Statistical characterization of salt bridges in proteins

The structure and folding mechanism of a given protein are determined by many factors, including the electrostatic interactions between charged residues of protein molecules known in general as salt bridges. In this study, analyses were conducted on 10,370 salt bridges in 2017 proteins and the results compared to previous statistical surveys of 36 protein structures. Although many of the general trends remained consistent with other studies, more detailed information was illuminated by the larger dataset. In particular, it was shown that there is a strong correlation between secondary structure and salt bridge formation, and that salt bridges display preferential formation in an environment of about 30% solvent accessible surface area.     

北京山区植被动态及生态恢复的遥感监测

基于北京地区1979、1988、1999、2005和2009年5期Landsat数据,利用基于植被指数的像元线性分解模型对植被覆盖度进行反演,分析了北京山区植被覆盖的时空动态,并通过提取植被退化和修复的区域,研究了海拔、坡度和土壤类型对生态修复的影响.结果表明：1979-1988年,北京山区植被覆盖基本稳定,其后由于社会经济的快速发展,1988-2000年北京山区植被严重退化,2000年以后由于采取多种保护措施,大部分区域生态恢复效果明显,2009年平均覆盖度达到72%,比1999年增加了13%.北京山区植被覆盖变化与地理特征密切相关,土壤贫瘠和坡度较大区域在自然状态下的退化比例相对较高,且退化后不易自然恢复,而低海拔区域受人为因素的影响更大.     

Simultaneous Determination of Dermatan Sulfate and Oversulfated Dermatan Sulfate in Plasma by High-Performance Liquid Chromatography with Postcolumn Fluorescence Derivatization

A chemical method for the determination of dermatan sulfate (DS) and oversulfated dermatan sulfate has been developed and applied to the pharmacokinetic study of these polysaccharides in experimental animals. The analytical procedure includes a simple preparation step of administered DS and oversulfated DS from blood plasma, HPLC for the separation and detection of DS and oversulfated DS using an Asahipak NH₂P-50 column, fluorometric reaction of the polysaccharides with guanidine in a strong alkaline medium. DS and oversulfated DS were extracted from plasma by treating it with proteinase to remove plasma proteins and recovered with endogenous plasma glycosaminoglycans by ethanol precipitation. Finally, DS and oversulfated DS were analyzed by fluorometric HPLC. The detection limits of DS and oversulfated DS were 10 and 20 ng, respectively. Furthermore, we demonstrated that artificial oversulfation of DS increased its biological half-life after intravenous administration to rats.     

共培养对小鼠囊胚质量及其表观遗传修饰的影响

本研究探讨了共培养对小鼠囊胚质量及其表观遗传修饰的影响。将小鼠的受精卵体外随机分别置于含颗粒细胞(试验组I)、输卵管上皮细胞(试验组Ⅱ)、输卵管组织块(试验组Ⅲ)的KSOM培养液中作为试验组进行共培养,同时设立对照组A(体外培养,仅含KSOM)和对照组B(体内培养)。比较各组受精卵的卵裂率和囊胚发育率;并应用碘化丙啶和Hoechest333258对囊胚进行染色,利用ICM/TE值评价各组胚胎体外发育的质量;同时将囊胚进行免疫荧光染色,观察其基因组甲基化和组蛋白乙酰化的水平。结果表明,与对照组A相比,试验组的卵裂率和囊胚发育率均有显著提高(P<0.05);同时其囊胚细胞数目及内细胞团细胞数与滋养层细胞数比值(ICM/TE)值均显著高于对照组A(P<0.05);各试验组囊胚基因组甲基化水平与对照组A差异不显著(P>0.05),但各体外培养组均与对照组B差异显著(P<0.05);试验组组蛋白乙酰化水平与对照组A、B差异均不显著(P>0.05)。共培养能够有效促进小鼠胚胎的体外发育,提高囊胚的发育质量,但是仍不能克服由体外培养造成的基因组甲基化异常。     

柞蚕微粒子病潜在生物标志物的挖掘

【目的】挖掘柞蚕Antheraea pernyi微粒子病的潜在生物标志物,为开发该病害检测方法及研究柞蚕被微孢子虫Nosema pernyi侵染后体内代谢产物的差异及功能奠定基础。【方法】利用高效液相色谱和高分辨率质谱进行非靶向代谢组学分析,调查健康和患微粒子病柞蚕雌成虫血淋巴中代谢物差异。【结果】正离子模式下从健康和患微粒子病柞蚕雌成虫血淋巴中共获得8 870个代谢物,注释代谢物5 390个,筛选到差异表达代谢物472个(上调260个,下调212个),其中二级鉴定差异表达代谢物12个(上调8个,下调4个);负离子模式下获得6 716个代谢物,注释代谢物3 848个,筛选到差异表达代谢物301个(上调207个,下调94个),其中二级鉴定差异表达代谢物9个(上调8个,下调1个)。正离子模式下二级鉴定的差异表达代谢物包括缬氨酸(valine)、苯并噻唑(benzothiazole)、3-脱羟基肉碱(3-dehydroxycarnitine)、1 甲基鸟嘌呤(1-methylguanine)、2-乙氧基萘(2-ethoxynaphthalene)、N6-乙酰基-L-赖氨酸(N6-acetyl-L-lysine)、生物素(biotin)、桑色素(morin)、噻吗洛尔(timolol)、酰基肉碱15∶0(acylcarnitine 15∶0)、酰基肉碱18∶4(acylcarnitine 18∶4)和异槲皮苷(isoquercitrin);负离子模式下二级鉴定的差异表达代谢物包括二甲基丙二酸(dimethylmalonic acid)、戊二酸(glutaric acid)、2,5-二羟基苯甲酸(2,5-dihydroxybenzoic acid)、1,3-二乙酰基丙烷(1,3-diacetylpropane)、3-(4-羟基苯基)乳酸(DL-p-hydroxyphenyllactic acid)、泛酸(pantothenate)、荧光素(fluorescein)、飞燕草素-3-O-beta-吡喃葡萄糖苷(delphinidin-3-O-beta-glucopyranoside)和溶血磷酯酰肌醇16∶1 (lysoPI 16∶1)。【结论】健康与患柞蚕微粒子病的柞蚕雌成虫血淋巴内代谢物具有显著差异,通过代谢组学挖掘出21个二级鉴定的差异表达代谢物,这些代谢物可作为潜在生物标志物用于开发柞蚕微粒子病的检测方法。     

3D pharmacophore based virtual screening of T-type calcium channel blockers

Virtual screening of the commercial databases was done by using a three dimensional pharmacophore previously developed for T-type calcium channel blockers using CATALYSTtrade mark program. Biological evaluation of 25 selected virtual hits resulted in the discovery of a highly potent compound VH04 with IC(50) value of 0.10 microM, eight times as potent as the known selective T-type calcium channel blocker, mibefradil. Search for similar compounds yielded several hits with micro-molar IC(50) values and high T-type calcium channel selectivity. Based on the structure of the virtual hits, small molecule libraries with novel scaffolds were designed, synthesis and biological evaluation of which are currently in progress. This result shows a successful example of ligand based drug discovery of potent T-type calcium channel blockers.     

中国人卵巢上皮性肿瘤nm23H1基因遗传不稳定性的研究

采用石蜡包埋组织抽提DNA,PCR-单链构象多态性(PCR-SSCP),常规银染、Envision免疫组织化学染色和Leica-Qwin计算机图像分析等方法,研究人类17号染色体D17S396位点微卫星不稳定(microsatellite instablility,MSI)和杂合性缺失(loss of heterozygosity,LOH),对卵巢上皮性肿瘤nm23H1蛋白表达的影响,阐明nm23H1基因遗传不稳定性与卵巢肿瘤进展的关系,为揭示nm23H1基因作用机制和肿瘤转移机制提供实验依据。本实验中,卵巢上皮性癌D17S396位点遗传不稳定发生率为40%,明显高于交界性肿瘤的9.52%,而在良性肿瘤和正常卵巢组织中,未见该位点遗传不稳定的发生。其中,LOH的发生率,随肿瘤恶性程度的增高而增加(P<0.05)。在卵巢上皮性癌中,淋巴转移组的LOH发生率高于无淋巴转移组(P<0.01)。FIGO Ⅲ Ⅳ期的LOH发生率高于Ⅰ Ⅱ期(P<0.05)。MSI发生率与卵巢上皮癌组织类型、分化程度、淋巴转移及FIGO分期均无关。nm23H1 蛋白阳性率在卵巢上皮性癌和交界性肿瘤组织中分别为56.00%和57.14%,高于良性肿瘤的13.64%和正常卵巢组织的8.33%(P<0.01)。卵巢上皮性癌中,淋巴转移组nm23H1蛋白阳性率低于无淋巴转移组;FIGO Ⅲ Ⅳ期nm23H1蛋白阳性率低于Ⅰ Ⅱ期(P<0.05)。此外,计算机图像定量分析显示,在各临床病理参数影响下,nm23H1蛋白的表达强度没有差异。在卵巢上皮性癌中,LOH阳性组中nm23H1蛋白阳性率为0.00%,显著低于LOH阴性组的73.68%(P<0.01)。实验结果提示, nm23H1基因的遗传不稳定性可能是卵巢上皮性癌发生、发展的一个重要机制。LOH的发生可作为卵巢组织恶变的判断指标。nm23H1基因的MSI和LOH,通过相互独立的途径调控卵巢上皮癌的发生和转移,后者可抑制卵巢上皮癌局部nm23H1蛋白的表达,并赋予卵巢上皮癌高淋巴结转移、低预后的特性。提高卵巢上皮癌局部nm23H1蛋白的表达,可减缓肿瘤的淋巴转移并提高预后率。     

Requirements for human embryonic stem cells

‘Requirements for Human Embryonic Stem Cells’ is the first set of guidelines on human embryonic stem cells in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies the technical requirements, test methods, test regulations, instructions for use, labelling requirements, packaging requirements, storage requirements and transportation requirements for human embryonic stem cells, which is applicable to the quality control for human embryonic stem cells. It was originally released by the China Society for Cell Biology on 26 February 2019 and was further revised on 30 April 2020. We hope that publication of these guidelines will promote institutional establishment, acceptance and execution of proper protocols, and accelerate the international standardization of human embryonic stem cells for applications.     

Biocidal properties of maltose reduced silver nanoparticles against American foulbrood diseases pathogens

Bee disease caused by spore-forming Paenibacillus larvae and Paenibacillus alvei is a serious problem for honey production. Thus, there is an ongoing effort to find an effective agent that shows broad biocidal activity with minimal environmental hazard. In this study, the biocidal effect of maltose reduced silver nanoparticles (AgNPs) is evaluated against American foulbrood and European foulbrood pathogens. The results demonstrate that the maltose reduced AgNPs are excellent short and long-term biocides against P. larvae isolates. The long-term effect suggests that the Ag⁺ ions are released from the AgNPs with increasing time in a controlled manner.