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Because of its significant impact on the cooperative regenerative braking performance of electrified vehicles, the modulation effect of a hydraulic brake is of great importance. To improve the hydraulic brake control performance further, a novel pressure-difference-limiting control method for hydraulic pressure modulation based on on-off solenoid valves is proposed. The linear relationship between the coil current and the pressure difference across the valve is obtained. The characteristics of pressure-difference-limiting modulation are simulated and analysed. Then, a cooperative regenerative braking control algorithm based on the pressure-difference-limiting modulation of the hydraulic brake is designed. Hardware-in-the-loop tests of the algorithm under typical braking procedures are carried out. The test results demonstrate the validity and feasibility of the developed regenerative braking control algorithm and indicate that the proposed pressure-difference-limiting modulation method, which has an advantage over the conventional control based on a pulse-width-modulated signal with respect to the control accuracy of the hydraulic brake pressure, has great potential to improve the braking performance of a vehicle.

Cinobufagin (CBF) is isolated from the skin and posterior auricular glands of the Asiatic toad (Bufo gargarizans). This study investigated the reversal effect of CBF on P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) in colon cancer. The effect of CBF on the cytotoxicity of anticancer drugs in P-gp overexpressing LoVo/ADR, HCT116/L, Cao-2/ADR cells and their parental cells was determined using CCK-8 assay. Apoptosis of anti-cancer drugs and accumulation of doxorubicin (DOX) and Rhodamine 123 (Rho123) in P-gp overexpressing cells were evaluated by flow cytometry. Results indicated that CBF significantly enhanced the sensitivity of P-gp substrate drugs on P-gp overexpressing cells, but had no effect on their parental cells. CBF enhanced the effect of DOX against P-gp-overexpressing LoVo/ADR cell xenografts in nude mice. Moreover, CBF also increased cell apoptosis of chemotherapy agents and intracellular accumulation of DOX and Rho123 in the MDR cells. Further research on the mechanisms revealed non-competitive inhibition of P-gp ATPase activity, but without altering the expression of P-gp. These findings demonstrated that CBF could be further developed into a safe and potent P-gp modulator for combination use with anticancer drugs in cancer chemotherapy.

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