Nano TodayPub Date : 2025-02-28DOI: 10.1016/j.nantod.2025.102694
Sicheng Zhang , Yun Wang , Dianri Wang , Xueting Yang , Yan Yang , Dingfen Zeng , Tong Liu , Ronghao Sun , Xu Wang , Ziao He , Mu Yang , Yunfeng Lin , Chao Li
{"title":"Tetrahedral DNA nanostructure based siRNA delivery vehicle for braf gene silencing and MEK-ERK pathway inhibition in the treatment of refractory thyroid cancer","authors":"Sicheng Zhang , Yun Wang , Dianri Wang , Xueting Yang , Yan Yang , Dingfen Zeng , Tong Liu , Ronghao Sun , Xu Wang , Ziao He , Mu Yang , Yunfeng Lin , Chao Li","doi":"10.1016/j.nantod.2025.102694","DOIUrl":"10.1016/j.nantod.2025.102694","url":null,"abstract":"<div><div>The BRAF V600E mutation induces sustained activation of the MEK-ERK signaling pathway, driving accelerated cell proliferation, enhanced migration, invasion, and resistance to apoptosis, which is recognized as a critical pathogenetic mechanism in refractory thyroid cancer. Small interfering RNA (siRNA) holds significant promise in cancer therapy due to its high specificity and silencing efficiency, ease of synthesis, and cost-effectiveness. However, its clinical application is limited by poor permeability and stability. DNA-assembled nanostructures, especially the tetrahedral DNA nanostructures (TDNs), are promising nanocarriers with preeminent biosafety, low biotoxicity, and high transport efficiency. In this study, we therefore synthesized a TDN-based BRAF V600E-siRNA delivery system (TDN-siBraf), which not only prolonged the half-life of siRNA, but also exhibited efficient siRNA delivery, excellent biocompatibility, and gene silencing efficiency. By establishing two distinct cell line models, a murine model and a notable <em>in vitro</em> patient-derived tumor organoids (PDTOs) model of refractory thyroid cancer, we demonstrated that TDN-siBraf could enhance targeted siBraf delivery and improve antitumor efficacy both <em>in vivo</em> and <em>in vitro</em> by inhibiting cancer cell proliferation and invasion while promoting apoptosis, with favorable biosafety and biocompatibility. Furthermore, treatment with the TDN-siBraf effectively inhibited the activation of the MEK-ERK signaling pathway, leading to mitochondrial dysfunction and elevated DNA damage, which ultimately culminated in cellular impairment. This study introduces a high-efficiency TDN-siBraf delivery system with prolonged siRNA half-life and enhanced antitumor activity in refractory thyroid cancer, offering a promising strategy with significant clinical translation potential.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"62 ","pages":"Article 102694"},"PeriodicalIF":13.2,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143519370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nano TodayPub Date : 2025-02-26DOI: 10.1016/j.nantod.2025.102697
Jingjing Tian , Jiahao Li , Zhihong Wu , Lan Yin , Xing Sheng , Zhou Li , Hai Wang , Huachun Wang , Yu Zhao
{"title":"Photo-driven electronic skin enable activation of calcium channel for refractory wound healing","authors":"Jingjing Tian , Jiahao Li , Zhihong Wu , Lan Yin , Xing Sheng , Zhou Li , Hai Wang , Huachun Wang , Yu Zhao","doi":"10.1016/j.nantod.2025.102697","DOIUrl":"10.1016/j.nantod.2025.102697","url":null,"abstract":"<div><div>The growing threat of refractory wound has created imperative need for the exploration of novel repair materials and therapeutic strategies. The disrupted endogenous electric fields in refractory wound may prolong the healing process. Hence, apply exogenous electrical stimulation to reestablish endogenous electric fields may be a promising way for refractory wounds treatment. Herein, a photo-driven electronic skin consist of p-type Si thin-film and near-infrared light was developed. This electronic skin could electrically modulate the intracellular calcium oscillation and significantly promote the fibroblasts’ adhesion, proliferation and migration. Specifically, the average spreading area achieved 1.23 times higher than plane group after 24 h seeding. The cell proliferation quantity was 117 % higher than plane group after 3 days’ PES treatment. As for cell migration, the complete wound closure was observed at 48 h in all the PES treatment group compared to 76.47 ± 1.23 coverage area in control group. Furthermore, it demonstrated rapid closure rate of a full-thickness circular diabetic skin defects with photoelectric stimulation (PES) derived from electronic skin, the wound was almost healed at 14 days’ treatment. Furthermore, the expression level of pro-inflammation factors of IL-1β and TNF-α were reduced. Proteomic analysis showed that the metabolism process, the cellular processes of transport and catabolism, cell motility were remarkably promoted after PES treatment. The transport and catabolism process may regulate by mTOR signal pathway, and the increased cellular processes of cell motility may result of actomyosin contractility. This photo-driven electronic skin not only provided a facile therapeutic strategy and theoretical basis for refractory wound, but also provided a novel insight into potential mechanism underlying electrical stimulation promoting tissue repair.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"62 ","pages":"Article 102697"},"PeriodicalIF":13.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nano TodayPub Date : 2025-02-26DOI: 10.1016/j.nantod.2025.102693
Yanping Zhao , Junhui Sui , Jian Chang , Jianxiong Liu , Xiaoqian Wang , Hongjun Wang , Wei Chen , Binlong Chen , Yiguang Wang
{"title":"Cascade-responsive nano-PROTACs for tumor-specific ALK protein degradation and enhanced cancer therapy","authors":"Yanping Zhao , Junhui Sui , Jian Chang , Jianxiong Liu , Xiaoqian Wang , Hongjun Wang , Wei Chen , Binlong Chen , Yiguang Wang","doi":"10.1016/j.nantod.2025.102693","DOIUrl":"10.1016/j.nantod.2025.102693","url":null,"abstract":"<div><div>PROteolysis TArgeting Chimeras (PROTACs), as a promising therapeutic modality, have been exploited to degrade specific pathogenic proteins. However, the <em>in vivo</em> antitumor efficacy of PROTACs is seriously impaired by its poor pharmacokinetics and insufficient tumor distribution, consequently restricting their clinical applications. Herein, we report a pH/enzyme cascade-responsive nano-PROTACs (CRNPs) by integrating the cathepsin B-cleavable Gly-Phe-Leu-Gly (GFLG) linked PROTAC onto ultra-pH-sensitive (UPS) nanoplatform for enhanced tumor-specific ALK degradation and precise cancer therapy. The CRNPs exhibit a stable nanostructure with a diameter of 33 nm under physiological conditions, while rapidly dissociate at pH 6.0 and are subsequently cleaved by cathepsins B to effectively release the PROTAC payload. This further results in efficient ALK degradation, p-ALK reduction, G0/G1 phase cell cycle arrest, and suppression of tumor cells proliferation. Moreover, the cascade-responsive design dramatically improves the <em>in vivo</em> pharmacokinetics via prolonged circulation lifetime as well as enhanced tumor specific accumulation and release of PROTAC. Consequently, CRNPs significantly augment the antitumor efficacy, achieving with over 94 % suppression in Karpas299 tumor models, while demonstrating good biocompatibility <em>in vivo</em>. These findings highlight the potential of cascade-responsive nanocarriers for delivering PROTACs to combat a wide range of cancers by attacking their pathogenic proteins.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"62 ","pages":"Article 102693"},"PeriodicalIF":13.2,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nano TodayPub Date : 2025-02-25DOI: 10.1016/j.nantod.2025.102691
Bin Xu , Hengliang Hou , Weijia Xu , Xiaoping Xie , Yucheng Huang , Fanjun Zeng , Weihuan Lin , Qiaxuan Li , Xiaoqiu Li , Xianzhu Yang , Haiyu Zhou
{"title":"An all-in-one polymeric nanomedicine as in situ cascade cancer vaccine for potent cancer immunotherapy","authors":"Bin Xu , Hengliang Hou , Weijia Xu , Xiaoping Xie , Yucheng Huang , Fanjun Zeng , Weihuan Lin , Qiaxuan Li , Xiaoqiu Li , Xianzhu Yang , Haiyu Zhou","doi":"10.1016/j.nantod.2025.102691","DOIUrl":"10.1016/j.nantod.2025.102691","url":null,"abstract":"<div><div>Cancer vaccines that exploit tumor antigens to induce specific immune responses hold great promise for cancer treatment, with several products already approved. However, limitations such as the lack of tumor-specific antigens, inadequate antigen processing by antigen-presenting cells (APCs), and the suppressive tumor microenvironment significantly hinder their therapeutic efficacy. In this study, we present a cascade cancer vaccine, PAEMA-PC<sub>R848</sub>, designed for efficient in situ vaccination against cancer in an “all in one” manner. PAEMA-PC<sub>R848</sub> rapidly disintegrates in response to the acidic tumor microenvironment, triggering protonation of its core and subsequent release of PEG-modified photosensitizer (PEG-Ce6), poly(2-azepane ethyl methacrylate) (PAEMA), and the immune adjuvant resiquimod (R848), which together elicit a cascade anticancer immune response. The PEG-Ce6 integrates into the phospholipid bilayer of tumor cell membranes, facilitating the release of endogenous tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs). Meanwhile, PAEMA, R848, and the released TAAs migrate to lymph nodes, where they promote the maturation of APCs and the generation of antigen-specific CD8<sup>+</sup> T cells. Additionally, R848 promotes M1 polarization of macrophages within the tumor microenvironment, enhancing tumor cell engulfment and modulating immune suppression. Notably, this cascade nanovaccine resulted in the complete eradication of distant tumors in some mice and induced long-term immune memory, providing potent protection against tumor recurrence and metastasis.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"62 ","pages":"Article 102691"},"PeriodicalIF":13.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nano TodayPub Date : 2025-02-25DOI: 10.1016/j.nantod.2025.102689
Hua-Ying Hou , Xu Chu , Meng-Die Duan , Yu-Juan Zhang , Hong-Li Chen , Yue Sun , Yi Liu , Shu-Lan Li
{"title":"Achieving apoptosis/cuproptosis co-activated synergistic anti-tumor therapy by charges transport engineering","authors":"Hua-Ying Hou , Xu Chu , Meng-Die Duan , Yu-Juan Zhang , Hong-Li Chen , Yue Sun , Yi Liu , Shu-Lan Li","doi":"10.1016/j.nantod.2025.102689","DOIUrl":"10.1016/j.nantod.2025.102689","url":null,"abstract":"<div><div>Nanocatalysts show great promise in nanomedicine due to their unique catalytic activities. However, the rapid recombination of excited electrons and holes leads to low efficacy of nanocatalytic therapy. Herein, ultrasmall S-Scheme heterojunction MoC/CuFeO<sub>x</sub> nanoparticles (MCFO NPs) with specific charge transport route are rationally designed and engineered for efficient apoptosis/cuproptosis co-activated nanocatalytic therapy. Thermal analysis revealed two steps of S-Scheme heterojunction formation: adsorption and internal structure change. In this structure, the staggered energy levels and band bending enhance the separation of photogenerated electrons and holes, improving redox capacity and catalytic activity, mediating O<sub>2</sub> production, regulating the hypoxic tumor microenvironment, increasing reactive oxygen species, and inducing apoptosis. Additionally, due to excessive copper, the oligomerization of lipoylated dihydrolipoamide S-acetyltransferase and disruption of tricarboxylic acid cycle are caused to evoke cuproptosis. This work proposes a feasible strategy to enhance the nanocatalytic therapeutic efficacy through charge transport engineering, thereby mediating apoptosis/cuproptosis co-activated synergistic anti-tumor therapy.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"62 ","pages":"Article 102689"},"PeriodicalIF":13.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nano TodayPub Date : 2025-02-25DOI: 10.1016/j.nantod.2025.102687
Juanjuan Cao , Huan Liu , Zihe Qi , Jianghua Liu , Guang Chen , Di Wu , Yongning Wu , Tony D. James , Guoliang Li
{"title":"The resistance of Salmonella enterica serovar Typhimurium to zinc oxide nanoparticles","authors":"Juanjuan Cao , Huan Liu , Zihe Qi , Jianghua Liu , Guang Chen , Di Wu , Yongning Wu , Tony D. James , Guoliang Li","doi":"10.1016/j.nantod.2025.102687","DOIUrl":"10.1016/j.nantod.2025.102687","url":null,"abstract":"<div><div>Zinc oxide nanoparticles (ZnO NPs) serve as promising antibiotic alternatives owing to their exceptional antibacterial properties. However, it is inconclusive whether bacteria can develop resistance to ZnO NPs under chronic exposure. In this study, we identified an acquired and irreversible resistance to sublethal concentrations of ZnO NPs, but not to Zn (II) ions, in a strain of <em>Salmonella enterica</em> serovar Typhimurium CVCC541 (<em>S. Typhimurium</em>) following prolonged exposure. Whole-population genome sequencing authenticated a <em>phoQ</em> mutation pertained to this heritable resistance. The <em>phoQ</em> G33A mutation was accompanied by a downregulation of <em>phoQ</em> expression, triggering a remodeling of the outer membrane (characterized by increased production of OmpF and lipopolysaccharides, as well as altered lipid properties) and enhanced biofilm formation. Accordingly, we propose that <em>S. Typhimurium</em> adapts to ZnO NPs exposure by fortifying its outer membrane and biofilm, thereby evolving resistance. Our findings provide an innovative paradigm for an in-depth knowledge of the antimicrobial resistance crisis.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"62 ","pages":"Article 102687"},"PeriodicalIF":13.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nano TodayPub Date : 2025-02-25DOI: 10.1016/j.nantod.2025.102675
Minghui Gu, Xiaochun Zheng, Cheng Li, Zixin Zheng, Guangchun Song, Le Xu, Li Chen, Dequan Zhang
{"title":"Halogen-controlled engineering of fluorescent carbon dots with adjustable color for food freshness detection","authors":"Minghui Gu, Xiaochun Zheng, Cheng Li, Zixin Zheng, Guangchun Song, Le Xu, Li Chen, Dequan Zhang","doi":"10.1016/j.nantod.2025.102675","DOIUrl":"10.1016/j.nantod.2025.102675","url":null,"abstract":"<div><div>Fluorescent carbon quantum dot-based visualization methods for food freshness analysis have gained increasing attention. However, traditional carbon quantum dots (CDs) exhibit single-color fluorescence and are prone to background light interference. Herein, a novel series of multi-color fluorescent CDs is successfully synthesized through a one-pot method, using o-phenylenediamine (OPD) ligands of the same halogen family as the precursor and citric acid as the carbon source. The CDs doped with different halogens exhibit a distinct color change from blue to red, attributed to differences in the key fluorophore molecules of corresponding pyridone derivatives. The halogen-doped CDs display pH-responsive characteristics based on color change sensitivity, enabling their use as putrescine-sensing probes. Excitingly, the chlorine-doped ratiometric fluorescent CDs (ClOPD-CDs) show the most significant color change (ΔE = 44.66), delivering a stark color shift from orange-red to yellow based on the deprotonation of edge amino groups in the presence of biogenic amine molecules. Furthermore, the relationship between total volatile basic nitrogen (TVB-N) and RGB outputs of a homemade fluorescent biosensor for meat spoilage (R² = 0.9386) confirms that ClOPD-CDs function effectively as an on-line fluorochromic probe for visual and quantitative food freshness monitoring via smartphone. The ratiometric fluorescence signals have facilitated the development of a smartphone-compatible sensing application, anticipated to provide a convenient tool for real-time food quality detection.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"62 ","pages":"Article 102675"},"PeriodicalIF":13.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143478590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nano TodayPub Date : 2025-02-24DOI: 10.1016/j.nantod.2025.102690
Dangfeng Wang , Yufeng Liu , Likun Ren , Yang Jiang , Yuqiong Meng , Rui Ma , Shulin Wang , Xuepeng Li , Fangchao Cui , Tingting Li , Jianrong Li
{"title":"Research progress on preparation, loading, and application of nanogels to protect food bioactive ingredients","authors":"Dangfeng Wang , Yufeng Liu , Likun Ren , Yang Jiang , Yuqiong Meng , Rui Ma , Shulin Wang , Xuepeng Li , Fangchao Cui , Tingting Li , Jianrong Li","doi":"10.1016/j.nantod.2025.102690","DOIUrl":"10.1016/j.nantod.2025.102690","url":null,"abstract":"<div><div>Food bioactive ingredients are widely used in food due to their excellent antioxidant, anti-inflammatory, anti-cancer and antibacterial properties, aiming at improving nutritional value and promoting human health. However, their complete absorption and use by the human body are difficult due to their poor water solubility and stability. In recent years, nanocarriers such as nanocapsules, liposomes, nanoparticles and nanomicelles have emerged as promising strategies to address these issues. Among these carriers, nanogels have become a research hotspot due to their smaller particle size, larger specific surface area, and higher loading capacity. This study aimed to discuss the research status of nanogels and their developmental direction. First, from the perspective of environmental responsiveness, three most commonly used and critical nanogels were briefly introduced: pH-responsive, temperature-responsive, and redox-responsive, and their synthetic materials were briefly summarized from two aspects of natural and synthetic polymers. Second, the preparation methods of nanogels were expounded from the perspective of physical chemistry, and their loading and release mechanisms were emphatically introduced, laying a foundation for further research. Finally, the study examined the application of nanogels in food and other fields, providing new ideas for developing advanced bioactive component delivery systems.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"62 ","pages":"Article 102690"},"PeriodicalIF":13.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nano TodayPub Date : 2025-02-23DOI: 10.1016/S1748-0132(25)00055-6
{"title":"Inside Back Cover - Graphical abstract TOC/TOC in double column continued from OBC if required, otherwise blank page","authors":"","doi":"10.1016/S1748-0132(25)00055-6","DOIUrl":"10.1016/S1748-0132(25)00055-6","url":null,"abstract":"","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"61 ","pages":"Article 102683"},"PeriodicalIF":13.2,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nano TodayPub Date : 2025-02-23DOI: 10.1016/S1748-0132(25)00056-8
{"title":"Outside Back Cover - Graphical abstract TOC/TOC in double column/Cover image legend if applicable, Bar code, Abstracting and Indexing information","authors":"","doi":"10.1016/S1748-0132(25)00056-8","DOIUrl":"10.1016/S1748-0132(25)00056-8","url":null,"abstract":"","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"61 ","pages":"Article 102684"},"PeriodicalIF":13.2,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}