Fms-like tyrosine kinase 3 (FLT3) is a well-characterized therapeutic target for acute myeloid leukemia (AML). Despite the approval of two generations of small molecular FLT3 kinase inhibitors for AML treatment, the acquired drug resistance inevitably emerges. Moreover, the complete and sustained suppression of FLT3 signaling was demonstrated to be required for an effective clinical response, but it is challenging to achieve this goal with kinase inhibitors that work in an occupancy-driven manner. Targeting protein degradation by proteolysis targeting chimera (PROTAC) is a catalytic and event-driven process, and several PROTAC degraders for FLT3 have been developed. This review focuses on the latest research progress on FLT3 degraders, providing a systematic perspective and in-depth insights for targeted therapy of FLT3-mutated AML.

With the advantages of high efficiency and flexibility, the flexible organic solar cells (FOSCs) showed great application in wearable electronics. However, degradation of device performance due to the infiltration of water and oxygen into the flexible substrate becomes the main obstacle to its development. The traditional encapsulation with a sandwich structure would reduce the optical and mechanical properties of the devices and increase the device's weight. In this work, a strategy of in situ fabrication of highly efficient and long-term stable FOSCs on the highly transparent barrier film (BF) substrates is developed. A kind of light-sensitive material, o-nitrobenzyl alcohol derivatives, which can convert from hydrophilic to hydrophobic, is induced to improve the wettability of AgNWs on the substrate and enable the printing fabrication of a uniform AgNWs transparent electrode. After light conversion, the NBE films are converted to hydrophobic, which sufficiently improved the barrier property. The efficiency of the BF/NBE devices reached 16.33% and retained 80% of its initial value after being stored in the air for 600 h, which is compared to the grid devices with the glass substrate. Besides, due to the superior mechanical properties and thin thickness, the in situ FOSCs with barrier substrates exhibited excellent mechanical bending durability.

There remains an ongoing challenge to develop facile methods for the preparation of chiral gamma,gamma-difluorinated amines, which are commonly considered a privileged motif in bioactive compounds. In this context, we report a straightforward protocol for the stereoselective nucleophilic difluoro(sulfoximidoyl)methylation of C & boxH;C bonds (considered to be more challenging than the reported C & boxH;O bonds), which exhibits high stereoselectivity and broad substrate scope. The key features of this chemistry include 1) stereoselective addition of the difluoro(sulfoximidoyl)methyl anion to C & boxH;C bonds, although it was considered to be highly unfavorable from the view of hard-soft acid-base (HSAB) theory; 2) intriguing neighboring group participation of the oxygen from the nitro group that was found to play a crucial role in controlling the stereoselectivity and efficiency of the transformation and was supported by mechanistic experiments and DFT calculations. This method has been applied to the late-stage modification of several complex molecules and the preparation of enantioenriched bioactive gamma-fluorinated amines, such as a phytopathogenic fungi inhibitor, TRPC6 and CDK11 inhibitors, and even monofluorinated lorcaserin, which further demonstrated the significance and potential of this approach.

Whether the fluorine atom (F) can engage in a halogen bond (XB) has remained a subject of ongoing debate. The discovery of N-fluoropyridinium triflate as a unique F-cation organocatalyst for aziridine synthesis has generally been considered the first instance of F-halogen bonding catalysis. Nevertheless, the mechanistic details of this reaction have remained elusive, and compelling evidence supporting the F-halogen bond catalysis has been lacking. In this study, we present an in-depth computational investigation of the mechanism of this reaction to gain insights into the intriguing role of the F-cation organocatalyst. Our results, however, are inconsistent with the previous prevalent F-halogen bonding catalysis mechanism but instead, bring to light a new fluorine cation transfer mechanism. This novel mechanism is supported by control experiments and can explain the observed cis-trans selectivity.

The integration of photocatalysts and enzymes within confined environments offers a promising approach to developing artificial photosynthetic systems for sustainable CO2 conversion. However, the efficient coupling of photocatalysts with multiple enzymes to enable photo-enzymatic cascade catalysis remains a significant challenge. Herein, we report the construction of hydrogen-bonded organic frameworks (HOFs) that integrate Ru-based photocatalysts with three-enzyme cascades of formate dehydrogenase (FDH), formaldehyde dehydrogenase (FaldDH), and alcohol dehydrogenase (ADH) via in situ co-assembly in water. The RuHOF exhibits exceptional nicotinamide adenine dinucleotide (NADH) photo-regeneration activity (4.5 mM h-1), while the FDH@RuHOF hybrid converts CO2 to formic acid with a turnover frequency (TOF) of 681 h-1 (238 mu M h-1) over 24 h. By engineering FDH/FaldDH/ADH@RuHOF ternary systems, we achieve sustained CO2-to-methanol conversion through photo-enzymatic cascade catalysis, delivering 2.2 mM methanol production with an apparent quantum efficiency (AQY) of 5.5% (92 mu M h-1) over 24 h with 85% activity retention after five catalytic cycles. This work opens a promising avenue for the development of efficient multi-enzyme cascade artificial photosynthetic systems toward steady and recyclable CO2 valorization.

Sepsis-induced lung injury, characterized by unregulated inflammation and impaired alveolar epithelial integrity, significantly contributes to sepsis-related mortality. Although receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is critical in regulating necroptosis and inflammation, its precise contribution to sepsis-induced lung injury remains poorly understood. In this study, selective activation of RIPK1 in type II alveolar epithelial cells (AECs) is observed during sepsis. CXCL1 is identified as a critical downstream target of RIPK1 through integrative transcriptomic and proteomic analyses. Mechanistically, RIPK1 interacts with JAK1 to induce STAT3 phosphorylation, facilitate its nuclear translocation, and promote its binding to the Cxcl1 promoter, thereby upregulating its expression and driving excessive neutrophil recruitment. Genetic or pharmacological inhibition of RIPK1 attenuated CXCL1 production, neutrophil infiltration, and alveolar damage, improving survival in septic mice. Compound 62, a selective RIPK1 inhibitor, has demonstrated efficacy in attenuating systemic inflammatory cascades, preserving epithelial barrier integrity, and improving survival rates in mice. These findings establish RIPK1 as a therapeutic target in sepsis-induced lung injury and redefine alveolar epithelial cells as positive contributors to inflammatory amplification. This work advances precision strategies to mitigate sepsis-induced lung injury, addressing a critical unmet need in critical care medicine.