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Recent years, the immunosuppressive properties of mesenchymal stem cells (MSCs) have been demonstrated in preclinical studies and trials of inflammatory and autoimmune diseases. Emerging evidence indicates that the immunomodulatory effect of MSCs is primarily attributed to the paracrine pathway. As one of the key paracrine effectors, mesenchymal stem cell-derived exosomes (MSC-EXOs) are small vesicles 30-200 nm in diameter that play an important role in cell-to-cell communication by carrying bioactive substances from parental cells. Recent studies support the finding that MSC-EXOs have an obvious inhibitory effect toward different effector cells involved in the innate and adaptive immune response. Moreover, substantial progress has been made in the treatment of autoimmune diseases, including multiple sclerosis (MS), systemic lupus erythematosus (SLE), type-1 diabetes (T1DM), uveitis, rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). MSC-EXOs are capable of reproducing MSC function and overcoming the limitations of traditional cell therapy. Therefore, using MSC-EXOs instead of MSCs to treat autoimmune diseases appears to be a promising cell-free treatment strategy. In this review, we review the current understanding of MSC-EXOs and discuss the regulatory role of MSC-EXOs on immune cells and its potential application in autoimmune diseases.

Bitong Mixture (BM) has shown efficacy in alleviating pain in knee osteoarthritis (OA) in clinical practice; however, the molecular mechanisms underlying its therapeutic effects remain to be fully elucidated. This study aimed to identified BM-related OA biomarkers and explore their functional implications. An integrative strategy combining bioinformatics prediction and experimental validation was used. Biomarkers were screened from public OA transcriptomic data using differential expression analysis, network pharmacology, and machine learning. Their functions were explored via enrichment and immune infiltration analyses. Molecular docking predicted interactions between herbal compounds and targets. Single-cell analysis characterized biomarker expression in chondrocyte subsets. A rat OA model and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were employed for validation. Bioinformatic prediction identified three potential biomarkers: MMP9, MMP2, and SPP1. They demonstrated certain diagnostic performance for OA and were implicated in pathways related to extracellular matrix organization and immune regulation. Immune analysis revealed significant correlations, notably between MMP2 and activated dendritic cells (cor = 0.66) and between SPP1 and CD4+ central memory T cells (cor = -0.75). Molecular docking suggested strong binding affinity between luteolin (a BM component) and MMP9. Single-cell analysis indicated high expression of these potential biomarkers in hypertrophic chondrocytes, inflammatory chondrocytes, and fibrochondrocytes. validation confirmed that BM alleviated OA symptoms and histopathological damage in rats. RT-qPCR results showed that BM treatment alleviated the OA-induced upregulation of MMP9, MMP2, and SPP1 expression. MMP9, MMP2, and SPP1 are potential therapeutic biomarkers for BM in OA. The efficacy of BM may be attributed to its regulation of extracellular matrix remodeling and immune responses, which provides a possible mechanistic explanation for its clinical use.

Bacteria and micro-eukaryotes play important roles in river ecological systems. The processes that govern bacterial and micro-eukaryotic communities in urban rivers are still uncertain. The spatiotemporal characteristics and assembly processes of bacterial and micro-eukaryotic communities in the Xiangjianghe River were explored using 16 S and 18 S rRNA gene amplicon sequencing in the present study. The results indicate that the bacterial and micro-eukaryotic community composition exhibited distinct temporal and spatial variation. The topological characteristics of co-occurrence networks demonstrate that the bacterial and micro-eukaryotic community coexistence patterns vary significantly between the four seasons. Water temperature (WT) and oxidation-reduction potential (ORP) were detected as the most critical factors affecting bacterial and micro-eukaryotic community structure. The stochastic process (dispersal limitation) was the dominant assembly process for bacteria and micro-eukaryotes in all seasons. Deterministic and stochastic processes influenced the bacteria and micro-eukaryotes differently. Compared to bacteria, the values of niche breadth were relatively lower, and the proportion of deterministic processes was relatively higher in micro-eukaryotes. These results expand our understanding of spatiotemporal patterns, assembly mechanisms, and influencing factors of bacterial and micro-eukaryotic communities in urban rivers.

Olfactory ecto-mesenchymal stem cells (OE-MSCs) are a novel population of resident stem cells in the olfactory lamina propria with strong immunosuppressive function. Exosomes released by MSCs are considered to carry various mRNAs, microRNAs and proteins from cells and function as an extension of MSCs. However, it remains unclear whether exosomes derived from OE-MSCs (OE-MSCs-Exos) possess any immunoregulatory functions. In this study, we found that OE-MSCs-Exos possessed strong suppressive function in CD4 + T cell proliferation, accompanied by reduced IL-17, IFN-γ and enhanced TGF-β, IL-10 secreted by T cells. In experimental colitis mice, treatment of OE-MSCs-Exos markedly alleviated the severity of disease, and Th1/Th17 subpopulations were remarkably reduced whereas Treg cells were increased after OE-MSCs-Exos treatment. Mechanistically, OE-MSCs-Exos were demonstrated to inhibit the differentiation of Th1 and Th17 cells, but promote the induction of Treg cells in vitro . Taken together, our findings identified a novel function of OE-MSCs-Exos in regulating T-cell responses, indicating that OE-MSCs-Exos may represent a new cell-free therapy for the treatment of IBD and other inflammatory diseases.

Although exosome therapy has been recognized as a promising strategy in the treatment of rheumatoid arthritis (RA), sustained modulation on RA specific pathogenesis and desirable protective effects for attenuating joint destruction still remain challenges. Here, silk fibroin hydrogel encapsulated with olfactory ecto-mesenchymal stem cell-derived exosomes (Exos@SFMA) was photo-crosslinked in situ to yield long-lasting therapeutic effect on modulating the immune microenvironment in RA. This in situ hydrogel system exhibited flexible mechanical properties and excellent biocompatibility for protecting tissue surfaces in joint. Moreover, the promising PD-L1 expression was identified on the exosomes, which potently suppressed Tfh cell polarization via inhibiting the PI3K/AKT pathway. Importantly, Exos@SFMA effectively relieved synovial inflammation and joint destruction by significantly reducing T follicular helper (Tfh) cell response and further suppressing the differentiation of germinal center (GC) B cells into plasma cells. Taken together, this exosome enhanced silk fibroin hydrogel provides an effective strategy for the treatment of RA and other autoimmune diseases.

This paper studies the consensus fault-tolerant control problem of a class of second-order leader–follower multi-agent systems with unknown disturbance and actuator faults, and proposes an integral non-singular terminal sliding mode control algorithm based on a finite-time observer. First, a finite-time disturbance observer was designed based on a combination of high-order sliding mode and dual layers adaptive rules to realize fast estimation and compensation of disturbance and faults. Then, a sliding surface with additional integral links was designed based on the conventional sliding surface, and an integral non-singular terminal sliding mode controller is proposed to realize the robust consensus in finite time and accurately diminish the chattering phenomena. Finally, a numerical example and simulation verify the effectiveness.

As the core component of rotating machinery, the fault diagnosis of rolling bearing has important engineering practical significance. Most of the current intelligent fault diagnosis methods are based on the premise that the training data and test data have similar probability distributions. However, in practical scenarios, there will inevitably be discrepancies in the distribution of vibration signals due to internal and external factors such as changes in working conditions, which will significantly affect the diagnostic performance of the intelligent diagnostic model. Aiming at problems that the vibration signal characteristic distribution of rolling bearings is inconsistent under different working conditions and the labels of the samples to be diagnosed are difficult to obtain, a new domain-adaptive fault diagnosis method is proposed in this paper. Firstly, the multi-scale feature extraction module is used to extract the features of the input signals, and the residual network structure is used to avoid the degradation of the model performance. Then, the APReLU activation function is used to make the vibration signals perform different nonlinear transformations according to their own characteristics through adaptive learning. Finally, the Joint Maximum Mean Discrepancy (JMMD) is used to reduce the displacement of both conditional and edge distributions between different domains. Therefore, this method can extract domain-invariant feature information and align the source and target domains, which can be used for cross-domain intelligent fault diagnosis. Six transfer fault diagnosis tasks based on the rolling bearing experimental platform are designed to evaluate the performance and effectiveness of the proposed method. At the same time, four popular methods are selected for comprehensive analysis and comparison. The results show that the method has good robustness and superiority under various diagnostic tasks.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that affects multiple systems. Its clinical manifestation varies across patients, from skin mucosa to multiorgan damage to severe central nervous system involvement. The exosome has been shown to play an important role in the pathogenesis of autoimmune diseases, including SLE. We review the recent knowledge of exosomes, including their biology, functions, mechanism, and standardized extraction and purification methods in SLE, to highlight potential therapeutic targets for SLE.

In this paper, a non-singular fast terminal sliding mode control (NFTSMC) strategy based on a finite-time observer and improved reaching rate is proposed to solve the control problem of aerial robot systems subject to actuator faults and internal and external disturbances. Using the control strategy proposed in this paper, rapid convergence and high robustness of the system are guaranteed. In addition, the proposed finite-time observer can observe information related to the actuator fault or internal and external disturbance of the system in an accurate and timely fashion, and actively compensate the fault. The improved reaching law introduced in this paper can cause the system reach the sliding surface quickly, effectively improving the response speed of the system and increasing the tracking performance of the system. The stability of the whole system is proved using Lyapunov stability analysis. Finally, the effectiveness of the proposed control strategy is verified on the basis of a numerical simulation of a six-rotor UAV model with manipulator.

In this paper, a new adaptive observer is proposed to estimate the actuator fault and disturbance of a quadrotor UAV system with actuator failure and disturbance. Based on this, a nonsingular fast terminal sliding mode controller is designed. Firstly, according to the randomness of faults and disturbances, the UAV system under faults and disturbances is regarded as one of the Markov jump nonlinear systems (MJNSs). Secondly, an adaptive observer is designed to simultaneously observe the system state, fault, and disturbance. In order to improve the precision, the fast adaptive fault estimation (FAFE) algorithm is adopted in the adaptive observer. In addition, a quasi-one-sided Lipschitz condition is used to deal with the nonlinear term, which relaxes the condition and contains more nonlinear information. Finally, a nonsingular fast terminal sliding mode controller is designed for fault-tolerant control of the system. The simulation results show that the faults and disturbances can be observed successfully, and that the system is stochastic stable.