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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...

Squalene has been used as a dietary supplement for a long history due to its potential cancer‐preventive function. However, the mechanism has not been investigated in detail yet. Therefore, the aim of this study is to see if the plasma coenzyme Q10 (CoQ10) level will be altered by gavage of squalene and oxidosqualenes to rats. In the present work, a sensitive and simple high‐performance analytical method based on ultra‐high‐performance liquid chromatography coupled with an Orbitrap mass spectrometry (UPLC‐Orbitrap‐MS) was developed for the quantification of CoQ10 in rat plasma. Coenzyme Q9 (CoQ9) was employed as the internal standard. CoQ10 was determined after acetonitrile‐mediated plasma protein precipitation using UPLC‐Orbitrap‐MS in negative ion mode. Intragastric administration of squalene and the two squalene epoxides into rats once daily for several days elevated the level of CoQ10 in their plasma, but there was no significant difference between high‐dose (286 mg/kg) and low‐dose (143 mg/kg) groups. Intragastric administration of squalene once a day for 5 consecutive days and oxidosqualenes once a day for 3 consecutive days is necessary for reaching the steady‐state level of CoQ10. Our present findings indicate that squalene and oxidosqualenes may be useful for stimulating the synthesis of CoQ10 in rats.

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