Disulfiram, an aldehyde dehydrogenase inhibitor, works as a potent drug against sepsis and cancer via NETosis, pyroptosis, apoptosis, ferroptosis, and cuproptosis

Regulated cell death (RCD) is essential for maintaining cell homeostasis and preventing diseases. Besides classical apoptosis, several novel nonapoptotic forms of RCD including NETosis, pyroptosis, ferroptosis, and cuproptosis have been reported and are increasingly being implicated in various cancers and inflammation. Disulfiram (DSF), an aldehyde dehydrogenase inhibitor, has been used clinically for decades as an anti-alcoholic drug. New studies have shown that DSF possesses potent anti-inflammatory and anti-cancer effects by regulating these new types of RCD. Here, we summarize the mechanisms and discuss the potential application of DSF in the treatment of cancers and inflammatory diseases

10 kV SiC MOSFET Based Medium Voltage Power Conditioning System for Asynchronous Microgrids

Distributed energy resources (DERs) and microgrids have seen tremendous growth and research activities in recent years. Flexible DERs and asynchronous microgrids (ASMG) can have many system-level benefits over fixed DERs and conventional microgrids. The key enabler for flexible DERs and ASMG is a power converter based power conditioning system (PCS) as the interface between DERs/microgrids and the medium voltage (MV) distribution grid. High voltage (HV, >3.3 kV) silicon carbide (SiC) based MV converter is now a promising solution for the PCS. This article presents development and testing of a 10 kV SiC MOSFET based MV PCS for 13.8 kV ASMG. MV PCS converter design addressing high dv/dt issue generated by fast switching of the 10 kV SiC MOSFET is presented. The developed PCS is successfully tested at 25 kV dc 13.8 kV ac voltages and 100 kVA power. Grid support functions are also demonstrated with the developed PCS prototype and hardware tests beds, validating HV SiC converter benefits for ASMG

Targeting NRF2 uncovered an intrinsic susceptibility of acute myeloid leukemia cells to ferroptosis

Abstract Drug resistance and poor treatment response are major obstacles to the effective treatment of acute myeloid leukemia (AML). A deeper understanding of the mechanisms regulating drug resistance and response genes in AML is therefore urgently needed. Our previous research has highlighted the important role of nuclear factor E2-related factor 2 (NRF2) in AML, where it plays a critical role in detoxifying reactive oxygen species and influencing sensitivity to chemotherapy. In this study, we identify a core set of direct NRF2 targets that are involved in ferroptosis, a novel form of cell death. Of particular interest, we find that glutathione peroxidase 4 (GPX4) is a key ferroptosis gene that is consistently upregulated in AML, and high expression of GPX4 is associated with poor prognosis for AML patients. Importantly, simultaneous inhibition of NRF2 with ML385 and GPX4 with FIN56 or RSL3 synergistically targets AML cells, triggering ferroptosis. Treatment with ML385 + FIN56/RSL3 resulted in a marked reduction in NRF2 and GPX4 expression. Furthermore, NRF2 knockdown enhanced the sensitivity of AML cells to the ferroptosis inducers. Taken together, our results suggest that combination therapy targeting both NRF2 and GPX4 may represent a promising approach for the treatment of AML