Reverse anti-breast cancer drug resistance effects by a novel two-step assembled nano-celastrol medicine.

Multidrug resistance (MDR) has become one of the most intractable problems in clinics as it would cause failure in chemotherapy. In this study, we demonstrated that a nanoscale self-assembled nanomedicine, which almost consisted of a pure chemo-drug, could efficiently overcome MDR. Celastrol (CST) was directly assembled into a discrete nanomedicine by precipitation, and then CST nanoparticles (CNPs) inhibited drug efflux pumps by activating HSF-1 expression and promoting HSF-1 translocation into nucleus to suppress the Pgp expression. The more drug accumulated in cells could activate apoptosis signals simultaneously and realize drug resistance reversal. CNPs significantly increased the level of ROS to regulate ERK/JNK signaling, which would further induce resistant cell apoptosis. The tandem apoptosis strategy used the same concentration of CST but achieved a higher antitumor effect. Overall, our study provides a new translational and alternative strategy using conventional natural products to overcome MDR with high efficacy.

Optimization and testing of suspension system of electric mini off-road vehicles.

Mini vehicles with a small wheelbase are extremely sensitive to road roughness. The aim of this study is to explore the influence of road information on ride comfort and enhance the ride comfort of mini vehicles. According to the 5-degree-of-freedom vibration model of an electric mini off-road vehicle, the partial differential matrix equation of system motion is established using the Lagrange method, and the frequency response characteristic of the system is analyzed. The input matrix of pavement unevenness is obtained by considering the mutual power spectrum density between front and rear wheels. Road surface roughness information is obtained using an instrument for measuring road roughness. A comprehensive objective function and a constraint condition are established for comfort and safety. Based on the parameters obtained through the optimum design of a 1/4 vehicle model, the optimized stiffness and damping coefficient of suspension are obtained using a MATLAB optimization program. The law of the vibration performance of off-road vehicles with respect to suspension stiffness and the damping coefficient is obtained through the analysis of optimized results. A driving simulation and a test are conducted on the electric mini off-road vehicle. The results show that the use of the measured pavement data as simulation input is closer to the actual situation and provides higher accuracy compared to the simulated pavement model. According to the optimization and test results, the parameters optimized by a 1/2 vehicle (5 degrees of freedom) vibration model are better than those optimized by the 1/4 vehicle vibration model. The optimization results confirm reduction in acceleration, acceleration power spectrum density, and the root mean square of the weighted acceleration of the seat. This shows that the electric mini off-road vehicle provides better ride comfortability after optimization.