Decoding m6A RNA methylome identifies PRMT6-regulated lipid transport promoting AML stem cell maintenance.

N6-methyladenosine (m6A) is a common chemical modification for mammalian mRNA and exhibits high dynamics in various biological processes. However, dynamics of m6A RNA methylome during leukemogenesis remains unknown. Here, we delineate a comprehensive m6A landscape during acute myeloid leukemia (AML) development and identify PRMT6 as a key for maintaining AML stem cells. We observe an obvious change in m6A methylome during leukemogenesis and find that protein arginine methyltransferase PRMT6 and m6A reader IGF2BP2 maintain the function of human and murine leukemia stem cells (LSCs). Genetic deletion or pharmacological inhibition of PRMT6 damages AML development and LSC function. Mechanistically, IGF2BP2 stabilizes PRMT6 mRNA via m6A-mediated manner, which catalyzes H3R2me2a and suppresses lipid transporter MFSD2A expression. PRMT6 loss upregulates MFSD2A expression that increases docosahexaenoic acid levels and impairs LSC maintenance. Collectively, our findings reveal a critical role of PRMT6-MFSD2A signaling axis in AML development and provide a therapeutic strategy for targeting LSCs.

RNA m6A Modification Plays a Key Role in Maintaining Stem Cell Function in Normal and Malignant Hematopoiesis.

N6-methyladenosine (m6A) is a commonly modification of mammalian mRNAs and plays key roles in various cellular processes. Emerging evidence reveals the importance of RNA m6A modification in maintaining stem cell function in normal hematopoiesis and leukemogenesis. In this review, we first briefly summarize the latest advances in RNA m6A biology, and further highlight the roles of m6A writers, readers and erasers in normal hematopoiesis and acute myeloid leukemia. Moreover, we also discuss the mechanisms of these m6A modifiers in preserving the function of hematopoietic stem cells (HSCs) and leukemia stem cells (LSCs), as well as potential strategies for targeting m6A modification related pathways. Overall, we provide a comprehensive summary and our insights into the field of RNA m6A in normal hematopoiesis and leukemia pathogenesis.

Access to Multisubstituted 2(5 H)-Furanones Using Hydrogen Bonding-Promoted Ring-Closing Metathesis and Polyamine Workup.

Structurally complex 2(5 H)-furanones are potentially challenging targets for ring-closing metathesis (RCM). A hydrogen bonding-guided RCM strategy was developed in this study to provide 3-substituted and 3,4-disubstituted 2(5 H)-furanones in moderate to high yields with broad functional group tolerance. A workup procedure using ethylenediamine-derived polyamines such as tetraethylenepentylamine was also established to effectively remove Ru residues in products.

Rapid fabrication of transparent film directly from wood fibers with microwave-assisted ionic liquids technology.

Presently flexibly transparent film or nanopaper from all cellulose was mostly fabricated by assembling cellulose nanofibers disintegrated from macroscopic wood fibers which mostly suffers from potential environmental toxicity or high cost. In this work, we firstly reported an all-cellulose transparent film fabricated by a novel microwave-assisted ionic liquids technology (MILT). The use of MILT for treating the original all-cellulose paper brings nearly 2.6 fold-increases in optical transmission, and 2.0 fold-increases in tensile property compared to those without microwave assistance. More importantly, by contrast with the partial dissolution of cellulose in typical DMAC/LiCl, ILs, NaOH/urea, the MILT is extremely time-saved with responding to the highest increase in mechanical property because the high efficient surface dissolution and welding bind individual sheets together under a micro environment.

Rapid ILs-polishing Processes Toward Flexible Nanostructured Paper with Dually High Transparency and Haze.

Biodegradable highly nanostructured paper has received great interest in past years due to its excellent optical properties which facilitate its wide applications in green flexible electronics and devices. However, energy and/or time-consuming procedure during the process of fabricating most nanostructured transparent paper are presently the main obstacle to their scalable production. In this work, we demonstrated a novel nanostructured paper with dually high transparency (∼91%) and high haze (∼89%) that was directly fabricated from original paper with rapid ILs-polishing processes. The whole fabricating time only requires 10 min. Compared to the previously reported nanopaper made of the isolated cellulose nanofibers by pure mechanical and/or chemical approaches, this work presented herein is devoted to use green ILs to polish directly the micrometer-sized fibrous paper into the nanostructured paper. This new method brings a rapid fabrication of transparent nanostructured paper while also retaining dual intriguing properties both in optical transmittance and haze. This work is capable of fabricating next-generation flexible and highly transparent and haze paper by a high-speed roll-to-roll manufacturing process with a much lower cost.

Transparent Electrode and Magnetic Permalloy Made from Novel Nanopaper.

We report a novel partial dissolution strategy to liberate uniform cellulose nanofibers with diameter of 5-10 nm from macroscopic cellulose fibers and promote separation of nanofibers in an aqueous environment by forming water-soluble sodium carboxymethylcellulose (CMC) through heterogeneous sodium acetoxylation of cellulose. With the obtained cellulose nanofibers, we fabricated nanopapers which exhibit high optical transparency of 90.5% (@550 nm) with promising mechanical properties and high thermal stability. By directly depositing Ag nanowires on a wet nanofiber sheet, we fabricated a flexible transparent electrode with 86.5% (@550 nm) transparency and 26.2 Ω/sq sheet resistance (Rs). Meanwhile, we studied the magnetic properties of sputter deposited thin film of permalloy on nanopaper which exhibited a similar magnetic coercivity and a close saturation magnetization to conventional silicon dioxide-based permalloy.

Rapid Dissolving-Debonding Strategy for Optically Transparent Paper Production.

Transparent paper is an alternative substrate for electronic devices due to its unique properties. However, energy-intensive and/or time-consuming procedures currently limit the scalable production of transparent paper. In this report, we demonstrate a rapid process to fabricate optically transparent paper with regenerative cellulose fibers (RCFs) by employing a dissolving-debonding strategy. The RCFs have an average width of 19.3 µm and length of several hundred microns and are prepared into transparent paper by vacuum filtration. This new dissolving-debonding approach enables high production efficiency while creating transparent paper with excellent optical and mechanical properties.