Drug resistance has remained an important issue in the treatment and prevention of various diseases, including cancer. Herein, we found that USP24 not only repressed DNA-damage repair (DDR) activity by decreasing Rad51 expression to cause the tumor genomic instability and cancer stemness, but also increased the levels of the ATP-binding cassette (ABC) transporters P-gp, ABCG2, and ezrin to enhance the pumping out of Taxol from cancer cells, thus resulted in drug resistance during cancer therapy. A novel USP24 inhibitor, NCI677397, was screened for specific inhibiting the catalytic activity of USP24. This inhibitor was identified to suppress drug resistance via decreasing genomic instability, cancer stemness, and the pumping out of drugs from cancer cells. Understanding the role and molecular mechanisms of USP24 in drug resistance will be beneficial for the future development of a novel USP24 inhibitor. Our studies provide a new insight of USP24 inhibitor for clinically implication of blocking drug resistance during chemotherapy.
Electrospray ionization (ESI) and desorption electrospray ionization (DESI) are common soft ionization method of mass spectrometry (MS). However, recent studies revealed that some chemical reactions can be induced or greatly accelerated in the sprayed microdroplets compared to the same reaction in the bulk. These open a new area in using microdroplet MS to explore new chemistry and develop new applications. This minireview will introduce microdroplet chemistries and explore various microdroplet techniques most of which are ESI‐ or DESI‐based extensions by incorporating transfer tube, supersonic nebulizing gas, droplet fusion, spray extraction, laser irradiation, or laser ablation for online/offline MS analysis. Potential applications associated with new techniques, including real‐time reaction monitoring, high‐throughput reaction screening, protein identification, and protein characterization, are also described. Future outlook, such as coupling microdroplet MS with separation techniques, is proposed and discussed.
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