维罗非尼对UGT1A1介导的伊立替康代谢的抑制作用研究

目的:应用体外人肝微粒体及重组人源代谢酶孵育体系观察维罗非尼对尿苷二磷酸葡萄糖醛酸基转移酶1A1（UDP-glucuronosyltransferases,UGT1A1）介导的伊立替康代谢的抑制作用，通过体外-体内外推（in vitro-in vivo extrapolation,IV-IVE）预测体内药物-药物相互作用（drug-drug interaction,DDI）的发生风险。方法:以混合人肝微粒体 （human liver microsomes,HLMs）及重组表达的人UGT1A1 作为酶源，观察维罗非尼对UGT1A1介导的伊立替康活性代谢产物SN-38葡糖醛酸化反应的抑制作用，求得半数最大抑制浓度（half maximum inhibitory concentration,IC50）和抑制动力学常数Ki及抑制类型；并基于体外参数预测了体内维罗非尼与伊立替康联合应用引发的潜在DDI风险。结果:维罗非尼对UGT1A1具有较强的非竞争性抑制作用，IC50 为4.35 μmol/L，Ki为9.77 μmol/L。口服治疗剂量的维罗非尼 （960 mg，每日两次）可导致SN-38的药时曲线下面积（area under the curve,AUC）增加7%～149% 。结论:维罗非尼与伊立替康联合应用时，可通过强效抑制UGT1A1而影响伊立替康在体内的代谢清除，具有引发DDI的风险。     

A contribution to the crystallochemistry of ternary 1:1:1 and 1:1:2 rare earth intermetallic phases with Pb and Pd

The ternary alloys of the rare earths with lead and palladium were studied for the stoichiometric ratios 1:1:1 and 1:1:2 with respect to the structure of these alloys and their existence field. RPbPd (R = La, Ce, Pr, Nd, Sm, Gd, Tb, Dy, Y, Ho, Er, Tm, Yb) compounds have a hexagonal structure, hP9 Fe₂P type, while RPbPd₂ (R = Pr, Sm, Gd, Tb, Dy, Ho, Er, Yb) alloys have the cubic AlCu₂Mn-type structure (cF16, BiF₃ superstructure).     

1(1/4)Cr—(1/2)Mo耐热钢焊接工艺试验

本文介绍美国引进的1(1/4)Cr—(1/2)Mo耐热钢匹配以国产焊丝、焊条的工艺评定试验及现场工程应用。     

Microstructures and mechanical properties of extruded Mg-1Mn-3.5Y and Mg-1Mn-1Y-2.5Nd alloys

Both Mg-1Mn-3.5Y and Mg-1Mn-1Y-2.5Nd alloys(mass fraction,%)were extruded at 380℃.Most of the(10 10) crystal planes in the Mg-1Mn-3.5Y alloy are parallel to the normal direction,while most of the(10 11)crystal planes in the Mg-1Mn-1Y-2.5Nd alloy are parallel to the normal direction.The tensile tests at room temperature,100℃ and 200℃ show that the Mg-1Mn-3.5Y alloy exhibits higher yield strength,but lower elongation to failure as compared with the Mg-1Mn-1Y-2.5Nd alloy. These differences in the tensile mechanical properties between the two alloys are mainly attributed to their different texture types and amount and distribution of the Mg24Y5 precipitates.The serration flow behavior is observed in the Mg-1Mn-1Y-2.5Nd alloy at 200℃,but does not occur in the Mg-1Mn-3.5Y alloy.The Mg-1Mn-3.5Y alloy shows the cleavage fracture mode,while the Mg-1Mn-1Y-2.5Nd alloy exhibits the dimple fracture mode.     

孤束核微注射内皮素-1(1-31)对心血管活动的影响

目的: 观察内皮素-1(1-31)[ET-1(1-31)] 在大鼠孤束核(Nucleus tracts solitarius, NTS)产生的心血管效应,并探讨其作用机制。方法: 雄性SD大鼠90只,其中50只随机分为双侧NTS注射组、单侧NTS注射组和人工脑脊液(aCSF)组,分别在双侧或单侧NTS微量注射ET-1(1-31) (0.5~2.0 pmoL)或aCSF (100 nL),观察ET-1(1-31) 在NTS内的心血管效应。11只大鼠观察ET-1(1-31) (1.0 pmoL)在NTS水平对动脉压力反射功能(BRS)产生的影响。其余29只大鼠分别预先给予ET_A受体拮抗剂BQ₁₂₃、ET_B受体拮抗剂BQ₇₈₈、非选择性谷氨酸受体拮抗剂犬尿烯酸(KYN)或对照(aCSF),探讨ET-1(1-31)在大鼠NTS内产生的心血管效应机制。结果: 在大鼠NTS双侧或单侧微量注射ET-1(1-31)剂量依赖性降低大鼠血压并减缓心率;NTS双侧微注射ET-1(1-31)(1 pmoL) 显著减弱大鼠BRS(P<0.05);ET_A受体拮抗剂BQ₁₂₃ 或KYN显著减弱单侧NTS微量注射ET-1(1-31)(1.0 pmoL)产生的降低血压和减缓心率作用(P<0.05);单侧NTS注射ET_B受体拮抗剂BQ₇₈₈对NTS微量注射ET-1(1-31)(1.0 pmoL)产生的降低血压和减缓心率作用没有显著的影响(P>0.05)。结论: NTS微量注射ET-1(1-31)能够降低麻醉大鼠的血压并减缓心率,其作用可能是由ET_A受体和谷氨酸受体所介导。     

大蒜素对肝脏药物转运体OATP1B1转运功能的影响

目的: 观察大蒜素对肝脏药物转运体-有机阴离子转运多肽1B1(Organic anion transporting polypeptide 1B1, OATP1B1)转运功能的影响。方法: 利用稳定表达人OATP1B1的人胚胎肾293(Human embryonic kidney 293, HEK293)细胞株,以[³H]硫酸雌酮和普伐他汀为底物进行OATP1B1摄取反应,观察大蒜素对OATP1B1摄取功能的影响。结果: 大蒜素对OATP1B1摄取[³H]硫酸雌酮和普伐他汀的功能有竞争性抑制作用,抑制常数K_i值分别为(18.3±5.2) μmol/L 和(15.4±6.8) μmol/L。结论: 大蒜素对肝脏药物转运体OATP1B1转运功能的抑制作用可诱导中药-西药相互作用。     

Li1+x(Fey/2Niy/2Mn1-y)1-xO2正极材料的合成及电化学性能

采用低温共沉淀-水热-煅烧法合成了锂离子电池Fe-Ni-Mn体系正极材料Li1+x(Fey/2Niy/2Mn1-y)1-xO2,并用XRD、SEM、ICP光谱和电化学性能测试对材料进行了表征.XRD测试和ICP分析表明,Fe、Ni取代Li2MnO3中的部分Mn,形成很好的固溶结构yLiFe1/2Ni1/2O2-(1-y)Li2MnO3 (y=0.l,0.2,0.3,0.4,0.5).SEM测试表明,取代量y不同,材料的表观形貌有所不同,y=0.4时材料的颗粒粒径均匀、较小,呈类球形结构.电化学性能测试表明,当y=0.4时,循环稳定性最好,充放电50次后放电比容量仍可维持在195.0 mAh/g,放电中值电压为3.5 V,y=0.4时样品在大倍率放电下的电化学性能表现良好.     

In situ STM study of the duplex passive films formed on Cu(1 1 1) and Cu(0 0 1) in 0.1 M NaOH

In situ electrochemical scanning tunneling microscopy (ECSTM) investigations of the anodic Cu(I)/Cu(II) duplex passive layers grown on Cu(1 1 1) and Cu(0 0 1) in 0.1 M NaOH are reported. The outer Cu(II) part of the duplex film formed on both substrates is crystalline with a terrace and step topography. The observed lattices are consistent with a bulk-like terminated CuO(0 0 1) surface on both substrates. This common crystallographic orientation is explained by the hydroxylation of the otherwise polar and unstable oxide surface at the passive film/electrolyte interface. The epitaxy of the oxide layers is governed by the parallel alignment of the close packed directions of the CuO outer layers and Cu₂O inner layers on both substrates. A granular and amorphous layer covering the crystalline CuO(0 0 1) oxide has been observed on Cu(0 0 1) but not on Cu(1 1 1). It is assigned to a film of copper hydroxide corrosion products formed by a dissolution-precipitation mechanism. Its absence on the passivated Cu(1 1 1) surface is explained by the higher stability of the Cu₂O(1 1 1) precursor oxide formed on this substrate in the initial stages of growth of the duplex passive film, resulting in a lower amount of dissolved copper.     

Electrical conductivity of 1 : 1 and 2 : 1 clay minerals

The A.C. impedance plots were used as tools to analyze the electrical response of two varieties of Tunisian halloysite 1: 1 and illitic samples 2: 1 as a function of frequency at different temperatures (80–800°C). The real and imaginary parts of the complex impedance trace semicircles in the complex plane. Except for the illite, It-1, the second sample analyzed in this study, these plots give evidence for the presence of both bulk and grain boundary effect, above 600°C onwards. The bulk resistance of the materials decreases with the rise in temperature. Impedance Spectroscopy data reveal a non-Debye type of dielectric relaxation. The Nyquist plots show the negative temperature coefficient of resistance of both pure Tunisian illite and halloysite samples. The results of bulk electrical conductivity and its activation energy are presented for the two mineral clay samples. For illite It-1, the activation energy values estimated from the AC conductivity pattern and modulus pattern are very similar and suggest a possibility of a long-range mobility of charge carriers (ions) via hopping mechanism of electrical transport processes at higher temperature. On the other hand, for the halloysite sample provided from kasserine, (Ha-Kass), the modulus analysis admit that the electrical transport processes of the material are very likely of electronic nature. Relaxation frequencies follow an Arrhenius behavior with the activation energy values not comparable to those found for the electrical conductivity.     

Li掺杂Ba(Ti1/7Sn1/7Zr1/7Hf1/7Nb1/7Ga1/7Li(1/7-x))O3高熵陶瓷的制备及介电性能研究

近年来,在高熵合金基础上发展起来的高熵陶瓷逐渐引起了研究者的广泛关注,其出现为开发高性能的无机非金属材料提供了新的设计思路。本文采用固相法制备了BaMO3基钙钛矿型高熵陶瓷Ba(Ti1/7Sn1/7Zr1/7Hf1/7Nb1/7Ga1/7Li(1/7-x))O3 (x = 0, 2.3%, 5.3%, 8.3%, 11.3%),并研究了Li含量对高熵陶瓷物相结构、微观形貌及介电性能的影响。结果表明,Li含量对陶瓷结构的影响不大,陶瓷均保持立方钙钛矿结构,且无杂相产生;陶瓷的晶粒尺寸相对较均匀。当x = 0时,即B位七元等摩尔比Ba(Ti1/7Sn1/7Zr1/7Hf1/7Nb1/7Ga1/7Li1/7)O3高熵陶瓷,其介电常数达到了最大值2920 (@100 Hz),相较于已报道的不掺Li的六元高熵钙钛矿陶瓷Ba(Ti1/6Sn1/6Zr1/6Hf1/6Nb1/6Ga1/6)O3提升了近50倍。     

子宫内膜异位症模型大鼠背根神经节神经元中TRPV1、TRPA1表达及其意义

目的: 探讨子宫内膜异位症模型大鼠背根神经节（DRG）神经元中瞬时受体电位通道蛋白V1（TRPV1）、瞬时受体电位通道蛋白A1（TRPA1）表达及其意义。方法: 选取雌性、成熟未交配Sprague-Dawley健康大鼠40只,分为模型组和假手术组,模型组采用自体移植方法建立子宫内膜异位症大鼠模型,假手术组仅做开腹手术。分别检测DRG中TRPV1、TRPA1表达情况,并使用TRPV1、TRPA1拮抗剂处理两组大鼠,观察其热板法痛阈、甩尾潜伏期变化。结果: 模型组大鼠TRPV1、TRPA1表达阳性率明显高于假手术组（P<0.05）。术前,两组大鼠热板法痛阈、甩尾潜伏期相近（P﹥0.05）。术后,模型组大鼠热板法痛阈、甩尾潜伏期较术前明显减小（P<0.05）,模型组大鼠热板法痛阈、甩尾潜伏期明显小于假手术组（P<0.05）。使用TRPV1、TRPA1拮抗剂前,两组大鼠热板法痛阈、甩尾潜伏期相近（P>0.05）。使用TRPV1、TRPA1拮抗剂后,两组大鼠热板法痛阈、甩尾潜伏期相近（P>0.05）,模型组大鼠使用TRPV1、TRPA1拮抗剂前后,热板法痛阈、甩尾潜伏期无明显变化（P>0.05）。结论: TRPV1、TRPA1在子宫内膜异位症模型大鼠中高表达,使用TRPV1、TRPA1拮抗剂降低子宫内膜异位症模型大鼠TRPV1、TRPA1表达,降低大鼠对痛觉的敏感性。     

Early stage oxidation of Ni–Cr binary alloy (1 1 1), (1 1 0) and (1 0 0) surfaces: A combined density functional and quantum chemical molecular dynamics study

First-principles and tight-binding quantum chemical molecular dynamics were used in this study. The chemisorption energies of O and OH on the Ni–Cr (1 1 0) surface are lower than those of other surfaces. The oxygen 2p orbitals hybridise with Ni 3d, 4s and small amounts of p orbitals for the (1 0 0) surface while Ni p orbitals have no contribution for the (1 1 0) surface, which might reduce the adsorption energy. Additionally, oxygen acquires the maximum depth into the Ni–Cr (1 1 0) surface. Applied strain increases the oxygen diffusivity. This study reveals that the Ni–Cr (1 1 0) surface is easier for oxygen diffusion accordingly oxidation accelerates.     

B10铜镍合金在NaCl溶液中腐蚀行为的研究

研究了BFe10-1-1铜镍合金在0.5mol/L NaCl溶液中的选择性腐蚀行为,测其在不同pH值的试验溶液中的阳极极化曲线,并选择一定电化学条件下进行恒电位腐蚀。通过对腐蚀后溶液中的Cu2 和Ni2 含量的分析和对试样断面的微区成分分析,了解不同条件下的BFe10-1-1铜镍合金的选择性腐蚀规律。试验结果表明,BFe10-1-1铜镍合金的选择性腐蚀取决于腐蚀介质的酸碱度及腐蚀电位等电化学条件。在碱性溶液中的耐蚀性比其在酸性溶液中要好,在酸性和弱碱性溶液中脱镍,在强碱性溶液中低电位下脱铜,高电位下脱镍。     

有机阴离子转运多肽1B1的遗传药理学进展

人体存在多种类型的药物转运体,对于药物的吸收、分布和排泄起重要作用。参与药物跨膜转运的转运体功能受影响,将可能导致诸多临床药物的疗效、毒副作用甚至药物相互作用的发生。在各种影响因素中,遗传多态性所起的作用最为重要,可导致基因表达和蛋白功能发生改变。目前,阐明转运体基因的多态性以及基因型与表型之间的相互关系已成为应用遗传信息指导临床个体化用药的必要步骤。本文就肝脏有机阴离子转运多肽1B1(OATP1B1[OATP-C],编码基因SLCO1B1)基因多态性对药代动力学和药效动力学的影响及其临床意义等方面的进展作一综述。     

Synthesis and electrochemical characterization of layered Li[Ni1/3CO1/3 Mn1/3]O2 cathode material for Li-ion batteries

1 INTRODUCTIONDue to the high cost of LiCoO2,a commonlyused cathode material in commercial rechargeablelithium-ion batteries , much efforts have been madeto develop cheaper cathode materials than LiCoO2,Li Ni O2and Li MnO2have been studied extensivelyas possible alternatives to LiCoO2[1 4 ]. Stoichio-metric Li Ni O2is knownto be difficult to synthesizeandits multi-phase reaction during electrochemicalcyclingleads to structural degradation,andlayeredLi MnO2has a significant drawback…     

BiFeO3 thin films of (1 1 1)-orientation deposited on SrRuO3 buffered Pt/TiO2/SiO2/Si(1 0 0) substrates

BiFeO₃ (BFO) thin films of varying degrees of (1 1 1) orientation were successfully grown on SrRuO₃-buffered Pt/TiO₂/SiO₂/Si(1 0 0) substrates by off-axis radio-frequency magnetron sputtering. They demonstrate much enhanced ferroelectric behavior, including a much enhanced remnant polarization (2P_r ～ 197.1 μC cm^?2 at 1 kHz) measured by positive-up negative-down (PUND), at an optimized deposition temperature of 590 °C. The effects of film deposition temperature on the degree of (1 1 1) orientation, film texture, ferroelectric behavior, leakage current and fatigue endurance of the BFO thin films were systematically investigated. While the degree of (1 1 1) orientation is optimized at 590 °C, the defect concentration in the film increases steadily with increasing deposition temperature, as demonstrated by the dependence of leakage behavior on the deposition temperature. The polarization behavior is shown to strongly depend on the degree of (1 1 1) orientation for the BFO thin film. Oxygen vacancies are shown to involve in the conduction and dielectric relaxation of the BFO thin films deposited at different temperatures, as demonstrated by their dielectric and conduction behavior as a function of both temperature (in the range 294–514 K) and frequency (in the range 10^?1–10⁶ Hz).     

BFe10-1-1合金在NaCl溶液中点蚀行为的研究

通过测定合金在不同pH值的05 mol/L NaCl溶液中的阳极极化曲线,以及用扫描电镜、原子吸收光谱对发生点蚀后的试样和溶液进行观察和成分分析,研究了铜镍合金BFe10-1-1在NaCl溶液中的腐蚀行为.结果表明：BFe10-1-1合金在酸性和弱碱性的05 mol/L NaCl溶液下的腐蚀规律基本相似,在强碱性溶液中的低电位下,合金表面可以形成较稳定的钝化膜,因而耐蚀性能较好;当合金发生点腐蚀时,在点蚀坑内发生了脱镍腐蚀.     

Temperature-dependent surface alloying in Au/Ni (1 1 0)

The kinetic Monte Carlo (KMC) simulations have been carried out to address the temperature dependence of the surface alloying in the Au/Ni (1 1 0) system. It was found that no surface alloying is observed when Au is grown on the Ni (1 1 0) surface at the low temperature (≤240 K). At the moderate temperature (255–300 K), the surface alloying forms with the dominated exchange mechanism of Au ad-dimmers. At the high temperature (350–400 K), the surface alloying with the dominated exchange mechanism of Au monomers is observed. The physical and chemical mechanisms of the unique surface alloying behaviors in the Au/Ni (1 1 0) were proposed on the basis of the atomic interactions.     

Calculation on Relation of Energy Bandgap to Composition and Temperature for Ga_xIn_（1－x）As_（1－y）Sb_y

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受体SLCO1B1 rs2291075位点多态性对肝移植术后早期他克莫司剂量校正谷浓度的影响

目的：探索肝移植术后早期SLCO1B1 rs2291075基因型对他克莫司（FK506）剂量校正谷浓度（dose-corrected trough concentration,C/D,ng·mL-1·mg-1·kg-1）的影响作用。方法：利用PCR扩增和DNA测序技术对210例肝移植受体及其供体进行SLCO1B1 rs2291075位点以及FK506代谢经典生物标志物CYP3A5 rs776746位点基因分型,分析多态性与FK506代谢表型C/D值的相关性。根据肝功能恢复和C/D值变化情况,肝移植术后早期分为恢复期（1～14 d）和平稳期（15～28 d）,分别进行统计分析。结果：供体和受体CYP3A5 rs776746联合分析可将FK506代谢表型区分为快（EM）、中（IM）、慢（PM）代谢3组,形成E-I-P分型体系。受体SLCO1B1 rs2291075 CC、CT+TT基因型患者C/D值在术后恢复期（P=0.019 5）和平稳期（P=0.015 2）差异均有统计学意义;供体SLCO1B1 rs2291075基因型与FK506 C/D值无关联。多因素分析显示FK506日剂量、总胆红素、E-I-P分型和受体SLCO1B1 rs2291075进入恢复期FK506剂量C/D值预测模型;而在平稳期,受体SLCO1B1 rs2291075未能进入C/D值多因素预测模型。PM亚组分析,排除供体和受体CYP3A5 rs776746影响后,受体SLCO1B1 rs2291075基因型在术后恢复期和稳定期均是FK506 C/D值的独立影响因素（P分别为0.030,0.040）。结论：受体SLCO1B1 rs2291075位点可能是影响肝移植早期FK506 C/D值的新遗传位点,其与供体和受体CYP3A5 rs776746基因型相结合,有助于形成精准用药指导体系。