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  • 1
    Publication Date: 2018-10-23
    Description: Genome-wide association studies have recently illuminated that WDFY4 is genetically associated with systemic lupus erythematosus (SLE) susceptibility in various ethnic groups. Despite strong genetic evidence suggesting a role of WDFY4 in SLE pathogenesis, its functional relevance is largely unknown. In this study, we generated Wdfy4 B lymphocyte conditional knockout ( Wdfy4 -CKO) mice and found that loss of Wdfy4 led to a decrease in number of total B cells and several subpopulations of B cells in the periphery and a defect in the transition from the pro– to pre–B cell stage in bone marrow. Also, Wdfy4 -CKO mice showed impaired Ab responses as compared with controls when challenged with Ag. SLE phenotypes were effectively alleviated in Wdfy4 -CKO mice, with significantly diminished pristane-elicited production of autoantibodies and glomerulonephritis. Genetic silencing of WDFY4 in B cells increased lipidation of LC3 independent of p62 and Beclin1, which are essential proteins of canonical autophagy. Our in vivo and in vitro data suggest that WDFY4 facilitates noncanonical autophagic activity. Our findings provide a novel functional link underlying the mechanism of SLE in which WDFY4 influences B cell fate via noncanonical autophagy.
    Print ISSN: 0022-1767
    Electronic ISSN: 1550-6606
    Topics: Medicine
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  • 2
    Publication Date: 2018-04-14
    Description: Objectives There are few data on the relationship between health-related quality of life (HRQoL) and physical activity among elderly individuals with pre-diabetes. This study aimed to determine if differences existed in HRQoL between individuals with pre-diabetes who were physically active compared with those who were physically inactive in rural China. Design, setting and participants A cross-sectional survey was conducted among the elderly (greater double equals60 years) in rural communities in Yiyang City of China. Multistage cluster random sampling was carried out to select 42 areas, and interviews were conducted among 434 elderly individuals with pre-diabetes. Pre-diabetes was screened using an oral glucose tolerance test. Main outcome measures The Medical Outcomes Study 36-Item Short Form Health Survey questionnaire was used to measure HRQoL. Physical activity was assessed using the International Physical Activity Questionnaire. Multivariate analysis of covariance (MANCOVA) was used to test for differences in HRQoL between the physically active group and the inactive group. Results A total of 434 individuals with pre-diabetes were included in this study. The physical component summary (PCS) score of HRQoL was 42.1±10.2 and the mental component summary score was 46.4±8.9. A median total physical activity of 524 metabolic equivalent-min/week was reported. A significant MANCOVA model (Wilks’ =0.962, F (2,423)=8.44, P〈0.001) indicated that elderly individuals with pre-diabetes who were physically active reported higher PCS scores (M diff =5.2, P〈0.001, effective size=0.47) compared with those physically inactive after adjusting for the following covariates: age, gender, marital status, education, smoking, chronic disease, body mass index and waist:hip ratio. Conclusions The HRQoL of elderly individuals with pre-diabetes is poor in rural China. These findings demonstrated that elderly individuals with pre-diabetes who were physically active had higher PCS scores than those who were physically inactive. Furthermore, these results support the rationale for developing a physical activity intervention for HRQoL of individuals with pre-diabetes. Trial registration number ChiCTR-IOR-15007033; Results.
    Keywords: Open access, Public health
    Electronic ISSN: 2044-6055
    Topics: Medicine
    Published by BMJ Publishing
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