MedChemComm最新文献

{"title":"Structural insights into the activity of carbapenemases: understanding the mechanism of action of current inhibitors and informing the design of new carbapenem adjuvants","authors":"Tahlia Hatzisarantinos, Elissar Mansour, Jonathan J. Du, Mohamed Fares, David E. Hibbs and Paul W. Groundwater","doi":"10.1039/D5MD00732A","DOIUrl":"10.1039/D5MD00732A","url":null,"abstract":"<p >Antimicrobial resistance challenges the effectiveness of carbapenem antibiotics as last-line therapy, due to the production of both serine and metallo-β-lactamase enzymes. β-Lactamase inhibitors currently available on the market include clavulanic acid, sulbactam, tazobactam, avibactam, relebactam and vaborbactam but, while they are active against serine β-lactamases, they are inactive against the zinc-containing metallo-β-lactamases. This review aims to discuss the distinctive structural qualities of β-lactamase enzymes and to summarise the efficacy of clinically approved and emerging β-lactamase inhibitors against clinically significant carbapenemases.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 12","pages":" 5770-5786"},"PeriodicalIF":3.597,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329757","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":"Bioactive assessment of hexahydroquinoline derivatives prepared via a biochar/Fe3O4@APTMS magnetic catalyst: focus on antidiabetic and antibacterial properties","authors":"A. Thoume, I. Nait Irahal, Z. Dahib, A. Chbel, Z. Loukhmi, F. Abdou-Allah, R. Achagar, M. Zertoubi, D. Benmessaoud Left, N. Bourhim and A. Elmakssoudi","doi":"10.1039/D5MD00594A","DOIUrl":"10.1039/D5MD00594A","url":null,"abstract":"<p >This study aims to develop a green and effective magnetic catalyst, biochar/Fe<small>₃</small>O<small>₄</small>@APTMS, for the one-pot synthesis of bioactive hexahydroquinolines derivatives. Following synthesis, some biological activities were assessed including antibacterial activity and antidiabetic potential through polyol inhibition assays. The reaction involved four-component condensation of ammonium acetate, malononitrile or ethylcyanoacetate, dimedone (5,5-dimethyl-1,3-cyclohexanedione) and some aromatic aldehydes by refluxing in ethanol to afford products in high yields (91–97%) in a short time (10 minutes). Additionally, heterogeneous catalyst provides several advantages, including operational simplicity, rapid reaction times, easy product isolation, and recyclability of unreacted starting materials. The nano catalyst was fully characterized with Fourier Transform Infrared Spectroscopy (FT-IR), Raman, Field Emission Scanning Electron Microscopy (FE-SEM), and energy dispersive X-ray mapping (EDX-Map) while the characterization of the products with Nuclear magnetic resonance spectroscopy (<small>¹³</small>C NMR and <small>¹</small>H NMR) confirmed their structure. Some of the compounds tested showed moderate but significant antidiabetic activity against aldose reductase (IC<small>₅₀</small> values 4.03 to 18.29 μg mL<small>⁻¹</small>) and antibacterial activity against Gram-positive strains of bacteria, <em>Staphylococcus aureus</em> and <em>Enterococcus faecalis</em>, with inhibition zones up to 15.5 mm. These results showed promise for the compounds being used as dual-function therapeutic agents for diabetic complications and microbial infection.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 11","pages":" 5702-5716"},"PeriodicalIF":3.597,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233485","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 lignan compound matairesinol monoglucoside induces type I interferon production in HBV infection immunity by regulating STING signaling","authors":"Mengxin Lin, Zhijun Su, Dawu Zeng, Jiangfu Liu, Minghui Zheng and Ruyi Guo","doi":"10.1039/D5MD00468C","DOIUrl":"10.1039/D5MD00468C","url":null,"abstract":"<p >Background: the urgent need for effective prevention and treatment strategies for hepatitis B virus (HBV) has driven extensive research into natural compounds. This study aims to explore the therapeutic potential of matairesinol monoglucoside (MMG) in the treatment of HBV infection. Methods: primary hepatocytes and Kupffer cells were isolated from wild-type (WT) or stimulator of interferon genes (STING) knockout mice and subsequently infected with AAV-HBV to establish an <em>in vitro</em> anti-HBV assay model. The anti-HBV effects of MMG were assessed by measuring HBV DNA, HBsAg, and HBeAg levels, as well as using qRT-PCR and ELISA to evaluate type I interferon markers (IFN-α and IFN-β), and a luciferase assay. <em>In vivo</em> anti-HBV effects were determined by pre-treating mice with MMG prior to AAV-HBV infection. Results: MMG treatment significantly reduced the expression of HBV DNA, HBsAg, and HBeAg in both primary hepatocytes and Kupffer cells. Additionally, MMG enhanced the production of type I interferons (IFN-α and IFN-β) in both cell types. The knockout of STING diminished the effects of MMG on type I interferon production. Mechanistically, MMG was shown to modulate the STING-TBK1-IRF3 signaling axis, leading to increased IFN production. Conclusions: MMG shows promise as a potential therapeutic agent against HBV by targeting the STING signaling pathway.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 11","pages":" 5686-5693"},"PeriodicalIF":3.597,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145233465","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":"Water-soluble cationic porphyrins with enhanced phototoxicity to cancer cell lines for G4-targeting photodynamic therapy","authors":"Çetin Çelik, Naoko Kakusho, Tianyu Xu, Sung Sik Lee, Naoko Yoshizawa-Sugata, Hisao Masai and Yoko Yamakoshi","doi":"10.1039/D5MD00706B","DOIUrl":"10.1039/D5MD00706B","url":null,"abstract":"<p >Porphyrins are well-known photosensitizers (PSs), a few of which are clinically approved drugs for use in photodynamic therapy (PDT). Porphyrin derivatives including tetra-cationic porphyrins, <em>e.g.</em><strong>TMPyP4</strong>, are also well-studied binders for G-quadruplex (G4) DNA. Since G4 DNAs are known to play a role in malignant transformation of cells, a variety of G4 binders have been used in cancer therapy by regulating the function of G4 DNA. In this study, two water-soluble porphyrins (<strong>1</strong> and <strong>2</strong>), with four terminal cationic moieties connected with alkyl linkers were synthesized as bifunctional molecules for simultaneous G4 binding and PDT-PS. Photoinduced singlet oxygen (<small>¹</small>O<small>₂</small>) generation and DNA cleavage were tested under visible light irradiation revealing the efficient generation of <small>¹</small>O<small>₂</small> in line with photoinduced DNA cleavages. Studies in a cancer cell line (HeLa) and a normal fibroblast (NHDF) cells revealed significantly stronger photocytotoxicities of these porphyrins (<strong>1</strong> and <strong>2</strong>) in comparison to <strong>TMPyP4</strong>, presumably due to better cellular internalization – as observed by flow cytometry. Interestingly, enhanced photocytotoxicity of <strong>1</strong> and <strong>2</strong> was observed in HeLa in comparison to NHDF. This may be related to the fact that more G4 DNAs are present in the nuclei of cancer cell lines to allow binding of porphyrins <strong>1</strong> and <strong>2</strong>, as observed by fluorescence microscopy. The interactions of porphyrins <strong>1</strong> or <strong>2</strong> with a G4-forming telomeric DNA were evaluated by a FRET assay and spectroscopic methods (fluorescence, UV-vis, and CD) and showed selective binding to G4 DNA. The results show the potential of porphyrins <strong>1</strong> and <strong>2</strong> as PDT-PSs targeting cancer cells with higher G4-forming domains.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 1","pages":" 225-235"},"PeriodicalIF":3.597,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12577588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145432078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging targeted kinase degradation as a novel therapeutic strategy for Alzheimer's disease","authors":"Elisa Tassinari and Andrea Milelli","doi":"10.1039/D5MD00681C","DOIUrl":"10.1039/D5MD00681C","url":null,"abstract":"<p >Despite recent advances, Alzheimer's disease (AD) remains largely a mystery more than a century after its discovery. Protein kinases are among the new targets under investigation, which is not surprising given their crucial role in maintaining cellular homeostasis and in the development of various diseases. Several protein kinase inhibitors have shown remarkable therapeutic efficacy in the context of AD, although none of them have yet received approval by regulatory agencies. Alongside the use of classic inhibitors, a new therapeutic approach has emerged in recent years, shifting the focus from modulation to targeted degradation of the protein. The purpose of this review is to highlight and discuss novel series of proteolysis-targeting chimeras (PROTACs) directed against protein kinases relevant to the development of AD.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 12","pages":" 5862-5872"},"PeriodicalIF":3.597,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12516347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145293699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of a first-in-class SLIT2 binder disrupting the SLIT2/ROBO1 axis via DNA-encoded library (DEL) screening","authors":"Shaoren Yuan, Somaya A. Abdel-Rahman, Nelson García Vázquez, Hossam Nada, Laura Calvo-Barreiro, Katarzyna Kuncewicz and Moustafa T. Gabr","doi":"10.1039/D5MD00555H","DOIUrl":"10.1039/D5MD00555H","url":null,"abstract":"<p >The SLIT2/ROBO1 signaling axis plays a critical role in neural development, immune regulation, and tumor progression, including glioblastoma. However, small molecule inhibitors targeting this protein–protein interaction remain unexplored. Herein, we report the discovery and validation of <strong>DEL-S1</strong>, a first-in-class small molecule that binds to SLIT2 and disrupts its interaction with ROBO1. Using a DNA-encoded library (DEL) screen of 4.2 billion compounds, <strong>DEL-S1</strong> was identified and confirmed to bind SLIT2 <em>via</em> temperature-related intensity change (TRIC) assay. Functional inhibition of the SLIT2/ROBO1 complex by <strong>DEL-S1</strong> was demonstrated using a time-resolved fluorescence resonance energy transfer (TR-FRET) assay, yielding an IC<small>₅₀</small> of 68.8 ± 12.5 μM. Molecular docking and molecular dynamics (MD) simulations revealed key interaction hotspots at the SLIT2 binding interface and confirmed that <strong>DEL-S1</strong> impairs SLIT2/ROBO1 complex formation by inducing conformational rearrangements. <strong>DEL-S1</strong> exhibited favorable ADME properties, including satisfactory plasma and microsomal stability, low cytotoxicity, and minimal hERG liability. To facilitate structure–activity relationship (SAR) exploration, we designed and implemented a modular, one-pot synthetic route leveraging cyanuric chloride reactivity, enabling rapid derivatization of the triazine scaffold of <strong>DEL-S1</strong>. This strategy yielded structurally diverse analogs, including water-soluble carboxylate derivatives with preserved SLIT2/ROBO1 inhibitory activity. Together, this work establishes a novel chemical scaffold targeting SLIT2 and introduces a flexible synthetic platform to support further optimization toward therapeutic development.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 12","pages":" 6059-6067"},"PeriodicalIF":3.597,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12508870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of novel SRPK1-targeting hybrid compounds incorporating antimetabolites for cancer therapy","authors":"George Leonidis, Ioanna Sigala, Michail Spathakis, George Kolios, Thomas Giannakouros, Eleni Nikolakaki and Vasiliki Sarli","doi":"10.1039/D5MD00731C","DOIUrl":"10.1039/D5MD00731C","url":null,"abstract":"<p >Serine/arginine protein kinase 1 (SRPK1) plays a pivotal role in the phosphorylation of SR/RS domain-containing proteins, which are involved in various cellular processes. Its overexpression has been associated with the progression of various malignancies, positioning SRPK1 as a promising target for cancer treatment. In this study, we report the design, synthesis, and preliminary biological evaluation of two hybrid molecules, <strong>geo15</strong> and <strong>geo140</strong>, which combine known SRPK1 inhibitors with the antimetabolites gemcitabine and 5-fluorouracil (5-FU), respectively. These conjugates were synthesized to assess whether hybridization enhances potency compared to the parent compounds, and to investigate potential novel mechanisms of action. <em>In vitro</em> assays were performed to evaluate SRPK1 inhibition and antiproliferative activity in selected cancer cell lines. Among the tested compounds, the JH-VII-139-1-based hybrid <strong>geo140</strong> exhibited notable SRPK1 inhibitory potency and cytotoxic effects, demonstrating a favorable profile for further optimization. Interestingly, treatment with <strong>geo140</strong> did not appear to alter the overall SRPK1 distribution in interphase cells but resulted in a notable increase of mitotic cells that displayed a substantial accumulation of SRPK1, thus suggesting that the hybrid compound may have an impact on cell cycle progression. This work supports the potential of molecular hybridization as a strategy for the development of novel SRPK1-targeting anticancer agents.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 12","pages":" 6285-6298"},"PeriodicalIF":3.597,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12574689/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145432061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-cancer analysis reveals HMOX1 as a cancer prognosis and immune infiltration-related biomarker","authors":"Yingli Men, Hui Wang, Xiaoyan Xu, Miling Yang, Ruiting Feng, Jizhi Zhao, Ying Liu, Lu Yang, Yinsen Song and Cong Ding","doi":"10.1039/D5MD00616C","DOIUrl":"10.1039/D5MD00616C","url":null,"abstract":"<p >HMOX1 has gained increasing recognition across multiple malignancies; however, its precise oncogenic or tumor-suppressive roles remain incompletely defined. In this study, we comprehensively investigated HMOX1 across diverse tumor types utilizing the cancer genome atlas (TCGA). We further integrated data from multiple bioinformatics platforms, including TIMER2, UALCAN, GEPIA2, cBioPortal, R, GSCA, and LinkedOmics. Western blotting and quantitative real-time PCR (qRT-PCR) confirmed differential HMOX1 expression between normal renal epithelial cells and KIRC cells. Functional assays <em>in vitro</em> and <em>in vivo</em> demonstrated that HMOX1 regulates proliferation, migration, and cell-cycle progression in 786-O and Caki-1 cells. Pan-cancer analyses revealed that HMOX1 is aberrantly expressed across multiple malignancies with significant associations with the tumor stage. Survival analyses indicated that elevated HMOX1 expression predicted poor overall survival (OS) in LGG (<em>P</em> = 0.025) but favorable OS and disease-free survival (DFS) in KIRC (OS: <em>P</em> = 0.00062; DFS: <em>P</em> = 9 × 10<small>⁻⁴</small>). Moreover, mutations were the predominant genetic alteration affecting HMOX1, while promoter methylation was broadly reduced across cancers. HMOX1 expression positively correlated with immune infiltration by CD8<small>⁺</small> T cells (KIRC: Spearman <em>ρ</em> = 0.26, FDR = 2.56 × 10<small>⁻⁸</small>) and macrophages (KIRC: Spearman <em>ρ</em> = 0.32, FDR = 2.77 × 10<small>⁻¹³</small>). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses in KIRC implicated HMOX1 in the chemokine and NF-κB signaling pathways. Both <em>in vitro</em> and <em>in vivo</em> experiments demonstrated that HMOX1 knockdown accelerates cell-cycle progression and enhances proliferation and migration in 786-O and Caki-1 cells. Collectively, our findings establish HMOX1 as a promising prognostic biomarker and potential immunotherapeutic target across multiple cancers.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 11","pages":" 5614-5628"},"PeriodicalIF":3.597,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145200578","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":"Design of galectin-1-conjugated nanoparticles as potential immunomodulatory agents","authors":"Chandradhish Ghosh, Ling Yao, Marilet Sigler, Santiago Di Lella, Alejandro J. Cagnoni, Gabriel A. Rabinovich and Peter H. Seeberger","doi":"10.1039/D5MD00539F","DOIUrl":"10.1039/D5MD00539F","url":null,"abstract":"<p >Autoimmune disorders are heterogeneous dynamic conditions characterized by dysregulated immune responses and caused by interruption of tolerogenic circuits. Although immunosuppressive drugs, including biological agents, are effective therapeutic options, several patients do not respond to these treatment or develop resistance mechanisms. Galectins, a family of soluble glycan-binding proteins, play central roles in the modulation of autoimmune inflammation. Galectin-1 (Gal-1), a prototype member of this family, interacts with specific <em>N</em>-acetyllactosamine (LacNAc) ligands present in <em>N</em>- and <em>O</em>-glycans <em>via</em> its conserved carbohydrate recognition domain (CRD). The immunomodulatory activity of Gal-1 involves regulation of T cell effector populations, inducing apoptosis of Th1 and Th17 cells, differentiation of tolerogenic dendritic cells and induction of myeloid-derived suppressor cells. To develop a rational galectin-based therapeutic strategy, we evaluated whether Gal-1 retains its function upon multivalent presentation on nanoparticles. Specifically, we report the design strategy, synthesis and characterization of galectin-1-conjugated glucose-stabilized gold nanoparticles, and compare their activities with unconjugated galectin-1. This formulation offers novel opportunities for treating a variety of autoimmune diseases, as well as chronic inflammatory disorders.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 12","pages":" 6041-6047"},"PeriodicalIF":3.597,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12507049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145259001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An innovative strategy to treat pathogenic biofilm-associated infections in vitro and in vivo using guanidinium-linked neomycin lipidation","authors":"Sourav Sarkar, Vedant Tripathi, Surajit Sadhukhan, Jhuma Bhadra and Santanu Bhattacharya","doi":"10.1039/D5MD00776C","DOIUrl":"10.1039/D5MD00776C","url":null,"abstract":"<p >To overcome neomycin's limited efficacy against complex Gram-positive and Gram-negative co-infections, we have developed a novel guanidinium-linked neomycin–lipid conjugate (guanidino Neo-lipid). This multifunctional construct integrates three synergistic components: a neomycin core for ribosomal targeting, a hydrophobic lipid chain to facilitate membrane interaction and cellular uptake, and a cationic guanidinium moiety that enhances electrostatic binding to negatively charged bacterial membranes. The resulting conjugate demonstrates significantly improved antibacterial activity in liquid cultures and effectively disrupts biofilm formation. This approach offers a promising therapeutic strategy for treating persistent infections caused by both Gram-positive and Gram-negative pathogens, including co-infective scenarios.</p>","PeriodicalId":88,"journal":{"name":"MedChemComm","volume":" 12","pages":" 6109-6123"},"PeriodicalIF":3.597,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329840","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}