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Aberrant cytokine signaling initiated from mutant receptor tyrosine kinases (RTKs) provides critical growth and survival signals in high risk acute myeloid leukemia (AML). Inhibitors to FLT3 have already been tested in clinical trials, however, drug resistance limits clinical efficacy. Mutant receptor tyrosine kinases are mislocalized in the endoplasmic reticulum (ER) of AML and play an important role in the non-canonical activation of signal transducer and activator of transcription 5 (STAT5). Here, we have tested a potent new drug called imipramine blue (IB), which is a chimeric molecule with a dual mechanism of action. At 200-300 nM concentrations, IB is a potent inhibitor of STAT5 through liberation of endogenous phosphatase activity following NADPH oxidase (NOX) inhibition. However, at 75-150 nM concentrations, IB was highly effective at killing mutant FLT3-driven AML cells through a similar mechanism as thapsigargin (TG), involving increased cytosolic calcium. IB also potently inhibited survival of primary human FLT3/ITD+ AML cells compared to FLT3/ITDneg cells and spared normal umbilical cord blood cells. Therefore, IB functions through a mechanism involving vulnerability to dysregulated calcium metabolism and the combination of fusing a lipophilic amine to a NOX inhibiting dye shows promise for further pre-clinical development for targeting high risk AML.

To address the issue of imbalanced electricity and hydrogen supply and demand in the flexible multi-energy port area system, a multi-regional operational optimization and energy storage capacity allocation strategy considering the working status of flexible multi-status switches is proposed. Firstly, based on the characteristics of the port area system, models for system operating costs, generation equipment, energy storage devices, flexible multi-status switches, and others are established. Secondly, the system is subjected to a first-stage optimization, where different regions are optimized individually. The working periods of flexible multi-status switches are determined based on the results of this first-stage optimization, targeting the minimization of the overall daily operating costs while ensuring 100% integration of renewable energy in periods with electricity supply-demand imbalances. Subsequently, additional constraints are imposed based on the results of the first-stage optimization to optimize the entire system, obtaining power allocation during system operation as well as power and capacity requirements for energy storage devices and flexible multi-status switches. Finally, the proposed approach is validated through simulation examples, demonstrating its advantages in terms of economic efficiency, reduced power and capacity requirements for energy storage devices, and carbon reduction. [ABSTRACT FROM AUTHOR]

Rhizosphere microbes play critical roles for plant's growth and health. Among them, the beneficial rhizobacteria have the potential to be developed as the biofertilizer or bioinoculants for sustaining the agricultural development. The efficient rhizosphere colonization of these rhizobacteria is a prerequisite for exerting their plant beneficial functions, but the colonizing process and underlying mechanisms have not been thoroughly reviewed, especially for the nonsymbiotic beneficial rhizobacteria. This review systematically analyzed the root colonizing process of the nonsymbiotic rhizobacteria and compared it with that of the symbiotic and pathogenic bacteria. This review also highlighted the approaches to improve the root colonization efficiency and proposed to study the rhizobacterial colonization from a holistic perspective of the rhizosphere microbiome under more natural conditions. [ABSTRACT FROM AUTHOR]

The semiconducting properties and applications of three dimensional (3D) covalent organic frameworks (COFs) are greatly hampered because of their long‐ranged non‐conjugated skeletons and relatively unstable linkages. Here, a robust imidazole‐linked fully conjugated 3D covalent organic framework (BUCT‐COF‐7) is synthesized through the one‐pot multicomponent Debus‐Radziszewski reaction of the saddle‐shaped aldehyde‐substituted cyclooctatetrathiophene, pyrene‐4,5,9,10‐tetraone, and ammonium acetate. The semiconducting BUCT‐COF‐7, as a metal‐free catalyst, shows excellent two electron oxygen reduction reaction (ORR) activity in alkaline medium with high hydrogen peroxide (H2O2) selectivity of 83.4 %. When the BUCT‐COF‐7 as cathode catalyst is assembled into the electrolyzer, the devices showed high electrochemical production rate of H2O2 up to 326.9 mmol g−1 h−1. The accumulative amount of H2O2 could totally degrade the dye methylene blue via Fenton reaction for wastewater treatment. This is the first report about intrinsic 3D COFs for efficient electrochemical synthesis of H2O2, revealing the promising applications of fully conjugated 3D COFs in the environment‐related field. [ABSTRACT FROM AUTHOR]

For the development of a full‐cell battery system, typically appropriate cathodes and anodes are characterized within a half‐cell setup where a metal counter electrode is installed to gather data about the employed electrodes. Ultimately, the individual capacity loadings allow for suitable balancing of the anode to cathode capacity in the full‐cell. This approach seems rather unproblematic for lithium‐ion batteries. For sodium‐ion batteries, however, we show that the high reactivity of sodium metal strongly influences hard carbon‐based electrode measurements within sodium‐ion half‐cells. As hard carbon is considered state‐of‐the‐art anode material, the presented results have high impact on the development of sodium ion batteries. Specifically, we show that the type of electrolyte, as well as cell‐ and measurement‐setup are key factors for reliable sodium half‐cell measurements of hard carbon. The investigated hard carbon electrodes have a high active material loading of 7.2 mg/cm2 (with 93 % active material content) resulting in an areal capacity of 2.4 mAh/cm2, which represent application‐relevant conditions. [ABSTRACT FROM AUTHOR]