Rational design, synthesis and biological evaluation of novel HIV-1 protease inhibitors containing 2-phenylacetamide derivatives as P2 ligands with potent activity against DRV-Resistant HIV-1 variants.

A novel kind of potent HIV-1 protease inhibitors, containing diverse hydroxyphenylacetic acids as the P2-ligands and 4-substituted phenyl sulfonamides as the P2' ligands, were designed, synthesized and evaluated in this work. Majority of the target compounds exhibited good to excellent activity against HIV-1 protease with IC50 values below 200 nM. In particular, compound 18d with a 2-(3,4-dihydroxyphenyl) acetamide as the P2 ligand and a 4- methoxybenzene sulfonamide P2' ligand exhibited inhibitory activity IC50 value of 0.54 nM, which was better than that of the positive control darunavir (DRV). More importantly, no significant decline of the potency against HIV-1DRVRS (DRV-resistant mutation) and HIV-1NL4_3 variant (wild type) for 18d was detected. The molecular docking study of 18d with HIV-1 protease (PDB-ID: 1T3R, www.rcsb.org) revealed possible binding mode with the HIV-1 protease. These results suggested the validity of introducing phenol-derived moieties into the P2 ligand and deserve further optimization which was of great value for future discovery of novel HIV-1 protease.

Comparison of muscle metabolomics between two Chinese horse breeds.

With their enormous muscle mass and athletic ability, horses are well-positioned as model organisms for understanding muscle metabolism. There are two different types of horse breeds-Guanzhong (GZ) horses, an athletic breed with a larger body height (~148.7 cm), and the Ningqiang pony (NQ) horses, a lower height breed generally used for ornamental purposes-both inhabited in the same region of China with obvious differences in muscle content. The main objective of this study was to evaluate the breed-specific mechanisms controlling muscle metabolism. In this study, we observed muscle glycogen, enzyme activities, and LC-MS/MS untargeted metabolomics in the gluteus medius muscle of six, each of GZ and NQ horses, to explore differentiated metabolites that are related to the development of two muscles. As expected, the glycogen content, citrate synthase, and hexokinase activity of muscle were significantly higher in GZ horses. To alleviate the false positive rate, we used both MS1 and MS2 ions for metabolite classification and differential analysis. As a result, a total of 51,535 MS1 and 541 MS2 metabolites were identified, and these metabolites can separate these two groups from each other. Notably, 40% of these metabolites were clustered into lipids and lipid-like molecules. Furthermore, 13 significant metabolites were differentially detected between GZ and NQ horses (fold change [FC] value ≥ 2, variable important in projection value ≥1, and Q value ≤ 0.05). They are primarily clustered into glutathione metabolism (GSH, p = 0.01), taurine, and hypotaurine metabolism (p < 0.05) pathways. Seven of the 13 metabolites were also found in thoroughbred racing horses, suggesting that metabolites related to antioxidants, amino acids, and lipids played a key role in the development of skeleton muscle in horses. Those metabolites related to muscle development shed a light on racing horses' routine maintenance and improvement of athletic performance.

Diversity of the fecal microbiota in Chinese ponies.

Introduction: The gut microbiomes of equine are plentiful and intricate, which plays an important part in the growth. However, there is a relative lack of information on the microbial diversity in the pony's gut. Methods: In this article, 118 fecal samples from DeBa pony, NiQi pony and GuZh horse were studied by 16S rRNA amplicon sequencing. Results: Diversity analysis was used to determine the difference of gut microbiota composition among different breeds. Alpha diversity analysis showed that the gut microbiota of NiQi ponies were abundant and various. Beta diversity analysis showed that the microorganisms constitution of DeBa ponies was more similar to that of NiQi ponies. LDA Effect Size (LEfSe) analysis result that the microorganism biomarkers for NiQi pony at the genus level were Phascolarctobacterium, Paludibacter, and Fibrobacter; the bacterial biomarker for DeBa pony was Streptococcus and Prevotella; and the bacterial biomarkers for GuZh horses was Treponema, Treponema Mogibacterium, Adlercreutzia, and Blautia. The correlation analysis between genera with >1% abundance and horse height found that Streptococcus (P < 0.01), Treponema (P < 0.01), Coprococcus (P < 0.01), Prevotella (P < 0.01), Phascolarctobacterium (P < 0.01), and Mogibacterium (P < 0.01) were significantly associated with horses' height. The functional prediction results indicated that DeBa pony have a microbiota functional more similar to NiQi pony. Discussion: For the first time, our results announce the species composition and structure of the gut microbiota in Chinese ponies. At the same time, our results can provide theoretical reference for further understanding the healthy breeding, feeding management and disease prevention of horses.

An Aqueous Facile Synthesis of 2,3-Dihydroquinazolin-4(1H)-One Derivatives by Reverse Zinc Oxide Micelles as Nanoreactor.

A green synthetic protocol has been developed for the efficient preparation of 2,3-dihydroquinazolin-4(1H)-one derivatives with excellent yield in aqueous media. Reverse zinc oxide micelles catalyzed the reactions efficiently and selectively as the hallow nanoreactor. Moreover, the catalyst was reusable without significant loss of catalytic efficiency. The notable advantages of the procedure are high yields and mild reaction conditions, simple operation, nonchromatographic purification, environmentally friendly and good versatile substrates.