Thimerosal has been widely used as a preservative in drug and vaccine products for decades.Due to the strong propensity to modify thiols in proteins,conformational changes could occur due to covalent bond formation be...Thimerosal has been widely used as a preservative in drug and vaccine products for decades.Due to the strong propensity to modify thiols in proteins,conformational changes could occur due to covalent bond formation between ethylmercury(a degradant of thimerosal)and thiols.Such a conformational change could lead to partial or even complete loss of desirable protein function.This study aims to investigate the effects of thimerosal on the capsid stability and antigenicity of recombinant human papillomavirus(HPV)18 virus-like particles(VLPs).Dramatic destabilization of the recombinant viral capsid upon thimerosal treatment was observed.Such a negative effect on the thermal stability of VLPs preserved with thimerosal was shown to be dependent on the thimerosal concentration.Two highly neutralizing antibodies,13H12 and 3C3,were found to be the most sensitive to thimerosal treatment.The kinetics of antigenicity loss,when monitored with 13H12 or 3C3 as probes,yielded two distinctly different sets of kinetic parameters,while the data from both monoclonal antibodies(mAbs)followed a biphasic exponential decay model.The potential effect of thimerosal on protein function,particularly for thiolcontaining proteinaceous active components,needs to be comprehensively characterized during formulation development when a preservative is necessary.展开更多
M_(3)A_(2)X phases,named 321 phases,are an atypical series of MAX phases featuring in the MA-triangular-prism bilayers,with the A=As/P,exhibiting excellent elastic properties.This work systematically studies the therm...M_(3)A_(2)X phases,named 321 phases,are an atypical series of MAX phases featuring in the MA-triangular-prism bilayers,with the A=As/P,exhibiting excellent elastic properties.This work systematically studies the thermal expansion properties of 321 phases.We found their average linear thermal expansion coefficients(TECs),α_(L)=5-6μK^(–1),are the lowest among the reported values of MAX phases.The lowest average TEC was found in Nb_(3)As_(2)C(αa=4.46(4)μK^(–1),αc=5.09(4)μK–1,αL=5.09(4)μK–1).The average TEC and anisotropy factor(αc/αa)of Nb_(3)As_(2)C and Nb_(3)P_(2)C were lower than the ones of the corresponding 211 phases.The best isotropy performance was found in Nb_(3)P_(2)C (αc/αa=1.11).Moreover,our first-principles calculations demonstrate that the weaker chemical bonding between Nb-As/P than Nb-C induces thermal expansion in M_(3)A_(2)X phases.Furthermore,a relatively weaker anharmonic effect in 321 phases than in the 211 phases was revealed by the as-calculated average Grüneisen parameters,which account for the lower TECs in 321 phases.The low TECs and enhanced thermal isotropy make 321 phases outstanding among MAX phases,which could be sound candidates for varying-temperature structural-functional components.展开更多
基金Thisworkwas funded by the National Natural Science Foundation of China(Grant Nos.:81993149041,and U1705283)the National Science and Technology Major Project,China(Project No.:2018ZX09303005-002)+1 种基金Fujian Health Education Joint Research Project,China(Project No.:2019-WJ-05)Xiamen Science and Technology Major Project,China(Project No.:3502Z20193009).
文摘Thimerosal has been widely used as a preservative in drug and vaccine products for decades.Due to the strong propensity to modify thiols in proteins,conformational changes could occur due to covalent bond formation between ethylmercury(a degradant of thimerosal)and thiols.Such a conformational change could lead to partial or even complete loss of desirable protein function.This study aims to investigate the effects of thimerosal on the capsid stability and antigenicity of recombinant human papillomavirus(HPV)18 virus-like particles(VLPs).Dramatic destabilization of the recombinant viral capsid upon thimerosal treatment was observed.Such a negative effect on the thermal stability of VLPs preserved with thimerosal was shown to be dependent on the thimerosal concentration.Two highly neutralizing antibodies,13H12 and 3C3,were found to be the most sensitive to thimerosal treatment.The kinetics of antigenicity loss,when monitored with 13H12 or 3C3 as probes,yielded two distinctly different sets of kinetic parameters,while the data from both monoclonal antibodies(mAbs)followed a biphasic exponential decay model.The potential effect of thimerosal on protein function,particularly for thiolcontaining proteinaceous active components,needs to be comprehensively characterized during formulation development when a preservative is necessary.
基金financially supported by the National Science Foundation for Young Scientists of China(No.51902055)the Natural Science Foundation of Fujian Province(No.2021J011077)the Fuzhou Science and Technology Plan Project(No.2021-P-049).
文摘M_(3)A_(2)X phases,named 321 phases,are an atypical series of MAX phases featuring in the MA-triangular-prism bilayers,with the A=As/P,exhibiting excellent elastic properties.This work systematically studies the thermal expansion properties of 321 phases.We found their average linear thermal expansion coefficients(TECs),α_(L)=5-6μK^(–1),are the lowest among the reported values of MAX phases.The lowest average TEC was found in Nb_(3)As_(2)C(αa=4.46(4)μK^(–1),αc=5.09(4)μK–1,αL=5.09(4)μK–1).The average TEC and anisotropy factor(αc/αa)of Nb_(3)As_(2)C and Nb_(3)P_(2)C were lower than the ones of the corresponding 211 phases.The best isotropy performance was found in Nb_(3)P_(2)C (αc/αa=1.11).Moreover,our first-principles calculations demonstrate that the weaker chemical bonding between Nb-As/P than Nb-C induces thermal expansion in M_(3)A_(2)X phases.Furthermore,a relatively weaker anharmonic effect in 321 phases than in the 211 phases was revealed by the as-calculated average Grüneisen parameters,which account for the lower TECs in 321 phases.The low TECs and enhanced thermal isotropy make 321 phases outstanding among MAX phases,which could be sound candidates for varying-temperature structural-functional components.
