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

Insulin-producing pancreaticβcell 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 pancreaticβcell 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 pancreaticβcells 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.

Transparent perovskite glass-ceramics for visual optical thermometry

Optical thermometers have aroused considerable attention in recent years,and the increasing demand of sensitivity for practical application encourages the investigation on developing innovative non-contact optical thermo metric materials with higher sensitivity and accuracy.Perovskite quantum dots(QDs)with excellent temperature-dependence optical properties,provide a feasible approach to realizing the detection of temperature change,however,their poor high temperature thermal stability and the facile realization to obtain the production remain a daunting challenge.Herein,growing Tb^(3+)-doped CsPbl_(3) QDs in situ in borosilicate glass is proposed,which ensures the phase stability,and high-efficiency florescence output of the all-inorganic perovskite as a temperature sensor.A higher absolute and relative temperature sensitivity(0.0398 K^(-1) and 7.12%/K,respectively),along with the visible color change from orange-red to yellow-green with the increase of temperature is accomplished.Notably,the repeatable florescence intensity of Tb^(3+)-doped CsPbl_(3) QDs under high temperature enables their temperature sensing application.