MicroRNA-451 from Human Umbilical Cord-Derived Mesenchymal Stem Cell Exosomes Inhibits Alveolar Macrophage Autophagy via Tuberous Sclerosis Complex 1/Mammalian Target of Rapamycin Pathway to Attenuate Burn-Induced Acute Lung Injury in Rats

Objective Our previous studies established that microRNA(miR)-451 from human umbilical cord mesenchymal stem cell-derived exosomes(hUC-MSC-Exos)alleviates acute lung injury(ALI).This study aims to elucidate the mechanisms by which miR-451 in hUC-MSC-Exos reduces ALI by modulating macrophage autophagy.Methods Exosomes were isolated from hUC-MSCs.Severe burn-induced ALI rat models were treated with hUC-MSC-Exos carrying the miR-451 inhibitor.Hematoxylin-eosin staining evaluated inflammatory injury.Enzyme-linked immunosorbnent assay measured lipopolysaccharide(LPS),tumor necrosis factor-α,and interleukin-1βlevels.qRT-PCR detected miR-451 and tuberous sclerosis complex 1(TSC1)expressions.The regulatory role of miR-451 on TSC1 was determined using a dual-luciferase reporter system.Western blotting determined TSC1 and proteins related to the mammalian target of rapamycin(mTOR)pathway and autophagy.Immunofluorescence analysis was conducted to examine exosomes phagocytosis in alveolar macrophages and autophagy level.Results hUC-MSC-Exos with miR-451 inhibitor reduced burn-induced ALI and promoted macrophage autophagy.MiR-451 could be transferred from hUC-MSCs to alveolar macrophages via exosomes and directly targeted TSC1.Inhibiting miR-451 in hUC-MSC-Exos elevated TSC1 expression and inactivated the mTOR pathway in alveolar macrophages.Silencing TSC1 activated mTOR signaling and inhibited autophagy,while TSC1 knockdown reversed the autophagy from the miR-451 inhibitor-induced.Conclusion miR-451 from hUC-MSC exosomes improves ALI by suppressing alveolar macrophage autophagy through modulation of the TSC1/mTOR pathway,providing a potential therapeutic strategy for ALI.

Structural design and optimization for vent holes of an industrial turbine sealing disk

Severe stress concentration occurs around circular vent holes of an industrial turbine sealing disk.This paper investigates the structural design and optimization for the vent holes to effectively reduce the maximum von Mises stress and improve the fatigue life of the turbine sealing disk.An efficient integrated design optimization method is presented based on a novel non-circular vent hole design method in combination with a variable dimension sub-model method,a self-developed modeling and meshing tool,and the Multi-Island Genetic Algorithm.The proposed non-circular vent hole is biaxial symmetric and consists of four smoothly connected arcs.The variable dimension sub-model method is utilized to obtain accurate results in the fields around the vent holes within the computationally acceptable time.The modeling and meshing tool is developed by using the Tcl/Tk Scripts to rebuild the geometry and generate the high-quality hexahedral mesh automatically.The Multi-Island Genetic Algorithm is adopted to solve the studied constrained optimization problem.After optimization,the maximum von Mises stress is reduced from 1305.644 MPa to 963.435 MPa,and the fatigue life is increased from 3091 cycles to 30,297 cycles.The results show that the proposed design and optimization methods can significantly improve the performance of the turbine sealing disk along with the remarkable drop in stress concentration.