Viruses最新文献

{"title":"Characterization of Avian Influenza Viruses Detected in Kenyan Live Bird Markets and Wild Bird Habitats Reveal Genetically Diverse Subtypes and High Proportion of A(H9N2), 2018–2020","authors":"Peninah Munyua, Eric Osoro, Joyce Jones, George Njogu, Genyan Yang, Elizabeth Hunsperger, Christine M. Szablewski, Ruth Njoroge, Doris Marwanga, Harry Oyas, Ben Andagalu, Romona Ndanyi, Nancy Otieno, Vincent Obanda, Carolyne Nasimiyu, Obadiah Njagi, Juliana DaSilva, Yunho Jang, John Barnes, Gideon O. Emukule, Clayton O. Onyango, C. Todd Davis","doi":"10.3390/v16091417","DOIUrl":"https://doi.org/10.3390/v16091417","url":null,"abstract":"Following the detection of highly pathogenic avian influenza (HPAI) virus in countries bordering Kenya to the west, we conducted surveillance among domestic and wild birds along the shores of Lake Victoria. In addition, between 2018 and 2020, we conducted surveillance among poultry and poultry workers in live bird markets and among wild migratory birds in various lakes that are resting sites during migration to assess introduction and circulation of avian influenza viruses in these populations. We tested 7464 specimens (oropharyngeal (OP) and cloacal specimens) from poultry and 6531 fresh fecal specimens from wild birds for influenza A viruses by real-time RT-PCR. Influenza was detected in 3.9% (n = 292) of specimens collected from poultry and 0.2% (n = 10) of fecal specimens from wild birds. On hemagglutinin subtyping, most of the influenza A positives from poultry (274/292, 93.8%) were H9. Of 34 H9 specimens randomly selected for further subtyping, all were H9N2. On phylogenetic analysis, these viruses were genetically similar to other H9 viruses detected in East Africa. Only two of the ten influenza A-positive specimens from the wild bird fecal specimens were successfully subtyped; sequencing analysis of one specimen collected in 2018 was identified as a low-pathogenicity avian influenza H5N2 virus of the Eurasian lineage, and the second specimen, collected in 2020, was subtyped as H11. A total of 18 OP and nasal specimens from poultry workers with acute respiratory illness (12%) were collected; none were positive for influenza A virus. We observed significant circulation of H9N2 influenza viruses in poultry in live bird markets in Kenya. During the same period, low-pathogenic H5N2 virus was detected in a fecal specimen collected in a site hosting a variety of migratory and resident birds. Although HPAI H5N8 was not detected in this survey, these results highlight the potential for the introduction and establishment of highly pathogenic avian influenza viruses in poultry populations and the associated risk of spillover to human populations.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206922","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":"Topical Protease Inhibitor Increases Tumor-Free and Overall Survival in CD4-Depleted Mouse Model of Anal Cancer","authors":"Evan Yao, Laura Gunder, Tyra Moyer, Kristina A. Matkowskyj, Kathryn Fox, Yun Zhou, Sakura Haggerty, Hillary Johnson, Nathan Sherer, Evie Carchman","doi":"10.3390/v16091421","DOIUrl":"https://doi.org/10.3390/v16091421","url":null,"abstract":"Patients with immunodeficiencies and older age are at an increased risk of anal cancer. Transgenic K14E6/E7 mice with established high-grade anal dysplasia were treated topically at the anus with the protease inhibitor saquinavir (SQV) in the setting of CD4+ T-cell depletion to mimic immunodeficiency. To ensure tumor development, specific groups were treated with a topical carcinogen (7,12-Dimethylbenz[a]anthracene (DMBA)). The treatment groups included the vehicle (control), DMBA only, topical SQV, and topical SQV with DMBA, as well as the same four groups with CD4 depletion. The mice were monitored weekly for tumor development. Upon reaching 20 weeks of treatment, the mice were sacrificed, and their anal tissue was harvested for histological analysis. None of the mice in the SQV or control groups developed overt anal tumors, except three mice that were CD4-depleted. The CD4-depleted mice treated with DMBA had significantly increased tumor-free survival and overall survival as well as decreased tumor-volume growth over time when treated with SQV. These data suggest that topical SQV, in the setting of CD4 depletion and high-grade anal dysplasia, can increase tumor-free and overall survival; thus, it may represent a viable topical therapy to decrease the risk of progression of anal dysplasia to anal cancer.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206925","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":"Case Report of Two Independent Moroccan Families with Syndromic Epidermodysplasia Verruciformis and STK4 Deficiency","authors":"Assiya El Kettani, Hind Ouair, Farida Marnissi, Jalila El Bakkouri, Rémi Chevalier, Lazaro Lorenzo, Halima Kholaiq, Vivien Béziat, Emmanuelle Jouanguy, Jean-Laurent Casanova, Ahmed Aziz Bousfiha","doi":"10.3390/v16091415","DOIUrl":"https://doi.org/10.3390/v16091415","url":null,"abstract":"Epidermodysplasia verruciformis (EV) is a rare genodermatosis caused by β-human papillomaviruses (HPV) in immunodeficient patients. EV is characterized by flat warts and pityriasis-like lesions and might be isolated or syndromic, associated with some other infectious manifestations. We report here three patients from two independent families, with syndromic EV for both of them. By whole exome sequencing, we found that the patients carry new homozygous variants in STK4, both leading to a premature stop codon. STK4 deficiency causes a combined immunodeficiency characterized by a broad infectious susceptibility to bacteria, viruses, and fungi. Auto-immune manifestations were also reported. Deep immunophenotyping revealed multiple cytopenia in the three affected patients, in particular deep CD4+ T cells deficiency. We report here the fourth and the fifth cases of the syndromic EV due to STK4 deficiency.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206900","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":"Translation of Overlapping Open Reading Frames Promoted by Type 2 IRESs in Avian Calicivirus Genomes","authors":"Yani Arhab, Tatyana V. Pestova, Christopher U. T. Hellen","doi":"10.3390/v16091413","DOIUrl":"https://doi.org/10.3390/v16091413","url":null,"abstract":"Caliciviruses have positive-sense RNA genomes, typically with short 5′-untranslated regions (5′UTRs) that precede the long open reading frame 1 (ORF1). Exceptionally, some avian caliciviruses have long 5′UTRs containing a picornavirus-like internal ribosomal entry site (IRES), which was likely acquired by horizontal gene transfer. Here, we identified numerous additional avian calicivirus genomes with IRESs, predominantly type 2, and determined that many of these genomes contain a ~200–300 codon-long ORF (designated ORF1*) that overlaps the 5′-terminal region of ORF1. The activity of representative type 2 IRESs from grey teal calicivirus (GTCV) and Caliciviridae sp. isolate yc-13 (RaCV1) was confirmed by in vitro translation. Toeprinting showed that in cell-free extracts and in vitro reconstituted reactions, ribosomal initiation complexes assembled on the ORF1* initiation codon and at one or two AUG codons in ORF1 at the 3′-border and/or downstream of the IRES. Initiation at all three sites required eIF4A and eIF4G, which bound to a conserved region of the IRES; initiation on the ORF1* and principal ORF1 initiation codons involved eIF1/eIF1A-dependent scanning from the IRES’s 3′-border. Initiation on these IRESs was enhanced by the IRES trans-acting factors (ITAFs) Ebp1/ITAF45, which bound to the apical subdomain Id of the IRES, and PTB (GTCV) or PCBP2 (RaCV1).","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206921","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":"Investigations on the Potential Role of Free-Ranging Wildlife as a Reservoir of SARS-CoV-2 in Switzerland","authors":"Juliette Kuhn, Iris Marti, Marie-Pierre Ryser-Degiorgis, Kerstin Wernike, Sarah Jones, Grace Tyson, Gary Delalay, Patrick Scherrer, Stéphanie Borel, Margaret J. Hosie, Anja Kipar, Evelyn Kuhlmeier, Tatjana Chan, Regina Hofmann-Lehmann, Marina L. Meli","doi":"10.3390/v16091407","DOIUrl":"https://doi.org/10.3390/v16091407","url":null,"abstract":"Amid the SARS-CoV-2 pandemic, concerns surfaced regarding the spread of the virus to wildlife. Switzerland lacked data concerning the exposure of free-ranging animals to SARS-CoV-2 during this period. This study aimed to investigate the potential exposure of Swiss free-ranging wildlife to SARS-CoV-2. From 2020 to 2023, opportunistically collected samples from 712 shot or found dead wild mustelids (64 European stone and pine martens, 13 European badgers, 10 European polecats), canids (449 red foxes, 41 gray wolves, one golden jackal) and felids (56 Eurasian lynx, 18 European wildcats), as well as from 45 captured animals (39 Eurasian lynx, 6 European wildcats) were tested. A multi-step serological approach detecting antibodies to the spike protein receptor binding domain (RBD) and N-terminal S1 subunit followed by surrogate virus neutralization (sVNT) and pseudotype-based virus neutralization assays against different SARS-CoV-2 variants was performed. Additionally, viral RNA loads were quantified in lung tissues and in oronasal, oropharyngeal, and rectal swabs by reverse transcription polymerase chain reactions (RT-qPCRs). Serologically, SARS-CoV-2 exposure was confirmed in 14 free-ranging Swiss red foxes (prevalence 3.1%, 95% CI: 1.9–5.2%), two Eurasian lynx (2.2%, 95% CI: 0.6–7.7%), and one European wildcat (4.2%, 95% CI: 0.2–20.2%). Two positive foxes exhibited neutralization activity against the BA.2 and BA.1 Omicron variants. No active infection (viral RNA) was detected in any animal tested. This is the first report of SARS-CoV-2 antibodies in free-ranging red foxes, Eurasian lynx, and European wildcats worldwide. It confirms the spread of SARS-CoV-2 to free-ranging wildlife in Switzerland but does not provide evidence of reservoir formation. Our results underscore the susceptibility of wildlife populations to SARS-CoV-2 and the importance of understanding diseases in a One Health Concept.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206927","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":"Targeting Yezo Virus Structural Proteins for Multi-Epitope Vaccine Design Using Immunoinformatics Approach","authors":"Sudais Rahman, Chien-Chun Chiou, Mashal M. Almutairi, Amar Ajmal, Sidra Batool, Bushra Javed, Tetsuya Tanaka, Chien-Chin Chen, Abdulaziz Alouffi, Abid Ali","doi":"10.3390/v16091408","DOIUrl":"https://doi.org/10.3390/v16091408","url":null,"abstract":"A novel tick-borne orthonairovirus called the Yezo virus (YEZV), primarily transmitted by the Ixodes persulcatus tick, has been recently discovered and poses significant threats to human health. The YEZV is considered endemic in Japan and China. Clinical symptoms associated with this virus include thrombocytopenia, fatigue, headache, leukopenia, fever, depression, and neurological complications ranging from mild febrile illness to severe outcomes like meningitis and encephalitis. At present, there is no treatment or vaccine readily accessible for this pathogenic virus. Therefore, this research employed an immunoinformatics approach to pinpoint potential vaccine targets within the YEZV through an extensive examination of its structural proteins. Three structural proteins were chosen using specific criteria to pinpoint T-cell and B-cell epitopes, which were subsequently validated through interferon-gamma induction. Six overlapping epitopes for cytotoxic T-lymphocytes (CTL), helper T-lymphocytes (HTL), and linear B-lymphocytes (LBL) were selected to construct a multi-epitope vaccine, achieving a 92.29% coverage of the global population. These epitopes were then fused with the 50S ribosomal protein L7/L12 adjuvant to improve protection against international strains. The three-dimensional structure of the designed vaccine construct underwent an extensive evaluation through structural analysis. Following molecular docking studies, the YEZV vaccine construct emerged as a candidate for further investigation, showing the lowest binding energy (−78.7 kcal/mol) along with favorable physiochemical and immunological properties. Immune simulation and molecular dynamics studies demonstrated its stability and potential to induce a strong immune response within the host cells. This comprehensive analysis indicates that the designed vaccine construct could offer protection against the YEZV. It is crucial to conduct additional in vitro and in vivo experiments to verify its safety and effectiveness.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206926","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":"New Viruses Infecting Hyperthermophilic Bacterium Thermus thermophilus","authors":"Matvey Kolesnik, Constantine Pavlov, Alina Demkina, Aleksei Samolygo, Karyna Karneyeva, Anna Trofimova, Olga S. Sokolova, Andrei V. Moiseenko, Maria Kirsanova, Konstantin Severinov","doi":"10.3390/v16091410","DOIUrl":"https://doi.org/10.3390/v16091410","url":null,"abstract":"Highly diverse phages infecting thermophilic bacteria of the Thermus genus have been isolated over the years from hot springs around the world. Many of these phages are unique, rely on highly unusual developmental strategies, and encode novel enzymes. The variety of Thermus phages is clearly undersampled, as evidenced, for example, by a paucity of phage-matching spacers in Thermus CRISPR arrays. Using water samples collected from hot springs in the Kunashir Island from the Kuril archipelago and from the Tsaishi and Nokalakevi districts in the Republic of Georgia, we isolated several distinct phages infecting laboratory strains of Thermus thermophilus. Genomic sequence analysis of 11 phages revealed both close relatives of previously described Thermus phages isolated from geographically distant sites, as well as phages with very limited similarity to earlier isolates. Comparative analysis allowed us to predict several accessory phage genes whose products may be involved in host defense/interviral warfare, including a putative Type V CRISPR-cas system.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206928","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":"The Anti-SARS-CoV-2 S-Protein IgG, Which Is Detected Using the Chemiluminescence Microparticle Immunoassay (CMIA) in Individuals Having Either a History of COVID-19 Vaccination and/or SARS-CoV-2 Infection, Showed a High-Titer Neutralizing Effect","authors":"Dilan Cin, Pinar Soguksu, Meryem Merve Oren, Nuray Ozgulnar, Ali Agacfidan, Sevim Mese","doi":"10.3390/v16091409","DOIUrl":"https://doi.org/10.3390/v16091409","url":null,"abstract":"Neutralizing antibodies plays a primary role in protective immunity by preventing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from entering the cells. Therefore, characterization of antiviral immunity is important for protection against SARS-CoV-2. In this study, the neutralizing effect of the anti-SARS-CoV-2 S1 protein IgG, which was detected using the chemiluminescence microparticle immunoassay (CMIA)-based SARS-CoV-2 IgG II Quant (Abbott, Waukegan, IL, USA) test in SARS-CoV-2 infected and/or vaccinated individuals, was investigated with a surrogate virus neutralization test (sVNT). In total, 120 Seropositive individuals were included in this study. They were divided into two groups: Vaccinated (n = 60) and Vaccinated + Previously Infected (n = 60). A commercial sVNT, the ACE2–RBD Neutralization Test (Dia.Pro, Milan, Italy), was used to assess the neutralizing effect. The assay is performed in two steps: screening and titration. The screening showed positive results in all seropositive samples. Low titration in 1.7%, medium titration in 5%, and high titration in 93.3% of the Vaccinated group, and medium titration in 1.7% and high titration in 98.3% of the other group, as obtained from the ACE2-RBD titration test. A strong positive and significant correlation was found between the SARS-CoV-2 IgG II Quant test and the ACE2-RBD titration test at the 1/32 titration level for both groups (p < 0.001 for both). This study shows that the SARS-CoV-2 IgG detected using the CMIA method after SARS-CoV-2 infection and/or vaccination has a high neutralizing titration by using the sVNT. In line with these data, knowledge that seropositivity determined by CMIA also indicates a strong neutralizing effect contributes to countrywide planning for protecting the population.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206929","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":"3D Head Shape Feature Analysis of Zika-Infected Children","authors":"Xiangyang Ju, Peter Mossey, Ashraf Ayoub","doi":"10.3390/v16091406","DOIUrl":"https://doi.org/10.3390/v16091406","url":null,"abstract":"Congenital Zika syndrome (CZS) has been identified a constellation of congenital anomalies caused by Zika Virus (ZKV) infection during pregnancy. The infection with ZKV could lead to microcephaly of the fetus due to a severe decrease in brain volume and reduced brain growth. The preliminary screening of CZS is based on measuring head circumference; the diagnosis is made if this measurement is below two standard deviations below the mean. The analyses of the 3D head features of infected infants are limited. This study analyzed 3D head images of 35 ZKV-positive cases with an average age of 16.8 ± 2 months and 35 controls with an average age of 14.4 ± 5 months. This study focused on identifying potential diagnostic characteristics of CZS. The 3D head images were captured using a 3D imaging system. The averaged images of the two groups were aligned to illustrate the size and shape differences. There were significant differences in centroid size, head circumference (HC), head height (HH), and chin height (CH) between the two groups. We also identified significant differences in the indices of chin height/total facial height (CH/TFH) and head height/head circumference ratio (HH/HC) between the CZS and control cases. An HH/HC of 0.49 showed a sensitivity of 0.86 and a specificity of 0.74 in diagnosing CZS, which is more sensitive than the routinely used HC measurement. The index of HH/HC has potential to be used as the gold standard for the early screening for the detection of CZS cases.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206986","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":"Unveiling the Connection: Viral Infections and Genes in dNTP Metabolism","authors":"Shih-Yen Lo, Meng-Jiun Lai, Chee-Hing Yang, Hui-Chun Li","doi":"10.3390/v16091412","DOIUrl":"https://doi.org/10.3390/v16091412","url":null,"abstract":"Deoxynucleoside triphosphates (dNTPs) are crucial for the replication and maintenance of genomic information within cells. The balance of the dNTP pool involves several cellular enzymes, including dihydrofolate reductase (DHFR), ribonucleotide reductase (RNR), and SAM and HD domain-containing protein 1 (SAMHD1), among others. DHFR is vital for the de novo synthesis of purines and deoxythymidine monophosphate, which are necessary for DNA synthesis. SAMHD1, a ubiquitously expressed deoxynucleotide triphosphohydrolase, converts dNTPs into deoxynucleosides and inorganic triphosphates. This process counteracts the de novo dNTP synthesis primarily carried out by RNR and cellular deoxynucleoside kinases, which are most active during the S phase of the cell cycle. The intracellular levels of dNTPs can influence various viral infections. This review provides a concise summary of the interactions between different viruses and the genes involved in dNTP metabolism.","PeriodicalId":501326,"journal":{"name":"Viruses","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142206931","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}