Polysaccharide hydrogel containing silver nanoparticle@catechol microspheres with photothermal, antibacterial and anti-inflammatory activities for infected-wounds repair.

Anti-infection hydrogels have recently aroused enormous attraction, particularly in the treatment of chronic wounds. Herein, silver nanoparticle@catechol formaldehyde resin microspheres (Ag@CFRs) were fabricated by one-step hydrothermal method and subsequently encapsulated in hydrogels which were developed by Schiff base reaction between aldehyde groups in oxidized hyaluronic acid and amino groups in carboxymethyl chitosan. The developed polysaccharide hydrogel exhibited microporous structure, high swelling capacity, favorable mechanical strength, enhanced tissue adhesion and photothermal activities.

Dual-crosslinked methacrylamide chitosan/poly(ε-caprolactone) nanofibers sequential releasing of tannic acid and curcumin drugs for accelerating wound healing.

The objective of this research study is to develop novel composite nanofibers based on methacrylamide chitosan (ChMA)/poly(ε-caprolactone) (PCL) materials by the dual crosslinking and coaxial-electrospinning strategies. The prepared ChMA/PCL composite nanofibers can sequentially deliver tannic acid and curcumin drugs to synergistically inhibit bacterial reproduction and accelerate wound healing. The rapid delivery of tannic acid is expected to inhibit pathogenic microorganisms and accelerate epithelialization in the early stage, while the slow and sustained release of curcumin is with the aim of relieving chronic inflammatory response and inducing dermal tissue maturation in the late stage.

[Spatial Distribution Characteristics and Influencing Factors of Soil Organic Carbon Density in Yellow River Basin Based on MGWR Model].

As the largest terrestrial carbon pool, the spatial distribution characteristics and influencing factors of soil organic carbon have important implications for global carbon cycle processes. Soil organic carbon density (SOCD) and influencing factors were predicted in the Yellow River basin using a mixed geographically weighted regression (MGWR) model based on soil organic carbon density data and environmental factors. The results showed that:① the SOCD ranged from 0-14.

Environmental effect and spatiotemporal pattern of stable isotopes in precipitation on the transition zone between the Tibetan Plateau and arid region.

In the transition zone between the Tibetan Plateau and the arid region of northwestern China, the spatiotemporal patterns and environmental controls of stable isotopes in precipitation remain unclear. A network of 19 sampling stations was established across the Qilian Mountains to observe stable isotopes in precipitation, and 1310 precipitation event-scale samples were collected. The local meteoric water line (LMWL) was obtained and expressed as δD = 7.

Sensing behavior and logic operation of a colorimetric fluorescence sensor for Hg(2+)/Cu(2+) ions.

A BODIPY-based 1 as a colorimetric fluorescence sensor was synthesized, and its metal sensing property was investigated. 1 displayed high selectivity and sensitivity towards Hg(2+) and Cu(2+) ions among 15 different metal cations. The addition of Hg(2+) and Cu(2+) ions into 1 in CH3CN resulted in a significant bathochromic shift of the UV absorption spectra from 533nm to 560nm and 593nm, respectively, changing the corresponding colors from pink to purple and blue.

Discovery of pyrroloaminopyrazoles as novel PAK inhibitors.

The P21-activated kinases (PAK) are emerging antitumor therapeutic targets. In this paper, we describe the discovery of potent PAK inhibitors guided by structure-based drug design. In addition, the efflux of the pyrrolopyrazole series was effectively reduced by applying multiple medicinal chemistry strategies, leading to a series of PAK inhibitors that are orally active in inhibiting tumor growth in vivo.

Azaindole N-methyl hydroxamic acids as HIV-1 integrase inhibitors-II. The impact of physicochemical properties on ADME and PK.

HIV-1 integrase is one of three enzymes encoded by the HIV genome and is essential for viral replication, and HIV-1 IN inhibitors have emerged as a new promising class of therapeutics. Recently, we reported the discovery of azaindole hydroxamic acids that were potent inhibitors of the HIV-1 IN enzyme. N-Methyl hydroxamic acids were stable against oxidative metabolism, however were cleared rapidly through phase 2 glucuronidation pathways.

4-methylpteridinones as orally active and selective PI3K/mTOR dual inhibitors.

Pteridinones were designed based on a non-selective kinase template. Because of the uniqueness of the PI3K and mTOR binding pockets, a methyl group was introduced to C-4 position of the peteridinone core to give compounds with excellent selectivity for PI3K and mTOR. This series of compounds were further optimized to improve their potency against PI3Kα and mTOR.

Azaindole hydroxamic acids are potent HIV-1 integrase inhibitors.

HIV-1 integrase (IN) is one of three enzymes encoded by the HIV genome and is essential for viral replication. Recently, HIV-1 IN inhibitors have emerged as a new promising class of therapeutics. Herein, we report the discovery of azaindole carboxylic acids and azaindole hydroxamic acids as potent inhibitors of the HIV-1 IN enzyme and their structure-activity relationships.

Discovery of novel hydantoins as selective non-hydroxamate inhibitors of tumor necrosis factor-alpha converting enzyme (TACE).

A series of novel hydantoins was designed and synthesized as structural alternatives to hydroxamate inhibitors of TACE. 5-Mono- and di-substituted hydantoins exhibited activity with IC50 values of 11-60 nM against porcine TACE in vitro and excellent selectivity against other MMPs.

A molecular modeling analysis of novel non-hydroxamate inhibitors of TACE.

Recently, an X-ray co-crystal structure of our hydroxamate inhibitor IK682 and TACE [Niu, X.; Umland, S.; Ingram, R.