According to the development trend in China＇ s radio and television industry, the requirements of the media for broadcasters and hosts are totally different from before, and they differ from each other. Good appearan...According to the development trend in China＇ s radio and television industry, the requirements of the media for broadcasters and hosts are totally different from before, and they differ from each other. Good appearance, elegant temperament and pleasant voice are no longer the sole criteria for being employed. This paper analyzes the problems with the education of broadcasting and hosting majors in China＇ s universities and proposes strategies and suggestions on this, so as to offer a guideline for its future development.展开更多
Previous studies through targeted mutagenesis of K-D-K-E motif have demonstrated that 2′-O-MTase activity is essential for efficient viral replication and immune evasion.However,the K-D-K-E catalytic motif of 2′-O-M...Previous studies through targeted mutagenesis of K-D-K-E motif have demonstrated that 2′-O-MTase activity is essential for efficient viral replication and immune evasion.However,the K-D-K-E catalytic motif of 2′-O-MTase is highly conserved across numerous viruses,including flaviviruses,vaccinia viruses,coronaviruses,and extends even to mammals.Here,we observed a stronger 2′-O-MTase activity in SARS-CoV-2 compared to SARS-CoV,despite the presence of a consistently active catalytic center.We further identified critical residues(Leu-36,Asn-138 and Ile-153)which served as determinants of discrepancy in 2′-O-MTase activity between SARS-CoV-2 and SARS-CoV.These residues significantly enhanced the RNA binding affinity of 2′-O-MTase and boosted its versatility toward RNA substrates.Of interest,a triple substitution(Leu^(36)→Ile^(36),Asn^(138)→His^(138),Ile^(153)→Leu^(153),from SARS-CoV-2 to SARS-CoV)within nsp16 resulted in a proportional reduction in viral 2′-O-methylation and impaired viral replication.Furthermore,it led to a significant upregulation of type I interferon(IFN-I)and proinflammatory cytokines both in vitro and vivo,relying on the cooperative sensing of melanoma differentiation-associated protein 5(MDA5)and laboratory of genetics and physiology 2(LGP2).In conclusion,our findings demonstrated that alterations in residues other than K-D-K-E of 2′-O-MTase may affect viral replication and subsequently influence pathogenesis.Monitoring changes in nsp16 residues is crucial as it may aid in identifying and assessing future alteration in viral pathogenicity resulting from natural mutations occurring in nsp16.展开更多
A unique feature of coronaviruses is their utilization of self-encoded nonstructural protein 16(nsp16),20-Omethyltransferase(20-O-MTase),to cap their RNAs through ribose 20-O-methylation modification.This process is c...A unique feature of coronaviruses is their utilization of self-encoded nonstructural protein 16(nsp16),20-Omethyltransferase(20-O-MTase),to cap their RNAs through ribose 20-O-methylation modification.This process is crucial for maintaining viral genome stability,facilitating efficient translation,and enabling immune escape.Despite considerable advances in the ultrastructure of SARS-CoV-2 nsp16/nsp10,insights into its molecular mechanism have so far been limited.In this study,we systematically characterized the 20-O-MTase activity of nsp16 in SARS-CoV-2,focusing on its dependence on nsp10 stimulation.We observed cross-reactivity between nsp16 and nsp10 in various coronaviruses due to a conserved interaction interface.However,a single residue substitution(K58T)in SARS-CoV-2 nsp10 restricted the functional activation of MERS-CoV nsp16.Furthermore,the cofactor nsp10 effectively enhanced the binding of nsp16 to the substrate RNA and the methyl donor Sadenosyl-L-methionine(SAM).Mechanistically,His-80,Lys-93,and Gly-94 of nsp10 interacted with Asp-102,Ser-105,and Asp-106 of nsp16,respectively,thereby effectively stabilizing the SAM binding pocket.Lys-43 of nsp10 interacted with Lys-38 and Gly-39 of nsp16 to dynamically regulate the RNA binding pocket and facilitate precise binding of RNA to the nsp16/nsp10 complex.By assessing the conformational epitopes of nsp16/nsp10 complex,we further determined the critical residues involved in 20-O-MTase activity.Additionally,we utilized an in vitro biochemical platform to screen potential inhibitors targeting 20-O-MTase activity.Overall,our results significantly enhance the understanding of viral 20-O methylation process and mechanism,providing valuable targets for antiviral drug development.展开更多
Nanoscale zerovalent iron/magnetic carbon(NZVI/MC) composites were successfully synthesized by simply calcining yellow pine and iron precursors. NZVI/MC pyrolyzed at 800°C(NZVI/MC800) had a higher percentage of N...Nanoscale zerovalent iron/magnetic carbon(NZVI/MC) composites were successfully synthesized by simply calcining yellow pine and iron precursors. NZVI/MC pyrolyzed at 800°C(NZVI/MC800) had a higher percentage of NZVI and displayed better resistance to aggregation and oxidation of NZVI than samples prepared at other temperatures. The NZVI/MC800 material was applied for the elimination of U(Ⅵ) from aqueous solutions. The results suggested that the NZVI/MC800 displayed excellent adsorption capacity(203.94 mg/g)toward U(Ⅵ). The significant adsorption capacity and fast adsorption kinetics were attributed to the presence of well-dispersed NZVI, which could quickly reduce U(Ⅵ) into U(Ⅳ), trapping the guest U(Ⅳ) in the porous biocarbon matrix. The removal of U(Ⅵ) on the NZVI/MC samples was strongly affected by solution pH. The NZVI/MC samples also displayed outstanding reusability for U(Ⅵ) removal after multiple cycles. These findings indicate that NZVI/MC has great potential for remediation of wastewater containing U(Ⅵ).展开更多
Mesenchymal stem cells(MSC)have been used in clinical trials for severe diabetes,a chronic disease with high morbidity and mortality.Bone marrow is the traditional source of human MSC,but human term placenta appears t...Mesenchymal stem cells(MSC)have been used in clinical trials for severe diabetes,a chronic disease with high morbidity and mortality.Bone marrow is the traditional source of human MSC,but human term placenta appears to be an alternative and more readily available source.Here,the therapeutic effect of human placenta-derived MSC(PD-MSC)was studied in type 2 diabetes patients with longer duration,islet cell dysfunction,high insulin doses as well as poor glycemic control in order to evaluate the safety,efficacy and feasibility of PD-MSC treatment in type 2 diabetes(T2D).Ten patients with T2D received three intravenous infusions of PDSC,with one month interval of infusion.The total number of PDSC for each patient was(1.22–1.51)×10^(6)/kg,with an average of 1.35×10^(6)/kg.All of the patients were followed up after therapy for at least 3 months.A daily mean dose of insulin used in 10 patients was decreased from 63.7±18.7 to 34.7±13.4 IU(P<0.01),and the C-peptide level was increased from 4.1±3.7 ng/mL to 5.6±3.8 ng/mL(P<0.05)respectively after therapy.In 4 of 10 responders their insulin doses reduced more than 50%after infusion.The mean levels of insulin and C-peptide at each time point in a total of 10 patients was higher after treatment(P<0.05).No fever,chills,liver damage and other side effects were reported.The renal function and cardiac function were improved after infusion.The results obtained from this pilot clinical trial indicate that transplantation of PD-MSC represents a simple,safe and effective therapeutic approach for T2D patients with islet cell dysfunction.Further large-scale,randomized and well-controlled clinical studies will be required to substantiate these observations.展开更多
文摘According to the development trend in China＇ s radio and television industry, the requirements of the media for broadcasters and hosts are totally different from before, and they differ from each other. Good appearance, elegant temperament and pleasant voice are no longer the sole criteria for being employed. This paper analyzes the problems with the education of broadcasting and hosting majors in China＇ s universities and proposes strategies and suggestions on this, so as to offer a guideline for its future development.
基金partially sponsored by contributions from the National Key R&D Program of China(2021YFA1300800)the China NSFC projects(82172243,82341061,and 82372223)the Fundamental Research Funds for Central Universities(2042023kf1028 and 2042022dx0003).
文摘Previous studies through targeted mutagenesis of K-D-K-E motif have demonstrated that 2′-O-MTase activity is essential for efficient viral replication and immune evasion.However,the K-D-K-E catalytic motif of 2′-O-MTase is highly conserved across numerous viruses,including flaviviruses,vaccinia viruses,coronaviruses,and extends even to mammals.Here,we observed a stronger 2′-O-MTase activity in SARS-CoV-2 compared to SARS-CoV,despite the presence of a consistently active catalytic center.We further identified critical residues(Leu-36,Asn-138 and Ile-153)which served as determinants of discrepancy in 2′-O-MTase activity between SARS-CoV-2 and SARS-CoV.These residues significantly enhanced the RNA binding affinity of 2′-O-MTase and boosted its versatility toward RNA substrates.Of interest,a triple substitution(Leu^(36)→Ile^(36),Asn^(138)→His^(138),Ile^(153)→Leu^(153),from SARS-CoV-2 to SARS-CoV)within nsp16 resulted in a proportional reduction in viral 2′-O-methylation and impaired viral replication.Furthermore,it led to a significant upregulation of type I interferon(IFN-I)and proinflammatory cytokines both in vitro and vivo,relying on the cooperative sensing of melanoma differentiation-associated protein 5(MDA5)and laboratory of genetics and physiology 2(LGP2).In conclusion,our findings demonstrated that alterations in residues other than K-D-K-E of 2′-O-MTase may affect viral replication and subsequently influence pathogenesis.Monitoring changes in nsp16 residues is crucial as it may aid in identifying and assessing future alteration in viral pathogenicity resulting from natural mutations occurring in nsp16.
基金supported by grants from the National Natural Science Foundation of China(82372223 and 82172243)the National Key R&D Program of China(2021YFF0702004)the Fundamental Research Funds for the Central Universities of China(2042022dx0003).
文摘A unique feature of coronaviruses is their utilization of self-encoded nonstructural protein 16(nsp16),20-Omethyltransferase(20-O-MTase),to cap their RNAs through ribose 20-O-methylation modification.This process is crucial for maintaining viral genome stability,facilitating efficient translation,and enabling immune escape.Despite considerable advances in the ultrastructure of SARS-CoV-2 nsp16/nsp10,insights into its molecular mechanism have so far been limited.In this study,we systematically characterized the 20-O-MTase activity of nsp16 in SARS-CoV-2,focusing on its dependence on nsp10 stimulation.We observed cross-reactivity between nsp16 and nsp10 in various coronaviruses due to a conserved interaction interface.However,a single residue substitution(K58T)in SARS-CoV-2 nsp10 restricted the functional activation of MERS-CoV nsp16.Furthermore,the cofactor nsp10 effectively enhanced the binding of nsp16 to the substrate RNA and the methyl donor Sadenosyl-L-methionine(SAM).Mechanistically,His-80,Lys-93,and Gly-94 of nsp10 interacted with Asp-102,Ser-105,and Asp-106 of nsp16,respectively,thereby effectively stabilizing the SAM binding pocket.Lys-43 of nsp10 interacted with Lys-38 and Gly-39 of nsp16 to dynamically regulate the RNA binding pocket and facilitate precise binding of RNA to the nsp16/nsp10 complex.By assessing the conformational epitopes of nsp16/nsp10 complex,we further determined the critical residues involved in 20-O-MTase activity.Additionally,we utilized an in vitro biochemical platform to screen potential inhibitors targeting 20-O-MTase activity.Overall,our results significantly enhance the understanding of viral 20-O methylation process and mechanism,providing valuable targets for antiviral drug development.
基金supported by the National Natural Science Foundation of China (No.21477133)the Key Lab of Photovoltaic and Energy Conservation Materials,Chinese Academy of Sciences is acknowledged
文摘Nanoscale zerovalent iron/magnetic carbon(NZVI/MC) composites were successfully synthesized by simply calcining yellow pine and iron precursors. NZVI/MC pyrolyzed at 800°C(NZVI/MC800) had a higher percentage of NZVI and displayed better resistance to aggregation and oxidation of NZVI than samples prepared at other temperatures. The NZVI/MC800 material was applied for the elimination of U(Ⅵ) from aqueous solutions. The results suggested that the NZVI/MC800 displayed excellent adsorption capacity(203.94 mg/g)toward U(Ⅵ). The significant adsorption capacity and fast adsorption kinetics were attributed to the presence of well-dispersed NZVI, which could quickly reduce U(Ⅵ) into U(Ⅳ), trapping the guest U(Ⅳ) in the porous biocarbon matrix. The removal of U(Ⅵ) on the NZVI/MC samples was strongly affected by solution pH. The NZVI/MC samples also displayed outstanding reusability for U(Ⅵ) removal after multiple cycles. These findings indicate that NZVI/MC has great potential for remediation of wastewater containing U(Ⅵ).
文摘Mesenchymal stem cells(MSC)have been used in clinical trials for severe diabetes,a chronic disease with high morbidity and mortality.Bone marrow is the traditional source of human MSC,but human term placenta appears to be an alternative and more readily available source.Here,the therapeutic effect of human placenta-derived MSC(PD-MSC)was studied in type 2 diabetes patients with longer duration,islet cell dysfunction,high insulin doses as well as poor glycemic control in order to evaluate the safety,efficacy and feasibility of PD-MSC treatment in type 2 diabetes(T2D).Ten patients with T2D received three intravenous infusions of PDSC,with one month interval of infusion.The total number of PDSC for each patient was(1.22–1.51)×10^(6)/kg,with an average of 1.35×10^(6)/kg.All of the patients were followed up after therapy for at least 3 months.A daily mean dose of insulin used in 10 patients was decreased from 63.7±18.7 to 34.7±13.4 IU(P<0.01),and the C-peptide level was increased from 4.1±3.7 ng/mL to 5.6±3.8 ng/mL(P<0.05)respectively after therapy.In 4 of 10 responders their insulin doses reduced more than 50%after infusion.The mean levels of insulin and C-peptide at each time point in a total of 10 patients was higher after treatment(P<0.05).No fever,chills,liver damage and other side effects were reported.The renal function and cardiac function were improved after infusion.The results obtained from this pilot clinical trial indicate that transplantation of PD-MSC represents a simple,safe and effective therapeutic approach for T2D patients with islet cell dysfunction.Further large-scale,randomized and well-controlled clinical studies will be required to substantiate these observations.
