Xiaoyu Li

Objective: Explore the influence of fear of COVID-19 on depression, with anxiety as a mediator and perceived social support and stress perception as moderates.Methods: From February to March 2020, 1,196 valid data were collected online through questionnaire by cluster sampling method. Fear of COVID-19 Questionnaire, the Patient Health Questionnaire 9-Item Scale (PHQ-9), the Generalized Anxiety Disorder 7-Item Scale (GAD-7), the Perceived Social Support Scale (PSSS) and the10-item Perceived Stress Scale (PSS-10) were used as the survey instrument, and the participants were female undergraduates from a liberal arts college of a Chinese university. Common method bias was assessed using Harman’s single-factor test in SPSS and confirmatory factor analysis in AMOS. The levels of participants’ anxiety, depression and perceived social support were described using frequency and percentage, Pearson Correlation test was used to measure the correlation between the variables. The PROCESS macro for SPSS (Model 1, Model 4, and Model 21) were applied to examine the mediating effect and moderating effect of the model.Results: Fear of COVID-19 can positively influence depression, anxiety plays a mediating role between fear of COVID-19 and depression, perceived social support negatively moderates the relationship between fear of COVID-19 and anxiety, and stress perception positively moderates the relationship between anxiety and depression. These five variables can form a moderated mediating effect model.Conclusion: Fear of COVID-19, anxiety and stress perception are risk factors for depression, perceived social support is a protective factor for depression. Reducing the fear of COVID-19, anxiety and stress perception and enhancing perceived social support are beneficial to reduce the level of depression.

Pyroptosis is a form of cell death mediated by inflammasomes and gasdermins, and the relevance of pyroptosis to neurodegenerative diseases is currently receiving increasing attention. Alzheimer’s disease (AD) is a chronic progressive neurodegenerative disease that is closely associated with neuroinflammation. Its main pathological features include β-amyloid (Aβ) deposition, Tau protein hyperphosphorylation and neuronal loss. Aβ, tau-induced microglia pyroptosis and polarization leading to neuroinflammation play an important role in the pathogenesis of AD. Studying the pathogenesis and treatment of AD based on cellular pyroptosis has become a new direction in AD research. In this paper, we review the research progress of pyroptosis and will focus on the pathogenic roles of pyroptosis in AD and the role of targeted inhibition of inflammasome-dependent pyroptosis in AD treatment. These results deepen our understanding of the pathogenesis of AD and provide ideas for the development of new drugs based on the regulation of pyroptosis in AD patients.

Teleost tetramer IgM is the predominant Ig in the immune system and plays essential roles in host defense against microbial infection. Due to variable disulfide polymerization of the monomeric subunits, tetrameric IgM possesses considerable structural diversity. Previous work indicated that the teleost IgM H chain was fully occupied with complex-type N-glycans. However, after challenge with trinitrophenyl (TNP) Ag, the complex N-glycans in the Asn-509 site of Oreochromis niloticus IgM H chain transformed into high mannose. This study, therefore, was conducted to examine the functional roles of the affinity-related high-mannose modification in tilapia IgM. The TNP-specific IgM Ab affinity maturation was revealed in tilapia over the response. A positive correlation between TNP-specific IgM affinity and its disulfide polymerization level of isomeric structure was demonstrated. Mass spectrometric analysis indicated that the relationship between IgM affinity and disulfide polymerization was associated with the Asn-509 site-specific highmannose modification. Furthermore, the increase of high mannose content promoted the combination of IgM and mannose receptor (MR) on the surface of phagocytes. Moreover, the increased interaction of IgM and MR amplified the phagocytic ability of phagocytes to Streptococcus agalactiae. To our knowledge, this study demonstrates that site-specific high-mannose modification associates with IgM Ab affinity and its structural disulfide polymerization and amplifies the phagocytosis of phagocytes by the combination of IgM and MR. The present study provides evidence for understanding the association of IgM structure and function during the evolution of the immune system.

Glycan modification prompts important concerns about the quality control of biopharmaceutical production. Conbercept is a multi-glycosylated recombinant fusion protein drug approved for the treatment of age-related macular degeneration (AMD). With 14 N-glycosites in the molecule and 7 N-glycosites in the monomer, the charge isomer separation and characterization of conbercept pose great challenges due to its enormous heterogeneities. The batch-to-batch stability on the charge isomer distribution and the possible causation of the pattern necessitate the development of effective analytical approaches. Here, the immobilized pH gradient (IPG)-based two-dimensional gel electrophoresis (2-DE) approach was first optimized to achieve high-resolution, high-reproducible separation and preparation of charge isomers. Then, combined with the quantitative analysis strategy of site-specific N-glycan heterogeneity based on the diagnostic MS2 ion (peptides+GlcNAc, Y1 ions) of glycopeptides, an integrated approach for the quantitation of site-specific N-glycan heterogeneities among charge isomers was established. Finally, the quantitation of site-specific N-glycoforms in each of the 2-DE resolved spots were performed, and the results showed that the sialylaion tends to increase for gel spots located in the acidic regions. This study provides an effective approach to separate the charge isomers of the heavily glycosylated protein drugs, and to quantitatively explore the site-specific N-glycans dynamics along with the different charge isomers.