The Invention of WM382, a Highly Potent PMIX/X Dual Inhibitor toward the Treatment of Malaria.

Drug resistance to first-line antimalarials-including artemisinin-is increasing, resulting in a critical need for the discovery of new agents with novel mechanisms of action. In collaboration with the Walter and Eliza Hall Institute and with funding from the Wellcome Trust, a phenotypic screen of Merck's aspartyl protease inhibitor library identified a series of plasmepsin X (PMX) hits that were more potent than chloroquine. Inspired by a PMX homology model, efforts to optimize the potency resulted in the discovery of leads that, in addition to potently inhibiting PMX, also inhibit another essential aspartic protease, plasmepsin IX (PMIX).

Distribution and transport of heavy metals in surface sediments of Chengbei Sea in the Bohai Sea.

It is of great significance to study the distribution characteristics and transport of heavy metals in complex sedimentary environments and areas with intensive human activities. This study analyzed sediment size, heavy metal contents (Cu, Zn, Cd, Cr, and Pb), organic carbon content, and sulfide content in surface sediments collected from 27 sites in Chengbei Sea. The main controlling factors of the distribution and transport of heavy metals were discussed from the perspective of sediment dynamics.

Selective N7 Alkylation of 7-Azaindazoles.

A general and mild procedure for alkylation of 7-azaindazoles at the N7 position using alkyl halides in butanone is reported, which requires no additives such as acids or bases. The scope of the reaction regarding substituents on 7-azaindazoles and the alkyl electrophiles is presented.

Role of interleukin-6 in differentiating interleukin-11 induced fever and early bacterial infection.

Objective: To evaluate the role of Th1/Th2 cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ) in differentiating interleukin 11 induced fever with C-reactive protein elevation from early bacterial infection.

Methods: A total of 74 patients were enrolled in this retrospective study. Serum Th1/Th2 cytokines were determined using cytometric bead array (CBA) techniques.

Axially chiral BINIM and Ni(II)-catalyzed highly enantioselective 1,3-dipolar cycloaddition reactions of azomethine ylides and N-arylmaleimides.

Axially chiral BINIM-Ni(II) complexes are effective catalysts in the asymmetric 1,3-dipolar cycloaddition reactions of azomethine ylides and N-arylmaleimides to give the corresponding adducts in good yields and up to 95% enantiomeric excesses.

[The mistakes of E. Dinc's double divisor-ratio spectra derivative method].

Double divisor-ratio spectra derivative method has been developed and applied to determining two ternary mixtures simultaneously by E. Dinc. In fact, E.