Discovery and SAR analysis of 5-chloro-4-((substituted phenyl)amino)pyrimidine bearing histone deacetylase inhibitors

Histone deacetylases (HDACs) are validated targets for the development of anticancer drugs in epigenetics. In the discovery of novel HDAC inhibitors with anticancer potency, the 5-chloro-4-((substituted phenyl)amino)pyrimidine fragment is assembled as a cap group into the structure of HDAC inhibitors. The SAR revealed that presence of small groups (such as methoxy substitution) is beneficial for the HDAC inhibitory activity. In the enzyme inhibitory selectivity test, compound L20 exhibited class I selectivity with IC₅₀ values of 0.684 µM (selectivity index of >1462), 2.548 µM (selectivity index of >392), and 0.217 µM (selectivity index of >4608) against HDAC1, HDAC2 and HDAC3 compared with potency against HDAC6 (IC₅₀ value of >1000 µM), respectively. In the antiproliferative assay, compound L20 showed both hematological and solid cancer inhibitory activities. In the flow cytometry, L20 promoted G0/G1 phase cell cycle arrest and apoptosis of K562 cells.     

FERONIA is involved in phototropin 1-mediated blue light phototropic growth in Arabidopsis

Plant shoot phototropism is triggered by the formation of a light-driven auxin gradient leading to bending growth. The blue light receptor phototropin 1(phot1) senses light direction, but how this leads to auxin gradient formation and growth regulation remains poorly understood. Previous studies have suggested phot1’s role for regulated apoplastic acidification, but its relation to phototropin and hypocotyl phototropism is unclear. Herein, we show that blue light can cause phot1 to interact with...     

中微量元素和有益元素对水稻生长和吸收镉的影响

采用盆栽试验,研究了中微量元素和有益元素对水稻生长和吸收镉的影响。结果表明,在所有测试的元素和施用方法中,硅酸钠叶面喷施显著增加稻谷产量,而碳酸钙、硼酸、硅酸钠土施和亚硒酸钠显著降低了稻谷产量。镁、锌、铁的盐酸盐形态对水稻籽粒的增产效果优于硫酸盐形态,而钙、铜的硫酸盐形态增产效果略高于盐酸盐形态。在钙、镁、硫三种中量元素中,钙增加了水稻籽粒中的Cd浓度和吸收量,而镁和硫则降低了籽粒中的Cd浓度和吸收量,以硫磺粉处理为最低。稻草中的Cd浓度和总量均以氯化镁处理为最高,硫磺粉处理最低。镁能有效抑制Cd从秸秆向籽粒的转移,其盐酸盐优于硫酸盐。在微量元素中,锌对水稻Cd的吸收抑制作用最为显著,其次是铜,而有益元素肥料硅酸钠叶面喷施则显著增加了稻谷中的Cd浓度和吸收量。硫酸亚铁、氯化锰、氯化铜、硼酸和硼砂处理都能有效地抑制Cd从秸秆向籽粒的转移,而硅酸钠叶面喷施和锌处理则促进了Cd的转移,表明硅酸钠抑制水稻吸收Cd的机制很可能发生在土壤中,而非在植株体内或地上部分。在Cd污染土壤上选用适宜的中微量和有益元素肥料及其施用方法,能有效降低水稻对镉的吸收和稻米中的Cd含量。     

大丽轮枝菌甘油-3-磷酸脱氢酶的功能分析

大丽轮枝菌可侵染棉花、马铃薯、番茄等660余种寄主植物,引致黄萎病,造成严重的经济损失。为了深入了解大丽轮枝菌的致病机制,本研究在前期棉花提取物诱导大丽轮枝菌转录组分析的基础上,选择上调差异表达的线粒体甘油-3-磷酸脱氢酶基因VdGut2(VD592＿6958＿Chr4)和非差异表达的胞质甘油-3-磷酸脱氢酶基因VdGpd(VD592＿10256＿Chr2),进行了功能分析。结果表明,两个VdGut2敲除突变体菌株的产孢量较野生型菌株分别下降了32%和41%,病情指数分别下降了70%和51%,菌落生长速率也显著下降;VdGpd过表达菌株产孢量和病情指数较野生型菌株显著下降,但在甘油为唯一碳源的培养基上其菌落生长速率显著上升。因此,VdGut2促进了大丽轮枝菌分生孢子的形成、碳源的利用以及对寄主植物的致病过程,VdGpd抑制了大丽轮枝菌分生孢子的形成和对寄主植物的致病力,却促进了甘油的代谢。     

不同颜色遮阳网遮光对丘陵茶园夏秋茶和春茶产量及主要生化成分的影响

为研究不同颜色遮阳网遮光对夏秋茶与春茶产量和品质的影响,在中国科学院桃源农业生态试验站以“碧香早”茶树为试验材料,选用不遮光和中度遮光（遮光率(50?4)%）的黑色、绿色、银灰色遮阳网开展遮光试验。结果表明：不同季节使用黑色遮阳网能显著增加氨基酸和咖啡碱含量,降低茶多酚含量和酚氨比,与对照茶园比较,夏季、秋季、春季茶叶氨基酸含量分别增加了14.22%、17.07%、6.23%,茶多酚含量分别降低了4.40%、6.43%、27.66%,咖啡碱含量分别增加了9.48%、8.10%、7.28%。夏秋季银灰色遮阳网效果最差,绿色遮阳网效果介于黑色和对照之间,春季三种颜色遮阳网效果均优于对照;茶树遮光后品质明显优于对照,夏秋茶经遮光可达到制高档茶的要求,春茶遮光可达到制名优茶的要求。     

Participation of lipopolysaccharide in hyperplasic adipose expansion: Involvement of NADPH oxidase/ROS/p42/p44 MAPK‐dependent Cyclooxygenase‐2

Obesity is a world‐wide problem, especially the child obesity, with the complication of various metabolic diseases. Child obesity can be developed as early as the age between 2 and 6. The expansion of fat mass in child age includes both hyperplasia and hypertrophy of adipose tissue, suggesting the importance of proliferation and adipogenesis of preadipocytes. The changed composition of gut microbiota is associated with obesity, revealing the roles of lipopolysaccharide (LPS) on manipulating adipose tissue development. Studies suggest that LPS enters the circulation and acts as a pro‐inflammatory regulator to facilitate pathologies. Nevertheless, the underlying mechanisms behind LPS‐modulated obesity are yet clearly elucidated. This study showed that LPS enhanced the expression of cyclooxygenase‐2 (COX‐2), an inflammatory regulator of obesity, in preadipocytes. Pretreating preadipocytes with the scavenger of reactive oxygen species (ROS) or the inhibitors of NADPH oxidase or p42/p44 MAPK markedly decreased LPS‐stimulated gene expression of COX‐2 together with the phosphorylation of p47^phox and p42/p44 MAPK, separately. LPS activated p42/p44 MAPK via NADPH oxidase‐dependent ROS accumulation in preadipocytes. Reduction of intracellular ROS or attenuation of p42/p44 MAPK activation both reduced LPS‐mediated COX‐2 expression and preadipocyte proliferation. Moreover, LPS‐induced preadipocyte proliferation and adipogenesis were abolished by the inhibition of COX‐2 or PEG₂ receptors. Taken together, our results suggested that LPS enhanced the proliferation and adipogenesis of preadipocytes via NADPH oxidase/ROS/p42/p44 MAPK‐dependent COX‐2 expression.     

A secreted ribonuclease effector from Verticillium dahliae localizes in the plant nucleus to modulate host immunity

The arms race between fungal pathogens and plant hosts involves recognition of fungal effectors to induce host immunity. Although various fungal effectors have been identified, the effector functions of ribonucleases are largely unknown. Herein, we identified a ribonuclease secreted by Verticillium dahliae (VdRTX1) that translocates into the plant nucleus to modulate immunity. The activity of VdRTX1 causes hypersensitive response (HR)‐related cell death in Nicotiana benthamiana and cotton. VdRTX1 possesses a signal peptide but is unlikely to be an apoplastic effector because its nuclear localization in the plant is necessary for cell death induction. Knockout of VdRTX1 significantly enhanced V. dahliae virulence on tobacco while V. dahliae employs the known suppressor VdCBM1 to escape the immunity induced by VdRTX1. VdRTX1 homologs are widely distributed in fungi but transient expression of 24 homologs from other fungi did not yield cell death induction, suggesting that this function is specific to the VdRTX1 in V. dahliae. Expression of site‐directed mutants of VdRTX1 in N. benthamiana leaves revealed conserved ligand‐binding sites that are important for VdRTX1 function in inducing cell death. Thus, VdRTX1 functions as a unique HR‐inducing effector in V. dahliae that contributes to the activation of plant immunity.     

不同植被恢复方式下红壤线虫数量特征

退化红壤不同植被恢复方式下土壤线虫数量的顺序为：保护荒地＞干扰荒地＞马尾松＞小叶栋＞木荷＞混交林（木荷—马尾松）。土壤线虫数量的季节波动明显：春季和冬季较多,秋季居中,而夏季极显著少于其它季节（尸＜ｏ．０１）。就线虫数量季节变异系数所体现的群落稳定性而言,马尾松林地的变异系数最高（Ｐ＜０．０５）,指示其群落最不稳定。线虫数量在土壤剖面中呈明显的垂直梯度分布。在表层土壤,线虫数量与代表碳氮和生物活性水平的土壤质量指标,如有机碳、全氮、速效氮磷、微生物量、潜在可矿化碳氮、基础呼吸、酶活性等,一般呈极显著正相关（Ｐ＜０．０１）;而与代表土壤物理性质及交换性能的指标,如含水量、容重、颗粒组成、速效钾等一般没有相关性。鉴别分析（ＣＤＡ）将不同植被下的祥地分为３组,自荒１和自荒２为１组,小叶栋、木荷和混交林为１组,而马尾松单独为１组。总之,不同植被恢复下线虫数量的分异韧步体现了线虫指示红壤质量的潜力。     

Discovery and SAR analysis of phenylbenzo[d][1,3]dioxole-based proprotein convertase subtilisin/kexin type 9 inhibitors

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as a novel therapeutic target for the development of cholesterol-lowering drugs. In the discovery of PCSK9/LDLR (low-density lipoprotein receptor) protein-protein interaction (PPI) impairing small molecules, a total of 47 phenylbenzo[d][1,3] dioxole-based compounds were designed and synthesised. The result revealed that the 4-chlorobenzyl substitution in the amino group is important for the PPI disrupting activity. In the hepatocyte-based functional tests, active compounds such as A12, B1, B3, B4 and B14, restored the LDLR levels on the surface of hepatic HepG2 cells and increased extracellular LDL uptake in the presence of PCSK9. It is notable that molecule B14 exhibited good performance in all the evaluations. Collectively, novel structures targeting PCSK9/LDLR PPI have been developed with hypolipidemic potential. Further structural modification of derived active compounds is promising in the discovery of lead compounds with improved activity for the treatment of hyperlipidaemia-related disorders.