Biomedical Journal最新文献

{"title":"Multifunctional nanozymes for disease diagnosis and therapy","authors":"","doi":"10.1016/j.bj.2024.100699","DOIUrl":"10.1016/j.bj.2024.100699","url":null,"abstract":"<div><p>The development of nanotechnology has brought about groundbreaking advancements in diseases’ diagnostics and therapeutics. Among them, multifunctional nanomaterials with enzyme-like activities (<em>i.e.</em>, nanozymes) featured with high stability, large surface area for bioconjugation, and easy storage, offer unprecedented opportunities for disease diagnostics and treatment. Recent years have witnessed the great progress of nanozyme-based theranostics. To highlight these achievements, this review first introduces the recent advancements on nanozymes in biosensing and diagnostics. Then, it summarizes the applications of nanozymes in therapeutics including anti-tumor and antibacterial treatment, anti-inflammatory treatment, and other diseases treatment. In addition, several targeted strategies to improve the therapeutic efficacy of nanozyme are discussed. Finally, the opportunities and challenges in the field of diagnosis and therapy are summarized.</p></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"47 4","pages":"Article 100699"},"PeriodicalIF":4.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2319417024000027/pdfft?md5=f13a97c2a8ee1a52300eb8bc48123647&pid=1-s2.0-S2319417024000027-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139555840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secreted proteins encoded by super enhancer-driven genes could be promising biomarkers for early detection of esophageal squamous cell carcinoma","authors":"","doi":"10.1016/j.bj.2023.100662","DOIUrl":"10.1016/j.bj.2023.100662","url":null,"abstract":"<div><h3>Background</h3><p>Early detection of cancer remains an unmet need in clinical practice, and high diagnostic sensitivity and specificity biomarkers are urgently required. Here, we attempted to identify secreted proteins encoded by super-enhancer (SE)-driven genes as diagnostic biomarkers for esophageal squamous cell carcinoma (ESCC).</p></div><div><h3>Methods</h3><p>We conducted an integrative analysis of multiple data sets including ChIP-seq data, secretome data, CCLE data and GEO data to screen secreted proteins encoded by SE-driven genes. Using ELISA, we further identified up-regulated secreted proteins through a small size of clinical samples and verified in a multi-centre validation stage (345 in test cohort and 231 in validation cohort). Receiver operating characteristic curves were used to calculate diagnostic accuracy. Artificial intelligence (AI) method named gradient boosting machine (GBM) were applied for model construction to enhance diagnostic accuracy.</p></div><div><h3>Results</h3><p>Serum EFNA1 and MMP13 were identified, and showed significantly higher levels in ESCC patients compared to normal controls. An integrated Five-Biomarker Panel (iFBPanel) established by combining EFNA1, MMP13, carcino-embryonic antigen, Cyfra21-1 and squmaous cell carcinoma antigen had AUCs of 0.881 and 0.880 for ESCC in test and validation cohorts, respectively. Importantly, the iFBPanel also exhibited good performance in detecting early-stage ESCC patients (0.872 and 0.864). Furthermore, the iFBPanel was further empowered by AI technology which showed excellent diagnostic performance in early-stage ESCC (0.927 and 0.907).</p></div><div><h3>Conclusions</h3><p>Our study suggested that serum EFNA1 and MMP13 could potentially assist ESCC detection, and provided an easy-to-use detection model that might help the diagnosis of early-stage ESCC.</p></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"47 4","pages":"Article 100662"},"PeriodicalIF":4.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2319417023000999/pdfft?md5=4504f2fd3690b113780b1da191002a7e&pid=1-s2.0-S2319417023000999-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41177950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sacral Magnetic Neuromodulation with Intermittent Theta Burst Waveform Enhances Overactive Bladder: In Vivo Study.","authors":"Nurida Khasanah, Hung-Yen Chin, Wei-Lun Lo, Bor-Shing Lin, Hung-Chou Chen, Jian-Chiun Liou, Chun-Wei Wu, Chih-Wei Peng","doi":"10.1016/j.bj.2024.100775","DOIUrl":"https://doi.org/10.1016/j.bj.2024.100775","url":null,"abstract":"<p><strong>Background: </strong>The current treatment options for overactive bladder (OAB) continue to pose challenges for refractory cases and may involve invasive procedures. To assess the potential benefit of non-invasive repetitive peripheral magnetic stimulation (rPMS) on sacral roots using intermittent theta burst stimulation (iTBS) as treatment option for OAB. The study involved a total of 33 rats, which were divided into three different experimental phases.</p><p><strong>Materials and methods: </strong>To induce bladder overactivity rats were pretreated with a continuous transvesical infusion of 0.5% acetic acid (AA). During bladder infusion, the intravesical pressure was recorded using cystometrography (CMG) to investigate the effects of AA pretreatment and the therapeutic intervention of acute sacral rPMS using iTBS.</p><p><strong>Results: </strong>Pre-application of rPMS with iTBS at a 100% intensity significantly extended the mean first voiding time (Tv) in normal healthy rats to 132%. Acute rPMS iTBS at a 100% intensity resulted in a significant increase of the inter-contraction interval (ICI) to 121%. An AA model was established with continuous saline infusion after 0.5% AA treatment and resulted in significant reductions of Tv to 42% and ICI to 56% of the corresponding control values. Subsequently, rPMS iTBS at a 100% intensity on the sacral nerve effectively inhibited AA-induced bladder overactivity and significantly increased the ICI to 167%∼222%. No significant changes in maximum bladder pressure (Pmax) were found.</p><p><strong>Conclusions: </strong>Sacral nerve rPMS with iTBS demonstrated the ability to suppress AA-induced bladder overactivity. This promising modality could be developed as an alternative approach to enhance bladder continence in OAB syndrome patients.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100775"},"PeriodicalIF":4.1,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141765197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-fat diet-induced increase in glucocorticoids contributes to adipogenesis in obese mice.","authors":"Sheng-Feng Tsai, Pei-Ling Hsu, Mei-Chen Yeh, Hao-Chang Hung, Monica Meng-Chun Shih, Bon-Chu Chung, Chia-Yih Wang, Chih-Jen Chang, Yu-Min Kuo","doi":"10.1016/j.bj.2024.100772","DOIUrl":"https://doi.org/10.1016/j.bj.2024.100772","url":null,"abstract":"<p><strong>Background: </strong>This study was designed to examine how glucocorticoids (GCs) induced by a long-term ingestion of high-fat diet (HFD) mediate the HFD-induced adipose expansion and obesity.</p><p><strong>Material and methods: </strong>To address this goal, we used a unique L/L mouse model that fails to induce its corticosterone (CORT) level, a major type of GCs in rodents, after prolonged exposure to an HFD.</p><p><strong>Results: </strong>We found that, after receiving a 12-week HFD feeding, the L/L mice show less weight gain, milder adipose expansion, and higher plasma levels of triglycerides than the wild-type mice. These changes were reversed by replenishing CORT to L/L mice. When examining the expression levels of various molecules linked to lipid uptake and de novo lipogenesis in CORT-induced adipose expansion, we observed a reduction in the expression of adipose preadipocyte factor 1 (Pref-1), a key regulator in adipogenesis. In 3T3-L1 preadipocyte-like cells, dexamethasone, an agonist of the glucocorticoid receptor, also reduced expressions of Pref-1 and facilitated intracellular accumulation of lipids.</p><p><strong>Conclusions: </strong>Our results suggest that fat ingestion-induced release of CORT contributes to adipose expansion and development of obesity and highlight the pathogenic role of CORT-mediated downregulation of adipose Pref-1 in diet-induced obesity.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100772"},"PeriodicalIF":4.1,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141756990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Pentoxifylline Use and Diabetic Retinopathy in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Multi-Institutional Cohort Study.","authors":"Tzu-Yi Lin, Eugene Yu-Chuan Kang, Nan-Kai Wang, Je-Ho Kang, Kuan-Jen Chen, Wei-Chi Wu, Chi-Chun Lai, Yih-Shiou Hwang","doi":"10.1016/j.bj.2024.100771","DOIUrl":"https://doi.org/10.1016/j.bj.2024.100771","url":null,"abstract":"<p><strong>Background: </strong>Pentoxifylline is administrated to improve the hemodynamics of patients with chronic kidney disease (CKD). Despite the improvement of capillary blood flow velocity in retina after pentoxifylline use, no evidence has been provided to prove the protective effect for diabetic retinopathy (DR). Therefore, this study aimed to assess the risk of DR in pentoxifylline users with CKD and diabetes mellitus (DM).</p><p><strong>Material and methods: </strong>In this retrospective cohort study, Chang Gung Research Database, which includes the data of patients with CKD and DM from 2003 to 2019, was used. Each calendar year was divided into 4 data units with 3 months each for every patient and every year during the follow-up. The ocular outcomes were new-onset DR, DR-related complications, and vitreoretinal interventions.</p><p><strong>Results: </strong>Total 56,439 patients without preexisting DR and 5,039 patients with preexisting DR were included in this study. Exposure to pentoxifylline was associated with elevated risk of new-onset DR (adjusted hazard ratio = 1.24, 95% confidence interval = 1.13-1.36) in patients without preexisting DR. Additionally, exposure to pentoxifylline was associated with elevated risk of DR-related complications and vitreoretinal interventions in patients with or without preexisting DR.</p><p><strong>Conclusions: </strong>Exposure to pentoxifylline is associated with elevated risk of DR, regardless of whether patients have preexisting DR.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100771"},"PeriodicalIF":4.1,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Basic implications on three pathways associated with SARS-CoV-2.","authors":"Jong Hoon Lee, Consolato Sergi, Richard E Kast, Badar A Kanwar, Jean Bourbeau, Sangsuk Oh, Mun-Gi Sohn, Chul Joong Lee, Michael D Coleman","doi":"10.1016/j.bj.2024.100766","DOIUrl":"10.1016/j.bj.2024.100766","url":null,"abstract":"<p><p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) interacts between the host and virus and govern induction, resulting in multiorgan impacts. Its pathophysiology involves the followings: 1) the angiotensin-converting enzyme (ACE2) and Toll-like receptor (TLR) pathways: 2) the neuropilin (NRP) pathway: 3) the spike protein pathway. Therefore, it is necessary to block the pathological course with modulating innate lymphoid cells against diverse corona variants in the future.</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100766"},"PeriodicalIF":4.1,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141615886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronobioethics: Symphony of biological clocks observed by 7-day/24-hour ambulatory blood pressure monitoring and cardiovascular health.","authors":"Kuniaki Otsuka, Larry A Beaty, Madoka Sato, Kazunobu Shitakura, Tomoko Kikuchi, Kiyotaka Okajima, Shigehiko Terada, Germaine Cornelissen","doi":"10.1016/j.bj.2024.100753","DOIUrl":"https://doi.org/10.1016/j.bj.2024.100753","url":null,"abstract":"<p><strong>Background: </strong>The high prevalence of desynchronized biological rhythms is becoming a primary public health concern. We assess complex and diverse inter-modulations among multi-frequency rhythms present in blood pressure (BP) and heart rate (HR).</p><p><strong>Subjects: </strong>and Methods: We performed 7-day/24-hour Ambulatory BP Monitoring in 220 (133 women) residents (23 to 74 years) of a rural Japanese town in Kochi Prefecture under everyday life conditions.</p><p><strong>Results: </strong>A symphony of biological clocks contributes to the preservation of a synchronized circadian system. (1) Citizens with an average 12.02-h period had fewer vascular variability disorders than those with shorter (11.37-h) or longer (12.88-h) periods (P<0.05), suggesting that the circasemidian rhythm is potentially important for human health. (2) An appropriate BP-HR coupling promoted healthier circadian profiles than a phase-advanced BP: lower 7-day nighttime SBP (106.8 vs. 112.9 mmHg, P=0.0469), deeper nocturnal SBP dip (20.5% vs. 16.8%, P=0.0101), and less frequent incidence of masked non-dipping (0.53 vs. 0.86, P=0.0378), identifying the night as an important time window.</p><p><strong>Conclusion: </strong>Adaptation to irregular schedules in everyday life occurs unconsciously at night, probably initiated from the brain default mode network, in coordination with the biological clock system, including a reinforced about 12-hour clock, as \"a biological clock-guided core integration system\".</p>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":" ","pages":"100753"},"PeriodicalIF":4.1,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141436624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long noncoding RNA TUG1 promotes malignant progression of osteosarcoma by enhancing ZBTB7C expression","authors":"Xueying An ,&nbsp;Wenshu Wu ,&nbsp;Pu Wang ,&nbsp;Abdurahman Mahmut ,&nbsp;Junxia Guo ,&nbsp;Jian Dong ,&nbsp;Wang Gong ,&nbsp;Bin Liu ,&nbsp;Lin Yang ,&nbsp;Yuze Ma ,&nbsp;Xingquan Xu ,&nbsp;Jianmei Chen ,&nbsp;Wangsen Cao ,&nbsp;Qing Jiang","doi":"10.1016/j.bj.2023.100651","DOIUrl":"10.1016/j.bj.2023.100651","url":null,"abstract":"<div><h3>Background</h3><p>Dysregulation of long non-coding RNAs (lncRNAs) is an important component of tumorigenesis. Aberrant expression of lncRNA taurine upregulated gene 1 (lncTUG1) has been reported in various tumors; however, its precise role and key targets critically involved in osteosarcoma (OS) progression remain unclear.</p></div><div><h3>Methods</h3><p>The expression profiles of lncRNAs and their regulated miRNAs related to OS progression were assessed by bioinformatics analysis and confirmed by qRT-PCR of OS cells. The miRNA targets were identified by transcriptome sequencing and verified by luciferase reporter and RNA pull-down assays. Several <em>in vivo</em> and <em>in vitro</em> approaches, including CCK8 assay, western blot, qRT-PCR, lentiviral transduction and OS cell xenograft mouse model were established to validate the effects of lncTUG1 regulation of miRNA and the downstream target genes on OS cell growth, apoptosis and progression.</p></div><div><h3>Results</h3><p>We found that lncTUG1 and miR-26a-5p were inversely up or down-regulated in OS cells, and siRNA-mediated lncTUG1 knockdown reversed the miR-26a-5p down-regulation and suppressed proliferation and enhanced apoptosis of OS cells. Further, we identified that an oncoprotein ZBTB7C was also upregulated in OS cells that were subjected to lncTUG1/miR-26a-5p regulation. More importantly, ZBTB7C knockdown reduced the ZBTB7C upregulation and ZBTB7C overexpression diminished the anti-OS effects of lncTUG1 knockdown in the OS xenograft model.</p></div><div><h3>Conclusions</h3><p>Our data suggest that lncTUG1 acts as a miR-26a-5p sponge and promotes OS progression <em>via</em> up-regulating ZBTB7C, and targeting lncTUG1 might be an effective strategy to treat OS.</p></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"47 3","pages":"Article 100651"},"PeriodicalIF":5.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2319417023000884/pdfft?md5=3064c0fef20489eefc4debd0e794f500&pid=1-s2.0-S2319417023000884-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9974615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acquired Immune Deficiency Syndrome correlation with SARS-CoV-2 N genotypes","authors":"","doi":"10.1016/j.bj.2023.100650","DOIUrl":"10.1016/j.bj.2023.100650","url":null,"abstract":"<div><h3>Background</h3><p>Epigenetics and clinical observations referring to Betacoronavirus lead to the conjecture that Sarbecovirus may have the ability to infect lymphocytes using a different way than the spike protein. In addition to inducing the death of lymphocytes, thus drastically reducing their population and causing a serious immune deficiency, allows it to remain hidden for long periods of latency using them as a viral reservoir in what is named Long-Covid Disease. Exploring possibilities, the hypothesis is focused on that N protein may be the key of infecting lymphocytes.</p></div><div><h3>Method</h3><p>The present article exhibits a computational assay for the latest complete sequences reported to GISAID, correlating N genotypes with an enhancement in the affinity of the complex that causes immune deficiency in order to determine a good docking with the N protein and some receptors in lymphocytes.</p></div><div><h3>Results</h3><p>A novel high-interaction coupling of N-RBD and CD147 is presented as the main way of infecting lymphocytes, allowing to define those genotypes involved in their affinity enhancement.</p></div><div><h3>Conclusion</h3><p>The hypothesis is consistent with the mutagenic deriving observed on the in-silico assay, which reveals that genotypes N/120 and N/152 are determinant to reduce the Immune Response of the host infecting lymphocytes, allowing the virus persists indefinitely and causing an Acquire Immune Deficiency Syndrome.</p></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"47 3","pages":"Article 100650"},"PeriodicalIF":4.1,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2319417023000872/pdfft?md5=1edaaac170d38d8c21d14f03478af8b3&pid=1-s2.0-S2319417023000872-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut mycobiome in metabolic diseases: Mechanisms and clinical implication","authors":"","doi":"10.1016/j.bj.2023.100625","DOIUrl":"10.1016/j.bj.2023.100625","url":null,"abstract":"<div><p>Obesity, type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) are three common metabolic diseases with high prevalence worldwide. Emerging evidence suggests that gut dysbiosis may influence the development of metabolic diseases, in which gut fungal microbiome (mycobiome) is actively involved. In this review, we summarize the studies exploring the composition changes of gut mycobiome in metabolic diseases and mechanisms by which fungi affect the development of metabolic diseases. The current mycobiome-based therapies, including probiotic fungi, fungal products, anti-fungal agents and fecal microbiota transplantation (FMT), and their implication in treating metabolic diseases are discussed. We highlight the unique role of gut mycobiome in metabolic diseases, providing perspectives for future research on gut mycobiome in metabolic diseases.</p></div>","PeriodicalId":8934,"journal":{"name":"Biomedical Journal","volume":"47 3","pages":"Article 100625"},"PeriodicalIF":4.1,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2319417023000628/pdfft?md5=afebb46db7828c38f6f0185daf91db90&pid=1-s2.0-S2319417023000628-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10045400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}