Berberine targets the electron transport chain complex I and reveals the landscape of OXPHOS dependency in acute myeloid leukemia with IDH1 mutation / 中国天然药物

Metabolic reprogramming, a newly recognized trait of tumor biology, is an intensively studied prospect for oncology medicines. For numerous tumors and cancer cell subpopulations, oxidative phosphorylation (OXPHOS) is essential for their biosynthetic and bioenergetic functions. Cancer cells with mutations in isocitrate dehydrogenase 1 (IDH1) exhibit differentiation arrest, epigenetic and transcriptional reprogramming, and sensitivity to mitochondrial OXPHOS inhibitors. In this study, we report that berberine, which is widely used in China to treat intestinal infections, acted solely at the mitochondrial electron transport chain (ETC) complex I, and that its association with IDH1 mutant inhibitor (IDH1mi) AG-120 decreased mitochondrial activity and enhanced antileukemic effect in vitro andin vivo. Our study gives a scientific rationale for the therapy of IDH1 mutant acute myeloid leukemia (AML) patients using combinatory mitochondrial targeted medicines, particularly those who are resistant to or relapsing from IDH1mi.

Design and implementation of the Walsh-Hadamard transform on a ternary optical computer.

Walsh-Hadamard is a commonly used mathematical transformation, a mathematical method for spectrum analysis in the real number domain, which has been widely used in many fields such as digital signal processing, spectral modulation, and image processing. Based on the characteristics of the ternary optical computer with a large number of processor bits, reconfigurable bit functions, and parallel computation, a ternary optical processor with all bits allocated is given, and the transformations T,W,T',W',T2 of modified signed-digit (MSD) addition are reconfigured. On this basis, by configuring AdderN MSD adders on the optical processor, the N-point Walsh-Hadamard transform fast parallel computing approach is given. It requires only 3×⌊N/AdderN⌋ clock cycles to compute the Walsh-Hadamard transform of N points under parallel computing. Furthermore, complexity analysis shows that the clock cycles in an electronic computer are N/3 times that of in a ternary optical computer under the fully parallel optical computation. The experiment of the Walsh-Hadamard transform with eight points shows that parallel optical computing has more advantages than the conventional electronic computer in fast computing the problems with characteristics of parallel computing. At the same time, it highlights the advantages and potential of ternary optical computers in data-intensive computing.

Design and implementation of the Walsh-Hadamard transform on a ternary optical computer: publisher's note.

This publisher's note serves to correct Appl. Opt.60, 9254 (2021).APOPAI0003-693510.1364/AO.435457.