Background. Oridonin is a powerful anticancer compound found in Rabdosia rubescens. However, its potential impact on bladder cancer remains uninvestigated. In this work, we aimed to detect the anticancer effect of oridonin on bladder cancer and explore the molecular mechanisms involved. Methods. The anticancer activity of oridonin was assessed in vitro with a CCK8 assay, an annexin V-FITC apoptosis analysis, and colony formation and Transwell migration assays which were performed with the human bladder cancer cell line T24. Levels of apoptosis-related proteins, melastatin transient receptor potential channel 7 (TRPM7), and signaling molecules were examined in oridonin-treated T24 cells by western blotting or RT-PCR. Oridonin anticancer efficacy was further validated in vivo with a T24 xenograft mouse model. Results. Oridonin repressed the proliferative, colony-forming, and migratory capacities of T24 cells, triggered extensive apoptosis in vitro, and retarded tumor growth in vivo. Moreover, oridonin treatment significantly increased expression levels of p53 and cleaved caspase-3 and reduced expression of TRPM7, p-AKT, and p-ERK. Conclusion. Oridonin exhibited outstanding antiproliferative and antimigratory effects on bladder cancer, and these effects were at least partially associated with targeting of TRPM7 through inactivation of the ERK and AKT signaling pathways. These findings provide insight for the clinical application of oridonin in bladder cancer prevention.
This study presents a robustness optimization method for rapid prototyping (RP) of functional artifacts based on visualized computing digital twins (VCDT). A generalized multiobjective robustness optimization model for RP of scheme design prototype was first built, where thermal, structural, and multidisciplinary knowledge could be integrated for visualization. To implement visualized computing, the membership function of fuzzy decision-making was optimized using a genetic algorithm. Transient thermodynamic, structural statics, and flow field analyses were conducted, especially for glass fiber composite materials, which have the characteristics of high strength, corrosion resistance, temperature resistance, dimensional stability, and electrical insulation. An electrothermal experiment was performed by measuring the temperature and changes in temperature during RP. Infrared thermographs were obtained using thermal field measurements to determine the temperature distribution. A numerical analysis of a lightweight ribbed ergonomic artifact is presented to illustrate the VCDT. Moreover, manufacturability was verified based on a thermal-solid coupled finite element analysis. The physical experiment and practice proved that the proposed VCDT provided a robust design paradigm for a layered RP between the steady balance of electrothermal regulation and manufacturing efficacy under hybrid uncertainties.
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