Discovery of GPR183 Agonists Based on an Antagonist Scaffold

The G protein-coupled receptor GPR183/EBI2, which is activated by oxysterols, is a therapeutic target for inflammatory and metabolic diseases where both antagonists and agonists are of potential interest. Using the piperazine diamide core of the known GPR183 antagonist (E)-3-(4-bromophenyl)-1-(4-(4-methoxybenzoyl)piperazin-1-yl)prop-2-en-1-one (NIBR189) as starting point, we identified and sourced 79 structurally related compounds that were commercially available. In vitro screening of this compound collection using a Ca²⁺ mobilization assay resulted in the identification of 10 compounds with agonist properties. To enable establishment of initial structure-activity relationship trends, these were supplemented with five in-house compounds, two of which were also shown to be GPR183 agonists. Taken together, our findings suggest that the agonist activity of this compound series is dictated by the substitution pattern of one of the two distal phenyl rings, which functions as a molecular efficacy-switch.     

Reusable water oxidation catalyst with dual active center for enhanced water oxidation: Iridium oxide nanoparticles immobilized on monodisperse-porous Mn5O8 microspheres

A reusable catalyst with dual active center for chemical water oxidation is synthesized for the first time by immobilization of iridium oxide nanoparticles (IrO₂ NPs) on monodisperse-porous manganese oxide microspheres acting both catalytic active center and support. Individual catalytic activity of manganese oxide microspheres is explained by multiple oxidation states of manganese which are capable of forming oxidative oxygen species. Monodisperse-porous microspheres in the form of Mn₅O₈, MnO₂ and Mn₂O₃ are used for synthesis of different catalysts and the highest activity in water oxidation is observed with the catalyst synthesized using Mn₅O₈ microspheres. The catalytic activity is correlated with the total Mn(II) and Mn(III) percentage of manganese oxide type selected for composite catalyst. The oxygen evolution up to 244 μmol is achieved in 30 min with the catalyst synthesized using Mn₅O₈ microspheres. Maximum TON and TOF numbers are obtained as 298 and 557 h^?1 with excellent reusability.     

An optional connection material in timber structures: densified poplar

The development of eco-friendly connection material instead of steel is a challenging problem in timber structures. Following densification, the mechanical properties of low-density species can be significantly improved. Densified wood may be a potential connection material in timber structures. This paper reviewed the different processing for densified wood, and obtained favorable mechanical properties and dimensional stability based on small specimen sizes, which are much less than the applicable sizes in practice. A densification processing with alkali pretreatment was adopted for poplar widely cultivated in the world to produce the densified poplar, which has been rarely reported as connection material. Various specimens of densified poplar were tested to obtain their main mechanical properties such as strength and deformability. The set recovery of densified poplar was also measured to observe their dimensional stability. In addition, the hygroscopic swelling strains for the diameter of densified poplar dowel were measured to present their moisture-dependent behavior. The improved mechanical properties and dimensional stability confirmed the fact that densified poplar with alkali pretreatment can be an optimal connection material.

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Effects of different dwell-times under low pelletization pressure on the physical properties of the Bi-2212 ceramics

Journal of Materials Science: Materials in Electronics - We reported the evaluation of superconducting properties of Bi-2212 ceramics prepared under different dwell times between 12 and...