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Background and Purpose: The role of the cartilage oligomeric matrix protein (COMP) in epithelial-mesenchymal transition (EMT) in tumor progression has been studied, but its exact regulatory mechanism remains unknown. Methods: The interaction between COMP and the actin-binding protein transgelin (TAGLN) was identified by interaction protein prediction and co-immunoprecipitation and verified through the stochastic optical reconstruction microscopy (STORM) and duolink experiments. Western blot and immunofluorescence analyses were conducted to detect the changes in EMT-related markers after COMP overexpression and knockdown. Molecular docking and Biacore of the interaction interface of COMP/TAGLN revealed that Chrysin directly targeted COMP. The promotion of COMP and the Chrysin inhibition of EMT were detected through the cell migration, invasion, apoptosis, and xenotransplantation of nude mice. Results: COMP interacts with TAGLN in EMT in colorectal cancer to regulate cytoskeletal remodeling and promote malignant progression. COMP is highly expressed in highly malignant colorectal cancer and positively correlated with TAGLN expression. COMP knockdown can inhibit colorectal cancer metastasis and invasion, whereas COMP overexpression promotes EMT in colorectal cancer. Through virtual screening of the protein interaction interface, Chrysin, a flavonoid compound extracted from Oroxylum indicum , was found to have the highest docking score to the COMP/TAGLN complex. Chrysin inhibited COMP, thereby preventing EMT and the malignant progression of colorectal cancer. Conclusions: This study illustrated the role of COMP in EMT and suggested that COMP/TAGLN may be a potential tumor therapeutic target. Chrysin exhibits obvious antitumor effects. This work provides a preliminary antitumor therapy to target COMP or its interaction protein to inhibit EMT.

Abstract:Increasing attention is being paid to the energy efficiency in metro systems to reduce the operational cost and to advocate the sustainability of railway systems. Classical research has studied the energy-efficient operational strategy and the energy-efficient system design separately to reduce the traction energy consumption. This paper aims to combine the operational strategies and the system design by analyzing how the infrastructure and vehicle parameters of metro systems influence the operational traction energy consumption. Firstly, a solution approach to the optimal train control model is introduced, which is used to design the Optimal Train Control Simulator(OTCS). Then, based on the OTCS, the performance of some important energy-efficient system design strategies is investigated to reduce the trains' traction energy consumption, including reduction of the train mass, improvement of the kinematic resistance, the design of the energy-saving gradient, increasing the maximum traction and braking forces, introducing regenerative braking and timetable optimization. As for these energy-efficient strategies, the performances are finally evaluated using the OTCS with the practical operational data of the Beijing Yizhuang metro line. The proposed approach gives an example to quantitatively analyze the energy reduction of different strategies in the system design procedure, which may help the decision makers to have an overview of the energy-efficient performances and then to make decisions by balancing the costs and the benefits.