The rapid growth of the global HIV/AIDS epidemic makes it a high priority to develop an effective vaccine.Since a live attenuated or inactivated HIV vaccine is not likely to be approved for clinical application due to...The rapid growth of the global HIV/AIDS epidemic makes it a high priority to develop an effective vaccine.Since a live attenuated or inactivated HIV vaccine is not likely to be approved for clinical application due to safety concerns,HIV virus like particles(VLPs) offer an attractive alternative because they are considered safer since they lack viral genome.We got a stable eukaryotic cell line by G418 resistance selection,engineered to express the HIV-1 structure protein Gag and Env efficiently and stably.We confirmed the presence of Gag and Env proteins in the cell culture supernatant and that they could self-assemble into VLPs.These VLPs were found to be able to elicit specific humoral and cellular immune response after immunization without any adjuvant.展开更多
Located at the carboxyl terminal of the human papillomavirus major capsid protein L1, helix-5（h5） is cru-cial to L1 folding and pentamer formation. Site-directed mutagenesis of the leucine residue on site 469 into l...Located at the carboxyl terminal of the human papillomavirus major capsid protein L1, helix-5（h5） is cru-cial to L1 folding and pentamer formation. Site-directed mutagenesis of the leucine residue on site 469 into lysine, alanine, serine and glycine was performed to explore the effect of the resultant mutations on L 1 pentamer formation. The soluble yields of the L1 pentamers of the L469A and L469K mutants were nearly two fold higher than that of the wild type. Molecular dynamics simulation was then performed to reveal the intrinsic mechanisms involved in the improvement of L 1 pentamer yield. Accordingly, the secondary structures of h5, β-G2, β-B1, β-C, β-D, and β-F were altered. The altered structures improved the hydrophobic interaction between h5 and fl-core ＂jelly＂ and the stability of h5. The hydrophobic surface area of residue 469 was reduced by 50% relative to that of the wild type. The C--O group of residue 469 and C--N group of L470 were both exposed to the solvent in the L469A mutant. These modifications may account for the increased solubility and stability and the promotion of pentamer formation induced by the point mutation. Therefore, the changes in the hydrophobic properties of h5 and the core structure determined the pentamer formation and solubility. This study may assist the development of a cost-effective platform for the production of prophylactic virus-like particle vaccines.展开更多
PtCo nanoalloys(NAs)deposited on carbon black are emerging as robust electrocatalysts for addressing the sluggish kinetic issue of oxygen reduction reaction(ORR).However,developing a simple and low-cost method to synt...PtCo nanoalloys(NAs)deposited on carbon black are emerging as robust electrocatalysts for addressing the sluggish kinetic issue of oxygen reduction reaction(ORR).However,developing a simple and low-cost method to synthesize PtCo/C with excellent performance is still a great challenge.In this work,a one-pot method was used to successfully obtain the PtCo NAs on commercial carbon supports of acetylene black and Ketjenblack ECP600JD,respectively.Compared with those grown on Ketjenblack ECP600JD,the PtCo NAs grown on acetylene black exhibited higher electrochemical surface area(ECSA)and mass activity(MA),which may be attributed to the different particle sizes of PtCo NAs,distinct hydrophilicity,electroconductivity and charge distribution between the carbon supports and PtCo NAs.Our study provides valuable insights into the optimal design of carbon-supported ORR electrocatalysts with exceptional activity and durability.展开更多
基金supported by the Na-tional Natural Science Foundation of China (Grant No. 30371317) to Kong Wei
文摘The rapid growth of the global HIV/AIDS epidemic makes it a high priority to develop an effective vaccine.Since a live attenuated or inactivated HIV vaccine is not likely to be approved for clinical application due to safety concerns,HIV virus like particles(VLPs) offer an attractive alternative because they are considered safer since they lack viral genome.We got a stable eukaryotic cell line by G418 resistance selection,engineered to express the HIV-1 structure protein Gag and Env efficiently and stably.We confirmed the presence of Gag and Env proteins in the cell culture supernatant and that they could self-assemble into VLPs.These VLPs were found to be able to elicit specific humoral and cellular immune response after immunization without any adjuvant.
基金Supported by the National Natural Science Foundation of China（Nos. 91027027, 21373101 ）.
文摘Located at the carboxyl terminal of the human papillomavirus major capsid protein L1, helix-5（h5） is cru-cial to L1 folding and pentamer formation. Site-directed mutagenesis of the leucine residue on site 469 into lysine, alanine, serine and glycine was performed to explore the effect of the resultant mutations on L 1 pentamer formation. The soluble yields of the L1 pentamers of the L469A and L469K mutants were nearly two fold higher than that of the wild type. Molecular dynamics simulation was then performed to reveal the intrinsic mechanisms involved in the improvement of L 1 pentamer yield. Accordingly, the secondary structures of h5, β-G2, β-B1, β-C, β-D, and β-F were altered. The altered structures improved the hydrophobic interaction between h5 and fl-core ＂jelly＂ and the stability of h5. The hydrophobic surface area of residue 469 was reduced by 50% relative to that of the wild type. The C--O group of residue 469 and C--N group of L470 were both exposed to the solvent in the L469A mutant. These modifications may account for the increased solubility and stability and the promotion of pentamer formation induced by the point mutation. Therefore, the changes in the hydrophobic properties of h5 and the core structure determined the pentamer formation and solubility. This study may assist the development of a cost-effective platform for the production of prophylactic virus-like particle vaccines.
基金supported by National Natural Science Foundation of China(No.22102086)the Shandong Provincial Natural Science Fund for Excellent Young Scientists Fund Program(Overseas),China(No.2023HWYQ-059)+5 种基金the Shandong Provincial Natural Science Foundation,China(No.ZR2022MB028)the Major Fundamental Research Project of Shandong Natural Science Fund,China(No.ZR2023ZD54)the Taishan Scholar Program of Shandong Province,China(No.tsqnz20221113)the Fundamental Research Funds for the Central Universities,China(Nos.862201013152,202412008)the Youth Innovation Plan of Shandong Province,China(No.2022KJ054)the Alexander von Humboldt Foundation.
文摘PtCo nanoalloys(NAs)deposited on carbon black are emerging as robust electrocatalysts for addressing the sluggish kinetic issue of oxygen reduction reaction(ORR).However,developing a simple and low-cost method to synthesize PtCo/C with excellent performance is still a great challenge.In this work,a one-pot method was used to successfully obtain the PtCo NAs on commercial carbon supports of acetylene black and Ketjenblack ECP600JD,respectively.Compared with those grown on Ketjenblack ECP600JD,the PtCo NAs grown on acetylene black exhibited higher electrochemical surface area(ECSA)and mass activity(MA),which may be attributed to the different particle sizes of PtCo NAs,distinct hydrophilicity,electroconductivity and charge distribution between the carbon supports and PtCo NAs.Our study provides valuable insights into the optimal design of carbon-supported ORR electrocatalysts with exceptional activity and durability.
