Elevated EPSTI1 promote B cell hyperactivation through NF-κB signalling in patients with primary Sjögren's syndrome.

BACKGROUND: Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease characterised by aberrant B cell hyperactivation, whose mechanism is partially understood. METHODS: We performed whole transcriptome sequencing of B cells from three pSS patients and three matched healthy controls (HC). Differentially expression genes (DEGs) were confirmed with B cells from 40 pSS patients and 40 HC by quantitative PCR and western blot. We measured the proliferation potential and immunoglobulins production of siRNA-transfected or plasmid-transfected B cells stimulated with cytosine-phosphate-guanine (CpG) or anti-IgM. We also explored Toll-like receptor 9 (TLR9) signalling to reveal the potential mechanism of B cell hyperactivation in pSS. RESULTS: We identified 77 upregulated and 32 downregulated DEGs in pSS B cells. We confirmed that epithelial stromal interaction (EPST1) expression in pSS B cells was significantly higher than that from HCs. EPSTI1-silencing B cells stimulated with CpG were less proliferated and produced lower level of IgG and IgM comparing with control B cells. EPSTI1-silencing B cells expressed lower level of p-p65 and higher level of IκBα, and B cells with overexpressed EPSTI1 showed higher level of p-p65 and lower level of IκBα. Finally, IκBα degradation inhibitor Dehydrocostus Lactone treatment attenuated p65 phosphorylation promoted by EPSTI1. CONCLUSION: Elevated EPSTI1 expression in pSS B cells promoted TLR9 signalling activation and contributed to the abnormal B cell activation, which was promoted by facilitating p65 phosphorylation and activation of NF-κB signalling via promoting IκBα degradation. EPSTI1 might be implicated in pSS pathogenesis and was a potential therapeutic target of pSS.

Electrolytes for Multivalent Metal-Ion Batteries: Current Status and Future Prospect.

Electrochemical energy storage has experienced unprecedented advancements in recent years and extensive discussions and reviews on the progress of multivalent metal-ion batteries have been made mainly from the aspect of electrode materials, but relatively little work comprehensively discusses and provides an outlook on the development of electrolytes in these systems. Under this circumstance, this Review will initially introduce different types of electrolytes in current multivalent metal-ion batteries and explain the basic ion conduction mechanisms, preparation methods, and pros and cons. On this basis, we will discuss in detail the research and development of electrolytes for multivalent metal-ion batteries in recent years, and finally, critical challenges and prospects for the application of electrolytes in multivalent metal-ion batteries will be put forward.

Clinical Profile and Significance of Mucocutaneous Lesions of Primary Sjögren's Syndrome: A Large Cross-sectional Study with 874 Patients.

BACKGROUND: Mucocutaneous lesions are common features of primary Sjögren's syndrome (pSS), but only a few studies have focused on them. To demonstrate the profile of mucocutaneous lesions of pSS and further explore their potential clinical significance, we performed a cross-sectional study on 874 patients. METHODS: Demographic data, clinical manifestations, and laboratory results of 874 pSS patients were collected. Patients were divided into two groups according to the presence of mucocutaneous lesions. Differences in primary symptoms and systemic impairments between the two groups were analyzed. Results of laboratory tests were also compared after excluding those who had taken corticosteroid from both groups. One-year follow-up was done, and occurrences of various new complications were compared. RESULTS: Among the 874 pSS patients, 181 patients had mucocutaneous lesions, accounting for 20.7%. Multiple mucocutaneous manifestations were displayed, and the top four most common types of lesions were purpuric eruptions (39.8%), urticaria (23.8%), Raynaud's phenomenon (14.9%), and angular stomatitis (9.9%). Incidences of pulmonary interstitial fibrosis, pulmonary bullae, leukopenia, and anemia were significantly higher among patients with mucocutaneous lesions (P < 0.05). Increase in IgG and decrease in C4 among patients with mucocutaneous lesions displayed statistical significance after excluding patients from both groups who had taken corticosteroid (P < 0.05). After one-year follow-up, patients with mucocutaneous lesions presented a slightly higher incidence of new complications compared to those without. CONCLUSIONS: Mucocutaneous manifestations of pSS patients were common and diverse. Patients with mucocutaneous manifestations had more systemic damages, higher level of IgG, and lower level of serum C4, suggesting a higher activity of the primary disease.