Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology最新文献

{"title":"Stemness, invasion, and immunosuppression modulation in recurrent glioblastoma using nanotherapy.","authors":"Shrita Sarkar, Jessica Greer, Nathaniel J Marlowe, Angeline Medvid, Michael E Ivan, Nagesh Kolishetti, Shanta Dhar","doi":"10.1002/wnan.1976","DOIUrl":"10.1002/wnan.1976","url":null,"abstract":"<p><p>The recurrent nature of glioblastoma negatively impacts conventional treatment strategies leading to a growing need for nanomedicine. Nanotherapeutics, an approach designed to deliver drugs to specific sites, is experiencing rapid growth and gaining immense popularity. Having potential in reaching the hard-to-reach disease sites, this field has the potential to show high efficacy in combatting glioblastoma progression. The presence of glioblastoma stem cells (GSCs) is a major factor behind the poor prognosis of glioblastoma multiforme (GBM). Stemness potential, heterogeneity, and self-renewal capacity, are some of the properties that make GSCs invade across the distant regions of the brain. Despite advances in medical technology and MRI-guided maximal surgical resection, not all GSCs residing in the brain can be removed, leading to recurrent disease. The aggressiveness of GBM is often correlated with immune suppression, where the T-cells are unable to infiltrate the cancer initiating GSCs. Standard of care therapies, including surgery and chemotherapy in combination with radiation therapy, have failed to tackle all the challenges of the GSCs, making it increasingly important for researchers to develop strategies to tackle their growth and proliferation and reduce the recurrence of GBM. Here, we will focus on the advancements in the field of nanomedicine that has the potential to show positive impact in managing glioblastoma tumor microenvironment. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.</p>","PeriodicalId":94267,"journal":{"name":"Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology","volume":"16 4","pages":"e1976"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877139","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":"Theranostic nanoparticles for detection and treatment of pancreatic cancer.","authors":"Happy Agarwal, Ryan C Bynum, Nada Saleh, Danielle Harris, William M MacCuaig, Vung Kim, Emma J Sanderson, Isabel S Dennahy, Rohit Singh, Bahareh Behkam, Jorge G Gomez-Gutierrez, Ajay Jain, Barish H Edil, Lacey R McNally","doi":"10.1002/wnan.1983","DOIUrl":"10.1002/wnan.1983","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) is one of the most recalcitrant cancers due to its late diagnosis, poor therapeutic response, and highly heterogeneous microenvironment. Nanotechnology has the potential to overcome some of the challenges to improve diagnostics and tumor-specific drug delivery but they have not been plausibly viable in clinical settings. The review focuses on active targeting strategies to enhance pancreatic tumor-specific uptake for nanoparticles. Additionally, this review highlights using actively targeted liposomes, micelles, gold nanoparticles, silica nanoparticles, and iron oxide nanoparticles to improve pancreatic tumor targeting. Active targeting of nanoparticles toward either differentially expressed receptors or PDAC tumor microenvironment (TME) using peptides, antibodies, small molecules, polysaccharides, and hormones has been presented. We focus on microenvironment-based hallmarks of PDAC and the potential for actively targeted nanoparticles to overcome the challenges presented in PDAC. It describes the use of nanoparticles as contrast agents for improved diagnosis and the delivery of chemotherapeutic agents that target various aspects within the TME of PDAC. Additionally, we review emerging nano-contrast agents detected using imaging-based technologies and the role of nanoparticles in energy-based treatments of PDAC. This article is categorized under: Implantable Materials and Surgical Technologies > Nanoscale Tools and Techniques in Surgery Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.</p>","PeriodicalId":94267,"journal":{"name":"Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology","volume":"16 4","pages":"e1983"},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11328968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141977612","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":"Exploring the properties and potential of the neural extracellular matrix for next-generation regenerative therapies.","authors":"J Alberto Ortega, Gisele P Soares de Aguiar, Palash Chandravanshi, Natacha Levy, Elisabeth Engel, Zaida Álvarez","doi":"10.1002/wnan.1962","DOIUrl":"10.1002/wnan.1962","url":null,"abstract":"<p><p>The extracellular matrix (ECM) is a dynamic and complex network of proteins and molecules that surrounds cells and tissues in the nervous system and orchestrates a myriad of biological functions. This review carefully examines the diverse interactions between cells and the ECM, as well as the transformative chemical and physical changes that the ECM undergoes during neural development, aging, and disease. These transformations play a pivotal role in shaping tissue morphogenesis and neural activity, thereby influencing the functionality of the central nervous system (CNS). In our comprehensive review, we describe the diverse behaviors of the CNS ECM in different physiological and pathological scenarios and explore the unique properties that make ECM-based strategies attractive for CNS repair and regeneration. Addressing the challenges of scalability, variability, and integration with host tissues, we review how advanced natural, synthetic, and combinatorial matrix approaches enhance biocompatibility, mechanical properties, and functional recovery. Overall, this review highlights the potential of decellularized ECM as a powerful tool for CNS modeling and regenerative purposes and sets the stage for future research in this exciting field. This article is categorized under: Implantable Materials and Surgical Technologies > Nanotechnology in Tissue Repair and Replacement Therapeutic Approaches and Drug Discovery > Nanomedicine for Neurological Disease Implantable Materials and Surgical Technologies > Nanomaterials and Implants.</p>","PeriodicalId":94267,"journal":{"name":"Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology","volume":"16 3","pages":"e1962"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900533","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":"A review of recent advances in the use of complex metal nanostructures for biomedical applications from diagnosis to treatment.","authors":"Maryam Hajfathalian, Katherine J Mossburg, Allan Radaic, Katherine E Woo, Pallavi Jonnalagadda, Yvonne Kapila, Paul L Bollyky, David P Cormode","doi":"10.1002/wnan.1959","DOIUrl":"10.1002/wnan.1959","url":null,"abstract":"<p><p>Complex metal nanostructures represent an exceptional category of materials characterized by distinct morphologies and physicochemical properties. Nanostructures with shape anisotropies, such as nanorods, nanostars, nanocages, and nanoprisms, are particularly appealing due to their tunable surface plasmon resonances, controllable surface chemistries, and effective targeting capabilities. These complex nanostructures can absorb light in the near-infrared, enabling noteworthy applications in nanomedicine, molecular imaging, and biology. The engineering of targeting abilities through surface modifications involving ligands, antibodies, peptides, and other agents potentiates their effects. Recent years have witnessed the development of innovative structures with diverse compositions, expanding their applications in biomedicine. These applications encompass targeted imaging, surface-enhanced Raman spectroscopy, near-infrared II imaging, catalytic therapy, photothermal therapy, and cancer treatment. This review seeks to provide the nanomedicine community with a thorough and informative overview of the evolving landscape of complex metal nanoparticle research, with a specific emphasis on their roles in imaging, cancer therapy, infectious diseases, and biofilm treatment. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Diagnostic Tools > Diagnostic Nanodevices.</p>","PeriodicalId":94267,"journal":{"name":"Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology","volume":"16 3","pages":"e1959"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11114100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140873895","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":"The development of nanocarriers for natural products.","authors":"Liying Huang, Shicui Luo, Sen Tong, Zhuo Lv, Junzi Wu","doi":"10.1002/wnan.1967","DOIUrl":"10.1002/wnan.1967","url":null,"abstract":"<p><p>Natural bioactive compounds from plants exhibit substantial pharmacological potency and therapeutic value. However, the development of most plant bioactive compounds is hindered by low solubility and instability. Conventional pharmaceutical forms, such as tablets and capsules, only partially overcome these limitations, restricting their efficacy. With the recent development of nanotechnology, nanocarriers can enhance the bioavailability, stability, and precise intracellular transport of plant bioactive compounds. Researchers are increasingly integrating nanocarrier-based drug delivery systems (NDDS) into the development of natural plant compounds with significant success. Moreover, natural products benefit from nanotechnological enhancement and contribute to the innovation and optimization of nanocarriers via self-assembly, grafting modifications, and biomimetic designs. This review aims to elucidate the collaborative and reciprocal advancement achieved by integrating nanocarriers with botanical products, such as bioactive compounds, polysaccharides, proteins, and extracellular vesicles. This review underscores the salient challenges in nanomedicine, encompassing long-term safety evaluations of nanomedicine formulations, precise targeting mechanisms, biodistribution complexities, and hurdles in clinical translation. Further, this study provides new perspectives to leverage nanotechnology in promoting the development and optimization of natural plant products for nanomedical applications and guiding the progression of NDDS toward enhanced efficiency, precision, and safety. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.</p>","PeriodicalId":94267,"journal":{"name":"Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology","volume":"16 3","pages":"e1967"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961411","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":"Sample-to-answer salivary miRNA testing: New frontiers in point-of-care diagnostic technologies.","authors":"Zhikun Zhang, Tianyi Liu, Ming Dong, Md Ahasan Ahamed, Weihua Guan","doi":"10.1002/wnan.1969","DOIUrl":"10.1002/wnan.1969","url":null,"abstract":"<p><p>MicroRNA (miRNA), crucial non-coding RNAs, have emerged as key biomarkers in molecular diagnostics, prognosis, and personalized medicine due to their significant role in gene expression regulation. Salivary miRNA, in particular, stands out for its non-invasive collection method and ease of accessibility, offering promising avenues for the development of point-of-care diagnostics for a spectrum of diseases, including cancer, neurodegenerative disorders, and infectious diseases. Such development promises rapid and precise diagnosis, enabling timely treatment. Despite significant advancements in salivary miRNA-based testing, challenges persist in the quantification, multiplexing, sensitivity, and specificity, particularly for miRNA at low concentrations in complex biological mixtures. This work delves into these challenges, focusing on the development and application of salivary miRNA tests for point-of-care use. We explore the biogenesis of salivary miRNA and analyze their quantitative expression and their disease relevance in cancer, infection, and neurodegenerative disorders. We also examined recent progress in miRNA extraction, amplification, and multiplexed detection methods. This study offers a comprehensive view of the development of salivary miRNA-based point-of-care testing (POCT). Its successful advancement could revolutionize the early detection, monitoring, and management of various conditions, enhancing healthcare outcomes. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > Diagnostic Nanodevices.</p>","PeriodicalId":94267,"journal":{"name":"Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology","volume":"16 3","pages":"e1969"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11141732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141088357","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":"Life at the interface: Engineering bio-nanomaterials through interfacial molecular self-assembly.","authors":"Michael A Miller, Scott Medina","doi":"10.1002/wnan.1966","DOIUrl":"10.1002/wnan.1966","url":null,"abstract":"<p><p>Interfacial self-assembly describes the directed organization of molecules and colloids at phase boundaries. Believed to be fundamental to the inception of primordial life, interfacial assembly is exploited by a myriad of eukaryotic and prokaryotic organisms to execute physiologic activities and maintain homeostasis. Inspired by these natural systems, chemists, engineers, and materials scientists have sought to harness the thermodynamic equilibria at phase boundaries to create multi-dimensional, highly ordered, and functional nanomaterials. Recent advances in our understanding of the biophysical principles guiding molecular assembly at gas-solid, gas-liquid, solid-liquid, and liquid-liquid interphases have enhanced the rational design of functional bio-nanomaterials, particularly in the fields of biosensing, bioimaging and biotherapy. Continued development of non-canonical building blocks, paired with deeper mechanistic insights into interphase self-assembly, holds promise to yield next generation interfacial bio-nanomaterials with unique, and perhaps yet unrealized, properties. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies.</p>","PeriodicalId":94267,"journal":{"name":"Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology","volume":"16 3","pages":"e1966"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11090466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900603","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":"The development of nanocarriers for natural products.","authors":"Liying Huang, Shicui Luo, Sen Tong, Zhuo Lv, Junzi Wu","doi":"10.1002/wnan.1967","DOIUrl":"https://doi.org/10.1002/wnan.1967","url":null,"abstract":"Natural bioactive compounds from plants exhibit substantial pharmacological potency and therapeutic value. However, the development of most plant bioactive compounds is hindered by low solubility and instability. Conventional pharmaceutical forms, such as tablets and capsules, only partially overcome these limitations, restricting their efficacy. With the recent development of nanotechnology, nanocarriers can enhance the bioavailability, stability, and precise intracellular transport of plant bioactive compounds. Researchers are increasingly integrating nanocarrier-based drug delivery systems (NDDS) into the development of natural plant compounds with significant success. Moreover, natural products benefit from nanotechnological enhancement and contribute to the innovation and optimization of nanocarriers via self-assembly, grafting modifications, and biomimetic designs. This review aims to elucidate the collaborative and reciprocal advancement achieved by integrating nanocarriers with botanical products, such as bioactive compounds, polysaccharides, proteins, and extracellular vesicles. This review underscores the salient challenges in nanomedicine, encompassing long-term safety evaluations of nanomedicine formulations, precise targeting mechanisms, biodistribution complexities, and hurdles in clinical translation. Further, this study provides new perspectives to leverage nanotechnology in promoting the development and optimization of natural plant products for nanomedical applications and guiding the progression of NDDS toward enhanced efficiency, precision, and safety. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.","PeriodicalId":94267,"journal":{"name":"Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology","volume":"45 7","pages":"e1967"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141052939","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":"Iron oxide nanoparticles for treatment and diagnosis of chronic inflammatory diseases: A systematic review.","authors":"Shaquib Rahman Ansari, Jessica Mahajan, Alexandra Teleki","doi":"10.1002/wnan.1963","DOIUrl":"10.1002/wnan.1963","url":null,"abstract":"<p><p>Chronic inflammatory conditions are among the most prevalent diseases worldwide. Several debilitating diseases such as atherosclerosis, inflammatory bowel disease, rheumatoid arthritis, and Alzheimer's are linked to chronic inflammation. These conditions often develop into complex and fatal conditions, making early detection and treatment of chronic inflammation crucial. Current diagnostic methods show high variability and do not account for disease heterogeneity and disease-specific proinflammatory markers, often delaying the disease detection until later stages. Furthermore, existing treatment strategies, including high-dose anti-inflammatory and immunosuppressive drugs, have significant side effects and an increased risk of infections. In recent years, superparamagnetic iron oxide nanoparticles (SPIONs) have shown tremendous biomedical potential. SPIONs can function as imaging modalities for magnetic resonance imaging, and as therapeutic agents due to their magnetic hyperthermia capability. Furthermore, the surface functionalization of SPIONs allows the detection of specific disease biomarkers and targeted drug delivery. This systematic review explores the utility of SPIONs against chronic inflammatory disorders, focusing on their dual role as diagnostic and therapeutic agents. We extracted studies indexed in the Web of Science database from the last 10 years (2013-2023), and applied systematic inclusion criteria. This resulted in a final selection of 38 articles, which were analyzed for nanoparticle characteristics, targeted diseases, in vivo and in vitro models used, and the efficacy of the therapeutic or diagnostic modalities. The results revealed that ultrasmall SPIONs are excellent for imaging arterial and neuronal inflammation. Furthermore, novel therapies using SPIONs loaded with chemotherapeutic drugs show promise in the treatment of inflammatory diseases. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vivo Nanodiagnostics and Imaging.</p>","PeriodicalId":94267,"journal":{"name":"Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology","volume":"16 3","pages":"e1963"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900584","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":"Soft mechanical sensors for wearable and implantable applications.","authors":"Rithvik Papani, Yang Li, Sihong Wang","doi":"10.1002/wnan.1961","DOIUrl":"10.1002/wnan.1961","url":null,"abstract":"<p><p>Wearable and implantable sensing of biomechanical signals such as pressure, strain, shear, and vibration can enable a multitude of human-integrated applications, including on-skin monitoring of vital signs, motion tracking, monitoring of internal organ condition, restoration of lost/impaired mechanoreception, among many others. The mechanical conformability of such sensors to the human skin and tissue is critical to enhancing their biocompatibility and sensing accuracy. As such, in the recent decade, significant efforts have been made in the development of soft mechanical sensors. To satisfy the requirements of different wearable and implantable applications, such sensors have been imparted with various additional properties to make them better suited for the varied contexts of human-integrated applications. In this review, focusing on the four major types of soft mechanical sensors for pressure, strain, shear, and vibration, we discussed the recent material and device design innovations for achieving several important properties, including flexibility and stretchability, bioresorbability and biodegradability, self-healing properties, breathability, transparency, wireless communication capabilities, and high-density integration. We then went on to discuss the current research state of the use of such novel soft mechanical sensors in wearable and implantable applications, based on which future research needs were further discussed. This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > Diagnostic Nanodevices Implantable Materials and Surgical Technologies > Nanomaterials and Implants.</p>","PeriodicalId":94267,"journal":{"name":"Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology","volume":"16 3","pages":"e1961"},"PeriodicalIF":0.0,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11108230/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140900605","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}