Frontiers in Molecular Biosciences最新文献

{"title":"Three semi-synthetic approaches to a set of curdlan sulfate polysaccharides with different sulfation patterns.","authors":"Fabiana Esposito, Agnieszka Zabłocka, Serena Traboni, Alfonso Iadonisi, Sabina Górska, Emiliano Bedini","doi":"10.3389/fmolb.2025.1635564","DOIUrl":"10.3389/fmolb.2025.1635564","url":null,"abstract":"<p><strong>Introduction: </strong>Curdlan is a linear homopolysaccharide composed of β-1→3-linked glucose units. It is extracted from some bacteria as an exopolysaccharide and employed in the food industry due to its remarkable rheological and thermal behaviors. Furthermore, its ability to form gel encapsulations with several drugs and its roles in innate and adaptive immunity have fueled an increasing interest in pharmaceutical applications of curdlan and its derivatives. Among them, curdlan sulfate derivatives disclosed not only a highly enhanced water solubility concerning native curdlan but also an efficient immunomodulatory potential in both <i>in vitro</i> and <i>in vivo</i> assays.</p><p><strong>Methods: </strong>To detect the effects of the sulfation degree and sulfation pattern on the immunological activity of curdlan sulfate, a set of regioselectively sulfated curdlan polysaccharides was semi-synthesized and fully characterized utilizing nuclear magnetic resonance (NMR) spectroscopy techniques.</p><p><strong>Results: </strong>Although some regioselectively sulfated curdlan derivatives were already reported some years ago, in this work, a comprehensive semi-synthetic study was developed by investigating three different, complementary approaches based on direct regioselective sulfation or desulfation reactions or multistep protection-sulfation-deprotection procedures.</p><p><strong>Discussion: </strong>Some of the semi-synthesized curdlan sulfate derivatives were selected as representatives of different sulfation degrees and patterns and subjected to a panel of immunological assays to define some structure-activity relationships.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1635564"},"PeriodicalIF":3.9,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global research trends in metabolism-related intraocular malignancies: a multi-database bibliometric analysis and cross-validation study.","authors":"Jianhao Bai, Zhongqi Wan, Zhiyong Wu, Qing Peng","doi":"10.3389/fmolb.2025.1683864","DOIUrl":"10.3389/fmolb.2025.1683864","url":null,"abstract":"<p><strong>Objective: </strong>To systematically characterize the global research landscape of metabolism-related intraocular malignancies and to validate the robustness of findings through a multi-database comparative approach.</p><p><strong>Methods: </strong>Publications from January 1, 1990, to July 31, 2025, were retrieved from the Web of Science Core Collection (WoSCC). To ensure the stability and generalizability of results, equivalent searches were performed in Scopus and PubMed, applying the same keyword set, time frame, and eligibility criteria. Bibliometric analyses were conducted using VOSviewer, CiteSpace, and GraphPad Prism to evaluate publication trends, geographic and institutional contributions, journal and author influence, keyword co-occurrence, co-citation patterns, and emerging research fronts. Cross-database validation assessed concordance in temporal trends, thematic focuses, and country rankings.</p><p><strong>Results: </strong>A total of 1,745 WoSCC publications were included, authored by researchers from 69 countries. Global output has increased markedly since 2010, peaking in 2021. Uveal melanoma consistently emerged as the dominant intraocular tumor type in metabolic research. Major thematic clusters encompassed oxidative stress, apoptosis, hypoxia, lipid metabolism, and metabolic reprogramming, with recent shifts toward long noncoding RNA, immune infiltration, and metabolomics, signaling a transition to precision oncology. Importantly, multi-database validation demonstrated high concordance in annual publication trends, as well as strong overlap in top keywords and stability in geographical and disease foci.</p><p><strong>Conclusion: </strong>This study provides a multi-database bibliometric assessment of metabolism-related intraocular malignancy research, with offering a reliable foundation for guiding future basic and translational research in ocular oncology.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1683864"},"PeriodicalIF":3.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454098/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into recent findings and therapeutic potential of nonhistone lactylation in cancer.","authors":"Jing Jia, Na Liu, Xiaoren Zhu, Minbin Chen","doi":"10.3389/fmolb.2025.1661697","DOIUrl":"10.3389/fmolb.2025.1661697","url":null,"abstract":"<p><p>Lactylation, a recently identified post-translational modification, has become a crucial regulatory mechanism beyond its conventional metabolic role. Unlike histone lactylation, which regulates gene expression, nonhistone lactylation directly acts on effector proteins involved in processes such as signal transduction, metabolic reprogramming, and DNA damage repair. This article systematically reviews how nonhistone lactylation regulates biological processes related to cancer via mechanisms such as modulating protein interactions, stability, subcellular localization, and enzymatic activity. In addition, it comprehensively examines the potential applications and challenges in targeting nonhistone lactylation modification in antitumor treatment.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1661697"},"PeriodicalIF":3.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Screening and characterization of DNA aptamers that modulate prime editing.","authors":"Mingxia Wang, Xia Wu, Xinbo Huang, Jing Ye, Yaoting Gui","doi":"10.3389/fmolb.2025.1565459","DOIUrl":"10.3389/fmolb.2025.1565459","url":null,"abstract":"<p><strong>Introduction: </strong>Precise genome editing is a critical focus in gene therapy, and the CRISPR-Cas9 system has become a powerful and versatile tool for this purpose. However, a significant limitation of the CRISPR-Cas9 system is its low homologous recombination rate, which can impede the restoration of normal gene function. To address some of these challenges, advanced gene-editing technologies, such as base editors and prime editors have been developed. Here, we explored whether Cas9-specific single-stranded DNA (ssDNA) aptamers could enhance the PE2 system's functionality.</p><p><strong>Methods: </strong>Systematic evolution of ligands by exponential enrichment (SELEX) was utilized to isolate high-affinity Cas9-specific ssDNA aptamers. Molecular docking simulations were subsequently performed to characterize the binding interactions between these aptamers and the PE2 protein. PE2 editing efficiency was quantitatively assessed using flow cytometry and Sanger sequencing. In bladder cancer cell lines, p53 mutation repair was evaluated by quantitative PCR and Western blot analysis, while cellular responses were examined through proliferation (CCK-8) and apoptosis assays.</p><p><strong>Results: </strong>Molecular docking analysis revealed the interaction sites between SELEX-screened Cas9-specific aptamers and the PE2 protein. The incorporation of these aptamers significantly enhanced PE2 editing efficiency. In bladder cancer cells, the aptamer-PE2 complex effectively restored p53 function, leading to suppressed cellular proliferation and enhanced apoptosis rates.</p><p><strong>Discussion: </strong>Our study demonstrates that Cas9-specific aptamers can effectively enhance prime editing efficiency. This provide new insights into the modulation of prime editing and hold potential for improving its clinical applications.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1565459"},"PeriodicalIF":3.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12454028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of protease-activated receptors (PARs) in the functioning of platelets and platelet-derived microparticles (PMPs).","authors":"Urszula Jakobsche-Policht, Agnieszka Bronowicka-Szydełko, Rajmund Adamiec, Dorota Bednarska-Chabowska, Magdalena Mierzchała-Pasierb, Łukasz Lewandowski, Kinga Gostomska-Pampuch, Joanna Adamiec-Mroczek, Maciej Rabczyński, Edwin Kuźnik, Paweł Lubieniecki, Olgierd Dróżdż, Helena Martynowicz, Anna Kwiecień, Małgorzata Strzelecka, Dawid Rudkiewicz, Marcin Piersiak, Maciej Ziomek, Mikołaj Kondracki, Zuzanna Galińska, Katarzyna Madziarska","doi":"10.3389/fmolb.2025.1636893","DOIUrl":"10.3389/fmolb.2025.1636893","url":null,"abstract":"<p><p>Protease-activated receptors (PARs), present on the surface of platelets and platelet-derived microparticles (PMPs), belong to a superfamily of membrane receptors that play a key role in initiating intracellular G protein-dependent signaling pathways. Although four types of PARs have been identified-PAR-1, PAR-2, PAR-3, and PAR-4 - their mechanisms and functions remain poorly understood. Nevertheless, they are considered promising therapeutic and diagnostic targets, as they play crucial roles in initiating and promoting processes such as coagulation, inflammatory responses, and vascular function. PAR-1 is expressed on various cell types, including endothelial cells, platelets, neurons, and immune cells. Its activation by thrombin initiates a G protein-dependent signaling cascade that stimulates the expression of cytokines, selectins, adhesion molecules, and growth factors. In addition to thrombin, PAR-1 can also be activated by activated protein C (APC) and matrix metalloproteinase-1 (MMP-1). APC triggers cytoprotective signaling pathways, while MMP-1 influences cellular dynamics through alternative signaling mechanisms. PAR-1 activation is also affected by epigenetic modifications and genetic polymorphisms in the PAR-1 gene. Variants such as -1426 C/T and -506 I/D influence receptor expression and are associated with an increased risk of thrombosis, potentially due to epigenetic changes linked to atherosclerosis. The complex signaling network of PAR-1 makes it a promising therapeutic target for the treatment of cardiovascular diseases, cancer, and neuroinflammatory disorders. This paper serves as a compendium on PAR-1 and its role, particularly in the activation of platelets and PMPs.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1636893"},"PeriodicalIF":3.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12455044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional stress in aging: integrating experimental data and modeling to quantify DNA damage accumulation.","authors":"Jacinta van de Grint, Marko Raseta, Renata Brandt, Yvette van Loon, Joris Demmers, Shannon Dealy, Jiang Chang, Jan Hoeijmakers, Joris Pothof","doi":"10.3389/fmolb.2025.1659589","DOIUrl":"10.3389/fmolb.2025.1659589","url":null,"abstract":"<p><p>Accumulating DNA damage plays a crucial role in aging, particularly in post-mitotic tissues by disrupting transcription and causing transcriptional stress-a state marked by reduced transcriptional productivity. Transcriptional stress disproportionately affects long genes, due to the random distribution of DNA lesions across the genome. An estimate for the total number of transcription-blocking lesions (TBLs) required to induce transcriptional stress and contribute to aging is lacking. Here, we estimated the number of TBLs accumulating with age, by integrating experimental data with a mathematical model based solely on fundamental biological principles. Using 5-ethynyluridine (EU) incorporation, we assessed transcriptional activity in dermal fibroblasts and liver tissue from <i>Ercc1</i> ^-/-, <i>Ercc1</i> ^<i>d</i>/-, and <i>Xpg</i> ^-/- mice-models with DNA repair deficiencies that exhibit a wide range of premature aging features between 5 and 26 weeks of age. We then compared the experimental data to our model, which captured the overall trend of transcriptional decline, supporting a correlation between accumulating DNA damage and reduced transcription during aging. Wildtype mice were found to accumulate approximately 62 TBLs per day, whereas DNA repair-deficient mice exhibited a markedly higher burden, accumulating 1,600-5,000 TBLs daily. These insights offer a quantitative understanding of transcriptional stress, which is crucial for elucidating the aging process.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1659589"},"PeriodicalIF":3.9,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12450475/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Editorial: Structural studies of bacteria and viruses.","authors":"","doi":"10.3389/fmolb.2025.1697351","DOIUrl":"https://doi.org/10.3389/fmolb.2025.1697351","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fmolb.2025.1605596.].</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1697351"},"PeriodicalIF":3.9,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12451235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145130316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative stress: from molecular studies to clinical intervention strategies.","authors":"Qing Gao, Linlin Jiang, Yuting Sun, Xuedong An, Wenjie Sun, Shanshan Tang, Xiaomin Kang, Xuefei Zhao, Zehua Li, Chenran Liu, Hangyu Ji, Fengmei Lian","doi":"10.3389/fmolb.2025.1638042","DOIUrl":"10.3389/fmolb.2025.1638042","url":null,"abstract":"<p><p>The imbalance between the generation of free radicals and the body's capacity to counteract their damaging effects on proteins, lipids, and nucleic acids is known as oxidative stress. Since it is essential for controlling many biological functions, this imbalance is intimately associated with the development and course of many diseases. In this study, we first outlined the submechanisms of oxidative stress, concentrating on the antioxidant system and reactive oxygen species. We also discussed common detection methods that can be beneficial for both clinical and scientific purposes. We examined prevalent diseases such as cardiovascular issues, diabetes, cancer, and neurodegenerative disorders to highlight the significant impact of oxidative stress. Additionally, we provided a list of common antioxidants to assist in clinical treatment and further exploration of underlying mechanisms. Our findings indicate that the molecular mechanisms of oxidative stress have been more thoroughly investigated, underscoring its scientific and clinical importance in understanding disease development and potential interventions. We propose that ongoing, in-depth research centered on oxidative stress could offer new insights for clinical interventions and mechanism exploration.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1638042"},"PeriodicalIF":3.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive lipoprotein and glycoprotein characterization in rheumatoid arthritis plasma and association with clinical markers.","authors":"Konstantina Ismini Tsezou, Mohan Ghorasaini, Aswin Verhoeven, Aikaterini Iliou, Dimitra Benaki, Panayiotis G Vlachoyiannopoulos, Martin Giera, Emmanuel Mikros","doi":"10.3389/fmolb.2025.1627273","DOIUrl":"10.3389/fmolb.2025.1627273","url":null,"abstract":"<p><strong>Introduction: </strong>Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and pain. This study investigates plasma lipoprotein and glycoprotein profiles in RA patients to identify clinically relevant markers for disease monitoring.</p><p><strong>Methods: </strong>Lipoprotein composition and subfractions were analyzed in plasma from 161 RA patients and 46 controls using proton nuclear magnetic resonance (¹H NMR) spectroscopy (Lipoprotein Subclass Analysis (B.I.LISA) platform) along with N-acetylglycoprotein signals GlycA and GlycB. Lipoprotein subclasses and glycoproteins in RA and disease-modifying anti-rheumatic drug (DMARD)-naive RA patients were compared to controls, and comprehensive profiles were evaluated in activity and remission. Correlations with disease activity score (DAS28), inflammation marker C-reactive protein (CRP), and Visual Analogue Scale (VAS) of pain were assessed using regression models, adjusting for age, gender, and CVD.</p><p><strong>Results: </strong>RA patients exhibited a distinct lipoprotein and glycoprotein profile, with increased triglycerides, cholesterol, apolipoproteins (A1, A2, B100), and changes in LDL, HDL, GlycA, and GlycB. Glycoproteins were significantly higher in DMARD-naive RA (AUC ≈ 0.9) validating these NMR signals as biomarkers of inflammation. Patients in remission had higher small dense HDL and lower LDL-triglycerides than those with high disease activity. VAS correlated with LDL-triglycerides, while DAS28 correlated with small dense LDL-triglycerides and glycoproteins, inversely with large LDL, small HDL lipids. H4A1 alone characterizes RA remission (AUC ≈ 0.8).</p><p><strong>Conclusion: </strong>Lipoprotein profiles in RA correlate with disease activity, inflammation, and pain. Large HDL, intermediate LDL and glycoproteins serve for RA monitoring as well as potential molecular markers of pain.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1627273"},"PeriodicalIF":3.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The interaction of Cu(II) and Zn(II) with peptide fragment of HSPB1 and its analogs.","authors":"Agnieszka Szebesczyk, Domenica Musumeci, Ettore Napolitano, Halyna Kukhtenko, Paulina Iwaniak","doi":"10.3389/fmolb.2025.1593661","DOIUrl":"10.3389/fmolb.2025.1593661","url":null,"abstract":"<p><strong>Introduction: </strong>Copper (II) and zinc (II) ions are essential microelements in the human body, interacting with numerous biologically active molecules, including proteins and peptides. The precise identification of binding sites, complete with the detailed characterization of binding amino acid residues, is of great importance. This is particularly significant in the context of uncovering the mechanisms of diseases associated with single nucleotide polymorphisms (SNPs), and consequently, developing effective treatments.</p><p><strong>Methods: </strong>Two methodological approaches were applied to study the complexation behavior. In the first, ligand and metal ions were mixed at low pH, and complexes formed upon gradual pH increase (via NaOH addition). The formation of different complex forms at changing pH was observed, and stability constants were determined. Spectroscopic data allowed prediction of coordination modes linked to structural changes. The second approach involved complex formation in buffered solutions at fixed pH. Here, metal ion solution was added to partially deprotonated ligands, potentially influencing the complexation behavior compared to the first method.</p><p><strong>Results and discussion: </strong>This study highlights the importance of His-131 and Glu-126 residues in Cu²⁺ and Zn²⁺ ion binding by peptide fragments of the HSPB1 protein. These residues are essential for both the stability of the complexes and the nature of their interaction with the metal ions. Analytical methods exploring complexation behavior across a pH range of 2-10 and in buffer solutions provide a comprehensive view of the thermodynamic properties of the studied systems. This enables the prediction of their behavior under diverse conditions.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"12 ","pages":"1593661"},"PeriodicalIF":3.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145112484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}