Design, synthesis, and biological evaluation of novel sesquiterpene lactone derivatives as PKM2 activators with potent anti-ulcerative colitis activities.

Pyruvate kinase isoform 2 (PKM2) is closely related to the regulation of Th17/Treg balance, which is considered to be an effective strategy for UC therapy. Parthenolide (PTL), a natural product, only possesses moderate PKM2-activating activity. Thus, five series of PTL derivatives are designed and synthesized to improve PKM2-activated activities and anti-UC abilities. Through detailed structure optimization, B4 demonstrates potent T-cell anti-proliferation activity (IC50 = 0.43 µM) and excellent PKM2-activated ability (AC50 = 0.144 µM). Subsequently, through mass spectrometry analysis, B4 is identified to interact with Cys423 of PKM2 via covalent-bond. Molecular docking and molecular dynamic simulation results reveal that the trifluoromethoxy of B4 forms a stronger hydrophobic interaction with Ala401, Pro402, and Ile403. In addition, B4 has a significant effect only on Th17 cell differentiation, thereby regulating the Th17/Treg balance. The effect of B4 on Th17/Treg imbalance can be attributed to inhibition of PKM2 dimer translocation and suppression of glucose metabolism. Finally, B4 can notably ameliorate the symptoms of dextran sulfate sodium (DSS)-induced colitis in mouse model in vivo. Thus, B4 is confirmed as a potent PKM2 activator, and has the potential to develop as a novel anti-UC agent.

Structural Modulation on NiCo2 S4 Nanoarray by N Doping to Enhance 2e-ORR Selectivity for Photothermal AOPs and Zn-O2 Batteries*.

As a H2 O2 generator, a 2e- oxygen reduction reaction active electrocatalyst plays an important role in the advanced oxidation process to degrade organic pollutants in sewage. To enhance the tendency of NiCo2 S4 towards the 2e- reduction reaction, N atoms are doped in its structure and replace S2- . The result implies that this weakens the interaction between NiCo2 S4 and OOH*, suppresses O-O bond breaking and enhances H2 O2 selectivity. This electrocatalyst also shows photothermal effect. Under photothermal heating, H2 O2 produced by the oxidation reduction reaction can decompose and releaseOH, which degrades organic pollutants through the advanced oxidation process. Photothermal effect induced by the advance oxidation process shows obvious advantages over the traditional Fenton reaction, such as wide pH adaptation scope and low secondary pollutant due to its Fe2+ free character. With Zn as anode and the electrocatalyst as cathode material, a Zn-O2 battery is assembled. It achieves electricity generation and photothermal effect induced by the advance oxidation process simultaneously.

Hydrophobic POM Electrocatalyst Achieves Low Voltage "Charge" in Zn-Air Battery Coupled with Bisphenol A Degradation.

Zn-air batteriesare a perspective power source for grid-storage. But, after they are discharged at1.1 to 1.2 V, large overpotential is required for their charging (usually 2.5 V). This is due to a sluggish oxygen evolution reaction (OER). Incorporating organic pollutants into the cathode electrolyte is a feasible strategy for lowering the required charging potential. In the discharge process, the related oxygen reduction reaction, hydrophobic electrocatalysts are more popular than hydrophilic ones. Here, a hydrophobic bifunctional polyoxometalate electrocatalyst is synthesized by precise structural design. It shows excellent activities in both bisphenol A degradation and oxygen reduction reactions. In bisphenol A containing electrolyte, to achieve 100 mA ⋅ cm-2 , its potential is only 1.32 V, which is 0.34 V lower than oxygen evolution reaction. In the oxygen reduction reaction, this electrocatalyst follows the four-electron mechanism. In both bisphenol A degradation and oxygen reduction reactions, it shows excellent stability. With this electrocatalyst as cathode material and bisphenol A containing KOH as electrolyte, a Zn-air battery was assembled. When "charged" at 85 mA ⋅ cm-2 , it only requires 1.98 V. Peak power density of this Zn-air battery reaches 120.5 mW ⋅ cm-2 . More importantly, in the "charge" process, bisphenol A is degraded, which achieves energy saving and pollutant removal simultaneously in one Zn-air battery.