First-in-human trial of SAR107375E, a novel small molecule anticoagulant with dual inhibition of factor Xa and factor IIa.

Background: SAR107375E is a direct dual inhibitor of both Factor Xa and Factor IIa and has shown potent anticoagulation activity in vitro and animals. This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending intravenous doses of SAR107375E in healthy Chinese adult subjects.

Methods: In this randomized, double-blind, placebo-controlled trial, 60 healthy Chinese adult subjects were administered intravenously single ascending doses (0.

Zero-valent iron is not always effective in enhancing anaerobic digestion performance.

Liquid nitrogen was employed as a low-temperature medium to activate zero-valent iron (ZVI) powder in an attempt to strengthen its enhancement effect on anaerobic digestion (AD) of swine manure (SM). Surprisingly, it was found that both pristine ZVI and liquid nitrogen-pretreated ZVI (LZVI) did not significantly improve the AD performance or change the archaeal community structure. It was hypothesized that ZVI might not be effective at stress-free environment like in these digesters.

A series of octahydroquinazoline-5-ones as novel inhibitors against dengue virus.

A series of octahydroquinazoline-5-ones (OHQs 1-50) were designed and synthesized via an improved five-component reaction (5CR). Their bioactivities against dengue virus (DENV) were evaluated by determining lacate dehydrogenase (LDH) in the BHK-21 cells infected with DENV-2. Primary structure-activity relationship showed that six of OHQs with suitable substituents displayed good activities with EC = 1.

Design, synthesis and antibacterial evaluation of 2,4-disubstituted-6-thiophenyl-pyrimidines.

The increasing incidences of multidrug resistant bacterial infections urge the development of novel antibacterial having a new mechanism of action. The small molecule-based inhibitors targeting at the cell division protein FtsZ has been recognized as a promising approach to search for new antibacterial with high potency. In the present study, a series of novel 2,4-disubstituted-6-thiophenyl-pyrimidine derivatives were synthesized and their antibacterial activities against clinically related pathogens were investigated.

Effect of oral nut supplementation on endothelium-dependent vasodilation - a meta-analysis.

Background: An inverse association was found between nut supplementation and the risk of cardiovascular disease. Identifying the direct effect of nut supplementation on endothelium-dependent vasodilation may partly explain that association.

Methods: Human intervention studies were identified by systematic electronic search of the databases EMBASE, MEDLINE, Pubmed, and Web of Science through January 2017 and by manually searching related articles.

A hydrophobic organelle probe based on aggregation-induced emission: Nanosuspension preparation and direct use for endoplasmic reticulum imaging in living cells.

Organic fluorophores have a wide range of biological uses and are usually needed to be prepared as water-soluble compounds or nanoparticles for applications in aqueous biosystems owing to their hydrophobic properties, which often is a complex, time-consuming and high-cost process. Here, the nanoparticle preparation of hydrophobic fluorophores and their application in cell imaging have been investigated. It was found: a) fetal bovine serum (FBS) shows an excellent dispersion effect on hydrophobic small-molecule organic compounds; b) a hydrophobic C6-unsubstituted tetrahydropyrimidine (Me-THP-Naph) can be prepared as nanosuspensions utilizing cell culture medium with 10% FBS and directly be used as a specific real-time imaging probe for the endoplasmic reticulum (ER), a dynamic organelle playing a crucial role in many cellular processes.

Moderate alcohol consumption and atherosclerosis : Meta-analysis of effects on lipids and inflammation.

Objective: Alcohol consumption plays an important role in the risk of major cardiovascular diseases. We conducted a meta-analysis to summarize the association between moderate alcohol consumption and atherosclerosis.

Design: In this study four databases and reference lists of retrieved articles were searched to identify eligible studies.

Efficient Synthesis of a Series of Novel Octahydroquinazoline-5-ones via a Simple on-Water Urea-Catalyzed Chemoselective Five-Component Reaction.

Multicomponent reactions (MCRs) have become a powerful tool for drug discovery and development owing to their advantages of fast and efficient construction of a large library of products with complexity and diversity. However, conventional MCRs usually proceed in environmentally unfriendly organic solvents rather than in water, a green solvent used by nature for biological chemistry. Herein, a simple and efficient on-water urea-catalyzed chemoselective five-component reaction (5CR) has been developed for the synthesis of a series of novel octahydroquinazoline-5-ones (6), the derivatives of quinazolinones possessing diverse biological activities.

Development of four-component synthesis of tetra- and pentasubstituted polyfunctional dihydropyrroles: free permutation and combination of aromatic and aliphatic amines.

We previously reported the novel efficient proton/heat-promoted four-component reactions (4CRs) of but-2-ynedioates, two same/different primary amines, and aldehydes for the synthesis of tetra- and pentasubstituted polyfunctional dihydropyrroles. If aromatic and aliphatic amines were used as reagents, four different series of products should be obtained via the permutation and combination of aromatic and aliphatic primary amines. However, only three/two rather four different series of tetra-/pentasubstisuted dihydropyrroles could be prepared via the proton/heat-promoted 4CRs.

A new series of C-6 unsubstituted tetrahydropyrimidines: convenient one-pot chemoselective synthesis, aggregation-induced and size-independent emission characteristics.

A new series of C-6 unsubstituted tetrahydropyrimidines 6 have been directly synthesized via a convenient urea-catalyzed chemoselective five-component reaction (5CR) under mild conditions. Compounds 6 show typical aggregation-induced emission enhancement (AIEE) characteristics because they are practically no emissive in solution but emit blue or green fluorescence in aggregates with fluorescence yield up to 93%. One of the 5CR products, 6aa, exhibits blue- and green-fluorescence aggregates (bf- and gf-aggregates).

A novel class of small-molecule caspase-3 inhibitors prepared by multicomponent reactions.

A series of tetra- and pentasubstituted polyfunctional dihydropyrroles 5 and 6 were synthesized via practical multicomponent reactions (MCRs) for research on their structure-activity relationship as caspase-3 inhibitors. Among 39 compounds evaluated, 14 of them exhibited inhibition against caspase-3 with IC(50) ranging from 5 to 20 μM. The inhibitory activities of 5 and 6 depend on the nature of substituents on different positions.