Virologica Sinica最新文献

{"title":"Gene flow and its sporadic spillover: H10 and N5 avian influenza viruses from wild birds and the H10N5 human cases in China","authors":"Weijie Chen ,&nbsp;Shuiping Lu ,&nbsp;Haiyan Xiong ,&nbsp;Zhiyu Xiang ,&nbsp;Yuxi Wang ,&nbsp;Jingjing Hu ,&nbsp;Yue Pan ,&nbsp;Yanjiao Li ,&nbsp;Qile Gao ,&nbsp;Qi Chen ,&nbsp;Siru Hu ,&nbsp;Weibing Wang ,&nbsp;Chenglong Xiong","doi":"10.1016/j.virs.2024.12.002","DOIUrl":"10.1016/j.virs.2024.12.002","url":null,"abstract":"<div><div>On January 30, 2024, China announced the first human case of H10N5 influenza infection. Prior to this, human cases of H10N7 and H10N8 had been reported. It is now appropriate to re-examine the evolution and future epidemiological trends of the H10 and N5 subtypes of avian influenza viruses (AIVs). In this study, we analyzed the reassortment characteristics of the first human-derived H10N5 AIV (A/Zhejiang/ZJU01/2023), as well as the evolutionary dynamics of the wild bird-derived H10 and N5 subtypes of AIVs over the past decade. Our findings indicate that the human-derived H10N5 AIV exhibited low pathogenicity. A/bean_goose/Korea/KNU-10/2022(H10N7) and A/mallard/Novosibirsk_region/962k/2018(H12N5) were identified as the potential reassortment parents. The virus has existed since 2022 and several isolations have been reported in Bangladesh. Phylogenetic analysis showed that H10Ny and HxN5 AIVs in China are clustered differently based on the East Asian-Australian (eastern) and Central Asian-Indian (western) migratory flyways. The H10Ny and HxN5 AIV reassortant strains may cause human infections through accidental spillover. It is possible that another center of AIV evolution, mutation, and reassortment may be developing along the migratory flyways in northeastern Asia, distinct from Europe, the Americas, and China's Yangtze River Delta and Pearl River Delta, which should be closely monitored to ensure the safety of the public.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 1","pages":"Pages 15-23"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Random forest algorithm reveals novel sites in HA protein that shift receptor binding preference of the H9N2 avian influenza virus","authors":"Yuncong Yin ,&nbsp;Wen Li ,&nbsp;Rujian Chen ,&nbsp;Xiao Wang ,&nbsp;Yiting Chen ,&nbsp;Xinyuan Cui ,&nbsp;Xingbang Lu ,&nbsp;David M. Irwin ,&nbsp;Xuejuan Shen ,&nbsp;Yongyi Shen","doi":"10.1016/j.virs.2024.12.010","DOIUrl":"10.1016/j.virs.2024.12.010","url":null,"abstract":"<div><div>A switch from avian-type α-2,3 to human-type α-2,6 receptors is an essential element for the initiation of a pandemic from an avian influenza virus. Some H9N2 viruses exhibit a preference for binding to human-type α-2,6 receptors. This identifies their potential threat to public health. However, our understanding of the molecular basis for the switch of receptor preference is still limited. In this study, we employed the random forest algorithm to identify the potentially key amino acid sites within hemagglutinin (HA), which are associated with the receptor binding ability of H9N2 avian influenza virus (AIV). Subsequently, these sites were further verified by receptor binding assays. A total of 12 substitutions in the HA protein (N158D, N158S, A160 ​N, A160D, A160T, T163I, T163V, V190T, V190A, D193 ​N, D193G, and N231D) were predicted to prefer binding to α-2,6 receptors. Except for the V190T substitution, the other substitutions were demonstrated to display an affinity for preferential binding to α-2,6 receptors by receptor binding assays. Especially, the A160T substitution caused a significant upregulation of immune-response genes and an increased mortality rate in mice. Our findings provide novel insights into understanding the genetic basis of receptor preference of the H9N2 AIV.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 1","pages":"Pages 109-117"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Issue Cover","authors":"","doi":"10.1016/S1995-820X(25)00008-2","DOIUrl":"10.1016/S1995-820X(25)00008-2","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 1","pages":"Page OFC"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143619351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery and characterization of a novel carlavirus in Ligularia jaluensis plants","authors":"Shifang Fei ,&nbsp;Jiaping Yu ,&nbsp;Yali Zhou ,&nbsp;Yi Xie ,&nbsp;Li Xie ,&nbsp;Shuai Fu ,&nbsp;Jianxiang Wu","doi":"10.1016/j.virs.2024.11.003","DOIUrl":"10.1016/j.virs.2024.11.003","url":null,"abstract":"<div><div><em>Ligularia jaluensis</em> is an important medicinal and ornamental plant in China. However, the viruses capable of infecting <em>Ligularia jaluensis</em> remains unknown. Here, we identified a novel carlavirus, tentatively named ligularia jaluensis carlavirus (LJCV), as well as a known iris severe mosaic virus (ISMV), in <em>L. jaluensis</em> plants displaying chlorosis and yellow ring spot symptoms, using RNA-seq analysis. The LJCV genome consists of an 8497 ​nt positive-sense, single-stranded RNA [excluding the poly(A) tail], and contains six open reading frames (ORFs). Phylogenetic analyses based on the full-length genome and RNA-dependent RNA polymerase (RdRp) amino acid (aa) sequences revealed that LJCV clusters within an evolutionary branch alongside known viruses in the <em>Carlavirus</em> genus. The RdRp protein encoded by ORF1 of LJCV shared 45.38%–67.41% identity with the corresponding proteins of eight closely related carlaviruses. ORFs 2–4 constitute the triple gene block (TGB), with TGBp1 and TGBp3 localized in the endoplasmic reticulum (ER), while TGBp2 is localized at plasmodesmata (PD) and facilitates viral intercellular movement, as demonstrated by its ability to complement the potato virus X with movement-deficient mutant (PVX-Δp25-GFP). Additionally, ORF6 encodes a cysteine-rich protein (CRP) that is localized in the chloroplast and functions as a viral pathogenicity factor, inducing severe viral symptoms in the heterologous PVX expression system. Furthermore, we successfully constructed an infectious cDNA clone of LJCV, and found that it can infect <em>Nicotiana benthamiana</em> plants through mechanical inoculation or agrobacterium-mediated infiltration of the LJCV infectious clone. These findings enhance our understanding of the characteristics and host range of carlaviruses, as well as the viruses capable of infecting <em>L. jaluensis</em>.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 1","pages":"Pages 71-79"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Geographical distribution and characterization of Jingmen tick virus in wild boars in China","authors":"Tong Wang ,&nbsp;Yu Guo ,&nbsp;Yu Xu ,&nbsp;Heting Sun ,&nbsp;Peng Peng ,&nbsp;Siyuan Qin ,&nbsp;Guoqiang Zhu ,&nbsp;Changchun Tu ,&nbsp;Zhongzhong Tu","doi":"10.1016/j.virs.2024.12.011","DOIUrl":"10.1016/j.virs.2024.12.011","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 1","pages":"Pages 137-140"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid preparation and characterization of pan-sarbecovirus mRNA vaccine candidates based on the receptor binding domain","authors":"Mei Wu,&nbsp;Tian-Shu Cao,&nbsp;Xiao-Chuan Xiong,&nbsp;Tao Ming,&nbsp;Pan-Deng Shi,&nbsp;Rong-Rong Zhang,&nbsp;Qing Ye,&nbsp;Cheng-Feng Qin","doi":"10.1016/j.virs.2024.11.004","DOIUrl":"10.1016/j.virs.2024.11.004","url":null,"abstract":"","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 1","pages":"Pages 144-146"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patterns of liver fibrosis evolution in Chinese HIV/HBV co-infected adults following 5-year antiretroviral treatment: A longitudinal study using non-invasive APRI and Fib-4 scores","authors":"Qingrong Zhang ,&nbsp;Lijun Sun ,&nbsp;Yuxuan Liang ,&nbsp;Wenlu Zou ,&nbsp;Jingtao Huang ,&nbsp;Yuan Zhang ,&nbsp;Yi Jin ,&nbsp;Na Zhou ,&nbsp;Jiangzhu Ye ,&nbsp;Huachun Zou ,&nbsp;Hao Wu ,&nbsp;Tong Zhang ,&nbsp;Bin Su ,&nbsp;Taiyi Jiang ,&nbsp;Haitao Chen","doi":"10.1016/j.virs.2024.12.009","DOIUrl":"10.1016/j.virs.2024.12.009","url":null,"abstract":"<div><div>The long-term effects of combined antiretroviral therapy (ART) on liver fibrosis patterns in adults living with human immunodeficiency virus (HIV) and chronic hepatitis B virus (HBV) are not well understood. Therefore, this study aimed to investigate the trajectories of liver fibrosis and identify the associations of baseline variables with different patterns of liver fibrosis evolution. A total of 333 individuals with HIV/HBV co-infection and undergoing long-term ART were enrolled in this study. Demographic, clinical, and biochemical data were collected at baseline and during annual visits. Group-based trajectory models (GBTMs) were used to detect the patterns of liver fibrosis evolution based on longitudinal data of fibrosis-4 (Fib-4) and aspartate aminotransferase to platelet ratio index (APRI) scores. Logistic regression analysis was performed to identify baseline predictors of liver fibrosis evolution. The median age of all participants was 33 years. Among them, 89.5% initially received TDF-containing ART. GBTMs identified two distinct patterns of liver fibrosis evolution using either APRI or Fib-4 scores. The majority of individuals (78.5% for APRI and 75.3% for Fib-4; pattern A) showed stable or low fibrosis with no progression, while the remaining participants showed regression from high fibrosis levels (21.5% for APRI and 24.7% for Fib-4; pattern B). Pattern A participants were younger and had higher CD4⁺ cell counts, higher lymphocyte cell counts, higher white blood cell counts, and lower platelet counts at baseline compared to pattern B participants. For HIV/HBV co-infected patients with varying degrees of initial liver fibrosis, long-term ART has shown distinct patterns of alleviating liver fibrosis.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"40 1","pages":"Pages 118-124"},"PeriodicalIF":5.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142923622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferritin nanoparticle-based Nipah virus glycoprotein vaccines elicit potent protective immune responses in mice and hamsters","authors":"Shaohong Chen ,&nbsp;Xinghai Zhang ,&nbsp;Yanfeng Yao ,&nbsp;Shengdong Wang ,&nbsp;Kangyin Li ,&nbsp;Baoyue Zhang ,&nbsp;Tianxi Ye ,&nbsp;Li Chen ,&nbsp;Yan Wu ,&nbsp;Entao Li ,&nbsp;Bichao Xu ,&nbsp;Pei Zhang ,&nbsp;Xia Chuai ,&nbsp;Yong Ran ,&nbsp;Rui Gong ,&nbsp;Huajun Zhang ,&nbsp;Sandra Chiu","doi":"10.1016/j.virs.2024.09.005","DOIUrl":"10.1016/j.virs.2024.09.005","url":null,"abstract":"<div><div>Nipah virus (NiV) is a zoonotic paramyxovirus in the genus <em>Henipavirus</em> that is prevalent in Southeast Asia. NiV leads to severe respiratory disease and encephalitis in humans and animals, with a mortality rate of up to 75%. Despite the grave threat to public health and global biosecurity, no medical countermeasures are available for humans. Here, based on self-assembled ferritin nanoparticles (FeNPs), we successfully constructed two candidate FeNP vaccines by loading mammalian cells expressing NiV sG (residues 71–602, FeNP-sG) and G_head (residues 182–602, FeNP-G_head) onto <em>E. coli</em>-expressed FeNPs (FeNP-sG and FeNP-G_head, respectively) through Spycatcher/Spytag technology. Compared with sG and G_head alone, FeNP-sG and FeNP-G_head elicited significant NiV specific neutralizing antibody levels and T-cell responses in mice, whereas the immune response in the FeNP-sG immunized group was greater than that in the FeNP-G_head group. These results further demonstrate that sG possesses greater antigenicity than G_head and that FeNPs can dramatically enhance immunogenicity. Furthermore, FeNP-sG provided 100% protection against NiV challenge in a hamster model when it was administered twice at a dose of 5 μg/per animal. Our study provides not only a promising candidate vaccine against NiV, but also a theoretical foundation for the design of a NiV immunogen for the development of novel strategies against NiV infection.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 6","pages":"Pages 909-916"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142257547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Viral load dynamics in asymptomatic and symptomatic patients during Omicron BA.2 outbreak in Shanghai, China, 2022: A longitudinal cohort study","authors":"Jingwen Ai ,&nbsp;Jiaxin Zhou ,&nbsp;Yang Li ,&nbsp;Feng Sun ,&nbsp;Shijia Ge ,&nbsp;Haocheng Zhang ,&nbsp;Yanpeng Wu ,&nbsp;Yan Wang ,&nbsp;Yilin Zhang ,&nbsp;Hongyu Wang ,&nbsp;Jianpeng Cai ,&nbsp;Xian Zhou ,&nbsp;Sen Wang ,&nbsp;Rong Li ,&nbsp;Zhen Feng ,&nbsp;Xiangyanyu Xu ,&nbsp;Xuemei Yan ,&nbsp;Yuchen Zhao ,&nbsp;Juanjuan Zhang ,&nbsp;Hongjie Yu ,&nbsp;Wenhong Zhang","doi":"10.1016/j.virs.2024.10.001","DOIUrl":"10.1016/j.virs.2024.10.001","url":null,"abstract":"<div><div>The SARS-CoV-2 virus, particularly the Omicron BA.2 variant, led to a significant surge in Shanghai, 2022. However, the viral load dynamic in Omicron infections with varying clinical severities remain unclear. This prospective cohort included 48,830 hospitalized coronavirus disease 2019 (COVID-19) patients across three hospitals in Shanghai, China, between 23 March and 15 May, 2022. Systematic nucleic acid testing was performed using RT-PCR Cycle threshold (Ct) value as a proxy of viral load. We analyzed the kinetic characteristics of viral shedding by clinical severity and identified associated risk factors. The study comprised 31.06% asymptomatic cases, 67.66% mild-moderate cases, 1.00% severe cases, 0.29% critical and fatal cases. Upon admission, 57% of patients tested positive, with peak viral load observed at 4 days (median Ct value 27.5), followed by a decrease and an average viral shedding time (VST) of 6.1 days (Interquartile range, 4.0–8.8 days). Although viral load exhibited variation by age and clinical severity, peak Ct values occurred at similar times. Unvaccinated status, age exceeding 60, and comorbidities including hypertension, renal issues kidney dialysis and kidney transplantation, neurological disorders, rheumatism, and psychotic conditions were found to correlate with elevated peak viral load and extended VST. Asymptomatic cases demonstrated a 40% likelihood of contagiousness within 6 days of detection, while mild-moderate and severe cases exhibited post-symptom resolution infectious probabilities of 27% and over 50%, respectively. These findings revealed that the initial Ct values serve as a predictive indicator of severe outcomes. Unvaccinated elderly individuals with particular comorbidities are at high-risk for elevated viral load and prolonged VST.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 6","pages":"Pages 851-859"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11738783/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142476077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction and validation of a mouse model for studying severe human adenovirus infections","authors":"Dingbin Chen ,&nbsp;Yuqian Yan ,&nbsp;Ting Mei ,&nbsp;Peipei Yang ,&nbsp;Siqi Deng ,&nbsp;Yiqiang Li ,&nbsp;Tie Zhao ,&nbsp;Ning Xin ,&nbsp;Biyan Duan ,&nbsp;Weifeng Liang ,&nbsp;Yuemei Yang ,&nbsp;Wei Zhao ,&nbsp;Donald Seto ,&nbsp;Junxian Ou ,&nbsp;Qiwei Zhang","doi":"10.1016/j.virs.2024.11.001","DOIUrl":"10.1016/j.virs.2024.11.001","url":null,"abstract":"<div><div>Human adenoviruses (HAdVs) are highly contagious pathogens with various genotypes implicated in acute respiratory disease (ARD) and linked to fatality, especially in immunosuppressed patients, young children, and military recruits. Currently, no vaccines or specific drugs are approved for clinical use. The hosts of adenoviruses are strictly species-specific, which strongly limits the development of vaccines and drugs against HAdVs. In this study, immunocompetent BALB/c mice were challenged with different doses of human adenovirus type 5 (HAdV-5) via tail intravenous injection (<em>i.v.</em>). All mice challenged with a high dose of HAdV-5 (3.2 ​× ​10¹⁰ TCID₅₀/kg) died within 3–5 days, while those receiving a low dose of HAdV-5 (8 ​× ​10⁹ or 4 ​× ​10⁹ TCID₅₀/kg) survived. Interestingly, among the mice receiving a medium dose of HAdV-5 (1.6 ​× ​10¹⁰ TCID₅₀/kg), 60% (n ​= ​3/5) of male mice died, while all female mice survived. This suggests that male mice may be more susceptible to HAdV-5 infection than female mice, consistent with clinical findings in children. HAdV-5 DNA was mainly distributed in the liver, followed by the spleen and lung. Pathological changes were observed in the lung, liver, and spleen, with severity increasing in correlation with the virus challenge dosage. Transcriptome and qPCR analyses of the liver indicated that the down-regulated expression of the <em>H2-Aa</em>, <em>H2-Ea-ps</em>, <em>CD74</em>, and <em>H2-Eb1</em> genes in male mice, as well as the <em>AHR</em> gene in female mice, may contribute to the observed higher mortality rates in male mice. Therefore, this effective, feasible, and cost-efficient mouse model could serve as a candidate for evaluating HAdV vaccines and anti-adenovirus therapeutics.</div></div>","PeriodicalId":23654,"journal":{"name":"Virologica Sinica","volume":"39 6","pages":"Pages 963-973"},"PeriodicalIF":5.5,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11738788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142629468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}