Diallyl disulfide synergizes with melphalan to increase apoptosis and DNA damage through elevation of reactive oxygen species in multiple myeloma cells.

Diallyl disulfide (DADS), one of the main components of garlic, is well known to have anticancer effects on multiple cancers. However, its efficacy in treating multiple myeloma (MM) is yet to be determined. We explored the effects of DADS on MM cells and investigated the synergistic effects of DADS when combined with five anti-MM drugs, including melphalan, bortezomib, carfilzomib, doxorubicin, and lenalidomide. We analyzed cell viability, cell apoptosis, and DNA damage to determine the efficacy of DADS and the drug combinations. Our findings revealed that DADS induces apoptosis in MM cells through the mitochondria-dependent pathway and increases the levels of γ-H2AX, a DNA damage marker. Combination index (CI) measurements indicated that the combination of DADS with melphalan has a significant synergistic effect on MM cells. This was further confirmed by the increases in apoptotic cells and DNA damage in MM cells treated with the two drug combinations compared with those cells treated with a single drug alone. The synergy between DADS and melphalan was also observed in primary MM cells. Furthermore, mechanistic investigations showed that DADS decreases reduced glutathione (GSH) levels and increases reactive oxygen species (ROS) production in MM cells. The addition of GSH is effective in neutralizing DADS cytotoxicity and inhibiting the synergy between DADS and melphalan in MM cells. Taken together, our study highlights the effectiveness of DADS in treating MM cells and the promising therapeutic potential of combining DADS and melphalan for MM treatment.

A Fast Prediction Model for Liquid Metal Transfer Modes during the Wire Arc Additive Manufacturing Process.

The liquid metal transfer mode in wire arc additive manufacturing (WAAM), plays an important role in determining the build quality. In this study, a fast prediction model based on the Young-Laplace equation, momentum equation, and energy conservation, is proposed, to identify the metal transfer modes, including droplet, liquid bridge, and wire stubbing, for a given combination of process parameters. To close the proposed model, high-fidelity numerical simulations are applied, to obtain the necessary inputs required by the former. The proposed model's accuracy and effectiveness are validated by using experimental data and high-fidelity simulation results. It is proved that the model can effectively predict the transition from liquid bridge, to droplet and wire stubbing modes. In addition, its errors in dripping frequency and liquid bridge height range from 6% to 18%. Moreover, the process parameter windows about transitions of liquid transfer modes have been established based on the model, considering wire feed speed, travel speed, heat source power, and material parameters. The proposed model is expected to serve as a powerful tool for the guidance of process parameter optimization, to achieve high-quality builds.