Biochimica et biophysica acta. General subjects最新文献

{"title":"Identification and functional validation of GREM2 and PIK3C2G as senescence-associated genes in esophageal squamous cell carcinoma.","authors":"Weifeng Zhao, Shuyan Zhao, Chaojie Wang, Guanzhong Dong, Facai Cui, Mengyao Wang, Zhirui Lin","doi":"10.1016/j.bbagen.2026.131014","DOIUrl":"https://doi.org/10.1016/j.bbagen.2026.131014","url":null,"abstract":"<p><p>Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with dismal clinical outcomes, and how cellular senescence modulates ESCC biology remains poorly understood. Here, we integrated transcriptomic profiles from the TCGA-ESCC cohort with a curated panel of cellular senescence-related genes to identify and functionally validate senescence-associated regulators in ESCC. Univariate Cox regression and consensus clustering stratified ESCC patients into two molecular subtypes with divergent survival. Through differential expression analysis, random forest prioritization, and independent validation in the GSE20347 cohort, we identified GREM2 and PIK3C2G as lead candidate genes. Both were consistently downregulated in ESCC tumors and cell lines, and low expression predicted poorer overall survival. Gain- and loss-of-function experiments demonstrated that GREM2 and PIK3C2G drive p16/p21-dependent cellular senescence, trigger the senescence-associated secretory phenotype (SASP), and restrict proliferation in esophageal epithelial cells. Immune correlation analyses linked both genes to immune cell infiltration, chemokine signaling, and MHC molecule expression in the tumor microenvironment. These findings establish GREM2 and PIK3C2G as senescence-associated tumor suppressors in ESCC, offering candidate biomarkers and a rationale for exploring senescence-directed therapies in this disease.</p>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":" ","pages":"131014"},"PeriodicalIF":2.9,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149190998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone Lactylation-mediated PKM2 promotes gemcitabine resistance in pancreatic adenocarcinoma via the AKT/mTOR/SREBP1 Axis.","authors":"QingHua Yin, Yang Zhou, Kai Liu, Xu Zhang","doi":"10.1016/j.bbagen.2026.130995","DOIUrl":"10.1016/j.bbagen.2026.130995","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor. The efficacy of its first-line chemotherapeutic agent, gemcitabine (GEM), is frequently compromised by acquired resistance. Although pyruvate kinase M2 (PKM2) is a potential target for mitigating GEM resistance, the underlying mechanism remains unclear.</p><p><strong>Methods: </strong>Two PAAD gemcitabine-resistant cell lines, Panc-1/Gem and SW1990/Gem, were constructed, and intracellular lactate levels were quantified. Histone lactylation levels were detected via western blotting (WB). Five pairs of GEM-resistant and GEM-sensitive PAAD tissue samples were collected for immunohistochemistry detection. PKM2 expression in PAAD and resistant cells was examined through bioinformatics analysis, qRT-PCR, and WB. PKM2 knockdown and overexpression models were constructed in GEM-resistant cells. Cell viability, apoptosis, DNA damage, and GEM sensitivity were subsequently assessed using CCK-8, flow cytometry, comet assay, and immunofluorescence. The association between PKM2 and H3K18la was examined by ChIP assay. The mechanism involving the AKT/mTOR/SREBP1 axis was explored using bioinformatics analysis and experimental validation.</p><p><strong>Results: </strong>Histone lactylation levels were elevated in PAAD and GEM-resistant cells. Furthermore, histone lactylation mediated PKM2 upregulation, which promoted cell viability, reduced apoptosis, attenuated DNA damage, and consequently induced GEM resistance. Mechanistically, histone lactylation upregulated PKM2 expression, stimulating the AKT/mTOR/SREBP1 signaling pathway, ultimately promoting GEM resistance in PAAD.</p><p><strong>Conclusion: </strong>This investigation suggests a potential mechanism by which histone lactylation-mediated PKM2 upregulation accelerates GEM resistance in PAAD through activating the AKT/mTOR/SREBP1 pathway.</p>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":" ","pages":"130995"},"PeriodicalIF":2.9,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149029826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to 'Interaction of mushroom tyrosinase with aromatic amines, o-diamines and o-aminophenols' [Biochim. Biophys. Acta (BBA) - General Subjects, 1673 (2004) 170-177].","authors":"Beata Gąsowska, Paweł Kafarski, Hubert Wojtasek","doi":"10.1016/j.bbagen.2026.131003","DOIUrl":"https://doi.org/10.1016/j.bbagen.2026.131003","url":null,"abstract":"","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":" ","pages":"131003"},"PeriodicalIF":2.9,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to \"Smoothened-independent activation of hedgehog signaling by rearranged during transfection promotes neuroblastoma cell proliferation and tumor growth\" [Biochim. Biophys. Acta (BBA) - Gen. Subj. 1860 (2016) 1961-1972].","authors":"Hongfeng Ruan, Huan Luo, Jirong Wang, Xing Ji, Zhongmiao Zhang, Junsong Wu, Xianning Zhang, Ximei Wu","doi":"10.1016/j.bbagen.2026.130998","DOIUrl":"10.1016/j.bbagen.2026.130998","url":null,"abstract":"","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":" ","pages":"130998"},"PeriodicalIF":2.9,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer activity of Pseudomonas fluorescens lectin (PFL) targeting high-mannose glycans on breast cancer cells","authors":"Yuichiro Sato ,&nbsp;Kohei Kawabata ,&nbsp;Chiho Murakami ,&nbsp;Yuta Hatori ,&nbsp;Takanori Kubo ,&nbsp;Yuya Ohtsuki ,&nbsp;Hiroyuki Nishi ,&nbsp;Akira Tokumura ,&nbsp;Kinjiro Morimoto","doi":"10.1016/j.bbagen.2026.130914","DOIUrl":"10.1016/j.bbagen.2026.130914","url":null,"abstract":"<div><div>Aberrant glycosylation is one of the key characteristics of cancer cells. High-mannose-type N-glycans are highly expressed in various types of cancer, making them potentially important therapeutic targets. As a basis for developing new therapeutic drugs targeting high-mannose glycans, we employed <em>Pseudomonas fluorescens</em> lectin (PFL) that specifically binds to high-mannose glycans as a model compound, and analyzed the cellular responses of MDA-MB-231 and T47D breast cancer cell lines. In both cell types, PFL induced the internalization and degradation of cancer-associated molecules such as epidermal growth factor receptor (EGFR), integrins, and immune checkpoint ligands via autophagy, ultimately leading to apoptotic cell death. In T47D cells, changes were observed in the cellular distribution and expression levels of hormone receptors and human epidermal growth factor receptor 2 (HER2) upon treatment with PFL, suggesting a possible compensatory response. Comprehensive analysis of cellular lipids revealed that lysophospholipids were dramatically increased by PFL treatment, regardless of breast cancer cell type. These changes may reflect the dynamic reorganization of lipid membranes associated with membrane traffic and autophagy. Time-lapse experiments using a redox sensor designed to localize to the cell membrane showed that cells transitioned to an oxidized state following PFL treatment. Furthermore, inflammatory substances such as interleukin 8 (IL-8) were significantly increased in MDA-MB-231 cells but not in T47D cells. The results provide insight into the responses and resistance of breast cancer cells to glycan-targeted therapies.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 5","pages":"Article 130914"},"PeriodicalIF":2.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146096750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-dose ascorbic acid prolongs the suppression of cell proliferation by enhancing intracellular oxidative stress–induced damage and inhibits invasion and adhesion in human fibrosarcoma HT-1080 cells","authors":"Yasukazu Saitoh ,&nbsp;Yusuke Tanimura ,&nbsp;Shun Ueda ,&nbsp;Tomoya Furuhata ,&nbsp;Manato Takeda ,&nbsp;Kouichi Okawachi ,&nbsp;Yusuke Fukukita","doi":"10.1016/j.bbagen.2026.130908","DOIUrl":"10.1016/j.bbagen.2026.130908","url":null,"abstract":"<div><div>Pharmacological vitamin C (VC) infusion therapy has shown efficacy against various cancer types; however, there are few reports on its effects on fibrosarcoma. This study investigated the impact of high-dose ascorbic acid (AsA), the reduced form of VC, on human fibrosarcoma HT-1080 cells. High-dose AsA (2–5 mM) markedly decreased HT-1080 cell viability compared with normal fibroblasts, indicating cancer cell selectivity. In contrast, dehydroascorbic acid (DehAsA), the oxidized form of AsA, exhibited no cytotoxicity toward cancer cells. Studies using D-AsA and AsA transport inhibitors demonstrated that intracellular AsA transport was not required for cytotoxicity in HT-1080 cells. Our results showed that high-dose AsA induced extracellular H₂O₂ production and increased intracellular H₂O₂, reactive oxygen species (ROS), and Fe²⁺ levels in HT-1080 cells compared with normal fibroblasts, suggesting that strong oxidative stress triggers actin disruption, ATP depletion, DNA damage, and reduced DNA synthesis. Additionally, a 1-h AsA exposure produced a sustained inhibitory effect on cell proliferation lasting at least 72 h. Moreover, high-dose AsA inhibited HT-1080 cell invasion and adhesion, with increased intracellular ROS likely contributing to these effects. These results indicate that high-dose AsA generates extracellular H₂O₂ and subsequently induces cancer cell-specific oxidative damage due to differences in intracellular H₂O₂ and Fe²⁺ levels, which differ between normal fibroblasts and HT-1080 cells. These actions lead to cancer cell-selective toxicity and prolonged growth-suppressive effects induced by high-dose AsA.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 4","pages":"Article 130908"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146050351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COX-2 downregulation via G-quadruplex structure induction in the PTGS2-promoter region by mononuclear octahedral cobalt(III) Schiff base complex [CoL3] in colorectal cancer cells","authors":"Abdolvahab Moshtaghian ,&nbsp;Abasalt Hosseinzadeh Colagar ,&nbsp;Ali Khaleghian ,&nbsp;Tahereh Zahedi","doi":"10.1016/j.bbagen.2026.130909","DOIUrl":"10.1016/j.bbagen.2026.130909","url":null,"abstract":"<div><div>G-quadruplex structures within the promoter regions of some oncogenes diminish transcriptional activity. The suppression and downregulation of Cyclooxygenase-2 (COX-2), which is encoded by the prostaglandin-endoperoxide synthase 2 (<em>PTGS2</em>) gene, could control the size of colorectal cancer tumors. This study aimed to investigate the impact of a mononuclear octahedral cobalt(III) Schiff base complex [CoL₃] (L = 2-((allylimino)methyl)-6-methoxyphenol) on the G-quadruplex structures in the <em>PTGS2</em> promoter region and to assess its downregulation effects in the human colorectal cancer cell line HT-29. At first, molecular docking was used to evaluate the binding of [CoL₃] to the <em>PTGS</em>2 promoter region. Then, the potential and stabilization of G-quadruplex formation in the PTGS2 promoter motifs were investigated using circular dichroism (CD) spectroscopy, polyacrylamide gel electrophoresis, and polymerase chain reaction (PCR) stop assays. COX-2 expression was also assessed by real-time PCR and western blot. Molecular docking analysis indicates that [CoL₃] has a potent interaction with the <em>PTGS2</em> promoter region. Additionally, [CoL₃] has an intense inhibitory effect on the <em>PTGS2</em>-PCR stop assay. The CD measurements confirmed the conformational property of G-quadruplex DNA structures induced by [CoL₃]. Treatment of colorectal cancer cells with the [CoL₃] resulted in a modest increase in <em>PTGS2</em> expression by a mean factor of 1.69 (<em>p</em> &lt; 0.05). Conversely, the expression of COX-2 proteins was downregulated significantly, with a mean protein intensity of 0.47 (<em>p</em> &lt; 0.001). Therefore, [CoL₃] induces G-quadruplex formation in the promoter region of <em>PTGS2</em>, which ultimately inhibits protein expression of COX-2. This means that [CoL₃] can be an effective agent for colorectal cancer treatment.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 4","pages":"Article 130909"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dendrimer-based therapeutics in neurological disorders: Innovations and clinical prospects","authors":"Karthikeya Lalitha Siddhartha Pallem,&nbsp;Anjali Jain,&nbsp;Anurag Aswal,&nbsp;Smita Jain,&nbsp;Umesh Gupta","doi":"10.1016/j.bbagen.2026.130903","DOIUrl":"10.1016/j.bbagen.2026.130903","url":null,"abstract":"<div><div>The incidence of brain tumors and other neurodegenerative diseases has been increasing, whereas the treatment opportunities are limited. Brain delivery of the therapeutics has been restricted because of the presence of blood-brain barrier (BBB). Only molecules of molecular weight &lt;400 Da and lipid-soluble are able to cross the BBB making it hard for the treatment. This demands the development of effective nano-carriers that can penetrate the BBB and deliver the therapeutics more efficiently and site specifically. Dendrimers are highly branched polymers having unique structural and functional properties, emerging as the promising carriers for delivering chemotherapy and gene therapy to the central nervous system (CNS). This review comprehensively explores the development of dendrimers, mechanisms in delivering therapeutic agents to the brain across the blood-brain barrier (BBB) and the progress over past years in utilizing the dendrimers for brain delivery of therapeutics.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 4","pages":"Article 130903"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145951245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterogeneous expression of the laminin-binding O-mannosyl glycan on α-dystroglycan in pancreatic cancer cell line MIA PaCa-2 and the correlation with cell properties","authors":"Rieko Imae ,&nbsp;Yuuki Shichi ,&nbsp;Satoshi Ninagawa ,&nbsp;Toshiyuki Ishiwata ,&nbsp;Hiroshi Manya","doi":"10.1016/j.bbagen.2026.130907","DOIUrl":"10.1016/j.bbagen.2026.130907","url":null,"abstract":"<div><div>α-Dystroglycan (α-DG) is a central component of the dystrophin-glycoprotein complex, with the characteristic O-mannosyl glycan modification, which binds to several extracellular matrix proteins such as laminin. Disruption in the synthesis of laminin-binding glycan on α-DG is related to muscular dystrophies. In addition, loss of this glycan is frequently observed in many cancers, including pancreatic ductal adenocarcinoma (PDAC), correlating with poor prognosis. However, the significance of this glycan in the pathology of cancer remains unclear. This study aimed to clarify the biological significance of laminin-binding O-mannosyl glycan on α-DG in PDAC cells. Since a tumor-derived cancer cell line consists of cells with diverse characteristics, we first obtained several single-cell-derived clones using MIA PaCa-2, a commonly used undifferentiated PDAC cell line, and found that the laminin-binding glycan modification level on α-DG differs among the various clones. The glycan modification level correlated well with the mRNA expression level of LARGE1, the enzyme that synthesizes the laminin-binding structure on the glycan. We analyzed several PDAC cell properties, such as cellular morphology, proliferation and migration/invasion abilities, and examined their correlation with the glycan modification. We found that a high level of laminin-binding O-mannosyl glycan modification on α-DG correlated with the elongated cell morphology, high invasion ability, and low membrane blebbing activity, and vice versa. Furthermore, manipulation of the laminin-binding O-mannosyl glycan synthesis confirmed that this glycan partially contributed to these properties. Overall, this study provides valuable insights into the roles of the laminin-binding glycan on α-DG in PDAC.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 4","pages":"Article 130907"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid in vivo loss of non-T-cell binding capacities of ATLG Grafalon® and ATG Thymoglobulin® explains selective effect on T-cell reconstitution after hematopoietic stem cell transplantation","authors":"Lisa V.E. Oostenbrink,&nbsp;Anja M. Jansen-Hoogendijk,&nbsp;Monique M. van Ostaijen-ten Dam,&nbsp;Carly Vervat,&nbsp;Cornelia M. Jol-van der Zijde,&nbsp;Maarten J.D. van Tol,&nbsp;Robbert G.M. Bredius,&nbsp;Arjan C. Lankester,&nbsp;Marco W. Schilham,&nbsp;Gertjan Lugthart","doi":"10.1016/j.bbagen.2026.130904","DOIUrl":"10.1016/j.bbagen.2026.130904","url":null,"abstract":"<div><div>Anti-thymocyte globulin (ATG Thymoglobulin®) and anti-T-lymphocyte globulin (ATLG Grafalon®) are commonly used in hematopoietic stem cell transplantation (HSCT) for <em>in vivo</em> T-cell depletion, aiming to reduce graft failure and graft-<em>versus</em>-host disease (GvHD). Despite their widespread use, the precise mechanisms by which ATG/ATLG affect immune recovery post-transplantation remain partially understood. In this study, in 289 pediatric HSCT patients treated with ATG (<em>n</em> = 213) or ATLG (<em>n</em> = 76), the relationship between longitudinal serum levels of the active T-lymphocyte-binding component of ATG/ATLG and immune reconstitution was evaluated. High levels of active ATG/ATLG did not prevent the recovery of neutrophils or NK-cells; however, T-cell recovery was delayed until active ATG/ATLG concentrations fell below 1 AU/mL. This is in apparent contradiction with the fact that ATG/ATLG are known not only to contain antibodies against antigens present on T-cells but also to antigens present on other immune and non-immune cells, including B-, NK-cells, granulocytes, monocytes and hematopoietic stem and progenitor cells (HSPC). To address this, we assessed the binding capacities of ATG and ATLG to immune cell subsets and HSPC both <em>in vitro</em> directly from the vial and <em>in vivo</em> from patients serum samples taken at multiple time points pre- and post-HSCT. Shortly after infusion, we observed a rapid reduction of ATG and ATLG binding to all cell types except for T-cells. This real-life specificity of ATG and ATLG explains their selective impact on T-cell reconstitution. These findings enhance our understanding of the mechanisms of action of ATG and ATLG and may contribute to optimization of these therapies.</div></div>","PeriodicalId":8800,"journal":{"name":"Biochimica et biophysica acta. General subjects","volume":"1870 4","pages":"Article 130904"},"PeriodicalIF":2.2,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145976108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}