Regulation of exercise ability and glycolipid metabolism by synthetic SR9009 analogues as new REV-ERB-α agonists.

SR9009 is an activator of REV-ERBs with diverse biological activities, including improving exercise tolerance and controlling skeletal muscle mass. To optimise the carbamate motif of SR9009, analogues of SR9009 were synthesised and evaluated. All of them showed REV-ERB-α agonist activities. Among them, 5a, 5f, 5 g, 5m, and 5p showed potencies equivalent to or slightly higher than the potency of SR9009 in vitro. These data indicate that the halogenated benzyl group is an indispensable active group in these compounds. 5m, 5p and SR9009 improved exercise tolerance in normal mice in vivo. Additionally, in hyperlipidemic mice, 5m and 5p not only improved exercise tolerance but also lowered blood lipid levels. 5m and 5p displayed stronger hypoglycaemic activity than SR9009.

Mechanical Properties Directionality and Permeability of Fused Triply Periodic Minimal Surface Porous Scaffolds Fabricated by Selective Laser Melting.

Titanium alloy porous scaffolds possess excellent mechanical properties and biocompatibility, making them promising for applications in bone tissue engineering. The integration of triply periodic minimal surface (TPMS) with porous scaffolds provides a structural resemblance to the trabecular and cortical bone structures of natural bone tissue, effectively reducing stress-shielding effects, enabling the scaffold to withstand complex stress environments, and facilitating nutrient transport. In this study, we designed fused porous scaffolds based on the Gyroid and Diamond units within TPMS and fabricated samples using selective laser melting technology. The effects of the rotation direction and angle of the inner-layer G unit on the elastic modulus of the fused TPMS porous scaffold were investigated through quasi-static compression experiments. Furthermore, the influence of the rotation direction and angle of the inner-layer G unit on the permeability, pressure, and flow velocity of the fused TPMS porous scaffold structure was studied using computational fluid dynamics (CFD) based on the Navier-Stokes model. The quasi-static compression experiment results demonstrated that the yield strength of the fused TPMS porous scaffold ranged from 367.741 to 419.354 MPa, and the elastic modulus ranged from 10.617 to 11.252 GPa, exhibiting stable mechanical performance in different loading directions. The CFD simulation results indicated that the permeability of the fused TPMS porous scaffold model ranged from 5.70015 × 10-8 to 6.33725 × 10-8 m2. It can be observed that the fused porous scaffold meets the requirements of the complex stress-bearing demands of skeletal structures and complies with the permeability requirements of human bone tissue.