المؤلفون: Li, Junsheng, Wang, Siyu, Chi, Xiaojing, He, Qiheng, Tao, Chuming, Ding, Yaowei, Wang, Jia, Zhao, Jizong, Wang, Wen

المساهمون: National Natural Science Foundation of China

المصدر: Frontiers in Immunology ; volume 14 ; ISSN 1664-3224

مصطلحات موضوعية: Immunology, Immunology and Allergy

الوصف: Objective Mitochondrial dysfunction and oxidative stress are known to involved in tumor occurrence and progression. This study aimed to explore the molecular subtypes of lower-grade gliomas (LGGs) based on oxidative stress-related and mitochondrial-related genes (OMRGs) and construct a prognostic model for predicting prognosis and therapeutic response in LGG patients. Methods A total of 223 OMRGs were identified by the overlap of oxidative stress-related genes (ORGs) and mitochondrial-related genes (MRGs). Using consensus clustering analysis, we identified molecular subtypes of LGG samples from TCGA database and confirmed the differentially expressed genes (DEGs) between clusters. We constructed a risk score model using LASSO regression and analyzed the immune-related profiles and drug sensitivity of different risk groups. The prognostic role of the risk score was confirmed using Cox regression and Kaplan-Meier curves, and a nomogram model was constructed to predict OS rates. We validated the prognostic role of OMRG-related risk score in three external datasets. Quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) staining confirmed the expression of selected genes. Furthermore, wound healing and transwell assays were performed to confirm the gene function in glioma. Results We identified two OMRG-related clusters and cluster 1 was significantly associated with poor outcomes (P<0.001). The mutant frequencies of IDH were significantly lower in cluster 1 (P<0.05). We found that the OMRG-related risk scores were significantly correlated to the levels of immune infiltration and immune checkpoint expression. High-risk samples were more sensitive to most chemotherapeutic agents. We identified the prognostic role of OMRG-related risk score in LGG patients (HR=2.665, 95%CI=1.626-4.369, P<0.001) and observed that patients with high-risk scores were significantly associated with poor prognosis (P<0.001). We validated our findings in three external datasets. The results of qRT-PCR ...

الإتاحة: https://doi.org/10.3389/fimmu.2023.1183475Test

المؤلفون: Chi, Xiaojing, Zhang, Xinhui, Pan, Shengnan, Yu, Yanying, Shi, Yujin, Lin, Tianli, Duan, Huarui, Liu, Xiuying, Chen, Wenfang, Yang, Xuehua, Chen, Lan, Dong, Xiaoqian, Ren, Lili, Ding, Qiang, Wang, Jianwei, Yang, Wei

المساهمون: National Natural Science Foundation of China

المصدر: Signal Transduction and Targeted Therapy ; volume 7, issue 1 ; ISSN 2059-3635

مصطلحات موضوعية: Cancer Research, Genetics

الوصف: The wide transmission and host adaptation of SARS-CoV-2 have led to the rapid accumulation of mutations, posing significant challenges to the effectiveness of vaccines and therapeutic antibodies. Although several neutralizing antibodies were authorized for emergency clinical use, convalescent patients derived natural antibodies are vulnerable to SARS-CoV-2 Spike mutation. Here, we describe the screen of a panel of SARS-CoV-2 receptor-binding domain (RBD) targeted nanobodies (Nbs) from a synthetic library and the design of a biparatopic Nb, named Nb1–Nb2, with tight affinity and super-wide neutralization breadth against multiple SARS-CoV-2 variants of concern. Deep-mutational scanning experiments identify the potential binding epitopes of the Nbs on the RBD and demonstrate that biparatopic Nb1–Nb2 has a strong escape-resistant feature against more than 60 tested RBD amino acid substitutions. Using pseudovirion-based and trans-complementation SARS-CoV-2 tools, we determine that the Nb1–Nb2 broadly neutralizes multiple SARS-CoV-2 variants at sub-nanomolar levels, including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2), Lambda (C.37), Kappa (B.1.617.1), and Mu (B.1.621). Furthermore, a heavy-chain antibody is constructed by fusing the human IgG1 Fc to Nb1–Nb2 (designated as Nb1–Nb2-Fc) to improve its neutralization potency, yield, stability, and potential half-life extension. For the new Omicron variant (B.1.1.529) that harbors unprecedented multiple RBD mutations, Nb1–Nb2-Fc keeps a firm affinity (KD < 1.0 × 10 −12 M) and strong neutralizing activity (IC 50 = 1.46 nM for authentic Omicron virus). Together, we developed a tetravalent biparatopic human heavy-chain antibody with ultrapotent and broad-spectrum SARS-CoV-2 neutralization activity which highlights the potential clinical applications.

الإتاحة: https://doi.org/10.1038/s41392-022-00912-4Test
https://www.nature.com/articles/s41392-022-00912-4.pdfTest
https://www.nature.com/articles/s41392-022-00912-4Test

المؤلفون: Lin, Tianli, Chi, Xiaojing, Liu, Xiuying, Pan, Shengnan, Chen, Wenfang, Duan, Huarui, Zhang, Xinhui, Yang, Wei

المصدر: Frontiers in Immunology ; volume 13 ; ISSN 1664-3224

مصطلحات موضوعية: Immunology, Immunology and Allergy

الوصف: An effective prophylactic vaccine would be beneficial for controlling and eradicating hepatitis C virus (HCV) infections. However, the high diversity across HCV genotypes is a major challenge for vaccine development. Selection of the appropriate immunogen is critical to elicit broad HCV neutralizing antibodies (NAbs). To increase the antigenic coverage of heterodimer glycoproteins, we designed and produced recombinant E1E2 antigens for genotypes 1a/1b/2a/3a/6a from an IgG Fc-tagged precursor protein in FreeStyle 293-F cells. The recombinant E1 and E2 antigens were localized and associated with the endoplasmic reticulum and co-purified from membrane extracts. By examining the interactions with HCV entry co-receptors and the blockade of HCV infection, we found that these purified Fc-E1E2 proteins displayed correct folding and function. Mouse immunization results showed that each recombinant E1E2 antigen could elicit a pangenotypic antibody response to itself and other genotypes. We also found that the pentavalent formula triggered a relatively higher and more uniform NAb titer and T cell response than monovalent antigens. Taken together, our findings may provide a useful strategy for the vaccine development of HCV and other viruses with highly heterogeneous surface glycoproteins.

الإتاحة: https://doi.org/10.3389/fimmu.2022.831285Test

المؤلفون: Chi, Xiaojing, Liu, Xiuying, Wang, Conghui, Zhang, Xinhui, Li, Xiang, Hou, Jianhua, Ren, Lili, Jin, Qi, Wang, Jianwei, Yang, Wei

المصدر: reponame:Expeditio Repositorio Institucional UJTL ; instname:Universidad de Bogotá Jorge Tadeo Lozano

مصطلحات موضوعية: SARS-CoV-2, Domain antibodies, Síndrome respiratorio agudo grave, COVID-19, Coronavirus

الوصف: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads worldwide and leads to an unprecedented medical burden and lives lost. Neutralizing antibodies provide efficient blockade for viral infection and are a promising category of biological therapies. Here, using SARS-CoV-2 spike receptor-binding domain (RBD) as a bait, we generate a panel of humanized single domain antibodies (sdAbs) from a synthetic library. These sdAbs reveal binding kinetics with the equilibrium dissociation constant (KD) of 0.99–35.5 nM. The monomeric sdAbs show half maximal neutralization concentration (EC50) of 0.0009–0.07 µg/mL and 0.13–0.51 µg/mL against SARS-CoV-2 pseudotypes, and authentic SARS-CoV-2, respectively. Competitive ligand-binding experiments suggest that the sdAbs either completely block or significantly inhibit the association between SARS-CoV-2 RBD and viral entry receptor ACE2. Fusion of the human IgG1 Fc to sdAbs improve their neutralization activity by up to ten times. These results support neutralizing sdAbs as a potential alternative for antiviral therapies.

وصف الملف: 7 páginas; application/pdf

العلاقة: https://doi.org/10.1038/s41467-020-18387-8Test; http://hdl.handle.net/20.500.12010/13397Test

الإتاحة: https://doi.org/20.500.12010/13397Test
https://doi.org/10.1038/s41467-020-18387-8Test
https://hdl.handle.net/20.500.12010/13397Test

المؤلفون: Yang, Xuehua, Duan, Huarui, Liu, Xiuying, Zhang, Xinhui, Pan, Shengnan, Zhang, Fangyuan, Gao, Peixiang, Liu, Bo, Yang, Jian, Chi, Xiaojing, Yang, Wei

المساهمون: Subbarao, Kanta, CAMS Innovation Fund for Medical Sciences, MOST | National Natural Science Foundation of China

المصدر: Journal of Virology ; volume 97, issue 7 ; ISSN 0022-538X 1098-5514

الوصف: The subgenus Sarbecovirus includes human SARS-CoV, SARS-CoV-2, and hundreds of genetically related bat viruses. The continuous evolution of SARS-CoV-2 has led to the striking evasion of neutralizing antibody (NAb) drugs and convalescent plasma.

الإتاحة: https://doi.org/10.1128/jvi.00610-23Test

المؤلفون: Fan, Jingjing, Cheng, Min, Chi, Xiaojing, Liu, Xiuying, Yang, Wei

المساهمون: National Natural Science Foundation of China, National Basic Research Program of China (973 Program)

المصدر: Frontiers in Immunology ; volume 10 ; ISSN 1664-3224

الإتاحة: https://doi.org/10.3389/fimmu.2019.01711Test

المؤلفون: Xu, Hua, Cheng, Min, Chi, Xiaojing, Liu, Xiuying, Zhou, Jia, Lin, Tianli, Yang, Wei

المساهمون: Heise, Mark T., CAMS Initiative for Innovative Medicine, National Basic Research Program of China, National Science and Technology Major Project, National Natural Science Foundation of China

المصدر: Journal of Virology ; volume 93, issue 18 ; ISSN 0022-538X 1098-5514

الوصف: Zika fever, an infectious disease caused by the Zika virus (ZIKV), normally results in mild symptoms. Severe infection can cause Guillain-Barré syndrome in adults and birth defects, including microcephaly, in newborns. Although ZIKV was first identified in Uganda in 1947 in rhesus monkeys, a widespread epidemic of ZIKV infection in South and Central America in 2015 and 2016 raised major concerns. To date, there is no vaccine or specific medicine for ZIKV. The significance of our research is the systematic discovery of small molecule candidates that modulate ZIKV infection, which will allow the development of antiviral therapeutics. In addition, we identified MLK3, a key mediator of host signaling pathways that can be activated during ZIKV infection and limits virus replication by inducing multiple inflammatory cytokines. These findings broaden our understanding of ZIKV pathogenesis.

الإتاحة: https://doi.org/10.1128/jvi.00758-19Test

المؤلفون: Zhou, Jia, Chi, Xiaojing, Cheng, Min, Huang, Xingyao, Liu, Xiuying, Fan, Jingjing, Xu, Hua, Lin, Tianli, Shi, Lei, Qin, Chengfeng, Yang, Wei

المساهمون: National Science and Technology Major Project, National Natural Science Foundation of China grants, CAMS Initiative for Innovative Medicine Grant, National Basic Research Program of China Grant

المصدر: Science Advances ; volume 5, issue 10 ; ISSN 2375-2548

الوصف: Both the endothelial transporter Mfsd2a and docosahexaenoic acid uptake are disrupted in Zika virus–induced microcephaly models.

الإتاحة: https://doi.org/10.1126/sciadv.aax7142Test

المؤلفون: Cheng, Min, Niu, Yuqiang, Fan, Jingjing, Chi, Xiaojing, Liu, Xiuying, Yang, Wei

المساهمون: Ministry of Science and Technology of the People's Republic of China (MOST), Chinese Academy of Medical Sciences (CAMS), National Natural Science Foundation of China (NSFC)

المصدر: Journal of Biological Chemistry ; volume 293, issue 16, page 5975-5986 ; ISSN 0021-9258

مصطلحات موضوعية: Cell Biology, Molecular Biology, Biochemistry

الإتاحة: https://doi.org/10.1074/jbc.ra117.000738Test
https://api.elsevier.com/content/article/PII:S0021925820409482?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0021925820409482?httpAccept=text/plainTest

المؤلفون: Chi, Xiaojing, Zhao, Xia, Wang, Wei, Niu, Yuqiang, Cheng, Min, Liu, Xiuying, Cui, Sheng, Yang, Wei

المساهمون: Wang, Tony T., National Basic Research Program of China, National Natural Science Foundation of China (CN), National Natural Science Foundation of China, CAMS Initiative for Innovative Medicine

المصدر: PLOS ONE ; volume 12, issue 4, page e0175516 ; ISSN 1932-6203

الإتاحة: https://doi.org/10.1371/journal.pone.0175516Test