{"title":"Polymeric silk fibroin hydrogel as a conductive and multifunctional adhesive for durable skin and epidermal electronics.","authors":"Fanfan Fu, Changyi Liu, Zhenlin Jiang, Qingyu Zhao, Aining Shen, Yilun Wu, Wenyi Gu","doi":"10.1002/SMMD.20240027","DOIUrl":"https://doi.org/10.1002/SMMD.20240027","url":null,"abstract":"<p><p>Silk fibroin (SF)-based hydrogels are promising multifunctional adhesive candidates for real-world applications in tissue engineering, implantable bioelectronics, artificial muscles, and artificial skin. However, developing conductive SF-based hydrogels that are suitable for the micro-physiological environment and maintain their physical and chemical properties over long periods of use remains challenging. Herein, we developed an ion-conductive SF hydrogel composed of glycidyl methacrylate silk fibroin (SilMA) and bioionic liquid choline acylate (ChoA) polymer chains, together with the modification of acrylated thymine (ThyA) and adenine (AdeA) functional groups. The resulting polymeric ion-conductive SF composite hydrogel demonstrated high bioactivity, strong adhesion strength, good mechanical compliance, and stretchability. The formed hydrogel network of ChoA chains can coordinate with the ionic strength in the micro-physiological environment while maintaining the adaptive coefficient of expansion and stable mechanical properties. These features help to form a stable ion-conducting channel for the hydrogel. Additionally, the hydrogel network modified with AdeA and ThyA, can provide a strong adhesion to the surface of a variety of substrates, including wet tissue through abundant hydrogen bonding. The biocompatible and ionic conductive SF composite hydrogels can be easily prepared and incorporated into flexible skin or epidermal sensing devices. Therefore, our polymeric SF-based hydrogel has great potential and wide application to be an important component of many flexible electronic devices for personalized healthcare.</p>","PeriodicalId":74816,"journal":{"name":"Smart medicine","volume":"3 3","pages":"e20240027"},"PeriodicalIF":0.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11425052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482610","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":"Dear-PSM: A deep learning-based peptide search engine enables full database search for proteomics.","authors":"Qingzu He, Xiang Li, Jinjin Zhong, Gen Yang, Jiahuai Han, Jianwei Shuai","doi":"10.1002/SMMD.20240014","DOIUrl":"https://doi.org/10.1002/SMMD.20240014","url":null,"abstract":"<p><p>Peptide spectrum matching is the process of linking mass spectrometry data with peptide sequences. An experimental spectrum can match thousands of candidate peptides with variable modifications leading to an exponential increase in candidates. Completing the search within a limited time is a key challenge. Traditional searches expedite the process by restricting peptide mass errors and variable modifications, but this limits interpretive capability. To address this challenge, we propose Dear-PSM, a peptide search engine that supports full database searching. Dear-PSM does not restrict peptide mass errors, matching each spectrum to all peptides in the database and increasing the number of variable modifications per peptide from the conventional 3-20. Leveraging inverted index technology, Dear-PSM creates a high-performance index table of experimental spectra and utilizes deep learning algorithms for peptide validation. Through these techniques, Dear-PSM achieves a speed breakthrough 7 times faster than mainstream search engines on a regular desktop computer, with a remarkable 240-fold reduction in memory consumption. Benchmark test results demonstrate that Dear-PSM, in full database search mode, can reproduce over 90% of the results obtained by mainstream search engines when handling complex mass spectrometry data collected from different species using various instruments. Furthermore, it uncovers a substantial number of new peptides and proteins. Dear-PSM has been publicly released on the GitHub repository https://github.com/jianweishuai/Dear-PSM.</p>","PeriodicalId":74816,"journal":{"name":"Smart medicine","volume":"3 3","pages":"e20240014"},"PeriodicalIF":0.0,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11425048/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482609","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}
Smart medicinePub Date : 2024-07-25DOI: 10.1002/smmd.20240020
Chuanhui Song, Rui Liu, Yile Fang, Hongcheng Gu, Yu Wang
{"title":"Developing functional hydrogels for treatment of oral diseases","authors":"Chuanhui Song, Rui Liu, Yile Fang, Hongcheng Gu, Yu Wang","doi":"10.1002/smmd.20240020","DOIUrl":"https://doi.org/10.1002/smmd.20240020","url":null,"abstract":"Oral disease is a severe healthcare challenge that diminishes people's quality of life. Functional hydrogels with suitable biodegradability, biocompatibility, and tunable mechanical properties have attracted remarkable interest and have been developed for treating oral diseases. In this review, we present up‐to‐date research on hydrogels for the management of dental caries, endodontics, periapical periodontitis, and periodontitis, depending on the progression of dental diseases. The strategies of hydrogels for treating oral mucosal diseases and salivary gland diseases are then classified. After that, we focus on the application of hydrogels related to tumor therapy and tissue defects. Finally, the review prospects the restrictions and the perspectives on the utilization of hydrogels in oral disease treatment. We believe this review will promote the advancement of more amicable, functional and personalized approaches for oral diseases.","PeriodicalId":74816,"journal":{"name":"Smart medicine","volume":"12 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141803678","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}
Smart medicinePub Date : 2024-07-17DOI: 10.1002/smmd.20240012
Yuxin Wang, Matthew Chae, Teak-Jung Oh, Kangqiang Qiu, Kritika Mehta, Adrian Tan, Nien‐Pei Tsai, Donglu Shi, Kai Zhang, Jiajie Diao
{"title":"Sustainable synthesis of carbon dots via bio‐waste recycling for biomedical imaging","authors":"Yuxin Wang, Matthew Chae, Teak-Jung Oh, Kangqiang Qiu, Kritika Mehta, Adrian Tan, Nien‐Pei Tsai, Donglu Shi, Kai Zhang, Jiajie Diao","doi":"10.1002/smmd.20240012","DOIUrl":"https://doi.org/10.1002/smmd.20240012","url":null,"abstract":"Bio‐waste is a side product of biomedical research containing carbon, which can be utilized for developing carbon dots (CDs). CDs are known to be useful for a variety of applications because of their unique photoluminescence, low toxicity, and straightforward synthesis. In this paper, we employed a one‐step hydrothermal method to prepare CDs from bio‐waste as the only reactant. The as‐synthesized Cell‐CDs were found to be chemically stable and biocompatible. In addition, the spectra of Cell‐CDs’ emissions covered the visible light, which is ideal for super‐resolution imaging. Particularly, dual‐color imaging can be achieved, for example, by staining the plasma membrane with Cell‐CDs emitting one color and staining cytosolic organelles with Cell‐CDs emitting a different color of fluorescence. Here, we demonstrate such applications by studying the subcellular dynamics of live cells.","PeriodicalId":74816,"journal":{"name":"Smart medicine","volume":" 46","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141830225","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":"Engineering strategies for apoptotic bodies","authors":"Zheyuan Hu, Shutong Qian, Qiuyu Zhao, Bolun Lu, Qian Lu, Yuhuan Wang, Liucheng Zhang, Xiyuan Mao, Danru Wang, Wenguo Cui, Xiaoming Sun","doi":"10.1002/smmd.20240005","DOIUrl":"https://doi.org/10.1002/smmd.20240005","url":null,"abstract":"Extracellular vesicles (EVs) are lipid bilayer vesicles containing proteins, lipids, nucleic acids, and metabolites secreted by cells under various physiological and pathological conditions that mediate intercellular communication. The main types of EVs include exosomes, microvesicles, and apoptotic bodies (ABs). ABs are vesicles released during the terminal stages of cellular apoptosis, enriched with diverse biological entities and characterized by distinct morphological features. As a result, ABs possess great potential in fields like disease diagnosis, immunotherapy, regenerative therapy, and drug delivery due to their specificity, targeting capacity, and biocompatibility. However, their therapeutic efficacy is notably heterogeneous, and an overdose can lead to side effects such as accumulation in the liver, spleen, lungs, and gastrointestinal system. Through bioengineering, the properties of ABs can be optimized to enhance drug‐loading efficiency, targeting precision, and multifunctionality for clinical implementations. This review focuses on strategies such as transfection, sonication, electroporation, surface engineering, and integration with biomaterials to enable ABs to load cargoes and enhance targeting, providing insights into the engineering of ABs.","PeriodicalId":74816,"journal":{"name":"Smart medicine","volume":"54 40","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141649714","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":"Photothermal responsive porous hollow microneedles as Chinese medicine versatile delivery system for wound healing","authors":"Wanyue Zhang, Lijun Cai, Jingjing Gan, Yuanjin Zhao","doi":"10.1002/smmd.20240007","DOIUrl":"https://doi.org/10.1002/smmd.20240007","url":null,"abstract":"Chinese medicine is identified as a candidate for wound healing. Attempts in this field tend to develop efficient dosage forms for delivering Chinese medicine with low side effects. In this paper, we proposed novel photothermal responsive porous hollow microneedles (PRPH‐MNs) as a versatile Chinese medicine delivery system for efficient antibacterial wound treatment. The PRPH‐MNs are composed of porous resin shells with good mechanical property, hydrogel cores, and a photothermal graphene oxide hybrid substrate. The hollow structure provides sufficient space for loading the drug dispersed hydrogel, while the porous resin shells could not only block the direct contact between drugs and wound sites but also provide channels for facilitating the drug release from the core. In addition, benefiting from the photothermal effect of their substrate, the PRPH‐MNs could be heated under near‐infrared (NIR) irradiation for controllable promotion of drug release. Based on these features, we have proved that the antibacterial Chinese medicine Rhein loaded PRPH‐MNs were effective in promoting wound healing due to their good antibacterial property and on‐demand drug release. Thus, we believe that the proposed PRPH‐MNs are valuable for delivery of different drugs for clinical applications.","PeriodicalId":74816,"journal":{"name":"Smart medicine","volume":"220 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141692713","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}
Smart medicinePub Date : 2024-06-28eCollection Date: 2024-06-01DOI: 10.1002/SMMD.20240010
Ruochen Qiao, Hui Wang, Dasheng Li, Yu Yang, Jiaxin Shu, Xiang Song, Xiaozhi Zhao, Li Lu
{"title":"Stevioside protects against acute kidney injury by inhibiting gasdermin D pathway.","authors":"Ruochen Qiao, Hui Wang, Dasheng Li, Yu Yang, Jiaxin Shu, Xiang Song, Xiaozhi Zhao, Li Lu","doi":"10.1002/SMMD.20240010","DOIUrl":"10.1002/SMMD.20240010","url":null,"abstract":"<p><p>Recent studies indicate a significant upregulation of gasdermin D (GSDMD) in acute kidney injury (AKI), a severe medical condition characterized by high morbidity and mortality globally. In this study, we identified and validated the therapeutic effects of small molecule inhibitors targeting the GSDMD pathway for AKI treatment. Using a drug screening assay, we evaluated thousands of small molecules from DrugBank against Lipopolysaccharide (LPS) and Nigericin-stimulated immortalized bone marrow-derived macrophages (iBMDMs) to discern GSDMD pathway activators. We simulated AKI in primary renal tubular epithelial cells using hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) exposure. Furthermore, AKI in mouse models was induced via cisplatin and ischemia/reperfusion. Our findings highlight stevioside as a potent GSDMD activator exhibiting minimal toxicity. Experimental results, both in vitro and in vivo, demonstrate stevioside's significant potential in alleviating renal tubular epithelial cell injury and AKI histological damage. After stevioside treatment, a notable decrease in cleaved GSDMD-N terminal levels was observed coupled with diminished inflammatory factor release. This observation was consistent in both cisplatin- and ischemia/reperfusion-induced AKI mouse models. Collectively, our research suggests that stevioside could be a promising candidate for modulating GSDMD signaling in AKI treatment.</p>","PeriodicalId":74816,"journal":{"name":"Smart medicine","volume":"3 2","pages":"e20240010"},"PeriodicalIF":0.0,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11235599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142074745","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}
Smart medicinePub Date : 2024-06-05DOI: 10.1002/smmd.20240008
Yuan Yuan, Perry Ellis, Ye Tao, Dimitri A. Bikos, E. Loveday, Mallory M. Thomas, J. Wilking, Connie B. Chang, Fangfu Ye, David A. Weitz
{"title":"Digital droplet RT‐LAMP increases speed of SARS‐CoV‐2 viral RNA detection","authors":"Yuan Yuan, Perry Ellis, Ye Tao, Dimitri A. Bikos, E. Loveday, Mallory M. Thomas, J. Wilking, Connie B. Chang, Fangfu Ye, David A. Weitz","doi":"10.1002/smmd.20240008","DOIUrl":"https://doi.org/10.1002/smmd.20240008","url":null,"abstract":"Nucleic acid amplification testing (NAAT) remains one of the most reliable methods for pathogen identification. However, conventional bulk NAATs may not be sufficiently fast or sensitive enough for the detection of clinically‐relevant pathogens in point‐of‐care testing. Here, we have developed a digital droplet RT‐LAMP (ddRT‐LAMP) assay that rapidly and quantitatively detects the SARS‐CoV‐2 viral E gene in microfluidic drops. Droplet partitioning using ddRT‐LAMP significantly accelerates detection times across a wide range of template concentrations compared to bulk RT‐LAMP assays. We discover that a reduction in droplet diameter decreases assay times up to a certain size, upon which surface adsorption of the RT‐LAMP polymerase reduces reaction efficiency. Optimization of drop size and polymerase concentration enables rapid, sensitive, and quantitative detection of the SARS‐CoV‐2 E gene in only 8 min. These results highlight the potential of ddRT‐LAMP assays as an excellent platform for quantitative point‐of‐care testing.","PeriodicalId":74816,"journal":{"name":"Smart medicine","volume":"25 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141382055","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}
Smart medicinePub Date : 2024-06-04DOI: 10.1002/smmd.20240006
Yuyu Li, Yujie Wang, Zequn Xia, Yangjing Xie, Daozheng Ke, Bing Song, Dan Mu, Ronghui Yu, Jun Xie
{"title":"Noninvasive platelet membrane‐coated Fe3O4 nanoparticles identify vulnerable atherosclerotic plaques","authors":"Yuyu Li, Yujie Wang, Zequn Xia, Yangjing Xie, Daozheng Ke, Bing Song, Dan Mu, Ronghui Yu, Jun Xie","doi":"10.1002/smmd.20240006","DOIUrl":"https://doi.org/10.1002/smmd.20240006","url":null,"abstract":"Vulnerable atherosclerotic plaques serve as the primary pathological basis for fatal cardiovascular and cerebrovascular diseases. The precise identification and treatment of these vulnerable plaques hold paramount clinical importance in mitigating the incidence of myocardial infarction and stroke. Nevertheless, the identification of vulnerable plaques within the diffuse atherosclerotic plaques dispersed throughout the systemic circulation continues to pose a substantial challenge in clinical practice. Double emulsion solvent evaporation method, specifically the water‐in‐oil‐in‐water (W/O/W) technique, was employed to fabricate Fe3O4‐based poly (lactic‐co‐glycolic acid) (PLGA) nanoparticles (Fe3O4@PLGA). Platelet membranes (PM) were extracted through hypotonic lysis, followed by ultrasound‐assisted encapsulation onto the surface of Fe3O4@PLGA, resulting in the formation of PM‐coated Fe3O4 nanoparticles (PM/Fe3O4@PLGA). Characterization of PM/Fe3O4@PLGA involved the use of dynamic light scattering, transmission electron microscopy, western blotting, and magnetic resonance imaging (MRI). A model of atherosclerotic vulnerable plaques was constructed by carotid artery coarctation and a high‐fat diet fed to ApoE−/− (Apolipoprotein E knockout) mice. Immunofluorescence and MRI techniques were employed to verify the functionality of PM/Fe3O4@PLGA. In this study, we initially synthesized Fe3O4@PLGA as the core material. Subsequently, a platelet membrane was employed as a coating for the Fe3O4@PLGA, aiming to enable the detection of vulnerable atherosclerotic plaques through MRI. In vitro, PM/Fe3O4@PLGA not only exhibited excellent biosafety but also showed targeted collagen characteristics and MR imaging performance. In vivo, the adhesion of PM/Fe3O4@PLGA to atherosclerotic lesions was confirmed in a mouse model of vulnerable atherosclerotic plaques. Simultaneously, PM/Fe3O4@PLGA as a novel contrast agent for MRI has shown effective identification of vulnerable atherosclerotic plaques. In terms of safety profile in vivo, PM/Fe3O4@PLGA has not demonstrated significant organ toxicity or inflammatory response in the bloodstream. In this study, we successfully developed a platelet‐membrane‐coated nanoparticle system for the targeted delivery of Fe3O4@PLGA to vulnerable atherosclerotic plaques. This innovative system allows for the visualization of vulnerable plaques using MRI, thereby demonstrating its potential for enhancing the clinical diagnosis of vulnerable atherosclerotic plaques.","PeriodicalId":74816,"journal":{"name":"Smart medicine","volume":"3 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141266595","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}
Smart medicinePub Date : 2024-05-22DOI: 10.1002/smmd.20240004
Xiwen Geng, Nan Zhang, Zhanrong Li, Mengyang Zhao, Hongbo Zhang, Jingguo Li
{"title":"Iron‐doped nanozymes with spontaneous peroxidase‐mimic activity as a promising antibacterial therapy for bacterial keratitis","authors":"Xiwen Geng, Nan Zhang, Zhanrong Li, Mengyang Zhao, Hongbo Zhang, Jingguo Li","doi":"10.1002/smmd.20240004","DOIUrl":"https://doi.org/10.1002/smmd.20240004","url":null,"abstract":"The development of non‐antibiotic pharmaceuticals with biocompatible and efficient antibacterial properties is of great significance for the treatment of bacterial keratitis. In this study, we have developed antibacterial iron‐doped nanozymes (Fe3+‐doped nanozymes, FNEs) with distinguished capacity to fight against bacterial infections. The iron‐doped nanozymes are composed of Fe3+ doped zeolitic imidazolate framework‐8 (Fe/ZIF‐8) and polyethylene imide (PEI), which were functionally coated on the surface of Fe/ZIF‐8 and imparted the FNEs with improved water dispersibility and biocompatibility. FNEs possess a significant spontaneous peroxidase‐mimic activity without the need for external stimulation, thus elevating cellular reactive oxygen species level by catalyzing local H2O2 at the infection site and resulting in bacteria damaged to death. FNEs eliminated 100% of Staphylococcus aureus within 6 h, and significantly relieved inflammation and bacterial infection levels in mice bacterial keratitis, exhibiting higher bioavailability and a superior therapeutic effect compared to conventional antibiotic eye drops. In addition, the FNEs would not generate drug resistance, suggesting that FNEs have great potential in overcoming infectious diseases caused by antimicrobial resistant bacteria.","PeriodicalId":74816,"journal":{"name":"Smart medicine","volume":"55 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141109284","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}