ABSTRACT
Posttranslational modifications of antibody products affect their stability,charge distribution,and drug activity and are thus a critical quality attribute.The comprehensive mapping of antibody modifications and different charge isomers(CIs)is of utmost importance,but is challenging.We intended to quanti-tatively characterize the posttranslational modification status of CIs of antibody drugs and explore the impact of posttranslational modifications on charge heterogeneity.The CIs of antibodies were fraction-ated by strong cation exchange chromatography and verified by capillary isoelectric focusing-whole column imaging detection,followed by stepwise structural characterization at three levels.First,the differences between CIs were explored at the intact protein level using a top-down mass spectrometry approach;this showed differences in glycoforms and deamidation status.Second,at the peptide level,common modifications of oxidation,deamidation,and glycosylation were identified.Peptide mapping showed nonuniform deamidation and glycoform distribution among CIs.In total,10 N-glycoforms were detected by peptide mapping.Finally,an in-depth analysis of glycan variants of CIs was performed through the detection of enriched glycopeptides.Qualitative and quantitative analyses demonstrated the dynamics of 24 N-glycoforms.The results revealed that sialic acid modification is a critical factor ac-counting for charge heterogeneity,which is otherwise missed in peptide mapping and intact molecular weight analyses.This study demonstrated the importance of the comprehensive analyses of antibody CIs and provides a reference method for the quality control of biopharmaceutical analysis.
ABSTRACT
Objective To explore the relationship among life meaning,spiritual health and life practice of college students.Methods Sense of Life Meaning Scale,Spiritual Health Scale and Life Practice Scale were applied to 708 college students.Results Life meaning was positively correlated with spiritual health and life practice,and spiritual health was positively correlated with life practice (r =0.51-0.79,P＜0.01).Spiritual health played fully mediating role between life meaning and life practice (x2=287.27,df=24,GFl=0.91,RMSEA=0.12),and accounted for 87％ of the mediating role.Conclusion Spiritual health serves as a mediator in the effect of life meaning on spiritual health in college students.