periodontitis model in mice with fluorescently labeled mononuclear/macrophages, and the results showed that as the modeling time extended, the alveolar bone destruction gradually worsened and was accompanied by gradually decreased Pink1 expression in osteoclasts and a significantly increased osteoclast number. In vitro experiments further demonstrated a negative correlation between Pink1 and osteoclast differentiation. In addition, alveolar bone destruction in the <i>Pink1</i> knockout mice was significantly more advanced than that in the littermate wild type mice after ligature-induced periodontitis and enhanced osteoclastogenesis and bone-resorptive capacity in vitro. RNA-sequencing analysis and in vitro validation revealed that the absence of Pink1 led to a decrease in oxidative phosphorylation levels and an enhancement of calcium-mediated signaling, specifically the calcineurin-NFATc1 pathway, via an intracellular calcium source. Further mechanistic studies found that the deficiency of Pink1 inhibited mitophagy but strengthened mitochondrial-endoplasmic reticulum coupling, which, by promoting the interaction of Mfn2-IP3R-VDAC1 proteins, increased the concentration of mitochondrial calcium ions, thereby triggering more active osteoclast differentiation. The aforementioned process can be reversed by the IP3R channel inhibitor Bcl-XL. These findings unveiled that Pink1 was involved in osteoclast differentiation by regulating mitochondrial calcium transport mediated by mitochondria-associated endoplasmic reticulum membranes, providing a new theoretical basis for the pathogenesis and treatment of periodontitis.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"753-762"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618002","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":"Response to Letter to the Editor, \"Oral Health Research in the WHO African Region between 2011 and 2022: A Scoping Review\".","authors":"A Carrasco-Labra, M Glick","doi":"10.1177/00220345251339397","DOIUrl":"10.1177/00220345251339397","url":null,"abstract":"","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"807"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144175599","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":"Cargo-less Nanoparticles Prevent Bone Loss in Periodontitis and Peri-implantitis.","authors":"M H A Saleh, A Roh, K Martin, M Mianecki, A Tariq Sheikh, P Singh, K Akorede, M N Saunders, L D Shea, A Decker, J T Decker","doi":"10.1177/00220345251319256","DOIUrl":"10.1177/00220345251319256","url":null,"abstract":"<p><p>Periodontal and peri-implant diseases are a significant public health problem worldwide, resulting in the destruction of the supporting bone. These bone defects can cause esthetic problems, increased relapse rate, and eventually tooth loss. The etiology of periodontal disease involves an influx of innate immune cells (neutrophils and monocytes) and upregulation of local inflammatory cytokines in the gingiva. Biodegradable polymeric nanoparticles are an inexpensive, safe, and effective means of preventing innate immune activation by bacterial biofilms. We therefore hypothesize that this technology is a potential means of managing periodontal disease. Polylactic acid (PLA) particles were fabricated using an oil-in-water emulsion and used as a therapy in ligature-induced periodontitis and peri-implantitis. Mice were treated daily with nanoparticles or saline control through intravenous injection for 5 or 7 d. Bone loss and quality were characterized using micro-computed tomography and histology, and immune cell infiltrate was characterized by flow cytometry and enzyme-linked immunosorbent assay. PLA particle therapy prevented bone loss in both periodontitis and peri-implantitis. Particle treatment was associated with decreased osteoclast activation. Flow cytometry showed particles were mainly taken up by macrophages and limited inflammatory monocyte recruitment to the ligature site. In vitro evaluation of particle therapy demonstrated the inhibition of toll-like receptor activation during particle treatment. These results extended to monocytes that had been presensitized by titania nanoparticles. Taken together, the results of these experiments demonstrated that cargo-less PLA particle therapy may be a safe, cost-effective therapy to manage inflammatory bone loss in periodontal disease.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"862-869"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143617962","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":"KMT2D Regulates Tooth Enamel Development.","authors":"J-M Lee, H Jung, Q Tang, L Li, S-K Lee, J W Lee, Y Park, H-J E Kwon","doi":"10.1177/00220345251320922","DOIUrl":"10.1177/00220345251320922","url":null,"abstract":"<p><p>Amelogenesis, the process of enamel formation, is tightly regulated and essential for producing the tooth enamel that protects teeth from decay and wear. Disruptions in amelogenesis can result in amelogenesis imperfecta, a group of genetic conditions characterized by defective enamel, including enamel hypoplasia, marked by thin or underdeveloped enamel. Mutations in the <i>KMT2D</i> (<i>MLL4</i>) gene, which encodes histone H3 lysine 4 methyltransferase, are associated with Kabuki syndrome, a developmental disorder that can involve dental anomalies such as enamel hypoplasia. However, the specific role of KMT2D in amelogenesis remains poorly understood. To address this gap, we generated a conditional knockout (cKO) mouse model with ectoderm-specific deletion of <i>Kmt2d</i> (<i>Krt14-Cre;Kmt2d</i>^<i>fl/fl</i>, or <i>Kmt2d</i>-cKO) and characterized the resulting enamel defects using gross, radiographic, histologic, cellular, and molecular analyses. Micro-computed tomography and scanning electron microscopy revealed that adult <i>Kmt2d</i>-cKO mice exhibited 100% penetrant amelogenesis imperfecta, characterized by hypoplastic and hypomineralized enamel, partially phenocopying human Kabuki syndrome. Additionally, <i>Kmt2d</i>-cKO neonates developed molar tooth germs with subtle cusp shape alterations and mild delays in ameloblast differentiation at birth. RNA sequencing analysis of the first molar tooth germ at birth revealed that 33.7% of known amelogenesis-related genes were significantly downregulated in the <i>Kmt2d</i>-cKO teeth. Integration with KMT2D CUT&RUN sequencing results identified 8 overlapping genes directly targeted by KMT2D. Reanalysis of a single-cell RNA sequencing data set in the developing mouse incisors revealed distinct roles for these genes in KMT2D-regulated differentiation across various cell subtypes within the dental epithelium. Among these genes, <i>Satb1</i> and <i>Sp6</i> are likely direct targets involved in the differentiation of preameloblasts into ameloblasts. Taken together, we propose that KMT2D plays a crucial role in amelogenesis by directly activating key genes involved in ameloblast differentiation, offering insights into the molecular basis of enamel development and related dental pathologies.</p>","PeriodicalId":94075,"journal":{"name":"Journal of dental research","volume":" ","pages":"920-928"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660147","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}