Advanced glycation end products promote the progression of endometrial cancer via activating the RAGE/CHKA/PI3K/AKT signaling pathway.

Endometrial cancer (EC) is a common malignant tumor that is closely associated with metabolic disorders such as diabetes and obesity. Advanced glycation end products (AGEs) are complex polymers formed by the reaction of reducing sugars with the amino groups of biomacromolecules, mediating the occurrence and development of many chronic metabolic diseases. Recent research has demonstrated that the accumulation of AGEs can affect the tumor microenvironment, metabolism, and signaling pathways, thereby affecting the malignant progression of tumors. However, the mechanism by which AGEs affect EC is unclear. Our research aimed to investigate how AGEs promote the development of EC through metabolic pathways and to explore their potential underlying mechanisms. Our experimental results demonstrated that AGEs upregulated the choline metabolism mediated by choline kinase alpha (CHKA) through the receptor for advanced glycation end products (RAGE), activating the PI3K/AKT pathway and enhancing the malignant biological behavior of EC cells. Virtual screening and molecular dynamics simulation revealed that timosaponin A3 (timo A3) could target CHKA to inhibit AGE-induced progression of EC and that a newly discovered CHKA inhibitor could be a novel targeted inhibitor for the treatment of EC. This study provides new therapeutic strategies and contributes to the treatment of EC.

Atomic structure evolutions and mechanisms of the crystallization pathway of liquid Al during rapid cooling.

The solidification of pure aluminum has been studied by a large-scale molecular dynamic simulation. The potential energy, position D, height H, and width W of the first peak and valley of PDF curves, and the local structures were investigated. It was found that the FCC-crystallization ability of pure Al is so strong that still local crystal regions exist in the amorphized solid. As the temperature decreases, besides the counter-intuitive increase in D p (D of the first peak), H p increases monotonically; W p, D v, and H v decrease monotonically; only W v first decreases and then increases. They all change critically when phase transition happens. After the nucleation, orientation-disordered HCP-regions, as the grain boundaries or defects of FCC crystals, rapidly transform into FCC structures, and then the surviving HCP-regions regularize into few parallel layers or orientation-disordered HCP-regions. If parallel layers result in dislocation pinning, structural evolution terminates; otherwise, it continues. These findings will have a positive impact on the development of the solidification and nucleation theory.