Design,synthesis and bioevaluation of 3-oxo-6-aryl-2,3-dihydropyridazine-4-carbohydrazide derivatives as novel xanthine oxidase inhibitors

In view of expanding the structure activity relationship of xanthine oxidase inhibitors, a series of 3-oxo-6-aryl-2,3-dihydropyridazine-4-carbohydrazide/carboxylic acid derivatives were designed by molecular docking and synthesized. All the target compounds were evaluated for their in vitro XO inhibition by using febuxostat and allopurinol as the standard controls. Most of the hydrazide derivatives exhibited potency levels in the micromolar range. From the view of docking study, hydrazide derivatives bind to the active site of XO through a novel interaction mode, which is different from that of febuxostat bearing a carboxyl group. The most promising compound 8b was further subjected to kinetic analysis to deduce their modes of inhibition.     

快中子辐照结合组织培养培育花生新品种宇花7号

为开拓新的花生育种方法,对辐照诱变结合组织培养创造花生新种质、培育新品种进行了研究。以我国北方地区主栽花生品种鲁花11号成熟种子为试材,经快中子辐照处理后取种子胚小叶进行组织培养,通过胚胎发生途径获得再生苗。再生苗经嫁接驯化后移栽田间,83个单株获得种子。后代按系谱法进行选育,从83个再生植株后代中获得了107份突变体,分别在主茎高、分枝数、荚果形状和大小、种皮颜色、内种皮颜色、含油率、蛋白含量等性状上发生了明显变异。从突变体后代中选育出了低油早熟耐涝大花生新品种宇花7号,其产量比亲本鲁花11号增产14%以上;其含油率(47.0%)比鲁花11号低5.1个百分点。宇花7号2016年参加辽宁省新品种登记试验,比对照品种白沙1017平均增产13.8%。2018年通过了国家非主要农作物品种登记,登记号为"GPD花生(2018) 370105"。研究结果说明,辐照结合组织培养是创造花生新种质、培育新品种的有效方法。     

Discovery,synthesis, biological evaluation and molecular docking study of (R)-5-methylmellein and its analogs as selective monoamine oxidase A inhibitors

(R)-5-Methylmellein (5-MM), the major ingredient in the fermented mycelia of the medicinal fungus Xylaria nigripes (called Wuling Shen in Chinese)¸ was found to be a selective inhibitor against monoamine oxidase A (MAO-A) and might play an important role in the clinical usage of this edible fungus as an anti-depressive traditional Chinese medicine (TCM). Based on the discovery and hypothesis, a variety of (R)-5-MM analogs were synthesized and evaluated in vitro against two monoamine oxidase isoforms (MAO-A and MAO-B). Most synthetic analogs showed selective inhibition of MAO-A with IC₅₀ values ranging from 0.06 to 29?µM, and compound 13aR is the most potent analog with high selectivity (IC₅₀, MAO-A: 0.06?µM; MAO-B: >50?µM). Interestingly, the enzyme kinetics study of 13aR indicated that this ligand seemed to bind in the MAO-A active site according to so-called “tight-binding inhibition” mode. The molecular docking study of 13aR was thereafter performed in order to rationalize the obtained biological results.     

OTUB2 Promotes Cancer Metastasis via Hippo-Independent Activation of YAP and TAZ

1. Download high-res image (157KB)
2. Download full-size image

     

Development of the fingerprints for the quality of the roots of Salvia miltiorrhiza and its related preparations by HPLC-DAD and LC-MS(n)

High-performance liquid chromatographic (HPLC) fingerprints were developed for identification of both lipophilic and hydrophilic components of the roots of Salvia miltiorrhiza and four related preparations. These samples were separated with an Agilent Zorbax Extend C(18) reserved-phase column (5 microm, 250 mm x 4.6 mm) by linear gradient elution using water-phosphoric acid (100:0.026, v/v) and acetonitrile as mobile phase. The flow rate was 0.8 ml/min and the detector wavelength was set at 280 nm. Mean chromatograms and correlation coefficients of samples were calculated by the software "Similarity Evaluation System for Chromatographic Fingerprint of TCM". The correlation coefficients of Danshen and Fufang Danshen tablets (FDT) samples were in the range of 0.352-0.993 and 0.768-0.987, respectively. The correlation coefficients of Compound Danshen dripping pills (CDDP), Danshen injection (DSI) and Xiangdan injection (XDI) samples were higher than 0.928, 0.850 and 0.960, respectively. It was the first time to identify 34 peaks by comparing with standard compounds and using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS(n)) technique. All results indicated that the developed fingerprint assay could be readily utilized as a quality control method for S. miltiorrhiza and its related preparations.     

A GC-based metabonomics investigation of type 2 diabetes by organic acids metabolic profile

"Metabonomics" method requires the development of rapid, advanced analytical tools and GC will play an important role for its special advantage. In this study we show the application of GC-based metabonomics to investigate the control and type 2 diabetes (DM2) patients by urinary organic acids metabolic profile. After peak matching, multivariate statistical analysis methods: principal components analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were used. The results showed that there was a relationship between organic acids metabolic profiles and DM2, and PLS-DA can distinguish the DM2 patients from the control. Five organic acids as potential biomarkers were identified.     

In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro

The in vitro scratch assay is an easy, low-cost and well-developed method to measure cell migration in vitro. The basic steps involve creating a "scratch" in a cell monolayer, capturing the images at the beginning and at regular intervals during cell migration to close the scratch, and comparing the images to quantify the migration rate of the cells. Compared to other methods, the in vitro scratch assay is particularly suitable for studies on the effects of cell-matrix and cell-cell interactions on cell migration, mimic cell migration during wound healing in vivo and are compatible with imaging of live cells during migration to monitor intracellular events if desired. Besides monitoring migration of homogenous cell populations, this method has also been adopted to measure migration of individual cells in the leading edge of the scratch. Not taking into account the time for transfection of cells, in vitro scratch assay per se usually takes from several hours to overnight.     

Growth in stem diameter of Larix principis-rupprechtii and its response to meteorological factors in the south of Liupan Mountain, China

Research related to daily and seasonal pattern of stem growth of Larix principis-rupprechtii was carried out with the help of a dendrometer from June to September in 2005 in the Liupan Mountain, Ningxia, Northwestern China. The results indicated that daily fluctuation of stem diameter was rhythmic and it could be divided into three continuous phases: contraction, expansion and stem diameter growth when daily rainfall < 10 mm during the measurement period. Comparatively, it showed a different pattern compared with the former when daily rainfall ≥10 mm and in the subsequent days. Based on the work done by Deslauriers et al. a modified method was designed to calculate daily and cumulative stem growth, and it showed that seasonal pattern of cumulative stem growth was similar among five sample trees. From June and July, stem growth rate was quick and the values were in the range 27.0–44.2 μm per day. Relatively, they took on a slow growth rate from August to September, and the values were under 10 μm per day. And it also showed that there existed a significant difference in stem growth among sample trees, which could be as a result of the difference in tree domain and their positions in the stand. The relationship between daily stem growth and meteorological factors was studied by principle component analysis and partial correlation analysis, and the result indicated that the daily rainfall, daily minimum temperature, daily average solar radiation and vapor pressure deficit were four significant factors which determined the daily stem growth.