Experimental Progress on Layered Topological Semimetals

We review recent experimental progresses on layered topological materials, mainly focusing on transitional metal dichalcogenides with various lattice types including 1T, Td and 1T' structural phases. Their electronic quantum states are interestingly rich, and many appear to be topological nontrivial, such as Dirac/Weyl semimetallic phase in multilayers and quantum spin hall insulator phase in monolayers. The content covers recent major advances from material synthesis, basic characterizations, angle-resolved photoemission spectroscopy measurements, transport and optical responses. Following those, we outlook the exciting future possibilities enabled by the marriage of topological physics and two dimensional van der Waals layered heterostructures.Comment: 2D Materials (2019

The novel norcantharidin derivative DCZ5417 suppresses multiple myeloma progression by targeting the TRIP13–MAPK–YWHAE signaling pathway

Abstract Background Multiple myeloma (MM), an incurable disease owing to drug resistance, requires safe and effective therapies. Norcantharidin (NCTD), an active ingredient in traditional Chinese medicines, possesses activity against different cancers. However, its toxicity and narrow treatment window limit its clinical application. In this study, we synthesized a series of derivatives of NCTD to address this. Among these compounds, DCZ5417 demonstrated the greatest anti-MM effect and fewest side effects. Its anti-myeloma effects and  the mechanism were further tested. Methods Molecular docking, pull-down, surface plasmon resonance-binding, cellular thermal shift, and ATPase assays were used to study the targets of DCZ5417. Bioinformatic, genetic, and pharmacological approaches were used to elucidate the mechanisms associated with DCZ5417 activity. Results We confirmed a highly potent interaction between DCZ5417 and TRIP13. DCZ5417 inhibited the ATPase activity of TRIP13, and its anti-MM activity was found to depend on TRIP13. A mechanistic study verified that DCZ5417 suppressed cell proliferation by targeting TRIP13, disturbing the TRIP13/YWHAE complex and inhibiting the ERK/MAPK signaling axis. DCZ5417 also showed a combined lethal effect with traditional anti-MM drugs. Furthermore, the tumor growth-inhibitory effect of DCZ5417 was demonstrated using in vivo tumor xenograft models. Conclusions DCZ5417 suppresses MM progression in vitro, in vivo, and in primary cells from drug-resistant patients, affecting cell proliferation by targeting TRIP13, destroying the TRIP13/YWHAE complex, and inhibiting ERK/MAPK signaling. These results imply a new and effective therapeutic strategy for MM treatment

Additional file 1 of The novel norcantharidin derivative DCZ5417 suppresses multiple myeloma progression by targeting the TRIP13–MAPK–YWHAE signaling pathway

Additional file 1: Figure S1. Development for a better effect and lower toxicity derivative of NCTD. Figure S2. DCZ5417 inhibits multiple myeloma. Figure S3. DCZ5417 inhibits MAPK signaling pathway