一种具备巯基点击化学功能的二硫代酯RAFT链转移剂的合成

以2,2-二硫二吡啶,2 巯基乙醇为原料,醋酸为催化剂,合成了2-羟乙基-二硫吡啶(PⅠ)。以PⅠ、4-氰基-4-(硫代苯甲酰)戊酸(PⅡ)为原料,1-(3-二甲氨基丙基)-3-乙基碳二亚胺盐酸盐(EDC)、4-二甲氨基吡啶(DMAP)为催化剂,合成了一种新的可逆加成 断裂链转移自由基聚合(RAFT)链转移剂4-氰基-4-(硫代苯甲酰)戊酸-2-二硫吡啶乙酯(PⅢ)。以PⅢ为RAFT链转移剂,偶氮二异丁腈（AIBN）为引发剂,甲基丙烯酸甲酯(MMA)为单体,采用RAFT制备了聚甲基丙烯酸甲酯（PMMA）。用1H-NMR分析了链转移剂的的分子结构,用GPC测得PMMA聚合物的分子量及其分布。结果表明：能用于巯基点击化学的二硫吡啶基团被接到PⅡ的末端,成功制备了一种具备巯基点击化学功能的二硫代酯RAFT链转移剂(PⅢ),利用PⅢ,通过RAFT聚合制备了分子量分布狭窄的PMMA聚合物。     

Stereoselective Synthesis and Anticancer Activity of 2,6-Disubstituted trans-3-Methylidenetetrahydropyran-4-ones

In this report, we present efficient and stereoselective syntheses of 2,6-disubstituted trans-3-methylidenetetrahydropyran-4-ones and 2-(4-methoxyphenyl)-5-methylidenetetrahydropyran-4-one that significantly broaden the spectrum of the available methylidenetetrahydropyran-4-ones with various substitution patterns. Target compounds were obtained using Horner–Wadsworth–Emmons methodology for the introduction of methylidene group onto the pyranone ring. 3-Diethoxyphosphoryltetrahydropyran-4-ones, which were key intermediates in this synthesis, were prepared by fully or highly stereoselective addition of Gilman or Grignard reagents to 3-diethoxyphosphoryldihydropyran-4-ones. Addition occurred preferentially by axial attack of the Michael donors on the dihydropyranone ring. Relative configurations and conformations of the obtained adducts were assigned using a detailed analysis of the NMR spectra. The obtained methylidenepyran-4-ones were evaluated for cytotoxic activity against two cancer cell lines (HL-60 and MCF-7). 2,6-Disubstituted 3-methylidenetetrahydropyran-4-ones with isopropyl and phenyl substituents in position 2 were more cytotoxic than analogs with n-butyl substituent. Two of the most cytotoxic analogs were then selected for further investigation on the HL-60 cell line. Both analogs induced morphological changes characteristic of apoptosis in cancer cells, significantly inhibited proliferation and induced apoptotic cell death. Both compounds also generated DNA damage, and one of the analogs arrested the cell cycle of HL-60 cells in the G2/M phase. In addition, both analogs were able to inhibit the activity of topoisomerase IIα. Based on these findings, the investigated analogs may be further optimized for the development of new and effective topoisomerase II inhibitors.     

基于UPLC-Q-TOF-MSn的化妆品中40种性激素非法添加分析方法及筛查数据库的建立

目的 建立基于 UPLC-Q-TOF-MSⁿ的化妆品中 40 种性激素非法添加分析方法及筛查数据库。方法 色谱柱为Agilent SB-C₁₈(2.1 mm×50 mm,1.8 μm),正离子模式以 0.1%甲酸水溶液-乙腈为流动相,负离子模式以水-乙腈为流动相,梯度洗脱,流速 0.2 mL·min^-1,柱温 35 ℃;采用电喷雾电离源(ESI),采集模式为 Scan MS 及 Targeted MS/MS,将 40 种性激素的精确质量数、保留时间、二级质谱图导入 PCDL 软件建立筛查数据库。结果 采用所建立的数据库方法快速筛查 100 批化妆品,1 批育发类产品检出少量黄体酮。结论 本研究所建立的 40 种性激素分析方法和筛查数据库具有简便、快速、灵敏和准确的特点,适合化妆品中非法添加性激素的高通量筛查和准确定性。     

Adding collagen to adipose tissue transplant increases engraftment by promoting cell proliferation,neovascularisation and macrophage activity in a rat model

To clarify the effect of collagen addition to transplanted adipose tissue on angiogenesis, cell proliferation and tissue remodelling process and reveal whether collagen addition contributes to improving transplanted adipose tissue engraftment in rats. Adipose tissue was harvested from the inguinal and injected into the back of the rat, in addition to collagen. Engraftment tissue was harvested, semi‐quantitatively evaluated and underwent haematoxylin and eosin or Perilipin staining. Moreover, we evaluated viable adipocyte counts and neovascularisation. Macrophages were evaluated using flow cytometry, and the adiponectin or vascular endothelial growth factor (VEGF) mRNA was detected using real‐time polymerase chain reaction. By collagen addition to transplanted adipose tissue, higher engraftment rate semi‐quantitatively and a greater number of new blood vessels histologically were identified. Perilipin staining revealed a higher adipocyte number. The total cell, M1 macrophage and M2 macrophage count were higher. There was increased adiponectin mRNA significantly at week 4 compared to that at week 1 after transplantation. Note that the expression levels of VEGF mRNA increased. In rats, adding collagen enhanced cell proliferation, induced M2 macrophages, which are involved in wound healing, and promoted adipocytes and neovascularisation. Therefore, collagen addition to transplanted adipose tissue could increase the engraftment rate of adipose tissue.     

炙甘草汤和生脉散加减治疗小儿气阴亏虚型病毒性心肌炎的临床观察

目的 探讨炙甘草汤和生脉散加减治疗小儿气阴亏虚型病毒性心肌炎(VMC)的临床效果.方法 选取2018年3月至2020年3月于灵宝市第一人民医院接受治疗的93例气阴亏虚型VMC患儿,依据抽签法分为对照组(n=46)与观察组(n=47).两组均接受常规治疗,在此基础上,对照组采用灸甘草汤治疗,观察组采用炙甘草汤和生脉散加减...     

Effect of Al and La Doping on the Structure and Magnetostrictive Properties of Fe73Ga27 Alloy

The changes of microstructure, magnetostriction properties and hardness of the Fe₇₃Ga_27−xAl_x alloy and (Fe₇₃Ga_27−xAl_x)_99.9La_0.1 alloy (x = 0, 0.5, 1.5, 2.5, 3.5, 4.5) were studied by doping Al into the Fe₇₃Ga₂₇ and (Fe₇₃Ga₂₇)_99.9La_0.1 alloy, respectively. The results show that both the Fe₇₃Ga_27−xAl_x alloy and (Fe₇₃Ga_27−xAl_x)_99.9La_0.1 alloy are dominated by the A2 phase, and the alloy grains are obvious columnar crystals with certain orientations along the water-cooled direction. A proportion of Al atoms replaced Ga atoms, which changed the lattice constant of the alloy, caused lattice distortion, and produced vacancy effects which affected the magnetostriction properties. La atoms were difficult to dissolve in the matrix alloy which made the alloy grains smaller and enhanced the orientation along the (100) direction, resulting in greater magneto-crystalline anisotropy and greater tetragonal distortion, which is conducive to improving the magnetostriction properties. Fe₇₃Ga_24.5Al_2.5 alloy has a saturation magnetostrictive strain of 74 ppm and a hardness value of 268.064 HV, taking into account the advantages of saturated magnetostrictive strain and high hardness. The maximum saturation magnetostrictive strain of the (Fe₇₃Ga_24.5Al_2.5)_99.9La_0.1 alloy is 115 ppm and the hardness is 278.096 HV, indicating that trace La doping can improve the magnetostriction properties and deformation resistance of Fe-Ga alloy, which provides a new design idea for the Fe-Ga alloy, broadening their application in the field of practical production.     

Influence of Tantalum Addition on the Corrosion Passivation of Titanium-Zirconium Alloy in Simulated Body Fluid

Ti-15%Zr alloy and Ti-15%Zr-2%Ta alloy were fabricated to be used in biomedical applications. The corrosion of these two alloys after being immersed in simulated body fluid for 1 h and 72 h was investigated. Different electrochemical methods, including polarization, impedance, and chronoamperometric current with time at 400 mV were employed. Also, the surface morphology and the compositions of its formed film were reported by the use of scanning electron microscope and energy dispersive X-ray. Based on the collected results, the presence of 2%Ta in the Ti-Zr alloy passivated its corrosion by minimizing its corrosion rate. The polarization curves revealed that adding Ta within the alloy increases the corrosion resistance as was confirmed by the impedance spectroscopy and current time data. The change of current versus time proved that the addition of Ta reduces the absolute current even at high anodic potential, 400 mV. The results of both electrochemical and spectroscopic methods indicated that pitting corrosion does not occur for both Ti-Zr and Ti-Zr-Ta alloys, even after their immersion in SBF solutions for 72 h.     

西维因与胡椒基丁醚对蚤状溞协同毒性作用

目的 探讨农药混合物联合毒性的评定方法。方法 选择蚤状溞作为受试生物,测定西维因和胡椒基丁醚对蚤状溞的单一毒性及其联合毒性,基于单一化合物的浓度-反应曲线,引入交互作用系数,运用浓度相加(CA)与独立作用(IA)模型对二元混合物的联合毒性进行预测,并将模型预测结果与混合物毒性实验数据进行比较分析。结果 西维因、胡椒基丁醚及2者混合物对蚤状溞的急性毒性数据均可通过Weibull方程拟合,R²分别为0.89005、0.92834、0.94441,由拟合方程得到的半数效应浓度(EC₅₀)分别为0.0714、5.7147、2.9680μmol/L;西维因与胡椒基丁醚对蚤状溞急性毒性呈协同作用;西维因与胡椒基丁醚混合物毒性引入交互作用系数K后,IA模型预测曲线与实验数据拟合曲线更接近。结论 农药混合物毒性可以通过模型预测,化合物的交互作用可通过K函数修饰。     

N-乙酰基-12-氨基亚甲基-14-脱氧穿心莲内酯衍生物的合成及其抗肿瘤活性

目的:设计和合成出新的穿心莲内酯衍生物并研究其抗肿瘤活性。方法:以穿心莲内酯(1)为原料,在醇钠作用下,和硝基甲烷发生Michael加成反应脱水生成12-硝基甲基-14-脱氧穿心莲内酯(2),再在醋酐的保护下在铁粉醋酸中还原生成N-乙酰基-12-氨基亚甲基-14-脱氧穿心莲内酯(3),然后再与酸在DCC、DMAP作用下酯化生成目标化合物。按MTT方法测定了目标化合物的抗肿瘤活性。结果和结论:合成了未见文献报道的10个穿心莲内酯衍生物(4a~4j),其结构经核磁、质谱和元素分析等数据确证。初步的抗肿瘤活性研究表明:10个目标化合物均具有不同程度的抗肿瘤活性;其中化合物4c对人肝细胞肝癌SMMC-7721的抑制百分率超过穿心莲内酯。     

紫外二阶导数光谱标准加入法测定中药复方制剂中合成鱼腥草素含量

将紫外二阶导数光谱与标准加入法相结合应用于药物分析,定量测定中药复方制剂中合成鱼腥草素的含量。根据比尔定律推导出标准加入体系的含量计算公式为Ｘ＿ｉ＝Ｘ＿ｉ×Ｃ＿ｉ／Ｋ－Ｃ＿ｉ×Ｖ＿ｉ。方法精密度ＣＶ１．３％;平均回收率９９．４０％,回收率ＣＶ１．９％。本法消除了中药复方制剂中样品基质的干扰,结果准确可靠。