{"title":"Melting and Rapid Solidification of Lunar Regolith Particles Returned by Chang'E-5 Mission.","authors":"Xian Zhang, Yiwei Liu, Shaofan Zhao, Jian Song, Wei Yao, Weihua Wang, Zhigang Zou, Mengfei Yang","doi":"10.34133/research.0486","DOIUrl":"10.34133/research.0486","url":null,"abstract":"<p><p>Melting and solidification of lunar regolith are pivotal for comprehending the evolutionary dynamics of lunar volcanism, geology, and impact history. Additionally, insights gained from these processes can contribute to the advancement of in situ resource utilization technologies, for instance additive manufacturing and resource extraction systems. Herein, we conduct the direct observation of the melting and rapid solidification of lunar particles returned by the Chang'E 5 mission. The melting temperature and melting sequence were obtained. Bubble generation, growth, and release were clearly observed, with a maximum bubble diameter of 5 µm, which is supposed to be according to the release of volatiles that embedded in the particles. During the solidification process, evident crystallization occurred with incremental crystal growth rate approximately of 27 nm/s. Scanning electron microscopy and energy-dispersive x-ray spectroscopy results verified that the Fe-rich mineral crystalizes first. These results would improve the understanding of the evolution of lunar volcanism, geology, and impact history.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0486"},"PeriodicalIF":11.0,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11417502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Amino Turbo Chirality and Its Asymmetric Control.","authors":"Ting Xu, Yu Wang, Shengzhou Jin, Anis U Rahman, Xianghua Yan, Qingkai Yuan, Hao Liu, Jia-Yin Wang, Wenxin Yan, Yinchun Jiao, Ruibin Liang, Guigen Li","doi":"10.34133/research.0474","DOIUrl":"10.34133/research.0474","url":null,"abstract":"<p><p>A series of new targets containing 3 chiral elements of central, orientational, and turbo chirality have been designed and synthesized asymmetrically. The absolute configurations and conformations of these types of chirality were concurrently controlled by using chiral sulfonimine auxiliary and unambiguously determined by x-ray diffraction analysis. These targets include alpha unnatural amino acid derivatives, which may play an important role for drug design, discovery, and development. Three propellers of turbo framework are covalently connected to a chiral C(sp<sup>3</sup>) center via C(sp<sup>2</sup>)-C(sp<sup>3</sup>) bonding along with a C-N axis, while one of them is orientated away from the same carbon chiral center. The turbo or propeller chirality is characterized by 2 types of molecular arrangements of propellers, clockwise (<i>PPP</i>) and counterclockwise (<i>MMM</i>), respectively. The turbo stereogenicity was found to depend on the center chirality of sulfonimine auxiliary instead of the chiral C(sp<sup>3</sup>) center, i.e., (<i>S</i>)- and (<i>R</i>)-sulfinyl centers led to the asymmetric formation of <i>PPP-</i> and <i>MMM</i>-configurations, respectively. Computational studies were conducted on relative energies for rotational barriers of a turbo target along the C-N anchor and the transition pathway between 2 enantiomers meeting our experimental observations. This work is anticipated to have a broad impact on chemical, biomedical, and materials sciences in the future.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0474"},"PeriodicalIF":11.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Gut Microbiota-Metabolite-Brain Axis Reconstitution Reverses Sevoflurane-Induced Social and Synaptic Deficits in Neonatal Mice.","authors":"Youyi Zhao, Sanxing Ma, Lirong Liang, Shuhui Cao, Ze Fan, Danyi He, Xiaotong Shi, Yao Zhang, Bing Liu, Meiting Zhai, Shengxi Wu, Fang Kuang, Hui Zhang","doi":"10.34133/research.0482","DOIUrl":"https://doi.org/10.34133/research.0482","url":null,"abstract":"<p><p><b>Background:</b> The mechanisms underlying social dysfunction caused by repeated sevoflurane in early life remain unclear. Whether the gut microbiota-metabolite-brain axis is involved in the mechanism of sevoflurane developmental neurotoxicity still lacks report. <b>Methods:</b> Mice received 3% sevoflurane at postnatal day (PND) 6, 7, and 8 for 2 h per day. Metagenomic sequencing and untargeted metabolomic analysis were applied to investigate the effects of sevoflurane on gut microbiota and metabolism. The animal social behavior and the synaptic development were analyzed during PND 35. Subsequently, fecal microbiota transplantation (FMT) from the control group and bile acid administration were performed to see the expected rescuing effect on socially related behaviors that were impaired by repeated sevoflurane exposure in the mice. <b>Results:</b> In the 3-chamber test, sevoflurane-exposed mice spent less time with stranger mice compared with the control group. The density of both the apical and basal spine decreased in mice exposed to sevoflurane. In addition, repeated sevoflurane exposure led to a notable alteration in the gut microbiota and metabolite synthesis, particularly bile acid. FMT reduced the production of intestinal bile acid and attenuated the effect of sevoflurane exposure on social function and synaptic development. Cholestyramine treatment mimics the protective effects of FMT. <b>Conclusions:</b> The gut microbiota-metabolite-brain axis underlies social dysfunction caused by sevoflurane exposure in early age, and bile acid regulation may be a promising intervention to this impairment.</p>","PeriodicalId":21120,"journal":{"name":"Research","volume":"7 ","pages":"0482"},"PeriodicalIF":11.0,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11411162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ResearchPub Date : 2024-09-18DOI: 10.34133/research.0478
Kang-Ning Wang,Zi-Zhan Li,Kan Zhou,Bing Liu,Lang Rao,Lin-Lin Bu
{"title":"Cell Membrane-Coated Nanoparticles for Dental, Oral, and Craniofacial Diseases.","authors":"Kang-Ning Wang,Zi-Zhan Li,Kan Zhou,Bing Liu,Lang Rao,Lin-Lin Bu","doi":"10.34133/research.0478","DOIUrl":"https://doi.org/10.34133/research.0478","url":null,"abstract":"Dental, oral, and craniofacial diseases can substantially impact the quality of human life, thereby posing a serious public health concern. Although conventional therapies such as surgery have solved these problems largely, the prognosis of patients is not always satisfactory. Cell membrane-coated nanoparticles (CMCNPs) carry nanodrugs with the help of natural cell membranes, therefore utilizing their remarkable ability to interface and interact with their surrounding environment. These nanoparticles have demonstrated substantial advantages in drug targeting, prolonging blood circulation time, penetrating biofilms, and immune escape. With the assistance of CMCNPs, the therapeutic effects of dental, oral, and craniofacial diseases can reach a higher level. CMCNPs have been applied for dental, oral, and craniofacial diseases for various conditions such as head and neck cancer, periodontal disease, and oral biosignal detection. For the therapies of head and neck cancer, CMCNPs have been widely utilized as a tool of chemotherapy, phototherapy, and immunotherapy, while yet to be exploited in imaging technique. In the end, we summarized the challenges and prospectives of CMCNPs for dental, oral, and craniofacial diseases: large-scale production with uniform standards and high quantity, extensive application directions in dental, oral, and craniofacial regions (implant, endodontics), and the promotion of its clinical application.","PeriodicalId":21120,"journal":{"name":"Research","volume":"27 1","pages":"0478"},"PeriodicalIF":11.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Mid-Infrared Photons Alleviate Tinnitus by Activating the KCNQ2 Channel in the Auditory Cortex.","authors":"Peng Liu,Xinmiao Xue,Chi Zhang,Hanwen Zhou,Zhiwei Ding,Li Wang,Yuke Jiang,Zhixin Zhang,Weidong Shen,Shiming Yang,Fangyuan Wang","doi":"10.34133/research.0479","DOIUrl":"https://doi.org/10.34133/research.0479","url":null,"abstract":"Tinnitus is a phantom auditory sensation often accompanied by hearing loss, cognitive impairments, and psychological disturbances in various populations. Dysfunction of KCNQ2 and KCNQ3 channels-voltage-dependent potassium ion channels-in the cochlear nucleus can cause tinnitus. Despite the recognized significance of KCNQ2 and KCNQ3 channels in the auditory cortex, their precise relationship and implications in the pathogenesis of tinnitus remain areas of scientific inquiry. This study aimed to elucidate the pathological roles of KCNQ2 and KCNQ3 channels within the auditory cortex in tinnitus development and examine the therapeutic potential of mid-infrared photons for tinnitus treatment. We utilized a noise-induced tinnitus model combined with immunofluorescence, electrophysiological recording, and molecular dynamic simulation to investigate the morphological and physiological alterations after inducing tinnitus. Moreover, in vivo irradiation was administered to verify the treatment effects of infrared photons. Tinnitus was verified by deficits of the gap ratio with similar prepulse inhibition ratio and auditory brainstem response threshold. We observed an important enhancement in neuronal excitability in the auditory cortex using patch-clamp recordings, which correlated with KCNQ2 and KCNQ3 channel dysfunction. After irradiation with infrared photons, excitatory neuron firing was inhibited owing to increased KCNQ2 current resulting from structural alterations in the filter region. Meanwhile, deficits of the acoustic startle response in tinnitus animals were alleviated by infrared photons. Furthermore, infrared photons reversed the abnormal hyperexcitability of excitatory neurons in the tinnitus group. This study provided a novel method for modulating neuron excitability in the auditory cortex using KCNQ2 channels through a nonthermal effect. Infrared photons effectively mitigated tinnitus-related behaviors by suppressing abnormal neural excitability, potentially laying the groundwork for innovative therapeutic approaches for tinnitus treatment.","PeriodicalId":21120,"journal":{"name":"Research","volume":"189 1","pages":"0479"},"PeriodicalIF":11.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ResearchPub Date : 2024-09-18DOI: 10.34133/research.0489
Xianji Qiao,Liguang Wang,Jun Lu
{"title":"The Tuning of Strain in Layered Structure Oxide Cathodes for Lithium-Ion Batteries.","authors":"Xianji Qiao,Liguang Wang,Jun Lu","doi":"10.34133/research.0489","DOIUrl":"https://doi.org/10.34133/research.0489","url":null,"abstract":"Layered structure oxides have emerged as highly promising cathode materials for lithium-ion batteries. In these cathode materials, volume variation related to anisotropic lattice strain during Li+ insertion/extraction, however, can induce critical structural instability and electrochemical degradation upon cycling. Despite extensive research efforts, solving the issues of lattice strain and mechanical fatigue remains a challenge. This perspective aims to establish the \"structure-property relationship\" between the degradation mechanism of the layered oxide cathode due to lattice strain and the structural evolution during cycling. By addressing these issues, we aim to guide the improvement of electrochemical performance, thereby facilitating the widespread adoption of these materials in future high-energy density lithium-ion batteries.","PeriodicalId":21120,"journal":{"name":"Research","volume":"48 1","pages":"0489"},"PeriodicalIF":11.0,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ResearchPub Date : 2024-09-16DOI: 10.34133/research.0476
Ming Cong,Dianlong Zhao,Jiayi Yang,Guanjun Xiao,Bo Zou
{"title":"Identifying Organic-Inorganic Interaction Sites Toward Emission Enhancement in Non-Hydrogen-Bonded Hybrid Perovskite via Pressure Engineering.","authors":"Ming Cong,Dianlong Zhao,Jiayi Yang,Guanjun Xiao,Bo Zou","doi":"10.34133/research.0476","DOIUrl":"https://doi.org/10.34133/research.0476","url":null,"abstract":"The interaction between organic and inorganic components in metal hybrid perovskites fundamentally determines the intrinsic optoelectronic performance. However, the underlying interaction sites have still remained elusive, especially for those non-hydrogen-bonded hybrid perovskites, thus largely impeding materials precise design with targeted properties. Herein, high pressure is utilized to elucidate the interaction mechanism between organic and inorganic components in the as-synthesized one-dimensional hybrid metal halide (DBU)PbBr3 (DBU = 1,8-diazabicyclo [5.4.0] undec-7-ene). The interaction sites are identified to be the N from DBU and the Br from inorganic framework by the indicative of enhanced Raman mode under high pressure. The change in interaction strength is indeed derived from the pressure modulation on both distance and spatial arrangement of the nearest Br and N, rather than traditional hydrogen-bonding effect. Furthermore, the enhanced interaction increased charge transfer, resulting in a cyan emission with photoluminescence quantum yields (PLQYs) of 86.6%. The enhanced cyan emission is particularly important for underwater communication due to the much less attenuation in water than at other wavelength emissions. This study provides deep insights into the underlying photophysical mechanism of non-hydrogen-bonded hybrid metal halides and is expected to impart innovative construction with superior performance.","PeriodicalId":21120,"journal":{"name":"Research","volume":"19 1","pages":"0476"},"PeriodicalIF":11.0,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"POP1 Facilitates Proliferation in Triple-Negative Breast Cancer via m6A-Dependent Degradation of CDKN1A mRNA.","authors":"Chao Zhang,Sifen Wang,Xiuqing Lu,Wenjing Zhong,Yunyun Tang,Weiling Huang,Fengjia Wu,Xiumei Wang,Weidong Wei,Hailin Tang","doi":"10.34133/research.0472","DOIUrl":"https://doi.org/10.34133/research.0472","url":null,"abstract":"Triple-negative breast cancer (TNBC) is currently the worst prognostic subtype of breast cancer, and there is no effective treatment other than chemotherapy. Processing of precursors 1 (POP1) is the most substantially up-regulated RNA-binding protein (RBP) in TNBC. However, the role of POP1 in TNBC remains clarified. A series of molecular biological experiments in vitro and in vivo and clinical correlation analyses were conducted to clarify the biological function and regulatory mechanism of POP1 in TNBC. Here, we identified that POP1 is significantly up-regulated in TNBC and associated with poor prognosis. We further demonstrate that POP1 promotes the cell cycle and proliferation of TNBC in vitro and vivo. Mechanistically, POP1 directly binds to the coding sequence (CDS) region of CDKN1A mRNA and degrades it. The degradation process depends on the N6-methyladenosine (m6A) modification at the 497th site of CDKN1A and the recognition of this modification by YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Moreover, the m6A inhibitor STM2457 potently impaired the proliferation of POP1-overexpressed TNBC cells and improved the sensitivity to paclitaxel. In summary, our findings reveal the pivotal role of POP1 in promoting TNBC proliferation by degrading the mRNA of CDKN1A and that inhibition of m6A with STM2457 is a promising therapeutic strategy for TNBC.","PeriodicalId":21120,"journal":{"name":"Research","volume":"8 1","pages":"0472"},"PeriodicalIF":11.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Inhibition of ALOX12-12-HETE Alleviates Lung Ischemia-Reperfusion Injury by Reducing Endothelial Ferroptosis-Mediated Neutrophil Extracellular Trap Formation.","authors":"Chongwu Li,Peigen Gao,Fenghui Zhuang,Tao Wang,Zeyu Wang,Guodong Wu,Ziheng Zhou,Huikang Xie,Dong Xie,Deping Zhao,Junqi Wu,Chang Chen","doi":"10.34133/research.0473","DOIUrl":"https://doi.org/10.34133/research.0473","url":null,"abstract":"Lung ischemia-reperfusion injury (IRI) stands as the primary culprit behind primary graft dysfunction (PGD) after lung transplantation, yet viable therapeutic options are lacking. In the present study, we used a murine hilar clamp (1 h) and reperfusion (3 h) model to study IRI. The left lung tissues were harvested for metabolomics, transcriptomics, and single-cell RNA sequencing. Metabolomics of plasma from human lung transplantation recipients was also performed. Lung histology, pulmonary function, pulmonary edema, and survival analysis were measured in mice. Integrative analysis of metabolomics and transcriptomics revealed a marked up-regulation of arachidonate 12-lipoxygenase (ALOX12) and its metabolite 12-hydroxyeicosatetraenoic acid (12-HETE), which played a pivotal role in promoting ferroptosis and neutrophil extracellular trap (NET) formation during lung IRI. Additionally, single-cell RNA sequencing revealed that ferroptosis predominantly occurred in pulmonary endothelial cells. Importantly, Alox12-knockout (KO) mice exhibited a notable decrease in ferroptosis, NET formation, and tissue injury. To investigate the interplay between endothelial ferroptosis and NET formation, a hypoxia/reoxygenation (HR) cell model using 2 human endothelial cell lines was established. By incubating conditioned medium from HR cell model with neutrophils, we found that the liberation of high mobility group box 1 (HMGB1) from endothelial cells undergoing ferroptosis facilitated the formation of NETs by activating the TLR4/MYD88 pathway. Last, the administration of ML355, a targeted inhibitor of Alox12, mitigated lung IRI in both murine hilar clamp/reperfusion and rat left lung transplant models. Collectively, our study indicates ALOX12 as a promising therapeutic strategy for lung IRI.","PeriodicalId":21120,"journal":{"name":"Research","volume":"100 1","pages":"0473"},"PeriodicalIF":11.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ResearchPub Date : 2024-09-12DOI: 10.34133/research.0471
Yixuan Shang,Dongyu Xu,Lingyu Sun,Yuanjin Zhao,Lingyun Sun
{"title":"A Biomimetic Optical Cardiac Fibrosis-on-a-Chip for High-Throughput Anti-Fibrotic Drug Screening.","authors":"Yixuan Shang,Dongyu Xu,Lingyu Sun,Yuanjin Zhao,Lingyun Sun","doi":"10.34133/research.0471","DOIUrl":"https://doi.org/10.34133/research.0471","url":null,"abstract":"Cardiac fibrosis has emerged as the primary cause of morbidity, disability, and even mortality in numerous nations. In light of the advancements in precision medicine strategies, substantial attention has been directed toward the development of a practical and precise drug screening platform customized for individual patients. In this study, we introduce a biomimetic cardiac fibrosis-on-a-chip incorporating structural color hydrogels (SCHs) to enable optical high-throughput drug screening. By cocultivating a substantial proportion of cardiac fibroblasts (CFBs) with cardiomyocytes on the SCH, this biomimetic fibrotic microtissue successfully replicates the structural components and biomechanical properties associated with cardiac fibrosis. More importantly, the structural color shift observed in the SCH can be indicative of cardiac contraction and relaxation, making it a valuable tool for evaluating fibrosis progression. By incorporating such fibrotic microtissue into a microfluidic gradient chip, we develop a biomimetic optical cardiac fibrosis-on-a-chip platform that accurately and efficiently screens potential anti-fibrotic drugs. These characteristics suggest that this microphysiological platform possesses the capability to establish a preclinical framework for screening cardiac drugs, and may even contribute to the advancement of precision medicine.","PeriodicalId":21120,"journal":{"name":"Research","volume":"45 1","pages":"0471"},"PeriodicalIF":11.0,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142264470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}