Identifying a Universal Activity Descriptor and a Unifying Mechanism Concept on Perovskite Oxides for Green Hydrogen Production.

Producing indispensable hydrogen and oxygen for social development via water electrolysis shows more prospects than other technologies. Although electrocatalysts have been explored for centuries, a universal activity descriptor for both hydrogen-evolution reaction (HER) and oxygen-evolution reaction (OER) is not yet developed. Moreover, a unifying concept is not yet established to simultaneously understand HER/OER mechanisms. Here, the relationships between HER/OER activities in three common electrolytes and over ten representative material properties on 12 3d-metal-based model oxides are rationally bridged through statistical methodologies. The orbital charge-transfer energy (Δ) can serve as an ideal universal descriptor, where a neither too large nor too small Δ (≈1 eV) with optimal electron-cloud density around Fermi level affords the best activities, fulfilling Sabatier's principle. Systematic experiments and computations unravel that pristine oxide with Δ ≈ 1 eV possesses metal-like high-valence configurations and active lattice-oxygen sites to help adsorb key protons in HER and induce lattice-oxygen participation in the OER, respectively. After reactions, partially generated metals in the HER and high-valence hydroxides in the OER dominate proton adsorption and couple with pristine lattice-oxygen activation, respectively. These can be successfully rationalized by the unifying orbital charge-transfer theory. This work provides the foundation of rational material design and mechanism understanding for many potential applications.

Discovery of IHMT-MST1-39 as a novel MST1 kinase inhibitor and AMPK activator for the treatment of diabetes mellitus.

Insulin-producing pancreatic ß cell death is the fundamental cause of type 1 diabetes (T1D) and a contributing factor to type 2 diabetes (T2D). Moreover, metabolic disorder is another hallmark of T2D. Mammalian sterile 20-like kinase 1 (MST1) contributes to the progression of diabetes mellitus through apoptosis induction and acceleration of pancreatic ß cell dysfunction. AMP-activated protein kinase (AMPK) is an energy sensing kinase and its activation has been suggested as a treatment option for metabolic diseases. Thus, pharmacological inhibition of MST1 and activation of AMPK simultaneously represents a promising approach for diabetes therapy. Here, we discovered a novel selective MST1 kinase inhibitor IHMT-MST1-39, which exhibits anti-apoptosis efficacy and improves the survival of pancreatic ß cells under diabetogenic conditions, as well as primary pancreatic islets in an ex vivo disease model. Mechanistically, IHMT-MST1-39 activated AMPK signaling pathway in hepatocytes in vitro, combination of IHMT-MST1-39 and metformin synergistically prevented hyperglycemia and significantly ameliorated glucose tolerance and insulin resistance in diabetic mice. Taken together, IHMT-MST1-39 is a promising anti-diabetic candidate as a single agent or in combination therapy for both T1D and T2D.

Discovery of IHMT-MST1-58 as a Novel, Potent, and Selective MST1 Inhibitor for the Treatment of Type 1/2 Diabetes.

The critical pathogenesis of type 1 diabetes (T1D)/type 2 diabetes (T2D) is the physical status, mass, and function of pancreatic ß cells. Mammalian STE20-like protein 1 kinase (MST1) plays vital roles in the apoptosis and insulin secretion of ß cells. Here, we discovered a novel, potent, and selective MST1 inhibitor 19 (IC50 = 23 nM), which inhibited the phosphorylation of MST1-protected ß cells from the damage of inflammatory cytokines in vitro. In vivo, it displayed acceptable pharmacokinetic properties in different species. In the STZ-induced T1D/T2D mouse models, both monotherapy of 19 and in combination with metformin led to the decline of fasting blood glucose and showed protective effect of ß cells. In addition, the combination of 19 and metformin decreased the hemoglobin A1c level. Together, our study suggested that 19 might be a useful pharmacological tool to study MST1-mediated physiology and pathology as well as a potential drug candidate for diabetes.

New Undisputed Evidence and Strategy for Enhanced Lattice-Oxygen Participation of Perovskite Electrocatalyst through Cation Deficiency Manipulation.

Oxygen evolution reaction (OER) is a key half-reaction in many electrochemical transformations, and efficient electrocatalysts are critical to improve its kinetics which is typically sluggish due to its multielectron-transfer nature. Perovskite oxides are a popular category of OER catalysts, while their activity remains insufficient under the conventional adsorbate evolution reaction scheme where scaling relations limit activity enhancement. The lattice oxygen-mediated mechanism (LOM) has been recently reported to overcome such scaling relations and boost the OER catalysis over several doped perovskite catalysts. However, direct evidence supporting the LOM participation is still very little because the doping strategy applied would introduce additional active sites that may mask the real reaction mechanism. Herein, a dopant-free, cation deficiency manipulation strategy to tailor the bulk diffusion properties of perovskites without affecting their surface properties is reported, providing a perfect platform for studying the contribution of LOM to OER catalysis. Further optimizing the A-site deficiency achieves a perovskite candidate with excellent intrinsic OER activity, which also demonstrates outstanding performance in rechargeable Zn-air batteries and water electrolyzers. These findings not only corroborate the key role of LOM in OER electrocatalysis, but also provide an effective way for the rational design of better catalyst materials for clean energy technologies.