Synthesis and Antibacterial Evaluation of a Series of 11,12-Cyclic Carbonate Azithromycin-3-O-descladinosyl-3-O-carbamoyl Glycosyl Derivatives.

A novel series of 11,12-cyclic carbonate azithromycin-3-O-descladinosyl-3-O-carbamoyl glycosyl derivatives were designed, synthesized, and evaluated for their antibacterial activities in vitro. Most of these compounds had significant antibacterial activity against seven kinds of susceptible strains. In particular, compound G1 exhibited the most potent activity against methicillin-resistant Streptococcus pneumoniae 943 (MIC: 1 µg/mL), Staphylococcus pneumoniae 746 (MIC: 2 µg/mL), Streptococcus pyogenes 447 (MIC: 8 µg/mL), and Escherichia coli 236 (MIC: 32 µg/mL), which were two-, four-, four-, four-, and eight-fold stronger activity than azithromycin, respectively. Additionally, compound G2 exhibited improved activity against methicillin-resistant Staphylococcus aureus MRSA-1 (MIC: 8 µg/mL), Streptococcus pneumoniae 943 (MIC: 2 µg/mL), Staphylococcus pneumoniae 746 (MIC: 2 µg/mL), and Escherichia coli 236 (MIC: 32 µg/mL), which were two-, two-, four-, and eight-fold better activity than azithromycin, respectively. As for methicillin-resistant Staphylococcus aureus MRSA-1, compound G6 presented the most excellent activity (MIC: 4 µg/mL), showing four-fold higher activity than azithromycin (MIC: 16 µg/mL) and erythromycin (MIC: 16 µg/mL). However, compared with other compounds, compounds G7 and G8 with the disaccharide side chain were observed the lower activity against seven strains.

Anti-neuroinflammatory effects of novel 5,6-dihydrobenzo[h]quinazolin-2-amine derivatives in lipopolysaccharide-stimulated BV2 microglial cells.

Neuroinflammation is an intricate process that is associated with both normal and pathological conditions. Microglia-mediated neuroinflammation is known to lead to various neurodegenerative and neurological disorders. A series of 3,4-dihydronaphthalen-1(2H)-one derivatives (1-15) and novel 5,6-dihydrobenzo[h]quinazolin-2-amine derivatives (16-30) were synthesized and characterized by various analytical methods, such as NMR and HRMS. All compounds were evaluated for toxicity, screened for their anti-neuroinflammatory properties, and investigated for the potential molecular mechanism of lipopolysaccharide (LPS) induction in BV2 microglia. Structure activity relationship analysis showed that compound 17 substituted by the 7-fluorine atom on the A-ring and the 3-methoxy on the D-ring had more potential anti-neuroinflammatory activity by inhibiting the secretion of cytokines TNF-α and IL-6. The results of western blotting assay showed that 17 significantly blocked the activation and phosphorylation of IκBα, significantly reduce the expression of NLRP3 inflammatory vesicle-associated proteins, and thus inhibit the activation of NF-κB pathway. Thus, compound 17 was demonstrated to be an excellent potential therapeutic agent for the treatment of neuroinflammation-related diseases.

Characteristics influencing high-risk sexual behaviours in elderly men.

With the objective of investigating the characteristics influencing high-risk sexual behaviours in elderly men (60-74 years of age) in Chongqing, China, a total of 1433 healthy elderly men with sexual intercourse frequencies of one to six times/month who were willing to participate in the questionnaires were studied at four hospitals. We measured serum testosterone levels and performed follow-ups every six months, with a total of 1128 elderly men followed up after two years. We also investigated socio-economic and demographic characteristics (age, education, income, location, marital status and number of marriages), types of sexual partners, age differences with fixed sexual partners, frequency of sexual intercourse, combined basic age-related diseases, sexually transmitted infections (STIs) education, elderly self-care ability and high-risk sexual behaviours (frequency of sexual intercourse and number of sexual partners) using questionnaires. We analysed the influencing factors of high-risk sexual behaviours in elderly men using a univariate analysis, multivariate logistic regression analysis, BP neural network prediction and cluster analysis. Finally, we found that serum total testosterone, age, types of sexual partners, age differences with fixed partners and frequency of sexual intercourse are five factors that influence high-risk sexual behaviours in elderly men.

Eis, a novel family of arylalkylamine N-acetyltransferase (EC 2.3.1.87).

Enhanced intracellular survival (Eis) proteins were found to enhance the intracellular survival of mycobacteria in macrophages by acetylating aminoglycoside antibiotics to confer resistance to these antibiotics and by acetylating DUSP16/MPK-7 to suppress host innate immune defenses. Eis homologs composing of two GCN5 N-acetyltransferase regions and a sterol carrier protein fold are found widely in gram-positive bacteria. In this study, we found that Eis proteins have an unprecedented ability to acetylate many arylalkylamines, are a novel type of arylalkylamine N-acetyltransferase AANAT (EC 2.3.1.87). Sequence alignment and phyletic distribution analysis confirmed Eis belongs to a new aaNAT-like cluster. Among the cluster, we studied three typical Eis proteins: Eis_Mtb from Mycobacterium tuberculosis, Eis_Msm from Mycobacterium smegmatis, and Eis_Sen from Saccharopolyspora erythraea. Eis_Mtb prefers to acetylate histamine and octopamine, while Eis_Msm uses tyramine and octopamine as substrates. Unlike them, Eis_Sen exihibits good catalytic efficiencies for most tested arylalkylamines. Considering arylalkylamines such as histamine plays a fundamental role in immune reactions, future work linking of AANAT activity of Eis proteins to their physiological function will broaden our understanding of gram-positive pathogen-host interactions. These findings shed insights into the molecular mechanism of Eis, and reveal potential clinical implications for many gram-positive pathogens.

A genetically encoded biosensor for in vitro and in vivo detection of NADP(.).

NADP(+), the oxidized form of nicotinamide adenine dinucleotide phosphate, plays an essential role as a coenzyme in cellular electron transfer reactions. The concentration of NADP(+) in cytoplasm or organelles is dynamic due to its conversion to many important derivatives. To track the NADP(+) concentration in single living cells, we developed a genetically encoded NADP(+) biosensor by inserting a reporter element, ketopantoate reductase (KPR), between the Förster resonance energy transfer (FRET) pair, cyan fluorescent protein (CFP) and yellow fluorescent protein (YFP). This recombinant sensor showed a NADP(+) concentration-dependent decrease in the fluorescence ratio in vitro assay. In order to optimize this biosensor, we performed peptide-length optimization and site-directed mutagenesis in the binding pocket of KPR guided by predictions from computational protein redesign. This modified biosensor showed a 70% Δratio increase compared to the wild type and was found to be highly specific to NADP(+), with a detection limit of 1 µM. The sensor also reported NADP(+) real-time cellular dynamics in Escherichia coli (E. coli) after the addition of its precursor, nicotinic acid (NA). Altogether, these results demonstrate the feasibility of the biosensor for visualizing NADP(+) both in vitro and in vivo.

A novel, colorimetric method for biogenic amine detection based on arylalkylamine N-acetyltransferase.

We developed a novel colorimetric method for rapid detection of biogenic amines based on arylalkylamine N-acetyltransferase (aaNAT). The proposed method offers distinct advantages including simple handling, high speed, low cost, good sensitivity and selectivity.

[Study on stem-tip tissue culture of the traditional Chinese medicine Chrysanthemum morifolium].

OBJECTIVE: To set up the optimums for the stem-tip tissue culture of Chrysanthemum morifolium cultivated in Anhui Province. METHOD: Small sections (about 0.5 mm in length) from the stem-tips were isolated and inoculated with different media, and induced to form the whole plantlet formation. RESULT AND CONCLUSION: The MS medium added with 6-BA 2 mg.L-1 + NAA 0.2 mg.L-1 was the optimum medium for the bud sprouting and the inducing rate was over 80% after 40 d cultivation on this modified medium. The MS medium supplemented with 6-BA 2 mg.L-1 and NAA 0.5 mg.L-1 was the optimum medium for the multiplication of the adventitious buds in which the bud multiplication was about 4-7 times higher after 25-30 d cultivation. The plantlet could root well on the MS medium with NAA 0.5 mg.L-1.