Research on reconfigurable topology layered equalization method based on maximum capacity utilization.

To maximize the driving range of electric vehicles, battery imbalance is the primary factor that hinders the full utilization of battery pack capacity. This article is based on a four-switch reconfigurable topology, which can flexibly connect, bypass, and parallel any battery cell within the module, and can maintain low voltage fluctuations without the need for a DC-DC converter. Based on this topology, a hierarchical equilibrium strategy combining inter-module K-means clustering analysis and intra-module splitting and recombination is proposed. This strategy can achieve full cell balance, thereby ensuring the maximum capacity utilization of the battery pack. The topology structure composed of 8 batteries was validated, and the experimental results confirmed that the proposed hierarchical balancing strategy supported by the reconfigurable topology increased the capacity utilization of the battery pack by 15.93%, and the maximum fluctuation rate of the battery pack terminal voltage was 0.9%.

The NLRP3 molecule influences the therapeutic effects of mesenchymal stem cells through Glut1-mediated energy metabolic reprogramming.

INTRODUCTION: Numerous studies demonstrated that NLRP3 has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Mesenchymal stem cells (MSCs) regulated the NLRP3 inflammasome, which has emerged as a novel therapeutic approach for treating IBD. OBJECTIVES: The exact role of NLRP3 in regulating MSCs' function is unclear. Our study aimed to explore how NLRP3 affects the therapeutic effects of MSCs in colitis. METHODS: We extracted MSCs from the bone marrow of C57BL/6 mice and Nlrp3 KO mice, and identified them using differentiation assays and flow cytometry. In vitro, Both WT MSCs and Nlrp3 KO MSCs were stimulated with inflammatory factor Lipopolysaccharide (LPS), and only WT MSCs were stimulated with varying concentrations of the NLRP3 inhibitor MCC950, then, quantified IL-10 levels in the supernatant. RNA-seq was performed to examine gene expression patterns and Seahorse was used to assess oxidative phosphorylation (OXPHOS) and glycolysis levels. Western blot was used to evaluate protein expression. In vivo, we treated DSS-induced colitis with either WT or Nlrp3 KO MSCs, monitoring weight, measuring colon length, and further evaluation. We also treated DSS-induced colitis with pretreated MSCs (BAY876, oe-Glut1, or oe-NLRP3), following the same experimental procedures as described above. RESULTS: Our results demonstrate that Nlrp3 deletion did not affect MSC phenotypes, but rather promoted osteogenic differentiation. However, the absence of Nlrp3 reduced IL-10 production in MSCs in the presence of LPS, leading to impaired protection on DSS-induced colitis. Conversely, overexpression of NLRP3 promotes the production of IL-10, enhancing therapeutic effects. Further investigation revealed that Nlrp3 deficiency downregulated Glut1 expression and glycolysis activation in MSCs, resulting in decreased IL-10 production. Notably, overexpressing Glut1 in Nlrp3 KO MSCs restored their therapeutic effect that was previously dampened due to Nlrp3 deletion. CONCLUSION: Our findings demonstrate that NLRP3 heightens the therapeutic effects of MSC treatment on DSS-induced colitis.

Incidence, risk factors, and prognosis of acute exacerbation of rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis.

INTRODUCTION: Acute exacerbation (AE) is a devastating complication of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and leads to high mortality. This study aimed to investigate the incidence, risk factors, and prognosis of acute exacerbation of rheumatoid arthritis-associated interstitial lung disease (AE-RA-ILD). METHODS: PubMed, EMBASE, Web of Science, and Medline were searched through 8 February 2023. Two independent researchers selected eligible articles and extracted available data. The Newcastle Ottawa Scale was used to assess the methodological quality of studies used for meta-analysis. The incidence and prognosis of AE-RA-ILD were investigated. Weighted mean differences (WMDs) with corresponding 95% confidence intervals (CIs) and pooled odds ratios (ORs) with 95% CIs were calculated to explore the risk factors of AE in RA-ILD. RESULTS: Twenty-one of 1,589 articles were eligible. A total of 385 patients with AE-RA-ILD, of whom 53.5% were male, were included. The frequency of AE in patients with RA-ILD ranged from 6.3 to 55.6%. The 1-year and 5-year AE incidences were 2.6-11.1% and 11-29.4%, respectively. The all-cause mortality rate of AE-RA-ILD was 12.6-27.9% at 30 days and 16.7-48.3% at 90 days. Age at RA diagnosis (WMD: 3.61, 95% CI: 0.22-7.01), male sex (OR: 1.60, 95% CI:1.16-2.21), smoking (OR: 1.50, 95% CI: 1.08-2.08), lower forced vital capacity predicted (FVC%; WMD: -8.63, 95% CI: -14.68 to - 2.58), and definite usual interstitial pneumonia (UIP) pattern (OR: 1.92, 95% CI: 1.15-3.22) were the risk factors of AE-RA-ILD. Moreover, the use of corticosteroids, methotrexate, and biological disease-modifying anti-rheumatic drugs, was not associated with AE-RA-ILD. CONCLUSION: AE-RA-ILD was not rare and had a poor prognosis. Age at RA diagnosis, male sex, smoking, lower FVC%, and definite UIP pattern increased the risk of AE-RA-ILD. The use of medications, especially methotrexate and biological disease-modifying anti-rheumatic drugs, may not be related to AE-RA-ILD. REGISTRATION: CRD42023396772.

Ferroptosis-Related Molecular Clusters and Diagnostic Model in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovitis, joint damage and deformity. A newly described type of cell death, ferroptosis, has an important role in the pathogenesis of RA. However, the heterogeneity of ferroptosis and its association with the immune microenvironment in RA remain unknown. Synovial tissue samples from 154 RA patients and 32 healthy controls (HCs) were obtained from the Gene Expression Omnibus database. Twelve of twenty-six ferroptosis-related genes (FRGs) were differentially expressed between RA patients and HCs. Furthermore, the patterns of correlation among the FRGs were significantly different between the RA and HC groups. RA patients were classified into two distinct ferroptosis-related clusters, of which cluster 1 had a higher abundance of activated immune cells and a corresponding lower ferroptosis score. Enrichment analysis suggested that tumor necrosis factor-α signaling via nuclear factor-κB was upregulated in cluster 1. RA patients in cluster 1 responded better to anti-tumor necrosis factor (anti-TNF) therapy, which was verified by the GSE 198520 dataset. A diagnostic model to identify RA subtypes and immunity was constructed and verified, in which the area under the curve values in the training (70%) and validation (30%) cohorts were 0.849 and 0.810, respectively. This study demonstrated that there were two ferroptosis clusters in RA synovium that exhibited distinct immune profiles and ferroptosis sensitivity. Additionally, a gene scoring system was constructed to classify individual RA patients.

Age-associated B cells indicate disease activity in rheumatoid arthritis.

Age-associated B cells (ABCs) are characterized by CD11c and T-bet expression. ABCs are elevated in several autoimmune diseases and may be associated with RA. This study aimed to investigate ABCs' role in RA and identify potential factors affecting ABCs in RA patients. Peripheral blood mononuclear cells (PBMCs) and plasma samples were collected from 75 RA patients and 27 sex- and age-matched healthy controls. Proportions of ABCs (CD19+CD11c+T-bet+), plasmablasts (CD19+CD27+CD38hi), Bregs (CD19+IL-10+), and T follicular helper (Tfh) cells (CD4+CXCR5+PD-1hi) in PBMCs were detected using flow cytometry. Plasma IL-21, IFN-γ, and IL-10 levels were detected by ELISA. Plasma miRNAs (miR-34a, -122, -133a, -142, -146a, -208a, and -155) were detected by RT-PCR. Naïve B cells transfected with different miRNA mimics were deteced after 3 days culture under stimulation of anti-IgM and anti-CD40 or IL-21, IFN-γ, anti-IgM and anti-CD40. ABC proportions in PBMCs were increased in RA patients with higher disease activity and decreased in those with good treatment responses. Additionally, ABC proportions in PBMCs in RA patients were positively correlated with DAS28 scores. Plasma levels of IL-21, miR-142, and miR-146a and proportions of Tfh cells were positively correlated with ABC percentages in PBMCs. Herein, ABCs were identified as potential biological indicators for disease activity and treatment responses. Moreover, miR-142 and miR-146a could induce the differentiation of ABCs in naïve B cells in conjunction with IL-21 and IFN-γ.