Sachin Kadian, Siba Sundar Sahoo, Shubhangi Shukla and Roger J. Narayan
{"title":"Development of 3D-printed conducting microneedle-based electrochemical point-of-care device for transdermal sensing of chlorpromazine†","authors":"Sachin Kadian, Siba Sundar Sahoo, Shubhangi Shukla and Roger J. Narayan","doi":"10.1039/D4TB01808G","DOIUrl":"10.1039/D4TB01808G","url":null,"abstract":"<p >Despite the various benefits of chlorpromazine, its misuse and overdose may lead to severe side effects, therefore, creating a user-friendly point-of-care device for monitoring the levels of chlorpromazine drug to manage the potential side effects and ensure the effective and safe use of the medication is highly desired. In this report, we have demonstrated a simple and scalable manufacturing process for the development of a 3D-printed conducting microneedle array-based electrochemical point-of-care device for the minimally invasive sensing of chlorpromazine. We used an inkjet printer to print the carbon and silver ink onto a customized 3D-printed ultrasharp microneedle array for the preparation of counter, working, and reference electrodes. After physical characterization and electrochemical parameter optimization, the developed microneedle array-based three-electrode system was explored for the detection of chlorpromazine. The analytical results showed high sensitivity and selectivity toward chlorpromazine with a good linearity range from 5–120 μM and a low detection limit (0.09 μM). The proof-of-concept study results obtained from the skin-mimicking model indicated that the developed conductive microneedle array-based sensor can easily monitor the micromolar levels of chlorpromazine in artificial interstitial fluid; this type of system can be further explored for the development of other minimally invasive electrochemical biosensors.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 6","pages":" 2114-2123"},"PeriodicalIF":6.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.rsc.org/en/content/articlepdf/2025/tb/d4tb01808g?page=search","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960672","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}
Sourav Barman, Sayoni Maitra Roy, Purvi Kishore, Malabika Ghosh, Pousali Bag, Ankan Kumar Sarkar, Tapas Ghatak, Partha Sona Maji, Arnab Basu, Rupam Mukherjee, Surya K. Ghosh, Ankan Dutta Chowdhury and Amit Ranjan Maity
{"title":"Concurrent targeted delivery of doxorubicin and curcumin to the cancer cells using simple and versatile ligand-installed multifaceted chitosan-based nanoconjugates†","authors":"Sourav Barman, Sayoni Maitra Roy, Purvi Kishore, Malabika Ghosh, Pousali Bag, Ankan Kumar Sarkar, Tapas Ghatak, Partha Sona Maji, Arnab Basu, Rupam Mukherjee, Surya K. Ghosh, Ankan Dutta Chowdhury and Amit Ranjan Maity","doi":"10.1039/D4TB01809E","DOIUrl":"10.1039/D4TB01809E","url":null,"abstract":"<p >Existing chemotherapeutic approaches against refractory cancers are ineffective due to off-target effects, inefficient delivery, and inadequate accumulation of anticancer drugs at the tumor site, which causes limited efficiency of drug treatment and toxicity to neighboring healthy cells. The development of nano-based drug delivery systems (DDSs) with the goal of delivering desired therapeutic doses to the diseased cells and has already proven to be a promising strategy to address these challenges. Our study focuses on achieving an efficient tumor-targeted delivery of a combination of drugs for therapeutic benefits by developing a versatile DDS by following a simple one-step chemical approach. We used low-molecular-weight chitosan and modified its primary amine groups with reactive forms of cholesterol and folic acid by simple chemical tools and thus prepared folic acid–chitosan–cholesterol graft copolymer. The polymer contains numerous residual primary amine groups, which offer enough water solubility and positive charge to its polymeric backbone to foster the interaction of negatively charged and/or hydrophobic drugs to load and encapsulate a wide variety of drugs within it <em>via</em> various non-bonding interactions. We used curcumin and doxorubicin as the combination of drugs and thus finally prepared targeted nanoconjugates (targeted NCs). <em>In vitro</em> cellular experiments show that our developed targeted NCs demonstrate 3–5 times higher cellular uptake than non-targeted NCs at various incubation times (2 h, 8 h, and 12 h) in KB cells where folate receptors are overexpressed. This enhanced cellular uptake of targeted NCs and the following delivery of drugs in the cytosol and its disposition to the nucleus exhibit a substantial amount of toxicity to KB cells towards an effective therapeutic strategy for treatment.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 7","pages":" 2490-2503"},"PeriodicalIF":6.1,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019137","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}
Yunyao Wang, Ruiqing Jiu, Zongda Li, Qiuying Wang, Xiangmin Lei, Jianan Chen, Haochi Liu and Jifeng Liu
{"title":"Tyrosine-modified tilapia skin antioxidant peptides and their hydroxyl radical quenching activities†","authors":"Yunyao Wang, Ruiqing Jiu, Zongda Li, Qiuying Wang, Xiangmin Lei, Jianan Chen, Haochi Liu and Jifeng Liu","doi":"10.1039/D4TB02200A","DOIUrl":"10.1039/D4TB02200A","url":null,"abstract":"<p >In an antioxidant peptide study, the number and position of active amino acid sites, as well as the peptides’ conformation, are found to be crucial for scavenging hydroxyl radicals (˙OH). Herein, ˙the OH scavenging activity of tilapia pentapeptide (P1, YGDQY) and its analogs including P2 (YYYGDQY), P3 (YYGDQYY) and P4 (YYGPDQYY) was investigated. The results showed that the tyrosine's amount, location and the peptides’ conformation played important roles in determining peptides’ scavenging activity (34.1 ± 0.8%, 45.1 ± 0.9%, 58.6 ± 1.3% and 48.4 ± 0.96% for P1, P2, P3, and P4, respectively). Density functional theory simulation showed that only the tyrosine sites located within the effective diffusion distance <img> of ˙OH could scavenge the radical. The peptides did not cause cytotoxicity in Caco-2 cells. And the peptide-treated group could increase the activities of glutathione peroxidase (GSH-PX), catalase (CAT) and superoxide dismutase (SOD), and reduced malondialdehyde (MDA) levels. This work may contribute to designing more active antioxidant peptides based on natural peptides’ analogs.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 7","pages":" 2400-2408"},"PeriodicalIF":6.1,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985779","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":"Multi-organelle imaging with dye combinations: targeting the ER, mitochondria, and plasma membrane†","authors":"Yogesh Dubey and Sriram Kanvah","doi":"10.1039/D4TB02456G","DOIUrl":"10.1039/D4TB02456G","url":null,"abstract":"<p >Multi-organelle imaging allows the visualization of multiple organelles within a single cell, allowing monitoring of the cellular processes in real-time using various fluorescent probes that target specific organelles. However, the limited availability of fluorophores and potential spectral overlap present challenges, and many optimized designs are still in nascency. In this work, we synthesized various sulfonamide-based organic fluorophores that emit in the blue, green, and red regions to target different sub-cellular organelles. By utilizing binary mixtures, we successfully demonstrated multiple imaging of the sub-cellular organelles, such as the endoplasmic reticulum, plasma membrane, and mitochondria in HeLa cells, and dual imaging of the endoplasmic reticulum and mitochondria in A549 lung carcinoma cells with the help of blue and red-emitting fluorophores without any spectral spillover. Additionally, these photostable probes allowed precise cell staining and differentiation, structural features, and live cell dynamics. This approach of utilizing fluorescent mixtures can gain traction for various cellular studies and investigations.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 7","pages":" 2446-2456"},"PeriodicalIF":6.1,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018892","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}
Wen Zhou, Qiang Li, Mingming Liu, Xuxuan Gu, Xiaowen He, Chen Xie and Quli Fan
{"title":"Biodegradable semiconducting polymer nanoparticles for phototheranostics","authors":"Wen Zhou, Qiang Li, Mingming Liu, Xuxuan Gu, Xiaowen He, Chen Xie and Quli Fan","doi":"10.1039/D4TB02437K","DOIUrl":"10.1039/D4TB02437K","url":null,"abstract":"<p >Semiconducting polymer nanoparticles (SPNs) have been widely applied for phototheranostics. However, the disadvantage of <em>in vivo</em> long-term metabolism greatly suppresses the clinical application of SPNs. To improve the metabolic rate and minimize the long-term toxicity of SPNs, biodegradable semiconducting polymers (BSPs), whose backbones may be degraded under certain conditions, have been designed. This review summarizes recent advances in BSP-constructed nanoparticles (BSPNs) for phototheranostics. BSPs are divided into two categories: conjugated backbone degradable BSPs (CBD-BSPs) and non-conjugated backbone degradable BSPs (NCBD-BSPs), based on the feature of chemical structure. The biological applications, including cancer imaging and combination therapy, of these BSPNs are described. Finally, the conclusion and future perspectives of this field are discussed.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 7","pages":" 2242-2253"},"PeriodicalIF":6.1,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019089","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}
Sheng-Nan Wang, Xin-Yu Li, Zhong-Xia Lu, Lu-Xin Liu, Xuan-Ping Xu, Wen-Gong Yu and Xin-Zhi Lu
{"title":"Effect and mechanism of oritavancin on hIAPP amyloid formation†","authors":"Sheng-Nan Wang, Xin-Yu Li, Zhong-Xia Lu, Lu-Xin Liu, Xuan-Ping Xu, Wen-Gong Yu and Xin-Zhi Lu","doi":"10.1039/D4TB02215G","DOIUrl":"10.1039/D4TB02215G","url":null,"abstract":"<p >Amyloidosis of the human islet amyloid polypeptide (hIAPP) is closely related to the pathogenesis of type 2 diabetes (T2D) and serves as both a diagnostic hallmark and a key therapeutic target for T2D. In this study, we discovered that oritavancin (Ori), a glycopeptide antibiotic primarily prescribed for Gram-positive bacterial infections, can dose-dependently inhibit recombinant hIAPP (rhIAPP) amyloid formation. Ori specifically inhibited rhIAPP amyloid formation at the initial nucleation stage but didn’t affect mature rhIAPP fibrils. As a result, Ori reduced amyloidosis of rhIAPP induced pancreatic NIT-1 cell apoptosis and reactive oxygen species (ROS) release. Based on the results from studies involving antibiotic homologues of Ori and its acid hydrolysates, we demonstrated that both the <em>N</em>-(4-chlorobiphenyl) methyl group (CBP) and glycopeptide backbone were necessary for inhibiting rhIAPP amyloid formation. The mechanism behind Ori on rhIAPP amyloid formation lies in the direct interaction of the two molecules identified by ESI-MS and molecular docking assays. Consequently, this research not only lays the groundwork for developing novel therapeutic approaches for T2D but also presents the opportunity to repurpose Ori as a treatment option.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 6","pages":" 2192-2202"},"PeriodicalIF":6.1,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973988","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}
Yuzhu Liu, Md Shariful Islam, Anna Bakker, Zihao Li, Alaa Ajam, Jamie J. Kruzic and Kristopher A. Kilian
{"title":"Improving the bioactivity and mechanical properties of poly(ethylene glycol)-based hydrogels through a supramolecular support network†","authors":"Yuzhu Liu, Md Shariful Islam, Anna Bakker, Zihao Li, Alaa Ajam, Jamie J. Kruzic and Kristopher A. Kilian","doi":"10.1039/D4TB02002B","DOIUrl":"10.1039/D4TB02002B","url":null,"abstract":"<p >Most synthetic hydrogels are formed through radical polymerization to yield a homogenous covalent meshwork. In contrast, natural hydrogels form through mechanisms involving both covalent assembly and supramolecular interactions. In this communication, we expand the capabilities of covalent poly(ethylene glycol) (PEG) networks through co-assembly of supramolecular peptide nanofibers. Using a peptide hydrogelator derived from the tryptophan zipper (Trpzip) motif, we demonstrate how <em>in situ</em> formation of nanofiber networks can tune the stiffness of PEG-based hydrogels, while also imparting shear thinning, stress relaxation, and self-healing properties. The hybrid networks show enhanced toughness and durability under tension, providing scope for use in load bearing applications. A small quantity of Trpzip peptide renders the non-adhesive PEG network adhesive, supporting adipose derived stromal cell adhesion, elongation, and growth. The integration of supramolecular networks into covalent meshworks expands the versatility of these materials, opening up new avenues for applications in biotechnology and medicine.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 4","pages":" 1286-1295"},"PeriodicalIF":6.1,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142960658","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}
Qianyang Zhang, Yiying Zhang, Wei Wu, Yingjie Wu, Zhuling Jiang and Narisu Hu
{"title":"Self-driven micromotors loaded with photosensitive adhesives and their application in dentin sensitivity†","authors":"Qianyang Zhang, Yiying Zhang, Wei Wu, Yingjie Wu, Zhuling Jiang and Narisu Hu","doi":"10.1039/D4TB02361G","DOIUrl":"10.1039/D4TB02361G","url":null,"abstract":"<p >Dentin hypersensitivity is primarily caused by the exposure of dentinal tubules due to various factors, so the key to treatment is to effectively seal these exposed tubules. However, traditional dentinal tubule sealants used in clinical practice often fail to adhere securely to the tubule surface when exposed to external stimuli, resulting in a recurrence of sensitivity. In this study, we developed a silicon micromotor that moved autonomously and loaded with silver nanoparticles and a photosensitive adhesive for dentin sensitivity therapy. These micromotors move autonomously to reach deep into the dentin tubules and surface loaded adhesives are solidified under blue light. The compact structure formed by the cross-linking of micromotors effectively seals the dentin tubules from the inside to the outside, and also forms a firm bond between the micromotor and the inner layer of the dentin, thereby improving the sealing effect and providing strong protection. Silver nanoparticles on the surface of micromotors can slowly release silver ions, effectively inhibiting the growth of caries-causing bacteria such as <em>S. mutans</em>, and preventing secondary caries. Our research demonstrates that the closure rate of dentinal tubules after treatment can reach 79.17% with a closure depth of 17.22 μm, while also withstanding various stimuli without detachment. In conclusion, the use of self-propelled micromotors presents a promising new strategy for treating dentin hypersensitivity in clinical settings.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 5","pages":" 1643-1652"},"PeriodicalIF":6.1,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142981093","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}
Ziyin Zhao, Haoyu Zhang, Wei Li, Yehan Wang, Yifei Wang, He Yang, Lichen Yin and Xun Liu
{"title":"Guanidyl-rich α-helical polypeptide enables efficient cytosolic pro-protein delivery and CRISPR-Cas9 genome editing†","authors":"Ziyin Zhao, Haoyu Zhang, Wei Li, Yehan Wang, Yifei Wang, He Yang, Lichen Yin and Xun Liu","doi":"10.1039/D4TB02009J","DOIUrl":"10.1039/D4TB02009J","url":null,"abstract":"<p >Intracellular delivery of proteins has attracted significant interest in biological research and cancer treatment, yet it continues to face challenges due to the lack of effective delivery approaches. Herein, we developed an efficient strategy <em>via</em> cationic α-helical polypeptide-mediated anionic proprotein delivery. The protein was reversibly modified with adenosine triphosphate <em>via</em> dynamic covalent chemistry to prepare an anionic proprotein (A-protein) with abundant phosphate groups. A guanidyl-decorated α-helical polypeptide (LPP) was employed not only to encapsulate A-protein through electrostatic attraction and hydrogen bonding, forming stable nanocomplexes, but also to enhance cell membrane penetration due to its rigid α-helical conformation. Consequently, this strategy mediated the effective delivery of various proteins with different isoelectric points and molecular weights, including α-chymotrypsin, bovine serum albumin, ribonuclease A, cytochrome <em>C</em>, saporin, horseradish peroxidase, β-galactosidase, and anti-phospho-Akt, into cancer cells. More importantly, it enabled efficient delivery of CRISPR-Cas9 ribonucleoproteins to elicit robust polo-like kinase 1 genome editing for inhibiting cancer cell growth. This rationally designed protein delivery system may benefit the development of intracellular protein-based cancer therapy.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 6","pages":" 1991-2002"},"PeriodicalIF":6.1,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142933899","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}
Nicolas Bondon, Clément Charlot, Lamiaa M. A. Ali, Alexandre Barras, Nicolas Richy, Denis Durand, Yann Molard, Grégory Taupier, Erwan Oliviero, Magali Gary-Bobo, Frédéric Paul, Sabine Szunerits, Nadir Bettache, Jean-Olivier Durand, Christophe Nguyen, Rabah Boukherroub, Olivier Mongin and Clarence Charnay
{"title":"FRET-based mesoporous organosilica nanoplatforms for in vitro and in vivo anticancer two-photon photodynamic therapy†","authors":"Nicolas Bondon, Clément Charlot, Lamiaa M. A. Ali, Alexandre Barras, Nicolas Richy, Denis Durand, Yann Molard, Grégory Taupier, Erwan Oliviero, Magali Gary-Bobo, Frédéric Paul, Sabine Szunerits, Nadir Bettache, Jean-Olivier Durand, Christophe Nguyen, Rabah Boukherroub, Olivier Mongin and Clarence Charnay","doi":"10.1039/D4TB02103G","DOIUrl":"10.1039/D4TB02103G","url":null,"abstract":"<p >We report the synthesis of multifunctional periodic mesoporous organosilica nanoparticles (PMO NPs) with substantial two-photon absorption properties and targeting capability for two-photon excitation fluorescence (TPEF) and photodynamic therapy (TPE-PDT). Prepared using an adapted sol–gel synthesis, the nanoplatforms integrated two silylated chromophores in their three-dimensional matrix to maximize non-radiative Förster resonance energy transfer from a high two-photon absorption fluorophore donor to a porphyrin derivative acceptor, leading to an enhanced generation of reactive oxygen species. Combinations of biodegradable and non-biodegradable bis(triethoxysilyl)alkoxysilanes were employed for the synthesis of the NPs, and the corresponding photophysical studies revealed high efficiency levels of FRET. Next, the cellular uptake and toxicities of pristine and functionalized NPs were evaluated on breast cancer cell lines upon TPEF and TPE-PDT. Notably, the use of TPE-PDT treatment led to high levels of phototoxicity on MCF-7 and MDA-MB-231 cancer cells with substantial effects when compared to one-photon excitation (OPE)-PDT treatment. Preliminary <em>in vivo</em> data on selective and biodegradable NPs showed a significant phototoxicity towards MDA-MB-231 on zebrafish xenograft embryos, making these advanced nanoplatforms promising candidates for future TPE-PDT-based cancer treatments.</p>","PeriodicalId":83,"journal":{"name":"Journal of Materials Chemistry B","volume":" 5","pages":" 1767-1780"},"PeriodicalIF":6.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883823","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}