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61.
Amila Turalić Prof. Jasmina Đeđibegović Dr. Zsófia Hegedüs Prof. Tamás A. Martinek 《Chembiochem : a European journal of chemical biology》2020,21(14):2060-2066
The incorporation of β-amino acids into a peptide sequence has gained particular attention as β- and α/β-peptides have shown remarkable proteolytic stability, even after a single homologation at the scissile bond. Several peptidases have been shown to cleave such bonds with high specificity but at a much slower rate compared to α-peptide bonds. In this study, a series of analogs of dipeptidyl peptidase-4 (DPP-4) substrate inhibitors were synthesized in order to investigate whether β-amino acid homologation at the scissile bond could be a valid approach to improving peptide stability towards DPP-4 degradation. DPP-4 cleaved the α/β-peptide bond after the N-terminal penultimate Pro with a broad specificity and retained full activity regardless of the β3-amino acid side chain and peptide length. Significantly improved half-lives were observed for β3Ile-containing peptides. Replacing the penultimate Pro with a conformationally constrained Pro mimetic led to proteolytic resistance. DPP-4 cleavage of α/β-peptide bonds with a broad promiscuity represents a new insight into the stability of peptide analogs containing β-amino acids as such analogs were thought to be stable towards enzymatic degradation. 相似文献
62.
Ji Eun Du Young Ah You Eun Jin Kwon Soo Min Kim Jeongae Lee Ki Hwan Han Young Ju Kim 《International journal of molecular sciences》2020,21(23)
Fetal programming implies that the maternal diet during pregnancy affects the long-term health of offspring. Although maternal diet influences metabolic disorders and non-alcoholic fatty liver disease in offspring, the hepatic mechanisms related to metabolites are still unknown. Here, we investigated the maternal diet-related alterations in metabolites and the biological pathway in male offspring at three months of age. Pregnant rats were exposed to 50% food restriction during the prenatal period or a 45% high-fat diet during the prenatal and postnatal periods. The male offspring exposed to food restriction and high-fat diets had lower birth weights than controls, but had a catch-up growth spurt at three months of age. Hepatic taurine levels decreased in both groups compared to controls. The decreased hepatic taurine levels in offspring affected excessive lipid accumulation through changes in hepatocyte nuclear factor 4 A methylation. Moreover, the alteration of gluconeogenesis in offspring exposed to food restriction was observed to a similar extent as that of offspring exposed to a high fat diet. These results indicate that maternal diet affects the dysregulation in hepatic metabolism through changes in taurine levels and HNF4A methylation, and predisposes the offspring to Type 2 diabetes and non-alcoholic fatty liver disease in later life. 相似文献
63.
《低温学》2018
High-frequency pulse tube cryocooler (HPTC) has advantages of compact structure, low vibration, high reliability and long operation time. In this study, Theoretical analysis and experimental tests have been conducted in four aspects based on a developed 4 K HPTC. Firstly, a compressor with larger power output capability was employed and the impedance match between the cold head and the compressor was discussed. Secondly, simply using inertance tube configuration to replace the traditional inertance tube-gas reservoir structure. Then, the type and the size of the regenerator materials working at 4–20 K have been experimentally optimized. Finally, the performance of double-inlet working at as low as 20 K has also been tested for the first time for the HPTC. The present prototype achieved a no-load temperature of 3.6 K, which is the lowest temperature record ever reported for HPTC using helium-4 as working gas. A cooling power of 6 mW/4.2 K was also obtained with 250 W input power and a precooling power of 12.1 W/77 K. 相似文献
64.
将17-4PH不锈钢锻棒固溶处理后油冷,然后选择在最佳的时效温度480 ℃时效保温0~5 h后空冷。通过光学显微镜(OM)、超景深显微镜、XRD、显微硬度仪等测试方法观察固溶、时效过程的组织演变和分析其沉淀硬化机理;采用电阻仪间接测试ε-Cu相动态时效析出过程对电阻的影响;并利用摩擦磨损试验机测试其耐磨性能。研究发现:17-4PH不锈钢固溶和时效过程没有残留奥氏体和逆转变奥氏体出现,热处理后出现板条状和块状两种马氏体形态,板条状马氏体硬度高于块状马氏体,随着时效时间的延长,两种马氏体硬度同步上升,时效析出明显提高了固溶态组织的硬度;时效2.0~2.5 h附近强化效果和耐磨性能最弱,可能与ε-Cu 相长大及与位错交互作用有关;硬度随时效时间的变化趋势与电阻正好相反。 相似文献
65.
目的:分析健康受试者口服pazopanib片后体内药代动力学(PK)规律,初步探讨pazopanib片PK个体差异的遗传学机制。方法:14例健康男性受试者分别在给药当天单次口服pazopanib片(200 mg)后,采集基线至96 h血液样本,用LC-MS/MS法测定服药后各时间点血药浓度,用WinNonlin 6.3软件计算药代动力学相关参数,采用SNapShot法测定细胞色素P450 3A4(CYP3A4)基因多态性。结果:Cmax变化范围(7 361.65-26 081.00) ng/mL,平均值±标准差(15 410.72±6 366.21) ng/mL ;tmax变化范围(1.50-4.00) h、平均值±标准差(2.50±0.83) h;AUC0-t变化范围(228 013.55-775 231.63)ng·mL-1·h,平均值±标准差(516 279.90±175 688.41)ng·mL-1·h。个体间Cmax、AUC相差达3倍以上,tmax可相差2倍以上;14例受试者CYP3A4(RS35599367)位点皆为野生型。结论:pazopanib片在中国健康男性志愿者中个体差异较大,未观察到CYP3A4(rs35599367)位点单核苷酸多态性,pazopanib个体间PK差异可能与其他药物代谢相关基因多态性有关。 相似文献
66.
采用湿化学法制备了Eu~(3+)掺杂Y_2P_4O_(13)荧光材料,通过X射线粉末衍射(XRD)、傅里叶变换红外光谱(FT-IR)和荧光光谱(FL)等手段表征制备产物的物相结构、荧光性能,并对合成原料中稀土与磷的比例(n(Y+Eu)/n(P))和pH调节剂种类对制备样品的物相结构及性能的影响进行分析。结果表明:合成原料中n(Y+Eu)/n(P)比值和pH调节剂种类直接影响着制备产物的物相结构与性能。在n(Y+Eu)/n(P)=12.1、以NH_4HCO_3为pH调节剂调节pH为6的条件下可获得正交晶系的Eu~(3+)掺杂Y_2P_4O_(13)荧光材料。所制备的Y_2P_4O_(13):2at%Eu~(3+)荧光材料在395nm光的激发下可发射出橙红光。 相似文献
67.
研究了退火和固溶时效处理对热轧态TC4钛合金的力学性能和组织的影响,并考察了其冲击磨损性能。结果表明:退火处理后试样组织中转变β相增加,强度、塑性和韧性均较热轧态有所提升;而固溶时效处理后试样组织的晶粒细化且尺寸更为均匀,同时具有最高的强度,而塑性和韧性则较热轧态有所降低。经过10 h的冲击磨损试验后,退火态试样的磨损率最低,而固溶时效态试样的磨损率最高。通过磨损断口观察发现退火态试样表面冲刷犁沟较短,且终点处存在合金的塑性堆积,同时磨损面组织发生塑性变形,晶粒延展拉长。退火态试样较高的塑性和韧性有助于吸收冲击能量,因此表现出较好的耐冲击磨损性能。 相似文献
68.
The corrosion performances of Mg–4Y–xAl (x = 1, 2, 3, and 4 wt%) alloys in the 3.5% NaCl electrolyte solution are investigated by electrochemical tests, weight loss measurement and corrosion morphology observation. The results indicate that corrosion modes for the alloys are localized corrosion and the filiform type of attack. With Al concentration increasing from 1 to 4 wt%, the corrosion rate of Mg–4Y–xAl alloys decreases firstly and then increases, and WA42 alloy shows the best corrosion resistance. The addition of Al element to Mg–4Y alloys leads to the formation of Al2Y and Al11Y3 intermetallic compounds and reduces the proportion of Mg24Y5 phase. Corrosion resistance of the Mg–4Y–xAl alloys mainly depends on the size and distribution of the second phases. Besides, the addition of excessive Al can greatly consumes the Y element in the matrix, thus leading to a less protective film on the alloys. The effect of the relative Volta potential changes between the second phases and α-Mg on corrosion resistance of Mg–4Y–xAl alloys is insignificant. The main corrosion products of the Mg–4Y–xAl alloys are Mg(OH)2, Mg3(OH)5Cl·4H2O, Mg0.72Al0.28(CO3)0.15(OH)1.98(H2O)0.48, and Mg4Al2(OH)12CO3·3H2O. 相似文献
69.
通过对42CrMo4风机主轴结构尺寸、性能要求、材质特点等方面进行分析,对原有锻后热处理工艺进行优化,制定出既能达到锻后热处理效果又经济节能的工艺参数。 相似文献
70.
Bo Wu Huiying Du Ping Hu Zhanyu Gao Ruikai Liu Chonghua Pei 《Journal of Energetic Materials》2021,39(1):10-22
ABSTRACT In recent years, the exploration of a practical strategy for novel energetic molecules with high energy and low sensitivity is very desirable but highly challenging. Novel ionic energetic molecules have attracted much attention in this area due to their prominent advantages including low sensitivities, high thermal stability, and excellent energy performances. Herein, five different ionic energetic molecules based on new monovalent and divalent 4-oxyl-3,5-dinitropyrazolate moieties with enhanced oxygen balance have been synthesized, characterized and evaluated as potential high-energy materials. Thermal stability, sensitivities and energy output test were measured and studied in detail. The heats of formation and energetic parameters were calculated by using Gaussian 09 suite of programs and EXPLO 5 code. The results suggest that all as-prepared new molecules exhibit good thermal stability with high decomposition temperature (3, 231°C; 5, 160°C; 6, 185°C; 7, 180°C; 8, 213°C), and relative low sensitivity (IS > 20 J, FS = 324 N). Inheriting the significant oxygen content of monovalent and divalent 4-oxyl-3,5-dinitropyrazolate moieties, they also possess good energy properties (v D = 8238 ~ 9208 m s?1, P = 26.8 ~ 36.7 GPa, V o = 481.8 ~ 959.4 L kg?1), which make them competitive high-energy materials. 相似文献