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Background: Osteoarthritis is characterized by the continuous degradation of the articular cartilage. The microRNA miR-448 has been found to be broadly involved in cellular processes, including proliferation, apoptosis, invasion and EMT. While aberrant expression of miR-448 has been found in multiple cancers, its level in osteoarthritis cartilage and its role in the progression of this disease are still unknown. Here, we examined the functional roles of miR-448 and its expression in osteoarthritis tissues, including IL-1β-stimulated osteoarthritis chondrocytes. Methods: Chondrocytes were isolated from human articular cartilage and stimulated with IL-1β. The expression levels of miR-448 in the cartilage and chondrocytes were both determined. After transfection with an miR-448 mimic or inhibitor, the mRNA levels of aggrecan, type II collagen and MMP-13 were determined. Luciferase reporter assay, qRT-PCR and western blot were performed to explore whether matrilin-3 was a target of miR-448. Furthermore, we co-transfected chondrocytes with miR-448 inhibitor and siRNA for matrilin-3 and then stimulated them with IL-1β to determine whether miR-448-mediated IL-1β-induced cartilage matrix degradation resulted from directly targeting matrilin-3. Results: The level of miR-448 was significantly higher and matrilin-3 expression was significantly lower in osteoarthritis cartilage and IL-1β-induced chondrocytes than in normal tissues and cells. Furthermore, matrilin-3 expression was reduced by miR-448 overexpression. MiR-448 downregulation significantly alleviated the IL-1β-induced downregulation of aggrecan and type II collagen expression, and upregulation of MMP-13 expression. MiR-448 overexpression had the opposite effects. Knockdown of matrilin-3 reversed the effects of the miR-448 inhibitor on the expressions of aggrecan, type II collagen and MMP-13. Conclusion: The findings showed that miR-448 contributed to the progression of osteoarthritis by directly targeting matrilin-3. This indicates that it has potential as a therapeutic target for the treatment of osteoarthritis.
To obtain a reasonable evaluation of the performance of waterjet propulsion at the design stage, a semi-theoretical and semi-empirical method is used to calculate the fundamental parameters of waterjet propulsion performance using an iterative approach. To calculate the ship’s resistance, a boundary element method based on three-dimensional potential flow theory is used to solve the wave-making resistance, and an empirical approach is used to evaluate the viscous resistance. Finally, the velocity and pressure of the capture area of the waterjet propulsion control volume are solved based on turbulent boundary layer theory. The iteration equation is established based on the waterjet-hull force-balance equation, and the change in the ship’s attitude and the local loss of the intake duct are considered. The performance parameters of waterjet propulsion, such as resistance, waterjet thrust, thrust deduction, and the physical quantity of the control volume, are solved by iteration. In addition, a PID-controlled free-running ship model is simulated using the RANS CFD method as a comparison. We apply the proposed approach and the RANS CFD method to a waterjetpropelled trimaran model, and the simulation process and the results are presented and discussed. Although there are some differences between the two methods in terms of the local pressure distribution and thrust deduction, the relative error in the evaluation results for the waterjet propulsion performance is generally reasonable and acceptable. This indicates that the present method can be used at the early stages of ship design without partial information about the waterjet propulsion system, and especially in the absence of a physical model of the pump
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