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Purpose: The implementation of targeted therapies for acute myeloid leukemia (AML) has been challenging. Fat mass and obesity associated protein (FTO), an mRNA N 6 -methyladenosine (m 6 A) demethylase, functions as an oncogene that promotes leukemic oncogene-mediated cell transformation and leukemogenesis. Here, we investigated the role of Saikosaponin-d (SsD) in broad anti-proliferation effects in AML and evaluated the m 6 A demethylation activity by targeting FTO of SsD. Methods: It was examined whether and how SsD regulates FTO/m 6 A signaling in AML. The pharmacologic activities and mechanisms of actions of SsD in vitro , in mice, primary patient cells, and tyrosine kinase inhibitors-resistant cells were determined. Results: SsD showed a broadly-suppressed AML cell proliferation and promoted apoptosis and cell-cycle arrest both in vitro and in vivo . Mechanistically, SsD directly targeted FTO, thereby increasing global m 6 A RNA methylation, which in turn decreased the stability of downstream gene transcripts, leading to the suppression of relevant pathways. Importantly, SsD also overcame FTO/m 6 A-mediated leukemia resistance to tyrosine kinase inhibitors. Conclusion: Our findings demonstrated that FTO-dependent m 6 A RNA methylation mediated the anti-leukemic actions of SsD, thereby opening a window to develop SsD as an epitranscriptome-base drug for leukemia therapy.

An innovative strategy for sustainably active oxygen capture using nitrogen (N 2 ) instead of helium (He) as direct analysis in real time (DART) gas is demonstrated in this work. DART MS was carried out to analyze different polarity compounds including organophosphorus pesticides, amino acids, hormones, and poly brominated diphenyl ethers by using He and N 2 as DART gas, respectively. The unexpectedly characteristic ionization reactions including replacement reaction where the sulfur atom of P=S group was replaced by oxygen atom, oxidation ([M+nO+H] + or [M+nO-H] -(n = 1, 2, 3, 4, 5)), and hydrogen loss (loss of two hydrogens) rapidly occurred in situ in the presence of N 2 under ambient conditions without any additives. The reaction mechanisms were proposed and further confirmed by high resolution tandem mass spectrometry. Our study under high temperature and high voltage provides a powerful tool for generating unique ionic species that may be difficult to form by other means, which also creates favorable conditions for the future study of the mechanism of DART MS.

The fluorescent nanoparticles based on 9,10-distyrylanthracene (DSA) derivatives (4,4'-((1E,1'E)-anthracene-9,10-diylbis(ethene-2,1-diyl))bis(N,N-dimethylaniline) (NDSA) and 4,4'-((1E,1'E)-anthracene-9,10-diylbis(ethene-2,1-diyl))dibenzonitrile (CNDSA)) were prepared by ultrasound aided nanoprecipitation method. The morphologies of the fluorescent nanoparticles could be controlled by...