Multisubstituted quinoxalines and pyrido[2,3-d]pyrimidines: Synthesis and SAR study as tyrosine kinase c-Met inhibitors

Two series of new analogues were designed by replacing the quinoline scaffold of our earlier lead 2 (zgwatinib) with quinoxaline and pyrido[2,3-d]pyrimidine frameworks. Moderate c-Met inhibitory activity was observed in the quinoxaline series. Among the pyrido[2,3-d]pyrimidine series, compounds 13a–c possessing an O-linkage were inactive, whilst the N-linked analogues 15a–c retained c-Met inhibitory potency. Highest activity was observed in the 3-nitrobenzyl analog 15b that showed an IC₅₀ value of 6.5 nM. Further structural modifications based on this compound were undergoing.     

Effects of taurine on male reproduction in rats of different ages

Background

It has been demonstrated that taurine is one of the most abundant free amino acids in the male reproductive system, and can be biosynthesized by male reproductive organs. But the effect of taurine on male reproduction is poorly understood.

Methods

Taurine and β-alanine (taurine transport inhibitor) were offered in water to male rats of different ages. The effects of taurine on reproductive hormones, testis marker enzymes, antioxidative ability and sperm quality were investigated.

Results

The levels of T and LH were obviously increased by taurine supplementation in rats of different ages, and the level of E was also significantly elevated in baby rats. The levels of SOD, ACP, SDH and NOS were obviously increased by taurine administration in adult rats, but the levels of AKP, AST, ALT and NO were significantly decreased. The levels of SOD, ACP, LDH, SDH, NOS, NO and GSH were significantly elevated by taurine administration in aged rats, but the levels of AST and ALT were significantly decreased. The motility of spermatozoa was obviously increased by taurine supplement in adult rats. The numbers and motility of spermatozoa, the rate of live spermatozoa were significantly increased by taurine supplement in aged rats.

Conclusions

The present study demonstrated that a taurine supplement could stimulate the secretion of LH and T, increase the levels of testicular marker enzymes, elevate testicular antioxidation and improve sperm quality. The results imply that taurine plays important roles in male reproduction especially in aged animals.

     

Effects of Dietary Iron on Manganese Utilization in Broilers Fed with Corn-Soybean Meal Diet

Biological Trace Element Research - To investigate the effects of dietary iron (Fe) levels on manganese (Mn) utilization, 900 8-day-old broilers were randomly assigned to 1 of 6 treatments in a 3...     

Dietary Manganese Supplementation Influences the Expression of Transporters Involved in Iron Metabolism in Chickens

To investigate the effects of dietary manganese (Mn) supplementation on iron (Fe) metabolism, a total of 480 50-week-old hens were fed the basal diet (control, 24.35 mg Mn/kg) without Mn supplementation for 6 weeks to reduce Mn storage in the body. Hens were then randomly assigned to one of three treatments, which included the control and control added with 60 or 300 mg Mn/kg diet (M-Mn or H-Mn). Duodenum, heart, liver, and tibia were collected in hens after 12-week feeding period. No significant differences were observed in egg production, feed/egg ratio, shell breaking strength, and shell thickness among different treatments. Compared with control or M-Mn, H-Mn decreased (P?P?P?P?P?>?0.10) Fe concentration in the heart and tibia. In conjunction with reduced Fe retention, DMT1 mRNA expression decreased (P?mRNA level was higher (P?mRNA expression was lower (P?相似文献   

Elevation-Related Variation in Leaf Stomatal Traits as a Function of Plant Functional Type: Evidence from Changbai Mountain,China

Understanding the variation in stomatal characteristics in relation to climatic gradients can reveal the adaptation strategies of plants, and help us to predict their responses to future climate changes. In this study, we investigated stomatal density (SD) and stomatal length (SL) in 150 plant species along an elevation gradient (540–2357 m) in Changbai Mountain, China, and explored the patterns and drivers of stomatal characteristics across species and plant functional types (PFTs: trees, shrubs, and herbs). The average values of SD and SL for all species combined were 156 mm^–2 and 35 µm, respectively. SD was higher in trees (224 mm^–2) than in shrubs (156 mm^–2) or herbs (124 mm^–2), and SL was largest in herbs (37 µm). SD was negatively correlated with SL in all species and PFTs (P<0.01). The relationship between stomatal characteristics and elevation differed among PFTs. In trees, SD decreased and SL increased with elevation; in shrubs and herbs, SD initially increased and then decreased. Elevation-related differences in SL were not significant. PFT explained 7.20–17.6% of the total variation in SD and SL; the contributions of CO₂ partial pressure (), precipitation, and soil water content (SWC) were weak (0.02–2.28%). Our findings suggest that elevation-related patterns of stomatal characteristics in leaves are primarily a function of PFT, and highlight the importance of differences among PFTs in modeling gas exchange in terrestrial ecosystems under global climate change.     

Dynamic Model and Motion Mechanism of Magnetotactic Bacteria with Two Lateral Flagellar Bundles

Magnetotactic Bacteria (MTB) propel themselves by rotating their flagella and swim along the magnetic field lines.To analyze the motion of MTB,MTB magneto-ovoid strain MO-1 cells,each with two bundles of flagella,were taken as research object.The six-degrees-of-freedom (6-DoF) dynamic model of MO-1 was established based on the Newton-Euler dynamic equations.In particular,the interaction between the flagellum and fluid was considered by the resistive force theory.The simulated motion trajectory of MTB was found to consist of two kinds of helices:small helices resulting from the imbalance of force due to flagellar rotation,and large helices arising from the different directions of the rotation axis of the cell body and the propulsion axis of the flagellum.The motion behaviours of MTB in various magnetic fields were studied,and the simulation results agree well with the experiment results.In addition,the rotation frequency of the flagella was estimated at 1100 Hz,which is consistent with the average rotation rate for Na+-driven flagellar motors.The included angle of the magnetosome chain was predicted at 40° that is located within 20° to 60° range of the observed results.The results indicate the correctness of the dynamic model,which may aid research on the operation and control of MTB-propelled micro-actuators.Meanwhile,the motion behaviours of MTB may inspire the development of micro-robots with new driving mechanisms.     

新型冠状病毒进化与变异

本文分析了新型冠状病毒(SARS-CoV-2,新冠病毒)的进化来源及刺突蛋白(spike protein,S)基因的突变情况.从GenBank数据库中下载相关病毒全基因组序列及S基因序列,运用DNAMAN9.0、MEGAX等生物信息学软件,进行多序列比对,构建系统进化树,并统计S基因位点突变情况.分析结果提示,新冠病毒...     

猪流感病毒抗原表位基因表达载体构建与免疫原性分析

根据猪流感病毒血凝素蛋白基因(Heamuglutinine, HA)的核苷酸序列, 设计、筛选HA蛋白氨基酸序列的主要表位多肽4个, 将4个片段以柔性连接串联成模拟蛋白, 核苷酸约为300 bp, 体外扩增该模拟蛋白基因, 插入到原核表达载体pET30a(+)中, 转染宿主菌诱导表达, 结果获得分子量为20 kD的表达蛋白, 该蛋白可与抗His-tag抗体、抗猪流感病毒H1N1、H3N2亚型高免血清发生免疫学反应。纯化后免疫小鼠, ELISA及血凝抑制(Heamuglutinine inhibitor, HI)试验检测, 小鼠产生针对多肽抗原的血清抗体, 同时还可检测到H1N1、H3N2亚型SIV血凝抗体。流氏细胞仪检测免疫组外周血淋巴细胞高于对照组, 说明该模拟蛋白具有与H1N1、H3N2亚型猪流感病毒相似的免疫原性及反应原性, 为H1N1、H3N2血清亚型猪流感病毒疫苗研制提供了新手段。     

典型森林和草地生态系统呼吸各组分间的相互关系

生态系统呼吸是陆地生态系统碳收支的重要组成部分,分析其组分间的相互关系对理解生态系统呼吸过程和精确评价生态系统碳收支具有重要意义,也是当前碳循环研究工作的一大难点。本研究利用ChinaFLUX的长白山温带针阔混交林（CBS）,鼎湖山亚热带常绿阔叶林（DHS）和海北灌丛草甸（HBGC）三个典型生态系统的通量观测数据,采用经验统计方法,分析了其在中国典型生态系统中的适用性及敏感性,揭示了生态系统呼吸各组分的动态变化特征及相互关系。结果表明：采用本研究中的呼吸组分拆分方法所获结果与理论推测及实测数据大致相同,拆分结果对净初级生产力与总初级生产力的比值（NPP/GPP）较为敏感,NPP/GPP变化0.1时,自养呼吸在生态系统呼吸中的比例（Ra/RE）改变0.05。各生态系统中,生态系统呼吸及其组分在年内均表现出明显的单峰型变化特征,在夏季生长旺盛的时节达到最大值。异养呼吸与生态系统呼吸的比值（Rh/RE）也具有明显的季节变化,但在生态系统间表现出明显差异,CBS和HBGC分别表现出先增大后减小和先减小后增大的变化趋势,DHS则相对稳定,在0.5附近波动, Ra/RE的季节动态与Rh/RE相反。在年总量上,HBGC主要通过异养呼吸向大气排放CO2,异养呼吸占生态系统呼吸的60%,而CBS和DHS的自养呼吸和异养呼吸所占比重大致相似,异养呼吸占生态系统呼吸的49%。这说明,该统计学模型可以用来进行生态系统呼吸组分的拆分,进而可以为生态系统碳循环过程的精细研究提供参考数据,但今后应加强NPP/GPP的测定,以提高生态系统呼吸拆分的精度。     

产木质纤维素降解酶真菌的筛选及产酶特性

【背景】利用微生物处理秸秆引起研究者的广泛关注。【目的】筛选生长速度快、木质纤维素降解酶活性强的真菌菌株,用于植物秸秆降解和高效利用。【方法】从自然界采集的样品中分离纯化真菌菌株,利用PDA-愈创木酚和PDA-羧甲基纤维素钠平板初筛,再经过液体发酵检测漆酶酶活、羧甲基纤维素酶酶活及菌丝生长速率复筛目的菌株,通过内转录间隔区(internal transcribed spacer,ITS)测序法对目的菌株进行鉴定,对目的菌株产漆酶和羧甲基纤维素酶活力进行测定及酶学性质研究。【结果】从样品中分离纯化到18株真菌,通过初筛筛选出9株产木质纤维素降解酶真菌菌株,再经过复筛,筛选出一株产漆酶、羧甲基纤维素酶活力高、菌丝生长快的菌株M1,经过分子生物学鉴定M1为糙皮侧耳(Pleurotus ostreatus),其漆酶酶活为(243.59±1.11)U/mL,羧甲基纤维素酶酶活为(36.03±0.63) U/mL。在5 d的培养期内,菌丝生长速率为(9.43±0.32) mm/d。对菌株M1的发酵粗酶液的酶学性质进行了检测分析,结果表明,所产的漆酶在pH5.0-6.5相对酶活为90%以上,在pH ...