Structure-Based Discovery and Development of Highly Potent Dihydroorotate Dehydrogenase Inhibitors for Malaria Chemoprevention.

Malaria remains a serious global health challenge, yet treatment and control programs are threatened by drug resistance. Dihydroorotate dehydrogenase (DHODH) was clinically validated as a target for treatment and prevention of malaria through human studies with DSM265, but currently no drugs against this target are in clinical use. We used structure-based computational tools including free energy perturbation (FEP+) to discover highly ligand efficient, potent, and selective pyrazole-based DHODH inhibitors through a scaffold hop from a pyrrole-based series.

Optimization of arc quenching parameters for enhancing surface hardness and line width in S45C steel using Taguchi method.

This study investigates the impact of arc length, current intensity, travel speed, and gas flow rate on surface hardness and line width during arc quenching process of S45C steel. The current intensity has the greatest influence on the surface hardness of S45C steel, followed by the travel speed, gas flow rate, and arc length. Using the Taguchi method, the optimal values of the parameters such as the arc length of 1.

Microbiome and Hemato-immune Aging.

The microbiome is a highly complex and diverse symbiotic component that undergoes dynamic changes with the organismal aging. Microbial perturbations, termed dysbiosis, exert strong influence on dysregulating the bone marrow niche and subsequently promoting the aging of hematopoietic and immune system. Accumulating studies have revealed the substantial impact of intestinal microbiome on the initiation and progression of age-related hematologic alteration and diseases, such as clonal hematopoiesis and blood cancers.