Journal of Nanobiotechnology最新文献

{"title":"Chemotherapeutic drug scavenger-based combination therapy toward treating triple-negative breast cancer.","authors":"Qingqing Yin, Yutong Zhong, Mengchun Chen, Weian Mao, Yuan Yang, Li Li, Dongyan Tian, Shuangshuang Liu, Ying Chen, Jiale Quan, Shiyu Li, Deli Zhuge, Xufei Zhang, Ledan Wang, Fang Wang, Yiming Chen, Xiaosheng Lu, Xiaoji Lin, Yijie Chen, Linzhi Yan","doi":"10.1186/s12951-025-03571-z","DOIUrl":"10.1186/s12951-025-03571-z","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is resistant to most antitumor treatments, leaving chemotherapy as the primary option. Although doxorubicin (Dox) in combination with other therapies is promising for TNBC management, the combined effect is still compromised by the dose-limiting toxicities of Dox. Here, we developed a chemotherapeutic drug scavenger (CDS) by encapsulating GC-rich DNA-preferred binding targets of Dox-within an erythrocyte membrane functionalized with a normal tissue-targeting (NTT) peptide. Mimicking the structure of the cell nucleus, CDS selectively absorbs and neutralizes Dox in susceptible normal organs while sparing tumor tissues. This targeted detoxification allows for safe escalation of the Dox dose to 15 mg/kg, three times the standard 5 mg/kg, without observable toxicity. Such a high Dox dose enabled by CDS pretreatment significantly inhibited the post-operative residual/metastasized 4T1 tumor growth, regardless of the early or later stages of the tumor. Also, delivery of a high dose of Dox into the 4T1 tumor could profoundly increase the G2/M arrest, facilitating the combination therapy with a low-powered radiation of 2 Gy. Further, tumor exposure to high Dox amounts could convert the 4T1 tumor microenvironment from 'cold' to 'hot', leading to improved infiltration of immune cells, including T cells, dendritic cells, and macrophages. Overall, this study demonstrates how the safe injection of high amounts of Dox enabled by CDS detoxification could augment and extend Dox's functionality combined with surgery, radiotherapy, and cell therapy for TNBC treatment.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"473"},"PeriodicalIF":10.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Normal stress on surface of mesenchymal stem cells boosts extracellular vesicle secretion and regenerative bioactivity.","authors":"Chengmeng Bai, Huifang Ren, Feng Zhang, Dandan Li, Qingyu Feng, Ying Li, Ting Chen, Chengxu Li, Xuan Xiao, Hengrui Zhang, Liang Hu","doi":"10.1186/s12951-025-03556-y","DOIUrl":"10.1186/s12951-025-03556-y","url":null,"abstract":"<p><p>Scalable approaches for enhancing therapeutic small extracellular vesicles (sEVs) production can facilitate the transition of sEVs from bench to bedside and beyond. Here, we present a user-friendly method to manipulate the extracellular mechanical microenvironment of umbilical cord-derived mesenchymal stem cells (MSCs), a promising cell type for generating sEVs with therapeutic benefits, to boost sEV secretion and regenerative bioactivity. The bioreactor system, called the programmable controlled rotating platform (PRP), is designed to apply normal stress on cell surface through centrifugal rotation culture. Experimental analyses suggested that the PRP can promote a 4-fold sEV secretion increase without affecting cell viability and sEV size when compared to the traditional static culture condition. More importantly, PRP-induced MSC-sEVs can significantly promote epithelial cell migration in vitro and accelerate corneal wound healing in a murine model, with suppressed inflammatory responses in wound bed tissue. Further mechanistic investigations revealed that this process involves the activation of cellular transcriptional signals implicated in sEV biogenesis. Concurrently, sEV cargo undergoes remodeling to enrich regenerative and immunoregulatory functions. These findings demonstrate the efficacy of our established platform in advancing sEV production and improving clinical performance, providing a novel sEV-based mechanism for ocular treatments, including corneal epithelialization and even retinal neural regeneration.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"476"},"PeriodicalIF":10.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced wound healing with Stimuli-Responsive nanozymes: mechanisms, design and applications.","authors":"Xiaoyang Liu, Huihui Zhang, Lianglong Chen, Zesen Zheng, Wenwen Li, Chaoyang Huang, Hai Zhou, Yanqi Chen, Ziwei Jiang, Jiaqi Liang, Qiuyi Yu, Lei Yang","doi":"10.1186/s12951-025-03558-w","DOIUrl":"10.1186/s12951-025-03558-w","url":null,"abstract":"<p><p>Wound healing outcomes critically depend on precise regulation of oxidative and antimicrobial microenvironments. Traditional dressings have limited wound responsiveness, insufficient infection control, and limited treatment accuracy. In contrast, nanozymes, featuring enzyme-mimetic activities, tunable catalysis, and engineered sizes that balance catalytic site accessibility with tissue penetration, offer spatiotemporal control of reactive oxygen species (ROS) and pathogen elimination. This review systematically examines recent advances in stimuli-responsive nanozymes for wound management, focusing on their catalytic mechanisms and therapeutic specificity. These intelligent systems dynamically adapt catalytic behaviors (e.g., ROS scavenging, bacterial lysis) to physical stimuli (temperature, light, ultrasound) and physiological signals (pH, redox imbalance, ATP levels, microbial metabolites), leveraging size-dependent targeting mechanisms to ensure localized therapeutic effects while minimizing off-target damage. Current evidence demonstrates their multifunctional capacity to synergistically accelerate infection clearance, inflammation resolution, and angiogenesis. Future development should prioritize biosafety validation alongside size-effect standardization, stimulus specificity, and scalable manufacturing to advance personalized nanomedicine for refractory wounds.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"479"},"PeriodicalIF":10.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210524/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel tetrahedral framework nucleic acid-based antibiotic delivery system: overcoming biofilm barriers to combat chronic infections.","authors":"Yue Hu, Zhou Chen, Xinggang Mao, Di Qu, Dongsheng Zhai, Na Li, Shan Zhou, Xiaoyan Xue, Mingkai Li","doi":"10.1186/s12951-025-03553-1","DOIUrl":"10.1186/s12951-025-03553-1","url":null,"abstract":"<p><strong>Background: </strong>Overcoming bacterial biofilm barriers to enhance the efficacy of antibiotics remains a major therapeutic challenge, necessitating the development of efficient and biocompatible drug delivery systems. While framework nucleic acids (FNAs) have emerged as promising candidates for overcoming biological barriers, their biofilm penetration efficiency and mechanistic interactions require systematic exploration. This study evaluates the biofilm-penetrating capacity of FNAs with distinct topological configurations (linear, triangular, and tetrahedral), investigates their antibiotic delivery performance in biofilm-infected models, and elucidates the structure-dependent interactions between FNAs and bacteria.</p><p><strong>Results: </strong>DNA tetrahedron (Td) demonstrated superior biofilm penetration, exhibiting 44-fold and 11-fold stronger fluorescence intensity at a biofilm depth of 20 μm compared to linear and triangular counterparts, respectively, while maintaining structural stability. The optimized polymyxin B-loaded Td (PMB@Td, with a PMB: Td ratio of 10:1) enhanced biofilm permeability by 6-fold relative to free PMB. PMB@Td outperformed conventional liposome-encapsulated PMB (PMB@Lipo), achieving half-maximal biofilm eradication concentrations (MBEC₅₀) of 12.8 µM versus 16.3 µM for PMB@Lipo. In murine models of biofilm- associated skin and pulmonary infections, PMB@Td effectively controlled bacterial burden and mitigated inflammatory responses without observable toxicity. Mechanistic studies revealed that the tetrahedral topology facilitated efficient diffusion within the biofilm matrix and enhanced Td adhesion to bacterial membranes.</p><p><strong>Conclusions: </strong>This work establishes Td as a robust nanoplatform for overcoming biofilm-mediated antibiotic resistance. The topology-dependent interactions provide critical design principles for engineering next-generation nanocarriers against biofilm-associated chronic infections, with significant translational potential in antibiofilm therapy.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"465"},"PeriodicalIF":10.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211533/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Self-Generated Electricity-Driven Sclera reinforcement bionic piezoelectric patch for Management of High Myopia.","authors":"Lingxi Jiang, Bo Zhao, Qi Li, Chunbao Xie, Jiale Hong, Yiwei Wan, Yukai Gong, Zhengzheng Wu, Liang Zou, Yang-Bao Miao, Yi Shi","doi":"10.1186/s12951-025-03493-w","DOIUrl":"10.1186/s12951-025-03493-w","url":null,"abstract":"<p><strong>Background: </strong>High myopia (HM) is a progressive ocular condition characterized by excessive axial elongation and severe refractive errors, often leading to sight-threatening complications. The underlying pathological driver of HM is the weakening of scleral biomechanics, making the sclera a key therapeutic target. While posterior scleral reinforcement (PSR) has been established as an effective intervention to strengthen the sclera, currently available PSR materials often fail to fully meet clinical demands.</p><p><strong>Results: </strong>Inspired by the electric eel, which generates surface electrolytes to facilitate electric discharge and influence interactions with its surroundings, we developed a biomimetic piezoelectric patch (BPP@PVDF) for HM treatment. This patch integrates a bovine pericardium (BPP) scaffold with a piezoelectric polyvinylidene fluoride (PVDF) film, endowing the BPP with electrical properties and improved cell adhesion. Through electrical activation, the BPP enhances scleral mechanical strength and promotes collagen synthesis, effectively mitigating axial elongation in myopia.</p><p><strong>Conclusions: </strong>Both in vitro and in vivo experiments demonstrate that our precisely designed patch provided a stable and effective solution for reducing progressive axial elongation in HM. By leveraging nanotechnology, electrical stimulation, and scleral reinforcement surgery, this study offers a groundbreaking approach with significant implications for both scientific research and clinical practice. Our strategy paves the way for enhanced surgical outcomes in HM treatment, offering a promising avenue for future therapeutic advancements.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"470"},"PeriodicalIF":10.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alternating magnetic field-responsive engineered probiotics for anxiety therapy via gut-brain axis modulation.","authors":"Xuejun Wang, Yuhan Zhang, Yuling Chang, Yuhao Zhu, Guo Xiang, Kehua Chen, Chuanxing Feng, Zhaofang Hang, Xingang Li, Di Zhang","doi":"10.1186/s12951-025-03551-3","DOIUrl":"10.1186/s12951-025-03551-3","url":null,"abstract":"<p><p>The discovery of the gut-brain axis demonstrated bidirectional regulation between the gut and the brain. The gastrointestinal branches of the vagal nerve have been proven to directly modulate multiple functions of the central nervous system (CNS), providing great opportunities to develop novel tools to remotely regulate CNS function from the gut. Engineered bacteria, acting as oral live biotherapeutics, offer a durable and controllable way of modulating neuronal function non-invasively and with low side effects. Here, we constructed an engineered bacterium by genetically modifying Escherichia coli Nissle 1917 (EcN) with Fe₃O₄ nanoparticles to release gamma-aminobutyric acid (GABA) under the control of the alternating magnetic fields (AMF). Bioavailability, assessed by survival rate in artificial gastric fluid, was further enhanced by encapsulating EcN with a poly-norepinephrine (NE) layer, which protected the probiotics from environmental stress and improved their viability during oral delivery. The oral administration of the EcN-GadABC@Fe-NE/AMF in restraint mice exhibited significant anxiolytic efficacy, which was attenuated by the chemogenetic counteraction of vagal sensory inhibition. Immunohistochemistry staining against c-fos showed reduced neuronal activation in both the nucleus of the solitary tract (NTS) and locus coeruleus (LC) area in the restraint mice treated by the EcN-GadABC@Fe-NE/AMF. Furthermore, acting as a probiotic, the EcN-GadABC@Fe-NE modulated gut microbiota homeostasis, additionally contributing to the alleviation of anxiety-like behaviors. This approach opens up a novel revenue for developing remote and non-invasive methods to modulate CNS function from the gut, and enhancing bacteriotherapy for mental disorders.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"463"},"PeriodicalIF":10.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced strategy for cancer detection based on volatile organic compounds in breath.","authors":"Ziqi Jia, Yiwen Jiang, Tongxuan Shang, Heng Cao, Jiayi Li, Lin Cong, Pengming Pu, Hengyi Xu, Yuchen Liu, Yansong Huang, Dongxu Ma, Jiang Wu, Ruijie Zhou, Xiang Wang, Chang Bao Han, Jiaqi Liu","doi":"10.1186/s12951-025-03526-4","DOIUrl":"10.1186/s12951-025-03526-4","url":null,"abstract":"<p><p>The analysis of volatile organic compounds (VOCs) in exhaled breath has emerged as a promising non-invasive approach for cancer diagnosis, offering advantages in speed, safety, cost-effectiveness, and real-time monitoring. Two primary methodologies are employed for VOCs detection: mass spectrometry (MS)-based techniques, which provide high-precision identification and quantification of individual compounds, and sensor-based pattern recognition methods, which detect disease-specific VOC signatures. Despite their diagnostic potential, inconsistencies in accuracy highlight the need for a comprehensive evaluation of these techniques. This review synthesizes evidence from clinical studies through meta-analysis to assess the diagnostic performance of MS and sensor-based approaches. Furthermore, we examine variations in VOC profiles across cancer types, which may influence diagnostic precision, and discuss key biomarkers, analytical methodologies, current challenges, and future directions in VOCs-based diagnostics. Meta-analysis revealed a high diagnostic accuracy, with a mean area under the receiver operating characteristic curve (AUC) of 0.94 (95% CI 0.91-0.96), sensitivity of 89% (95% CI 87%-90%), and specificity of 87% (95% CI 84%-88%). Notably, no significant difference was observed between MS and sensor-based methods (AUC: 0.91 vs. 0.93, p = 0.286), supporting the potential of sensor technologies for clinical application. Subgroup analysis further indicated no statistical difference in AUCs between heterogeneous and homogeneous sensor groups, suggesting that simplified detection systems may be feasible. Despite these promising results, standardization of protocols and methodological consistency remain critical challenges. Future efforts should focus on large-scale, well-designed clinical trials to validate and optimize VOCs-based breath tests, enhancing their diagnostic reliability and translational potential in oncology.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"468"},"PeriodicalIF":10.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210820/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomaterials mediated 3R (remove-remodel-repair) strategy: holistic management of Helicobacter pylori infection.","authors":"Tinglin Zhang, Yating Zheng, Tielou Chen, Yuankai Gu, Yingli Gong, Dewei Wang, Zhaoshen Li, Yiqi Du, Li Zhang, Jie Gao","doi":"10.1186/s12951-025-03455-2","DOIUrl":"10.1186/s12951-025-03455-2","url":null,"abstract":"<p><p>Helicobacter pylori (HP) is a major etiological agent of gastric cancer, with a global prevalence of around 50%. Current treatments, primarily based on antibiotics, face challenges such as increasing drug resistance and disruption of the gut microbiota. This review proposes a holistic integrative medicine (HIM) approach, guided by the 3R concept (Remove, Remodel, and Repair), to address these limitations. The 3R concept offers a novel paradigm for the integrated prevention and treatment of HP infections: Remove targets the direct eradication of HP by overcoming antibiotic resistance, Remodel focuses on reshaping the immune microenvironment to clear pathogens, and Repair emphasizes the restoration of the gastric mucosa and protection of the gut microbiota. We discuss the potential of biomaterials, including nanoparticles for targeted drug delivery and ROS generation, hydrogels for sustained release and mucosal repair, microspheres for enhanced drug loading and controlled release, and probiotics for microbiota restoration. Additionally, multimodal therapies such as phototherapy, sonodynamic therapy, and magnetic hyperthermia provide non-invasive, targeted treatments. These innovations align with HIM principles, integrating pathogen eradication with mucosal healing and microbiome protection. Future research should focus on optimizing these materials and validating their clinical applicability to improve patient outcomes and combat antibiotic resistance.</p>","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"475"},"PeriodicalIF":10.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12211381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted-theranostic nanoparticles induce anti-tumor immune response in lung cancer.","authors":"Zeinaf Muradova, Léna Carmès, Needa Brown, Fabien Rossetti, Romy Guthier, Sayeda Yasmin-Karim, Michael Lavelle, Toby Morris, Eder Jose Guidelli, Mileni Isikawa, Sandrine Dufort, Guillaume Bort, Olivier Tillement, François Lux, Ross Berbeco","doi":"10.1186/s12951-025-03542-4","DOIUrl":"10.1186/s12951-025-03542-4","url":null,"abstract":"","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"466"},"PeriodicalIF":10.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting YTHDF2 with pH-responsive siRNA nanoparticles suppresses MYC m6A modification and restores antitumor immunity in hepatocellular carcinoma.","authors":"Ziqi Guo, Qiuling Huang, Zhenzhen Cui, Cheng Yang, Liu Yang","doi":"10.1186/s12951-025-03538-0","DOIUrl":"10.1186/s12951-025-03538-0","url":null,"abstract":"","PeriodicalId":16383,"journal":{"name":"Journal of Nanobiotechnology","volume":"23 1","pages":"469"},"PeriodicalIF":10.6,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12210728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144540480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}