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Exosomes participate in many physiological and pathological processes by regulating cell-to-cell communication. This affects the etiology and development of diseases, such as osteoarthritis (OA). Although exosomes in the OA tissue microenvironment are involved in the progression of OA, exosomes derived from therapeutic cells represent a new therapeutic strategy for OA treatment. Recent studies have shown that exosomes participate in OA treatment by regulating the proliferation, apoptosis, inflammation, and extracellular matrix synthesis of chondrocytes. However, studies in this field are scant. This review summarizes the therapeutic properties of exosomes on chondrocytes in OA and their underlying molecular mechanisms. We also discuss the challenges and prospects of exosome-based OA treatment.

A genetic algorithm-based method is proposed to globally optimize the stacking sequence of multi-sandwich-panel composite structures for minimum weight with strength and buckling considerations. The prerequisites for the continuity between sandwich panels are first studied. To implement the summarized continuity rules in the evolutionary optimization, three newly constructed chromosomes are developed to encode the global stacking sequence with no additional repair. Genetic operators, including specialized mutation, swapping and crossover operators, are also developed to effectively explore the design space and keep the continuity rules followed. The Hashin criterion and maximum stress criterion are used to evaluate the strength of sandwich panels. A typical multi-sandwich-panel composite structure with identical and different core thicknesses is optimized to verify the validity and efficiency of the proposed method. It is found that much lighter solutions are obtained with an acceptable efficiency in all cases. It is also found that the weight of the multi-sandwich-panel composite structures can be further reduced when the core thicknesses are not identical.

In this paper, a new type of assembled RC beam–column joint with a beam-end steel cover-plate connection is proposed to achieve seismic toughness and damage control of the joint. Energy-dissipation plates with different structural forms are proposed, and a series of seismic performance indexes of the joints are calculated and analyzed by using the finite element method. The energy-dissipation plate with an arc notch can reach the yield condition faster, and the ultimate bearing capacity of the joint reaches the maximum. The bending design of energy-dissipation plates is carried out by calculating the demand bending moment, and energy-dissipation plates of different structural forms are simulated and verified. The results show that the proposed design formula can ensure that the bending moment at the beam end still maintains elastic deformation when the energy-dissipation plate yields. The important parameters affecting the bending moment of the weakened part in the middle of the energy-dissipation plate are analyzed. Finally, this paper also analyzes the important parameters affecting the seismic performance of the joints. The results show that the seismic performance of the newly assembled RC beam–column joints proposed in this paper is better than that of cast-in-place joints. Increasing the longitudinal reinforcement ratio appropriately can greatly improve the ultimate bearing capacity and ductility of the joints. Increasing the thickness of the energy-dissipation plate, increasing the strength of the energy-dissipation plate, increasing the axial compression ratio of the column, increasing the strength of the concrete, and increasing the strength of the shear web can improve the ultimate bearing capacity of the joints but also reduce their ductility. Under different axial compression ratios, the strain in the core area of the joints is low, and the compressive damage of the concrete is zero, which verifies the effectiveness of the damage-control design of the proposed model. [ABSTRACT FROM AUTHOR]

There is a growing appreciation for the specific health benefits conferred by commensal microbiota on their hosts. Clinical microbiota analysis and animal studies in germ-free or antibiotic-treated mice have been crucial for improving our understanding of the role of the microbiome on the host mucosal surface; however, studies on the mechanisms involved in microbiome-host interactions remain limited to small animal models. Here, we demonstrated that rhesus monkeys under short-term broad-spectrum antibiotic treatment could be used as a model to study the gut mucosal host-microbiome niche and immune balance with steady health status. Results showed that the diversity and community structure of the gut commensal bacteria in rhesus monkeys were both disrupted after antibiotic treatment. Furthermore, the 16S rDNA amplicon sequencing results indicated that Escherichia-Shigella were predominant in stool samples 9 d of treatment, and the abundances of bacterial functional genes and predicted KEGG pathways were significantly changed. In addition to inducing aberrant morphology of small intestinal villi, the depletion of gut commensal bacteria led to increased proportions of CD3 + T, CD4 + T, and CD16 + NK cells in peripheral blood mononuclear cells (PBMCs), but decreased numbers of Treg and CD20 + B cells. The transcriptome of PBMCs from antibiotic-treated monkeys showed that the immune balance was affected by modulation of the expression of many functional genes, including IL-13, VCAM1, and LGR4.

Respirovirus infection can cause viral pneumonia and acute lung injury (ALI). The interleukin-1 (IL-1) family consists of proinflammatory cytokines that play essential roles in regulating immune and inflammatory responses in vivo . IL-1 signaling is associated with protection against respiratory influenza virus infection by mediation of the pulmonary anti-viral immune response and inflammation. We analyzed the infiltration lung immune leukocytes and cytokines that contribute to inflammatory lung pathology and mortality of fatal H1N1 virus-infected IL-1 receptor 1 (IL-1R1) deficient mice. Results showed that early innate immune cells and cytokine/chemokine dysregulation were observed with significantly decreased neutrophil infiltration and IL-6, TNF-α, G-CSF, KC, and MIP-2 cytokine levels in the bronchoalveolar lavage fluid of infected IL-1R1 -/- mice in comparison with that of wild type infected mice. The adaptive immune response against the H1N1 virus in IL-1R1 -/- mice was impaired with downregulated anti-viral Th1 cell, CD8+ cell, and antibody functions, which contributes to attenuated viral clearance. Histological analysis revealed reduced lung inflammation during early infection but severe lung pathology in late infection in IL-1R1 -/- mice compared with that in WT infected mice. Moreover, the infected IL-1R1 -/- mice showed markedly reduced neutrophil generation in bone marrow and neutrophil recruitment to the inflamed lung. Together, these results suggest that IL-1 signaling is associated with pulmonary anti-influenza immune response and inflammatory lung injury, particularly via the influence on neutrophil mobilization and inflammatory cytokine/chemokine production.

We sought to investigate the expression of EpCAM and Trop2 in Pituitary adenomas (PAs) and study the correlation of protein expression with invasiveness, proliferation, clinical functioning, recurrence/progression, and some other factors. We investigated the expression of EpCAM and Trop2 in 74 samples of PAs by immunohistochemistry and made correlative analysis of protein overexpression with clinicopathological parameters. Follow-up data was analyzed for recurrence/progression with Kaplan-Meier method and Multivariate Cox regression analysis. Immunohistochemistry results showed that overexpression rates of EpCAM and Trop2 were 51/74 (68.9%) and 43/74 (58.1%), respectively. For both EpCAM and Trop2, PAs with invasiveness showed a higher overexpression rate than PAs without invasiveness (PEpCAM = 0.001; PTrop2 = 0.006). Nonfunctional Pituitary adenomas (NFPAs) demonstrated a higher EpCAM overexpression than functional Pituitary adenomas (FPAs) (P = 0.026). Both EpCAM and Trop2 overexpression correlated significantly with expression of proliferation factor Ki-67 (PEpCAM = 0.011; PTrop2 = 0.000), but not with gender and age. Follow-up analysis revealed that Trop2 overexpression was a significantly predictive factor for recurrence/progression by means of Kaplan-Meier method d (P = 0.028) and Multivariate Cox regression analysis (P = 0.025). This study reveals that both EpCAM and Trop2 overexpression in PAs correlate significantly with invasiveness and proliferation. EpCAM presents a potential target for differential diagnosis and immunotherapy for NFPAs. Follow-up analysis shows that Trop2 is a predictive factor for recurrence/progression for PAs.