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Sepsis is a life-threatening condition caused by an immune response triggered by infection, and highly elevated cytokine/chemokine levels in the blood play crucial roles in the progression of sepsis. Serum exosomes are nanovesicles that have multiple biological functions, playing roles in antigen presentation, intercellular signal communication, inflammatory response and immune surveillance. However, the biological functions and related molecular bases remain to be elucidated. In this study, we investigated the profiles of cytokines/chemokines harbored in the exosomes of septic mice and explored the mechanisms of immunomodulation on T cells treated with exosomes harvested from septic mice. Blood cytokines/chemokines existed in both the soluble form and in the insoluble exosomal form; the profiles of the cytokines/chemokines in these two forms displayed different dynamics in the blood of mice challenged with LPS. Exosomes from septic mice induced the differentiation of Th1/Th2 cells, which was blocked by specific antibodies targeting IL-12 and IL-4. In addition, these exosomes significantly augmented the proliferation and migration of T lymphocytes. Furthermore, preadministration of exosomes by intravenous injection restrained the inflammatory response, attenuated lung and liver tissue damage, and prolonged the survival of cecal ligation and puncture (CLP) mice. Our results indicate that exosomes enriched with cytokines/chemokines play critical roles in T cell differentiation, proliferation and chemotaxis during the sepsis process and have a protective effect on cecal ligation and puncture (CLP) mice. Thus, these findings not only strengthen our understanding of the role of sepsis via exosomes but also provide potential targets for therapeutic applications.

The mechanisms underlying immunomodulatory ability of mesenchymal stromal cells (MSCs) remain unknown. Recently, studies suggested that the immunomodulatory activity of MSCs is largely mediated by paracrine factors. Among which, exosome is considered to play a major role in the communication between MSCs and target tissue. The aim of our study is to investigate the effect of MSCs-derived exosome on peripheral blood mononuclear cells (PBMCs), especially T cells. We find that the MSCs-derived exosome extracted from healthy donors’ bone marrow suppressed the secretion of pro-inflammatory factor TNF-α and IL-1β, but increased the concentration of anti-inflammatory factor TGF-β during in vitro culture. In addition, exosome may induce conversion of T helper type 1 (Th1) into T helper type 2 (Th2) cells and reduced potential of T cells to differentiate into interleukin 17-producing effector T cells (Th17). Moreover, the level of regulatory T cells (Treg) and cytotoxic T lymphocyte-associated protein 4 were also increased. These results suggested that MSC-derived exosome possesses the immunomodulatory properties. However, it showed no effects on the proliferation of PBMCs or CD3+ T cells, but increases the apoptosis of them. In addition, indoleamine 2, 3-dioxygenase (IDO) was previously shown to mediate the immunoregulation of MSCs, which was increased in PBMCs co-cultured with MSCs. In our study, IDO showed no significant changes in PBMCs exposed to MSCs-derived exosome. We conclude that exosome and MSCs might differ in their immune-modulating activities and mechanisms.

To compare the proteomics of synovial fluid (SF)-derived exosomes in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), gout, and osteoarthritis (OA) patients. Exosomes were separated from SF by the Exoquick kit combined ultracentrifugation method. Tandem mass tags (TMT)-labeled liquid chromatography mass spectrometry (LC-MS/MS) technology was used to analyze the proteomics of SF-derived exosomes. Volcano plot, hierarchical cluster, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted. A total of 1,678 credible proteins were detected. Sixty-nine differentially expressed proteins were found in gout, compared with OA, axSpA, and RA simultaneously. Twenty-five proteins were found highly expressed in gout uniquely, lysozyme C and protein S100-A9 included, whose bioinformatic analysis was significantly involved in \"neutrophil degranulation\" and \"prion diseases\". Eighty-four differentially expressed proteins were found in axSpA, compared with OA, gout, and RA simultaneously. Thirty-nine proteins were found highly expressed in axSpA uniquely, RNA-binding protein 8A and protein transport protein Sec24C included, whose bioinformatic analysis was significantly involved in \"acute-phase response\" and \"citrate cycle\". One hundred and eighty-four differentially expressed proteins were found in RA, compared with OA, gout, and axSpA simultaneously. Twenty-eight proteins were found highly expressed in RA uniquely, pregnancy zone protein (PZP) and stromelysin-1 included, whose bioinformatic analysis was significantly involved in \"serine-type endopeptidase inhibitor activity\" and \"complement and coagulation cascades\". Enzyme-linked immunosorbent assay (ELISA) result showed that the exosome-derived PZP level of SF in RA was higher than that in OA ( < 0.05). Our study for the first time described the protein profiles of SF-derived exosomes in RA, axSpA, gout, and OA patients. Some potential biomarkers and hypothetical molecular mechanisms were proposed, which may provide helpful diagnostic and therapeutic insights for inflammatory arthritis (IA).

Objective To investigate the role of albumin-to-globulin ratio (AGR) in systemic lupus erythematosus (SLE) and its relationship with disease activity. Methods This retrospective study consecutively selected patients with SLE and healthy controls. Patients were divided into three groups according to the SLE Disease Activity Index 2000 (SLEDAI-2K): group 1 (mild disease activity, SLEDAI-2K ≤ 6), group 2 (moderate disease activity, SLEDAI-2K 7–12) and group 3 (severe disease activity, SLEDAI-2K > 12). Predictors of SLE disease activity were analysed by ordinal logistical regression. Results A total of 101 Chinese patients with SLE and 75 healthy Chinese controls were included. Patients with SLE had lower AGR values than healthy individuals, and group 3 patients with SLE displayed lower AGR values than those in group 1, but similar values to group 2. AGR was inversely correlated with SLEDAI-2K (r = −0.543). Ordinal logistic regression analysis showed that lower AGR (β = −1.319) and lower complement C4 (β = −1.073) were independent risk factors for SLE disease activity. Conclusions AGR was decreased in patients with SLE and may be utilized as a useful inflammatory biomarker for monitoring SLE disease activity.

Five severe floods occurred in the Yangtze River Basin, China, between July and August 2020, and the Three Gorges Reservoir (TGR) located in the middle Yangtze River experienced the highest inflow since construction. The world’s largest cascade-reservoir group, which counts for 22 cascade reservoirs in the upper Yangtze River, cooperated in real time to control floods. The cooperation prevented evacuation of 600,000 people and extensive inundations of farmlands and aquacultural areas. In addition, no water spillage occurred during the flood control period, resulting in a world-record annual output of the TGR hydropower station. This work describes decision making challenges in the cooperation of super large reservoir groups based on a case-study, controlling the 4th and 5th floods (from Aug-14 to Aug-22), the efforts of technicians, multi-departments, and the state, and reflects on these. To realize the full potential of reservoir operation for the Yangtze River Basin and other basins with large reservoir groups globally, we suggest: (i) improve flood forecast accuracy with a long leading time; (ii) strengthen and further develop ongoing research on reservoir group cooperation; and (iii) improve and implement institutional mechanisms for coordinated operation of large reservoir groups.

Osteosarcoma (OS) is the most prevalent secondary sarcoma associated with retinoblastoma (RB). However, the molecular mechanisms driving the interactions between these two diseases remain incompletely understood. This study aims to explore the transcriptomic commonalities and molecular pathways shared by RB and OS, and to identify biomarkers that predict OS prognosis effectively. RNA sequences and patient information for OS and RB were obtained from the University of California Santa Cruz (UCSC) Xena and Gene Expression Omnibus databases. When RB and OS were first identified, a common gene expression profile was discovered. Weighted Gene Co-expression Network Analysis (WGCNA) revealed co-expression networks associated with OS after immunotyping patients. To evaluate the genes shared by RB and OS, univariate and multivariate Cox regression analysis were then carried out. Three machine learning methods were used to pick key genes, and risk models were created and verified. Next, medications that target independent prognostic genes were found using the Cellminer database. The comparison of differential gene expression between OS and RB revealed 1216 genes, primarily linked to the activation and proliferation of immune cells. WGCNA identified 12 modules related to OS immunotyping, with the grey module showing a strong correlation with the immune-inflamed phenotype. This module intersected with differential genes from RB, producing 65 RB-associated OS Immune-inflamed Genes (ROIGs). Analysis identified 6 hub genes for model construction through univariate Cox regression and three machine learning techniques. A risk model based on these hub genes was established, demonstrating significant prognostic value for OS. Genes shared between OS and RB contribute to the progression of both cancers through multiple pathways. The ROIGs risk score model independently predicts the overall survival of OS patients. Additionally, this study highlights genes with potential as therapeutic targets or biomarkers for clinical use.

Aicardi-Goutières syndrome (AGS) is characterized by progressive neurologic decline, cerebral calcification, and variable manifestations of autoimmunity. Seven subtypes of AGS have been defined and aberrant activation of the type I interferon system is a common theme among these conditions. We describe a 13-year-old boy who presented with an unusual constellation of psoriasis, interstitial lung disease (ILD), and pulmonary hypertension in addition to cerebral calcifications and glomerulonephritis. He was found to have late-onset AGS due to a gain-of-function mutation in and over-activation of the type I interferon pathway was confirmed by RNA sequencing. The majority of his clinical manifestations, including ILD, psoriasis and renal disease improved markedly after treatment with the combination of corticosteroids, cyclophosphamide, and the Janus-kinase inhibitor tofacitinib. This case extends the clinical spectrum of AGS and suggests the need for lung disease screening in patients with AGS.

To eliminate the harmonics caused by nonlinear loads, repetitive controllers are widely applied as current controllers for active power filters (APF). In practice, a variation in grid frequency leads to the appearance of a fractional-order delay filter. As a result, the resonant frequency of the repetitive controller will deviate from the fundamental frequency and the controller cannot compensate for harmonics accurately. To solve this problem, an improved frequency-adaptive repetitive controller based on virtual variable sampling (IMFA-VVS-RC) for APF is proposed in this paper. To enhance the system stability margin, the proposed RC introduces an infinite impulse response (IIR) low-pass filter. The proposed RC has a high stability margin at high frequencies due to the low gain of the IIR low-pass filter in the region above the cutoff frequency. In this way, the influence of model uncertainty and parameter uncertainty on system stability are reduced at high frequencies. At the same time, compared with the conventional repetitive controller (CRC), the proposed RC for APF has a better harmonic suppression ability when the frequency varies. Experiments have verified the effectiveness of the scheme adopted for APF.

The mRNA vaccine technology was developed rapidly during the global pandemic of COVID-19. The crucial role of the COVID-19 mRNA vaccine in preventing viral infection also have been beneficial to the exploration and application of other viral mRNA vaccines, especially for non-replication structure mRNA vaccines of viral disease with outstanding research results. Therefore, this review pays attention to the existing mRNA vaccines, which are of great value for candidates for clinical applications in viral diseases. We provide an overview of the optimization of the mRNA vaccine development process as well as the good immune efficacy and safety shown in clinical studies. In addition, we also provide a brief description of the important role of mRNA immunomodulators in the treatment of viral diseases. After that, it will provide a good reference or strategy for research on mRNA vaccines used in clinical medicine with more stable structures, higher translation efficiency, better immune efficacy and safety, shorter production time, and lower production costs than conditional vaccines to be used as preventive or therapeutic strategy for the control of viral diseases in the future.

To characterize the inflammatory proteome in both serum and synovial fluid (SF) of patients with gout, in comparison to healthy controls and individuals with osteoarthritis (OA), by utilizing a high-quality, high-throughput proteomic analysis technique. Using the Olink Target 48 Inflammation panel, we measured serum concentrations of 45 inflammatory proteins in gout, OA, and healthy controls. We analyzed protein levels in SF samples from gout and OA, performed ROC curve analyses to identify diagnostic biomarkers, evaluate efficacy, and set cut-off values. Additionally, A protein-protein interaction (PPI) network was used to study protein relationships and significance. We have delineated the proteomic landscape of gout and identified 20 highly differentially expressed proteins (DEPs) in the serum of gout patients in comparison to that of healthy controls, which included VEGF-A, MMP-1, TGF-α, and OSM with corresponding area under the curve (AUC) values of 0.95, 0.95, 0.92, and 0.91 respectively. For the analysis of synovial fluid, 6 proteins were found to be elevated in gout in contrast to osteoarthritis (OA), among which IP-10, VEGF-A, IL-8, and MIP-3β had corresponding AUC values of 0.78, 0.78, 0.76, and 0.75 respectively. The protein-protein interaction (PPI) network analysis identified significantly prominent pathways in gout. This research marks a significant advancement in elucidating the inflammatory profile present in the serum and synovial fluid of individuals suffering from gout. Our discoveries have identified several novel proteins in both serum and synovial fluid that are potential biomarkers for diagnostic purposes and are believed to have critical roles as pathogenic factors in the pathophysiology of gout.