Microstructure, Mechanical Properties and Fatigue Crack Growth Behavior of Gas Tungsten Arc Welding Welded Joint of the Hastelloy N Alloy.

Hastelloy N alloy is an excellent oxidation and corrosion-resistant material, which is selected as the shell material for the main vessel of molten salt reactors (MSRs). In this work, we conducted double-sided gas tungsten arc welding (GTAW) on 4 mm thick Hastelloy N alloy plates to examine the microstructure and mechanical properties of the welded joints. The S-N curve was obtained by fatigue test. The experimental results show that fatigue cracks initiate along the weld toe and propagate inward in a fan-shaped pattern. The hardness is highest in the heat-affected zone (HAZ). The fracture mode observed was trans-granular. The plastic zone in the initial stages of crack propagation remained relatively minimal. However, it gradually expanded during subsequent stages of the process. It is noteworthy that the crack propagation process often involves the development of secondary cracks, accompanied by profound plasticity-induced closure effects. The results of our investigation demonstrate that the welded joint exhibits excellent fatigue performance.

Discovery of cyanopyridine scaffold as novel indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors through virtual screening and preliminary hit optimisation.

With the aim of discovering novel IDO1 inhibitors, a combined similarity search and molecular docking approach was employed to the discovery of 32 hit compounds. Testing the screened hit compounds has led to several novel submicromolar inhibitors. Especially for compounds LVS-019 with cyanopyridine scaffold, showed good IDO1 inhibitory activity. To discover more compounds with similar structures to LVS-019, a shape-based model was then generated on the basis of it and the second-round virtual screening was carried out leading to 23 derivatives. Molecular docking studies suggested a possible binding mode of LVS-019, which provides a good starting point for the development of cyanopyridine scaffold compounds as potent IDO1 inhibitor. To improve potency of these hits, we further designed and synthesised another 14 derivatives of LVS-019. Among these compounds, LBJ-10 showed improved potency compared to the hits and displayed comparable potency to the control GDC-0919 analogue. LBJ-10 can serve as ideal leads for further modifications as IDO1 inhibitors for cancer treatment.