Journal of Materials Chemistry B最新文献

{"title":"Formulation and evaluation of PVA-based composite hydrogels: physicochemical, leachables, and in vitro immunogenicity studies†","authors":"Achmad Himawan, Anna Korelidou, Ana M. Pérez-Moreno, Juan L. Paris, Juan Dominguez-Robles, Lalitkumar K. Vora, Andi Dian Permana, Eneko Larrañeta, Robert Graham, Christopher J. Scott and Ryan F. Donnelly","doi":"10.1039/D4TB02181A","DOIUrl":"10.1039/D4TB02181A","url":null,"abstract":"<p >This study explores the formulation and characterization of poly(vinyl alcohol) (PVA)-based composite hydrogels synthesized through solid-state crosslinking. Comprehensive assessments were conducted on their physicochemical properties, leachables, and immunogenicity. Swelling experiments demonstrated that the incorporation of poly(vinylpyrrolidone) (PVP) enhanced water retention, while chitosan had a minimal effect on swelling behavior. Qualitative analysis of leachables identified water-soluble components, including dehydrated PVA and PVP. Fourier-transform infrared (FTIR) spectroscopy confirmed the formation of ester bonds and indicated increased hydrogen bonding post-crosslinking. Thermal stability was validated by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), with decomposition observed at 320–330 °C. X-ray diffraction (XRD) analysis revealed enhanced crystallinity following crosslinking. Solid-state nuclear magnetic resonance (NMR) further confirmed chemical changes consistent with the results from other characterization techniques. <em>In vitro</em> assays using DC2.4 mouse dendritic cells showed that hydrogel extracts inhibited cell proliferation without causing cytotoxicity or triggering significant immune responses. These findings highlight the hydrogels’ biocompatibility and stability, supporting their potential for biomedical applications.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 7","pages":" 2431-2445"},"PeriodicalIF":6.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/tb/d4tb02181a?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985711","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":"Biological activation of Fenton reaction in polymeric nanoreactors driven by ferrocene-containing membranes: a microenvironment dependent study†","authors":"Alejandro González Vivancos, Yang Zhou, Uwe Lappan, Susanne Boye, Laura Muñoz-Moreno, Dietmar Appelhans and Silvia Moreno","doi":"10.1039/D4TB01776E","DOIUrl":"10.1039/D4TB01776E","url":null,"abstract":"<p >Nanocatalytic medicine for treating cancer requires effective, versatile and novel tools and approaches to significantly improve the therapeutic efficiency for the interactions of (non-)enzymatic reactions. However, it is necessary to develop (non-)enzymatic nanotechnologies capable of selectively killing tumour cells without harming normal cells. Their therapeutic characteristics should be the adaption of tumours’ extra- and intracellular environment to being specifically active. To contribute to this common goal, we propose the use of pH- and redox-responsive ferrocene containing polymersomes (FcPsomes). This allows the regulation of their biological activities for the controlled production of radicals <em>via</em> the Fenton reaction and the transport and release of cargo molecules <em>via</em> (destroying) host–guest interactions. This is provided by the Fc-membrane composition of FcPsomes showing different pH responsive active membrane, meaning the membrane permeability is triggering the Fenton reaction. The modulation of radical production is validated by various spectroscopic techniques. Moreover, these nanocontainers allow biological action of glucose oxidase (GOx) as therapeutic enzyme to produce glucono-1,5-lactone as proton source and hydrogen peroxide, initiating the Fenton reaction, in their interior. This provides a synergistic cancer therapeutic treatment for the starvation of hydrogen peroxide, but also ROS-mediated chemodynamic therapy at defined pH values. By modulating membrane permeability, we achieve environmentally regulated and locally driven therapeutic activity in the confinement of FcPsomes, ensuring specificity and safety treatments. The versatility of this platform extends beyond their specific application, allowing for their beneficial therapeutic use, for example, in signaling pathways of cells through the integration of various enzymes in FcPsomes.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 6","pages":" 1980-1990"},"PeriodicalIF":6.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/tb/d4tb01776e?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934334","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":"Flexible deformation and special interface structure in nanoparticle-stabilized Pickering bubbles strengthen the immunological response as adjuvant†","authors":"Qiuting Chen, Jie Teng, Cuixiao Zhu, Jinzhi Du, Guixiang Wang and Jie Wu","doi":"10.1039/D4TB01763C","DOIUrl":"10.1039/D4TB01763C","url":null,"abstract":"<p >Adjuvants can enhance an immunological response, which is an important part of vaccine research. Pickering bubbles have been a mega-hit for biomedical applications, including <em>in vivo</em> visualization and targeted drug delivery. However, there have been no studies on Pickering bubbles as an immunological adjuvant, and the special properties and structures of Pickering bubbles may play an important role in immunization. In this study, poly(lactic-<em>co</em>-glycolic acid) (PLGA) particles were used to construct nanoparticle-stabilized Pickering bubbles (PPBs). PPBs were evaluated as immunological adjuvants based on immune response effects and mechanisms and aiming at future applications. PPBs have a flexible gas core and a special surface structure that can increase the cell contact area to promote phagocytosis and enhance the immune response. Quartz crystal microbalance with dissipation (QCM-D) data showed the flexibility of PPBs, and confocal images captured the deformability of PPBs during cell uptake. Flow cytometry and antibody titer detection showed that PPBs significantly promoted antigen uptake and activation of bone-marrow-derived dendritic cells (BMDCs) and induced an immune response with upregulated SIINFEKL MHC I and CD127 molecules on the surface of CD8<small>⁺</small> T cells, indicating excellent antigen cross-presentation and cellular immune triggering effects. The upregulation of CD44 and CD62L on CD4<small>⁺</small> T cells and the IgG2a/IgG1 ratio bias further demonstrated the excellent adjuvant role of PPBs in immunity. Finally, the biosafety of PPBs as an immunological adjuvant was also demonstrated. Our study demonstrates the potential of particle-stabilized bubbles as immune adjuvants, which provides innovative ideas for vaccine development and design.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 8","pages":" 2725-2736"},"PeriodicalIF":6.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030578","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":"Correction: Hedgehog-inspired immunomagnetic beads for high-efficient capture and release of exosomes","authors":"Jia Cheng, Nanhang Zhu, Yujia Zhang, Yue Yu, Ke Kang, Qiangying Yi and Yao Wu","doi":"10.1039/D4TB90208D","DOIUrl":"10.1039/D4TB90208D","url":null,"abstract":"<p >Correction for ‘Hedgehog-inspired immunomagnetic beads for high-efficient capture and release of exosomes' by Jia Cheng <em>et al., J. Mater. Chem. B</em>, 2022, <strong>10</strong>, 4059–4069, https://doi.org/10.1039/D2TB00226D.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 3","pages":" 1118-1119"},"PeriodicalIF":6.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/tb/d4tb90208d?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933830","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":"The application of aptamers in the repair of bone, nerve, and vascular tissues","authors":"Yu-Wei Hsu, Le Ma, Ye Tang, Mengen Li, Chengkai Zhou, Yan Geng, Chenxi Zhang, Tianbing Wang, Wei Guo, Ming Li and Yanhua Wang","doi":"10.1039/D4TB02180K","DOIUrl":"10.1039/D4TB02180K","url":null,"abstract":"<p >Aptamers represent a distinct category of short nucleotide sequences or peptide molecules characterized by their ability to bind to specific targets with high precision. These molecules are predominantly synthesized through SELEX (Systematic Evolution of Ligands by Exponential Enrichment) technology. Recent findings indicate that aptamers may have significant applications in regenerative medicine, particularly in the domain of tissue repair. In comparison to other bioactive agents, aptamers exhibit superior specificity and affinity, are more readily accessible, and can be chemically modified, thereby presenting a promising avenue for the functionalization of tissue engineering materials in tissue repair applications. This review delineates the properties of aptamers and examines the methodologies and advancements related to aptamer-functionalized hydrogels, nanoparticles, and electrospun materials. It categorizes the four primary functions of aptamers in tissue repair, namely regeneration, delivery systems, anti-inflammatory actions, and pro-coagulation effects. Furthermore, the review explores the utilization of aptamer-functionalized tissue engineering materials in the repair of bone, nerve, and vascular tissues, highlighting the mechanisms by which aptamers facilitate tissue growth and repair through regenerative properties and their role in transporting substances that promote repair. Lastly, the review addresses the future prospects and challenges associated with the application of aptamers in tissue repair, offering novel insights and directions for further research and application in this domain.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 6","pages":" 1872-1889"},"PeriodicalIF":6.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933909","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":"A dendritic drug–drug conjugate self-assembled hypoxia-responsive supramolecular nanoparticle for combination therapy†","authors":"Tianlong Ling, Xiaogang Huang, Yu Xie, Liangshun Zheng, Yue Ding, Chang Du and Jianjun Chen","doi":"10.1039/D4TB02400A","DOIUrl":"10.1039/D4TB02400A","url":null,"abstract":"<p >Hypoxia, a condition that enhances tumor invasiveness and metastasis, poses a significant challenge for diverse cancer therapies. There is a pressing demand for hypoxia-responsive nanoparticles with integrated photodynamic functions in order to address the aforementioned issues and overcome the reduced efficacy caused by tumor hypoxia. Here, we report a hypoxia-responsive supramolecular nanoparticle SN@IR806-CB consisting of a dendritic drug–drug conjugate (IR806-Azo-CB<small>₄</small>) and anionic water-soluble [2]biphenyl-extended-pillar[6]arene modified with eight ammonium salt ions (AWBpP6) <em>via</em> the synergy of π–π stacking interaction, host–guest complexation, and hydrophobic interactions for synergistic photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy (CT; <em>i.e.</em>, PTT–PDT–CT). Under near-infrared (NIR) irradiation, the IR806-based PTT and PDT could generate hyperthermia to thermally ablate tumor tissue and deplete oxygen to generate singlet oxygen (<small>¹</small>O<small>₂</small>), respectively. The resulting hypoxia exacerbation further accelerated the release of activated CB. Consequently, this nanoparticle could be a potential candidate for achieving significant therapeutic efficacy through PTT–PDT–CT.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 6","pages":" 1961-1968"},"PeriodicalIF":6.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981060","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":"Ultrasound-controllable dexamethasone-loaded nanobubbles for highly effective rheumatoid arthritis therapy†","authors":"Hang-yi Hu, Ying-jian Sun, Xiao-feng Yuan, Jiang-fan Han, Tian-tian Liao, Fei-yue Zhang, Jin-dong Mao, Lin Zhang and Wei-liang Ye","doi":"10.1039/D4TB01120A","DOIUrl":"10.1039/D4TB01120A","url":null,"abstract":"<p >Rheumatoid arthritis (RA) is an autoimmune disease that seriously threatens human health and affects the quality of life of patients. At present, pharmacotherapy is still the mainstream treatment for RA, but most methods have shortcomings, such as poor drug targeting, a low effective drug dosage at the inflammatory site, and high systemic toxicity. The combined application of drug-loaded nanobubbles and ultrasound technology provides a new technique for the treatment of RA. Low-intensity focused ultrasound (LIFU) traces the transmission of drug-loaded nanobubbles in the body, and high-intensity focused ultrasound (HIFU) causes the nanobubbles to rupture to release drugs at the inflammatory site, thereby reducing their toxicity to normal tissues. In this study, a drug-loaded nanobubble delivery system (DEXsp@Liposomes/C<small>₃</small>F<small>₈</small>) with ultrasonic response characteristics was successfully constructed, and its therapeutic effect was evaluated for the treatment of RA <em>in vitro</em> and <em>in vivo</em>. DEXsp@Liposomes/C<small>₃</small>F<small>₈</small> + LIFU had good biocompatibility and excellent ultrasound imaging ability. DEXsp@Liposomes/C<small>₃</small>F<small>₈</small> +HIFU distinctly increased the cellular uptake of DEXsp and significantly reduced the secretion of related inflammatory factors in RAW264.7 cells. Moreover, DEXsp@Liposomes/C<small>₃</small>F<small>₈</small> + HIFU effectively alleviated the symptoms of RA in model rats and significantly improved their exercise capacity. In conclusion, the prepared ultrasound-mediated DEXsp@Liposomes/C<small>₃</small>F<small>₈</small> system exhibits good imaging, monitoring and therapeutic effects, and the results of this study provide a new direction for the diagnosis and treatment of RA.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 6","pages":" 2052-2066"},"PeriodicalIF":6.1,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933860","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":"Probing the orientation and membrane permeation of rhodamine voltage reporters through molecular simulations and free energy calculations†","authors":"Yajing Qi, Lap Yan Fung, Christophe Chipot and Yi Wang","doi":"10.1039/D4TB02670E","DOIUrl":"10.1039/D4TB02670E","url":null,"abstract":"<p >The transmembrane potential of plasma membranes and membrane-bound organelles plays a fundamental role in cellular functions such as signal transduction, ATP synthesis, and homeostasis. Rhodamine voltage reporters (RhoVRs), which operate based on the photoinduced electron transfer (PeT) mechanism, are non-invasive, small-molecule voltage sensors that can detect rapid voltage changes, with some of them specifically targeting the inner mitochondrial membrane. In this work, we conducted extensive molecular dynamics simulations and free-energy calculations to investigate the physicochemical properties governing the orientation as well as membrane permeation barriers of three RhoVRs. Our results indicate that the positioning of the most polarized functional group relative to the hydrophobic molecular wire dictates the alignment of RhoVRs with the membrane normal, thereby, significantly affecting their voltage sensitivity. Free-energy calculations in different membrane systems identify significantly higher barriers against the permeation of RhoVR 1 compared to SPIRIT RhoVR 1, explaining their distinct subcellular localization profiles. Subsequent free-energy calculations of the distinguishing components from the two different RhoVRs provide additional insight into the physicochemical properties governing their membrane permeation. The connection between chemical composition and membrane orientation, as well as permeation behaviors of RhoVRs revealed by our calculations provides general guiding principles for the rational design of PeT-based fluorescent dyes with enhanced voltage sensitivity and desired subcellular distribution.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 6","pages":" 2015-2028"},"PeriodicalIF":6.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960771","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":"Vacancy engineering enhanced photothermal-catalytic properties of Co9S8−x nanozymes for mild NIR-II hyperthermia-amplified nanocatalytic cancer therapy†","authors":"Yongyu Hao, Nan Wang, Jiaxu Wang, Shuilin Shao, Bo Gao, Youping Tao, Litao Huo, Lang Yan, Jigong Wu and Zhiming Chen","doi":"10.1039/D4TB02032D","DOIUrl":"10.1039/D4TB02032D","url":null,"abstract":"<p >While nanozymes are commonly employed in nanocatalytic therapy (NCT), the efficacy of NCT is hampered by the limited catalytic activity of nanozymes and the intricate tumor microenvironment (TME). In this work, we design a high-efficiency nanozyme with NIR-II photothermal property for the mild hyperthermia-augmented NCT. In order to endow a single-component nanomaterial the ability to simultaneously catalyze and exhibit NIR-II photothermal properties, a straightforward template method is utilized to fabricate sulfur vacancies (V<small>_S</small>)-doped Co<small>₉</small>S<small>_{8−<em>x</em>}</small> nanocages. Introducing V<small>_S</small> not only lowers the bandgap structure of Co<small>₉</small>S<small>₈</small>, enhancing its NIR-II photothermal properties, but also facilitates the control of the Co<small>²⁺</small> and Co<small>³⁺</small> ratio in Co<small>₉</small>S<small>₈</small>, leading to a boost in its catalytic activity. Furthermore, the catalytic efficiency of Co<small>₉</small>S<small>_{8−<em>x</em>}</small> nanocages was boosted by the mild hyperthermia. Moreover, the Co<small>₉</small>S<small>_{8−<em>x</em>}</small> nanocages exhibited high-efficiency GSH-px-mimic catalytic activity, facilitating the cascade amplification of ROS production. Through the integrated multifunctionality of Co<small>₉</small>S<small>_{8−<em>x</em>}</small> nanocages, we successfully enhanced the effectiveness of antitumor treatment with a single drug injection and a single 1064 nm laser irradiation for mild hyperthermia-augmented NCT. This work provides a distinct paradigm of endowing nanomaterials with catalytic activity and photothermal property for mild NIR-II PTT-amplified NCT through a vacancy engineering strategy.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 7","pages":" 2480-2489"},"PeriodicalIF":6.1,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018965","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":"The effect of microenvironmental viscosity on the emergence of colon cancer cell resistance to doxorubicin†","authors":"Tianjiao Zeng, Chengyu Lu, Man Wang, Huajian Chen, Toru Yoshitomi, Naoki Kawazoe, Yingnan Yang and Guoping Chen","doi":"10.1039/D4TB02334J","DOIUrl":"10.1039/D4TB02334J","url":null,"abstract":"<p >The colon possesses a unique physiological environment among human organs, where there is a highly viscous body fluid layer called the mucus layer above colonic epithelial cells. Dysfunction of the mucus layer not only contributes to the occurrence of colorectal cancer (CRC) but also plays an important role in the development of chemoresistance in CRC. Although viscosity is an essential property of the mucus layer, it remains elusive how viscosity affects chemoresistance in colon cancer cells. In this study, the influence of viscosity on their chemoresistance was elucidated by culturing colon cancer cells in media of different viscosities supplemented with doxorubicin (DOX). The viscosity range was adjusted from 99.4 mPa s to 776.6 mPa s by adding polyethylene glycol of different molecular weights in culture medium. Cell viability in the high viscosity medium was higher than that in the low viscosity medium. Expression of chemoresistance-related genes such as ABCC2 and ABCG2 increased when cells were cultured in the high viscosity medium. Furthermore, cell migration increased while proliferation decreased when cells were cultured in the high viscosity medium. The colon cancer cells cultured in the high viscosity medium exhibited high expression of p21 mRNA. The results suggested that viscosity could affect the resistance of colon cancer cells to DOX by regulating the expression of chemoresistance-related and proliferation-related genes.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 6","pages":" 2180-2191"},"PeriodicalIF":6.1,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974021","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}