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We report here on a novel pro-leukemogenic role of FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) that interferes with microRNAs (miRNAs) biogenesis in acute myeloid leukemia (AML) blasts. We showed that FLT3-ITD interferes with the canonical biogenesis of intron-hosted miRNAs such as miR-126, by phosphorylating SPRED1 protein and inhibiting the "gatekeeper" Exportin 5 (XPO5)/RAN-GTP complex that regulates the nucleus-to-cytoplasm transport of pre-miRNAs for completion of maturation into mature miRNAs. Of note, despite the blockage of "canonical" miRNA biogenesis, miR-155 remains upregulated in FLT3-ITD+ AML blasts, suggesting activation of alternative mechanisms of miRNA biogenesis that circumvent the XPO5/RAN-GTP blockage. MiR-155, a BIC-155 long noncoding (lnc) RNA-hosted oncogenic miRNA, has previously been implicated in FLT3-ITD+ AML blast hyperproliferation. We showed that FLT3-ITD upregulates miR-155 by inhibiting DDX3X, a protein implicated in the splicing of lncRNAs, via p-AKT. Inhibition of DDX3X increases unspliced BIC-155 that is then shuttled by NXF1 from the nucleus to the cytoplasm, where it is processed into mature miR-155 by cytoplasmic DROSHA, thereby bypassing the XPO5/RAN-GTP blockage via "non-canonical" mechanisms of miRNA biogenesis.

Acute myeloid leukemia (AML) harboring inv(16)(p13q22) expresses high levels of miR-126. Here we show that the CBFB-MYH11 (CM) fusion gene upregulates miR-126 expression through aberrant miR-126 transcription and perturbed miR-126 biogenesis via the HDAC8/RAN-XPO5-RCC1 axis. Aberrant miR-126 upregulation promotes survival of leukemia-initiating progenitors and is critical for initiating and maintaining CM-driven AML. We show that miR-126 enhances MYC activity through the SPRED1/PLK2-ERK-MYC axis. Notably, genetic deletion of miR-126 significantly reduces AML rate and extends survival in CM knock-in mice. Therapeutic depletion of miR-126 with an anti-miR-126 (miRisten) inhibits AML cell survival, reduces leukemia burden and leukemia stem cell (LSC) activity in inv(16) AML murine and xenograft models. The combination of miRisten with chemotherapy further enhances the anti-leukemia and anti-LSC activity. Overall, this study provides molecular insights for the mechanism and impact of miR-126 dysregulation in leukemogenesis and highlights the potential of miR-126 depletion as a therapeutic approach for inv(16) AML.

Layered composite oxide materials with O3/P2 biphasic crystallographic structure typically demonstrate a combination of high capacities of the O3 phase and high operation voltages of the P2 phase. However, their practical applications are seriously obstructed by difficulties in thermodynamic phase regulation, complicated electrochemical phase transition, and unsatisfactory cycling life. Herein, we propose an efficient structural evolution strategy from biphase to monophase of Na0.766+xLixNi0.33−xMn0.5Fe0.1Ti0.07O2 through Li+ substitution. The role of Li+ substitution not only simplifies the unfavorable phase transition by altering the local coordination of transition metal (TM) cations but also stabilizes the cathode–electrolyte interphase to prevent the degradation of TM cations during battery cycling. As a result, the thermodynamically robust O3‐Na0.826Li0.06Ni0.27Mn0.5Fe0.1Ti0.07O2 cathode delivers a high capacity of 139.4 mAh g−1 at 0.1 C and shows prolonged cycling life at high rates, with capacity retention of 81.6% at 5 C over 500 cycles. This work establishes a solid relationship between the thermodynamic structure evolution and electrochemistry of layered cathode materials, contributing to the development of long‐life sodium‐ion batteries. [ABSTRACT FROM AUTHOR]

Rechargeable potassium-ion batteries (PIBs) have shown great potential as an alternative to lithium-ion batteries (LIBs) owing to the abundant and available potassium reserves. However, their applications are hindered by unsatisfactory cycling stability of cathode materials. Herein, through electrochemical ion-exchange of the Na0.85Li0.12Ni0.22Mn0.66O2 compound, we reported P2-K0.56Na0.11Li0.12Ni0.22Mn0.66O2 (P2-KNaLNM) as a potential high-performance cathode for PIBs. The presence of Li plays a key role in suppressing the K+/vacancy ordering within transition metal slabs. Therefore, P2-KNaLNM underwent a simple single-phase reaction during intercalation/extraction of K+ ions. Consequently, P2-KNaLNM delivers a reversible capacity of 90.2 mA h g−1 and good capacity retention of 89.6% over 150 cycles at 0.2C between 1.5 and 4.6 V (vs. K+/K). Furthermore, a satisfactory capacity retention of 91.5% after 300 cycles is achieved at 0.5C because of the excellent K+ kinetics during the charge and discharge process. This work provides a feasible way to develop a promising cathode candidate for PIBs. [ABSTRACT FROM AUTHOR]

In spite of the competitive performance at room temperature, the development of sodium‐ion batteries (SIBs) is still hindered by sluggish electrochemical reaction kinetics and unstable electrode/electrolyte interphase under subzero environments. Herein, a low‐concentration electrolyte, consisting of 0.5M NaPF6 dissolving in diethylene glycol dimethyl ether solvent, is proposed for SIBs working at low temperature. Such an electrolyte generates a thin, amorphous, and homogeneous cathode/electrolyte interphase at low temperature. The interphase is monolithic and rich in organic components, reducing the limitation of Na+ migration through inorganic crystals, thereby facilitating the interfacial Na+ dynamics at low temperature. Furthermore, it effectively blocks the unfavorable side reactions between active materials and electrolytes, improving the structural stability. Consequently, Na0.7Li0.03Mg0.03Ni0.27Mn0.6Ti0.07O2//Na and hard carbon//Na cells deliver a high capacity retention of 90.8 % after 900 cycles at 1C, a capacity over 310 mAh g−1 under −30 °C, respectively, showing long‐term cycling stability and great rate capability at low temperature. [ABSTRACT FROM AUTHOR]

This study shows the investigations of Multi‐resonance thermally activated delayed fluorescence (MR‐TADF) materials and solution‐processed holes injection/transport layers (HITLs) in organic light‐emitting diodes (OLEDs), while extending to Organic Light Emitting Transistors (OLETs). Firstly, we explore TBN‐TPA, a blue MR‐TADF material, in single‐unit and tandem OLEDs via optical simulation. The tandem architecture enhances color purity, achieving a narrow full width at half maximum down to 24 nm, thus meeting BT 2020 standards. This marks the first instance of tandem OLEDs improving both efficiency and color performance of a multi‐resonance TADF emitter. Concurrently, we investigate the regulation of solution‐processed HITL compositions in OLEDs, aiming to improve charge injection and optical waveguiding. The adoption of solution‐processed HITLs reduces the turn‐on voltage and enhances power efficiency by 8.81% at a brightness of 5000 cd/m2 compared to vacuum‐deposited HITLs. By adjusting the composition of solution‐based PEDOT:PSS/TAPC as HITL, we effectively mitigate hole injection barriers and improve surface morphology, establishing an optical waveguide within the OLED structure. This holistic investigation employs optical simulation to advance high‐performance and cost‐effective OLEDs and OLETs for lighting and displays. [ABSTRACT FROM AUTHOR]

Endometrial cancer (EC) is a reproductive system disease that occurs in perimenopausal and postmenopausal women. However, its etiology is unclear. Melatonin (MT) has been identified as a therapeutic agent for EC; however, its exact mechanism remains unclear. In the present study, we determined that GATA‐binding protein 2 (GATA2) is expressed at low levels in EC and regulated by MT. MT upregulates the expression of GATA2 through MT receptor 1A (MTNR1A), whereas GATA2 can promote the expression of MTNR1A by binding to its promoter region. In addition, in vivo and in vitro experiments showed that MT inhibited the proliferation and metastasis of EC cells by upregulating GATA2 expression. The protein kinase B (AKT) pathway was also affected. In conclusion, these findings suggest that MT and GATA2 play significant roles in EC development. [ABSTRACT FROM AUTHOR]

Although many studies have evaluated plant ecophysiological responses to increasing atmospheric carbon dioxide concentration (CO2) and increasing temperature, few studies have addressed the interactive effects of these two factors, especially on high-altitude trees that are more sensitive. To address this issue, we used Abies faxoniana and Picea purpurea seedlings to evaluate the effects of elevated CO2 (CeTa, 700 ppm), elevated temperature (CaTe, 2 °C above ambient temperature) and elevated CO2 combined with elevated temperature (CeTe) on plant growth, morphology and physiological responses. We found that CaTe increased conifer total dry mass, specific root length, net photosynthesis rate and translocation rates of 15NH4+ and 15NO3−, but CeTe had stronger responses (except net photosynthesis rate of A. faxoniana). These results indicate that the effect of elevated temperature on the growth and physiological responses is enhanced by elevated CO2. Furthermore, effect of CeTe on physiological traits was higher in P. purpurea , which possessed a higher total dry mass, specific leaf area, water use efficiency (δ 13C), δ 15NO3−-N level, translocation rates of 15NH4+ and 15NO3− and total nonstructural carbohydrates than A. faxoniana. Overall, these findings suggest that the interactive effects of CO2 × temperature should be considered when assessing conifer responses to future climates. [ABSTRACT FROM AUTHOR]