Nrf2及天然产物导向的Nrf2激活剂研究进展

氧化应激能够破坏细胞内氧化还原平衡,造成系统和组织损伤,最终引起一系列疾病的产生。转录因子E2相关因子2(Nrf2),受Kelch样环氧氯丙烷相关蛋白1(Keap1)蛋白的调控,是细胞氧化应激反应中的关键因子,在氧化应激条件下,Nrf2从Keap1中分离,然后进入细胞核与抗氧化反应元件(ARE)结合,增加了Ⅱ相解毒酶的表达,保护细胞免受氧化损伤。天然产物对于药物发现具有重要意义,研究显示,Nrf2激活剂绝大多数也是天然产物或天然产物的衍生物。本文介绍Nrf2-Keap1信号通路的作用机制以及常见的天然产物导向的Nrf2激活剂。     

靶向肿瘤血管生成的天然产物研究进展

血管生成在肿瘤的发生发展过程中起着非常重要的作用。促血管生成因子及其受体可以通过调节血管生成促进肿瘤发生发展。因此,发现和开发靶向血管生成因子药物已经成为治疗肿瘤的重要策略。近年来,天然产物因其结构多样、毒副作用低及作用机制独特等优势已然成为开发抗肿瘤药物的主要来源。本文归纳阐述了近年来靶向血管生成因子具有抗肿瘤活性的天然产物研究进展,为进一步发现和开发靶向肿瘤血管生成的天然药物提供重要的理论依据。     

福州市生态系统生产总值核算

开展生态系统生产总值(GEP)核算是推进生态文明制度建设的必要措施,也是将生态效益纳入经济社会发展评价体系的重要举措。本研究以福州市为研究对象,通过构建具有“山、海、城”特色的生态系统价值核算体系,对2015和2018年福州市GEP进行核算,从时空变化角度对福州市GEP进行对比。结果表明: 2015、2018年福州市GEP分别为9205.92、10472.42亿元,人均GEP分别为13.02、14.39万元,生态产品供给服务价值分别为941.81、1102.61亿元,生态调节服务价值分别为6364.20、5988.51亿元,生态文化服务价值分别为1899.91、3381.3亿元。与2015年相比,2018年福州市GEP增加1266.50亿元,增幅为13.8%,主要得益于生态产品供给服务价值和生态文化服务价值的增加。然而,生态调节服务价值减少375.69亿元,降幅为5.9%,主要源于气候调节、水流动调节和水质净化服务价值的减少。福州率先探索建立一套具有山、海、城特色的核算体系,可以为福建省其他城市及我国其他地区的核算工作提供“福州样板”,同时助推建立生态价值实现的长效机制。     

行距和播种量对冬小麦冠层光合有效辐射垂直分布、生物量和籽粒产量的影响

为明确行距和播种量对冬小麦冠层光合有效辐射(PAR)垂直分布、生物量和籽粒产量的影响,在不增加水肥等投入的基础上,设置等行距(R₁,20 cm+20 cm)、宽窄行(R₂,12 cm+12 cm+12 cm+24 cm)两种行距方式和低(D₁,120 kg·hm^-2)、中(D₂,157.5 kg·hm^-2)、高(D₃,195 kg·hm^-2)3个播种量水平,分析不同处理组合下冬小麦主要生育时期冠层PAR的截获率及利用率、群体光合能力、生物量和产量差异。结果表明: 冬小麦冠层总PAR截获率、上层PAR截获率均表现为R₁行距显著大于R₂,而中层和下层PAR截获率则表现为R₂大于R₁,且在中层差异显著;从小麦开花至成熟期,相同播种量下R₂行距光合势(LAD)、群体光合速率(CAP)、PAR转化率和利用率都显著高于R₁,并以R₂D₂处理最大;冬小麦的群体生物量(BA)和不同层次叶片生物量(BL)均表现为随播种量增加而增加,但单株生物量(BP)则相反。在同一播种量下,BA、BL和BP均在开花期之后表现为R₂行距高于R₁,其中,BA、BP在成熟期行距间差异显著,中层和下层BL在D₂、D₃播种量下行距间差异显著;不同处理组合间冬小麦的穗数、穗粒数、千粒重、籽粒产量分别以R₂D₃、R₂D₁、R₂D₁、R₂D₂最大,其中,R₂行距下千粒重、穗粒数和籽粒产量显著大于R₁。综上,改变行距可以改善小麦冠层中下层PAR的截获量,增强冬小麦单株和群体光合能力、光合有效辐射的利用及转化效率,提高生物量和籽粒产量。在冬小麦高产栽培中,应重视通过优化田间结构,塑造麦田理想的群体光合结构,以充分利用单位土地面积上光照资源,挖掘作物自身的光合生产潜力,达到高产高效的目的。在本试验条件下,以R₂D₂配置群体光合能力、光合有效辐射利用率和产量最佳。     

引入新型异戊二烯醇利用途径促进解脂耶氏酵母中β-胡萝卜素的合成*

目的:微生物体内异戊二烯类化合物的前体物异戊烯焦磷酸酯的天然合成路径受到严格的代谢调控,因此限制了异戊二烯类化合物的高效生物合成,而新型异戊二烯醇利用途径独立于生物体内源性代谢路径,通过在微生物中引入IUP能够进行异戊烯焦磷酸酯的大量合成,从而促进异戊二烯类化合物的大量合成。方法:在油脂酵母解脂耶氏酵母中引入IUP,强化异戊烯焦磷酸酯生物合成,促进β-胡萝卜素的高效积累。结果:通过生物信息学的方法预测IUP中两个关键蛋白酿酒酵母来源的胆碱激酶ScCK和拟南芥来源的异戊烯磷酸激酶AtIPK,均为酸性亲水性蛋白,无跨膜区和信号肽,二者都具有疏松不稳定的结构特征,显著富集于磷酸类物质的合成通路中。在解脂耶氏酵母中利用同源重组技术引入外源β-胡萝卜素合成关键基因carRP和carB,强化甲羟戊酸途径的关键基因thmgR和ggs1,使工程菌株中积累2.68 mg/L β-胡萝卜素。通过Cre-loxP系统回收基因组上的ura标签,再将IUP进一步整合到工程菌株染色体上。当培养基中含有20 mM异戊二烯醇作为底物、碳氮比为4/3且发酵96 h后,重组解脂耶氏酵母中β-胡萝卜素的产量提高到410.2 mg/L,较原始工程菌的产量提高了近200倍。结论:IUP能够促进解脂耶氏酵母中β-胡萝卜素的高效积累,为利用IUP开展β-胡萝卜素和其他异戊二烯类化合物的高效生物合成提供新思路。     

米槁群落主要物种资源利用特征分析

开展米槁群落物种生态位研究,可了解米槁群落物种对资源的利用特征,为米槁的保护与管理提供科学依据。基于贵州省米槁天然林群落的实际调查数据,通过生态位宽度、生态位重叠指数,分析该群落主要物种的资源利用特征。群落中米槁(Cinnamomum migao)、杜茎山(Maesa japonica)、菝葜(Smilax china)的生态位宽度最大,在群落中处于明显优势地位,具有较强竞争力和资源利用能力;生态位宽度越大的物种间生态位重叠越大,但在相同或相似环境条件下,生态位宽度值小的种对也会拥有较高的生态位重叠;米槁群落主要物种间的生态位重叠指数偏低,说明物种间对资源利用的相似性较低,物种的生态位分化明显,竞争不激烈,群落结构较为稳定,物种间能够较好地相互共存。     

Effects of supplementing a CP-reduced diet with rumen-protected methionine on Fleckvieh bull fattening

The objective of this study was to evaluate the effect of supplementing a CP-reduced diet with rumen-protected methionine on growth performance of Fleckvieh bulls. A total of 69 bulls (367 ± 25 kg BW) were assigned to three feeding groups (n = 23 per group). The control (CON) diet contained 13.7% CP and 2.11 g methionine/kg diet (both DM basis) and was set as positive control. The diet reduced in CP (nitrogen) (RED) diet as negative control and the experimental RED + rumen-protected methionine (MET) diet were characterised by deficient CP concentrations (both 9.04% CP). The RED + MET diet differed from the RED diet in methionine concentration (2.54 g/kg DM vs. 1.56 g/kg DM, respectively) due to supplementation of rumen-protected methionine. Rumen-protected lysine was added to both RED and RED + MET at 2.7 g/kg DM to ensure a sufficient lysine supply relative to total and metabolisable protein intake. Metabolisable energy (ME) and nutrient composition were similar for CON, RED, and RED + MET. Bulls were fed for 105 days (d) on average. Individual feed intake was recorded daily; individual BW was recorded at the beginning of the experiment, once per month, and directly before slaughter. At slaughter, blood samples were collected and carcass traits were assessed. Reduction in dietary CP concentration reduced feed intake, and in combination with lower dietary CP concentration, daily intake of CP for RED and RED + MET was lower compared with CON (P < 0.01). Daily ME intake was reduced in RED and RED + MET compared with CON (P < 0.01). Consequently growth performance and carcass weights were reduced (both P < 0.01) in both RED and RED + MET compared with CON. Supplemental rumen-protected methionine was reflected in increased serum methionine concentration in RED + MET (P < 0.05) as compared to RED but it did not affect growth performance, carcass traits and serum amino acid (AA) concentrations, except for lysine which was reduced (P < 0.01) compared to CON and RED. In conclusion, bulls fed RED or RED + MET diets were exposed to a ruminal CP deficit and subsequently a deficit of prececal digestible protein, but methionine did not appear to be the first-limiting essential AA for growth under the respective experimental conditions.     

A C6/C5 co‐fermenting Saccharomyces cerevisiae strain with the alleviation of antagonism between xylose utilization and robustness

During second‐generation bioethanol production from lignocellulosic biomass, the desired traits for fermenting microorganisms, such as Saccharomyces cerevisiae, are high xylose utilization and high robustness to inhibitors in lignocellulosic hydrolysates. However, as observed previously, these two traits easily showed the antagonism, one rising and the other falling, in the C6/C5 co‐fermenting S. cerevisiae strain. In this study, LF1 obtained in our previous study is an engineered budding yeast strain with a superior co‐fermentation capacity of glucose and xylose, and was then mutated by atmospheric and room temperature plasma (ARTP) mutagenesis to improve its robustness. The ARTP‐treated cells were grown in 50% (v/v) leachate from lignocellulose pretreatment with high inhibitors content for adaptive evolution. After 30 days, the generated mutant LF1‐6 showed significantly enhanced tolerance, with a six‐fold increase in cell density in the above leachate. Unfortunately, its xylose utilization dropped markedly, indicating the recurrence of the negative correlation between xylose utilization and robustness. To alleviate this antagonism, LF1‐6 cells were iteratively mutated with ARTP mutagenesis and then anaerobically grown using xylose as the sole carbon source, and xylose utilization was restored in the resulting strain 6M‐15. 6M‐15 also exhibited increased co‐fermentation performance of xylose and glucose with the highest ethanol productivity reported to date (0.525 g g^?1 h^?1) in high‐level mixed sugars (80 g L^?1 glucose and 40 g L^?1 xylose) with no inhibitors. Meanwhile, its fermentation time was shortened by 8 h compared to that of LF1. During the fermentation of non‐detoxified lignocellulosic hydrolysate with high inhibitor concentrations at pH ~3.5, 6M‐15 can efficiently convert glucose and xylose with an ethanol yield of 0.43 g g^?1. 6M‐15 is also regarded as a potential chassis cell for further design of a customized strain suitable for production of second‐generation bioethanol or other high value‐added products from lignocellulosic biomass.     

草地利用方式对温性典型草原优势种植物功能性状的影响

当外界环境发生变化后植物能够改变自身功能性状及时调整适应策略, 因此植物功能性状能够有效地反映植物对草地利用变化的响应, 然而在内蒙古草原从植物功能性状角度开展草地利用方式影响的研究略少。该研究以内蒙古典型草原大针茅(Stipa grandis)、羊草(Leymus chinensis)、糙隐子草(Cleistogenes squarrosa)和冷蒿(Artemisia frigida) 4种主要优势种为研究对象, 探讨在长期自由放牧、割草、短期围封和长期无干扰的影响下优势种植物功能性状的差异, 以期从功能性状视角, 揭示植物在受到外界干扰后的适应策略, 旨为天然草地的可持续管理提供基础数据支持和科学依据。结果表明: 1)除糙隐子草外, 在长期放牧后内蒙古典型草原优势植物植株高度、根长和植物碳氮含量降低, 这些性状的变化能够使植物个体小型化, 适口性降低, 表明植物通过逃避放牧的策略适应长期自由放牧的干扰; 在割草管理方式下, 优势种的高度和比叶面积有增加的趋势, 其中冷蒿的氮含量对割草响应最敏感, 其根、茎、叶中的氮含量均在割草样地最低; 围封和长期无干扰处理下植物的碳氮含量增加, 表明在干扰强度降低后, 植物通过功能性状的改变从资源获取策略向资源储藏策略转变。2)对优势种功能性状集合分析表明, 糙隐子草具有较低的植株高度和较高的比叶面积, 冷蒿具有较高的木质素含量和氮含量, 这些性状能够使两种植物被家畜采食量减少, 并保证其具有较强的再生能力, 这可能是糙隐子草和冷蒿耐牧的原因; 大针茅具有最高的植株高度、最大的叶片干物质含量, 以及最高的茎、叶纤维素含量, 说明大针茅是非常典型的竞争物种, 在干扰较低的条件下, 大针茅采取竞争策略对其他物种产生较大的竞争压力可能是其占优势的重要原因。     

来源卤化二型聚酮类生物合成基因簇的两种关键功能基因鉴定与表达

为催化卤化产物,挖掘具有生物活性的新卤化物提供新的方法途径,拟构建卤化酶原核表达载体催化天然卤化物的卤化过程。对链霉菌Streptomyces sp. FJS31-2基因组中一个II型PKS类产物zunyimycin生物合成基因簇进行系列分析,针对其中的后修饰酶卤化酶基因和单加氧酶基因进行原核表达纯化。通过分子生物学手段成功构建卤化酶基因(65 kD)和单加氧酶基因(37 kD)的原核表达载体,并对其进行鉴定。卤化酶和单加氧酶在催化化合物的卤化过程中,会产生疑似新卤化产物。