Age‐related memory vulnerability to interfering stimuli is caused by gradual loss of MAPK‐dependent protection in Drosophila

Age‐related memory impairment (AMI) is a common phenomenon across species. Vulnerability to interfering stimuli has been proposed to be an important cause of AMI. However, the molecular mechanisms underlying this vulnerability‐related AMI remain unknown. Here we show that learning‐activated MAPK signals are gradually lost with age, leading to vulnerability‐related AMI in Drosophila. Young flies (2‐ or 3‐day‐old) exhibited a significant increase in phosphorylated MAPK levels within 15 min after learning, whereas aged flies (25‐day‐old) did not. Compared to 3‐day‐old flies, significant 1 h memory impairments were observed in 15‐, 20‐, and 30‐day‐old flies, but not in 10‐day‐old flies. However, with post‐learning interfering stimuli such as cooling or electric stimuli, 10‐day‐old flies had worse memory performance at 1 h than 3‐day‐old flies, showing a premature AMI phenomenon. Increasing learning‐activated MAPK signals through acute transgene expression in mushroom body (MB) neurons restored physiological trace of 1 h memory in a pair of MB output neurons in aged flies. Decreasing such signals in young flies mimicked the impairment of 1 h memory trace in aged flies. Restoring learning‐activated MAPK signals in MB neurons in aged flies significantly suppressed AMI even with interfering stimuli. Thus, our data suggest that age‐related loss of learning‐activated neuronal MAPK signals causes memory vulnerability to interfering stimuli, thereby leading to AMI.     

Design,synthesis, and biological evaluation of novel carbazole derivatives as potent DNMT1 inhibitors with reasonable PK properties

The DNA methyltransferases (DNMTs) were found in mammals to maintain DNA methylation. Among them, DNMT1 was the first identified, and it is an attractive target for tumour chemotherapy. DC_05 and DC_517 have been reported in our previous work, which is non-nucleoside DNMT1 inhibitor with low micromolar IC₅₀ values and significant selectivity towards other S-adenosyl-_L-methionine (SAM)-dependent protein methyltransferases. In this study, through a process of similarity-based analog searching, a series of DNMT1 inhibitors were designed, synthesized, and evaluated as anticancer agents. SAR studies were conducted based on enzymatic assays. And most of the compounds showed strong inhibitory activity on human DNMT1, especially WK-23 displayed a good inhibitory effect on human DNMT1 with an IC₅₀ value of 5.0 µM. Importantly, the pharmacokinetic (PK) profile of WK-23 was obtained with quite satisfying oral bioavailability and elimination half-life. Taken together, WK-23 is worth developing as DNMT1-selective therapy for the treatment of malignant tumour.     

青藏高原地区的光质对高原春小麦生长发育、光合速率和干物质含量影响的研究

本文模拟研究了高原地区的不同光质对春小麦的生长发育、光合速率和干物质含量等方面的影响。实验结果表明:(1)蓝光和蓝紫光的照射能使春小麦植株趋于矮壮。提高总叶绿素含量,增加叶绿素b值,并能延迟春小麦的生育期和干物质积累的时间。(2)红光和蓝紫光对春小麦品种的光合速率都比对照有提高效应,其中红光最显著,蓝紫光次之,而蓝光下最低。(3)红光和蓝紫光下积累的干物质含量均大于对照,蓝光下的较低。从而论证了青藏高原地区较好的光质,尤其丰富的蓝紫光是高原春小麦屡出高产的重要生态因素之一。为在这一地区充分利用这一得天独厚的有利条件挖掘更大的高产潜力提供了科学依据。     

畜牧业在农业生态系统中的地位——窦店畜牧业的系统分析

本研究把畜牧业看作整个农业生态系统中的一个亚系统,定量分析了各种畜禽对能量、蛋白质和营养物质的转化效率,分析了畜牧亚系统与其它亚系统间以及与环境间的能量与物质的交流,从而对窦店畜牧业的生产力水平及其在整个农业生态系统中的地位做出客观评价,对畜牧结构的调整提出了建议,并讨论了农区畜牧业和农业生态系统的开放等问题。     

羊草草原枯枝落叶分解的研究——主要优势植物的分解速率和损失率

分解速率和损失率从不同侧面反映了枯枝落叶分解动态,羊草草原主要优势植物,羊草（Leymus chinensis),拂子茅（Calamagrostis epigejos),减蓬（Suaeda glauca),碱茅（Puccinellia tenuiflora),五脉山黎豆（Lathyrus quinqueneruivs),碱蒿（Artemisia anethifolia)分解速率的季节变化动态近似倒“V”字型,损失率的季节变化呈S型,反了枯枝落叶的失重情况,枯枝落叶的化学组成成分是造成不同种植物间分解差异的主要原因,特别是C／N比与分解快慢有密切关系,分解初期,枯枝落叶的损失符合指数衰减模型,枯枝落叶损失95％所需时间,羊草群落约为8．8a,杂类草群落约为9．7a,碱茅群落约为7．1a,碱蓬群落约为4．7a。     

弱氧化醋杆菌阿拉伯糖醇脱氢酶基因克隆及其在大肠杆菌中的表达

The partial genomic library of Acetobacter suboxydans was constructed using Yeast\| E.coli shuttle plasmid YEp352 as vector.Two positive transformants,designated as DH5α(pAD91) and DH5α(pAD98),were obtained by screening the growth of transformants on the agar plate in which D\|arabitol was used as the sole carbon source.The results of Southern blot and restriction endonuclease analysis showed that the two recombinants are identical.The insert is about 2.3kb.Arabitol dehydrogenase activity assay indic…     

Response of physiologic metabolism and cell structures in mango fruit to exogenous methyl salicylate under low-temperature stress

We explored the effects of exogenous methyl salicylate (MeSA) on the development of chilling injury symptom, and the structure and composition of the pericarp, in mango ( Mangifera indica L. cv. 'Red 6') fruit under low-temperature stress using histochemical analysis and scanning electron microscopy together with Fourier transform infrared (FTIR) analysis. The results indicated that chilling injury symptom was remarkably limited in the fruit treated with MeSA at 0.1 m M as compared to the 5°C control, demonstrating the positive effects of MeSA in reducing chilling injury of mango fruit in low-temperature storage. In MeSA-treated fruit, the pericarp wax surface showed many cracks, and exocarp cells exhibited normal separation. The cell wall of exocarp contained lower amounts of pectic substances, aliphatics and phenolics in MeSA-treated fruit. In addition, MeSA-treated fruit contained more esterified substances and less carboxylate and carboxyl substances. Our work revealed the importance of MeSA in enhancing fruit tolerance to low-temperature stress and suggested a contribution of cellular structure and composition to this effect, which has not been reported previously.     

Determination of cefazedone in human plasma by high performance liquid chromatography–tandem mass spectrometry: Application to a pharmacokinetic study on Chinese volunteers

A rapid, sensitive and simple high performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method was developed for determination of cefazedone in human plasma using metronidazole as internal standard (IS). The chromatographic separation was achieved on an Ultimate XB-CN column (2.1 mm × 150 mm, 5 μm) with an isocratic mobile phase of acetonitrile and 20 mM ammonium acetate in 0.1% formic acid in water (15:85, v/v). Detection was performed using electrospray ionization in positive ion multiple reaction-monitoring mode (SRM), monitoring the transitions m/z 548.2 → 344.1 for cefazedone and m/z 172.2 → 128.1 for IS. Calibration curves were linear over a wide range of 0.20–401.12 μg/mL for cefazedone in plasma. The lower limit of quantification (LLOQ) was 0.20 μg/mL. The intra- and inter-day precisions were less than 7.2%. The average recovery of cefazedone was 90.8–91.0%. The validated method was successfully applied to the pharmacokinetic study of cefazedone in Chinese healthy volunteers following intravenous (IV) administration of 500, 1000 and 2000 mg cefazedone injection.     

辽宁和江苏两省杂草稻植物性状多样性

辽宁和江苏两省是我国杂草稻(Oryza sativa f. spontanea)发生最为严重的地区之一, 为明确两省杂草稻识别特征和类型, 我们在两省14个市29个样点采集样品, 与当地栽培水稻品种一并在南京种植, 观测了营养生长期和生殖生长期的23个植物性状。结果表明, 两省杂草稻在营养生长期的1月株高、1月和2月分蘖数, 在生殖生长期的果皮色、谷粒长/宽比、百粒重、落粒性、秆硬度、剑叶宽、剑叶长、有效穗数、50%黄熟、50%黄熟–50%抽穗和全黄熟等性状与相应的当地栽培稻存在差异;主成分1和主成分2组成的二维散点图(累计贡献率达43.24%)也显示出两省杂草稻间以及与栽培稻间的差异性。采用欧氏距离对两省杂草稻进行系统聚类可以将杂草稻分为籼型和粳型。其中辽宁省杂草稻全部聚在粳型类群中, 它们又可细分为两类; 江苏省杂草稻既有粳型, 又有籼型, 其中粳型与辽宁省杂草稻聚在粳型类群中, 籼型又可分为3类。这6个类群分别具有如下突出特点: 第1类为强落粒、粒轻、秆矮、早熟、偏粳等; 第2类为无芒、穗多、强休眠、剑叶窄、偏粳等; 第3类为长芒、弱分蘖、穗少、弱落粒、偏粳等; 第4类为硬秆、剑叶宽、迟熟、强休眠、偏籼等; 第5类为红果皮、粒长、软秆、粒重、偏籼等; 第6类为无芒、株高、穗长、剑叶长、偏籼等。上述杂草稻的形态学指标和类型的研究将为两省开展杂草稻危害防治工作提供理论依据。