Inhibition of DNA-dependent Protein Kinase Catalytic Subunit by Small Molecule Inhibitor NU7026 Sensitizes Human Leukemic K562 Cells to Benzene Metabolite-induced Apoptosis

Benzene is an established leukotoxin and leukemogen in humans. We have previously re- ported that exposure of workers to benzene and to benzene metabolite hydroquinone in cultured cells induced DNA-dependent protein kinase catalytic subunit （DNA-PKcs） to mediate the cellular response to DNA double strand break （DSB） caused by DNA-damaging metabolites. In this study, we used a new, small molecule, a selective inhibitor of DNA-PKcs, 2-（morpholin-4-yl）-benzo[h]chomen-4-one （NU7026）, as a probe to analyze the molecular events and pathways in hydroquinone-induced DNA DSB repair and apoptosis. Inhibition of DNA-PKcs by NU7026 markedly potentiated the apoptotic and growth inhibitory effects of hydroquinone in proerythroid leukemic K562 cells in a dose-dependent manner. Treatment with NU7026 did not alter the production of reactive oxygen species and oxidative stress by hydroquinone but repressed the protein level of DNA-PKcs and blocked the induction of the kinase mRNA and protein expression by hydroquinone. Moreover, hydroquinone increased the phos- phorylation of Akt to activate Akt, whereas co-treatment with NU7026 prevented the activation of Akt by hydroquinone. Lastly, hydroquinone and NU7026 exhibited synergistic effects on promoting apop- tosis by increasing the protein levels of pro-apoptotic proteins Bax and caspase-3 but decreasing the protein expression of anti-apoptotic protein Bcl-2. Taken together, the findings reveal a central role of DNA-PKcs in hydroquinone-induced hematotoxicity in which it coordinates DNA DSB repair, cell cycle progression, and apoptosis to regulate the response to hydroquinone-induced DNA damage.

Catalytic Synthesis of Isopropyl Benzene over SO_4 ^(2-)/ZrO_ 2-MCM-41

Super acid catalyst SO4^2-/ZrO2 was introduced into pure silicone MCM-41 via the impregnation method and the catalyst samples obtained at different temperatures were characterized by means of XRD, IR, and Py-IR techniques. The selectively catalytic gas-phase flow reactions of benzene with propene over the catalyst samples were carried out in a made-to-measure high-pressure flow reactor equipped with a thermostat and a condenser. Effect of the preparative condition on the catalytic synthesis of isopropyl benzene over the catalyst samples was tested. The results show that SO4^2-/ZrO2-MCM-41 （ SZM-41 ） can be used as a catalyst for the title reaction, in which there are a higher conversion （97%） for the propene and a higher selectivity（93% ） for the isopropyl benzene.

Solid-Liquid Equilibria of Musk Ketone, Musk Xylene and 1,3-Dimethyl-2,4-Dinitro-5-Tert-Butyl Benzene

The solid-liquid equilibria of musk ketone + musk xylene, musk xylene +l,3-dimethyl-2,4-dinitro-5-tert-butyl benzene are measured by differential scanning calorimeter (DSC), these systems are proved to be simple eutectics. Moreover the melting points and the fusion enthalpies of musk ketone, musk xylene and 1,3-dimethyl-2,4-dinitro-5-tert-butyl benzene are also measured by the DSC. These solid-liquid equilibrium data and the heats of fusion are reported for the first time. Then UNIFAC model is used to correlate the sofid-liquid equilibrium data. It is shown that the solid-liquid equilibria of musk systems can be predicted by the UNIFAC model.

Synthesis,Crystal Structure,and Magnetic Property of One 3D Nickel Coordination Polymer Based on 2-Hydroxy-5-(3',5'-terephthalic acid)Pyridine and 1,4-Bis(1-imdazoly)benzene

One novel nickel coordination polymer, {[Ni（OTP）（bib）1.5（H2O）]·2H2O}n（1, H2 OTP = 2-hydroxy-5-（3＇,5＇-terephthalic acid） pyridine, bib = 1,4-bis（1-imdazoly）benzene）, has been synthesized and characterized by elemental analysis（EA）, IR, powder X-ray diffraction（PXRD）, and thermogravimetric（TG） analyses. The crystal of 1 crystallizes in monoclinic, space group P21/n with a = 12.2860（5）, b = 13.8246（6）, c = 19.0140（8） A, β = 104.3870（1）°, V = 3128.2（2） A3, Z = 4, C32H28N7 Ni O8, Mr = 697.32, Dc = 1.481 g/cm^3, F（000） = 1444 and μ（Mo Kα） = 0.684 mm-1. The final R = 0.0704 and w R = 0.1764 for 5485 observed reflections with I 2σ（I） and R = 0.1087 and wR = 0.2010 for all data. Topology analysis reveals that complex 1 is a 3D 2-fold interpenetrated {4^4·6^6}-nov net based on the 1D [Ni（OTP）]n chain and the 2D [Ni2（bib）3]n sql sheet. And the variable-temperature magnetic susceptibility measurements exhibit weak antiferromagnetic coupling interaction.

Nondoped-type White Organic Light-Emitting Diode Using Star-Shaped Hexafluorenylbenzene as an Energy Transfer Layer

White organic light-emitting diodes （WOLEDs） with a structure of indium-tin-oxide （ITO）/N,N＇-bis- （1-naphthyl）-N,N＇-diphenyl- （1, 1＇-biphenyl）-4,4＇-diamine （NPB）/1,2,3,4,5,6-hexakis（9,9-diethyl-9H-fluoren-2- yl）benzene （HKEthFLYPh）/5,6,11,12-tetraphenylnaphtacene （rubrene）/tris（8-hydroxyquinoline） aluminum （Alq3）/Mg：Ag were fabricated by vacuum deposition method, in which a novel star-shaped hexafluorenyl- benzene HKEthFLYPh was used as an energy transfer layer, and an ultrathin layer of rubrene was inserted between HKEthFLYPh and Alq3 layers as a yellow light-emitting layer instead of using a time-consuming doping process. A fairly pure WOLED with Commissions Internationale De L＇Eclairage （CIE） coordinates of （0.32, 0.33） was obtained when the thickness of rubrene was 0.3 nm, and the spectrum was insensitive to the applied voltage. The device yielded a maximum luminance of 4816 cd/m2 at 18 V.

Test on oxygen and benzene contents in gasoline by mid-infrared spectroscopy

This paper aims at testing oxygen and benzene contents in gasoline by mid-infrared spectroscopy.The experimental results prove that infrared spectroscopy(IR)is reliable.Compared with gas chromatography(GC)technology,this paper draws a conclusion that IR has several advantages,including rapid analysis,excellent repeatability and low analysis cost.

Synthesis and Crystal Structure of 1,4-Dimethyl-2,5-di{[2’-(3-pyridylmethylamino-formyl)phenoxyl]methyl}benzene Perchlorate

The title compound, 1,4-dimethyl-2,5-di { [2′-（3-pyridylmethylaminoformyl）phenoxyl]- methyl}benzene perchlorate （C36H36Cl2N4O12, Mr = 787.59）, has been synthesized and structurally determined by single-crystal X-ray diffraction. The crystal crystallizes in the orthorhombic system, space group Pbca with a = 14.366（4）, b = 15.159（4）, c = 16.443（5）A, V = 3580.9（17）/A3 Z = 4, De = 1.461 g/cm^3, /t = 0.253 mm^-1, F（000） = 1640, R = 0.0618 and wR = 0.1525 for 1615 observed reflections （I 〉 2σ（I））. In the structure of the title compound, a two-dimensional supramolecular layer is formed via intermolecular hydrogen bonding interactions.

Assessment of Some Density Functional Theory Methods and Force Field Models in Describing Various Interaction Modes of Benzene Dimer

Benzene dimer （bz2） is the simplest prototype of the π-π interactions. Such interactions are ubiquitous in diverse areas of science and molecular engineering. In the present work, we have made assessment on some modern density functional methods including B97-D, BLYP-D3, M06-2X, XYG3, and force field models including CHARMM, AMBER, MM3, AMOEBA on six important interaction modes of bz2. Our results not only highlight the usefulness of these cost-effective methods, which can be used as economic substitutes of the expensive CCSD（T） for complex real-world systems, but also indicate their weakness in the description of the π-π interactions, which points to the future direction for further improvements.

Continuous Saccharification of Laminarin by Immobilized Laminarinase ULam111 Followed by Ethanol Fermentation with a Marine-Derived Yeast

We isolated a novel laminarinase ULam111 from Flavobacterium sp. strain UMI-01. Purified ULam111 showed degradation activity against laminarin with the specific activity of 224 ± 18 U/mg at 30°C and pH 6.0. Its optimum temperature was 50°C, and degradation activities against laminarin were observed at 4°C - 80°C. With a laminarin degradation system, we investigated the preparation and properties of immobilized ULam111 with the use of the 11 types of carriers. The high activity recoveries of immobilized ULam111 were as follows: 19.4% for IB-S60P carrier beads (the non-ionic type), 15.6% for IB-S60S carrier beads (the non-ionic type), 11.9% for IB-150P carrier beads (the covalent type), and 7.1% for IB-C435 carrier beads (the cationic type). With the repeated use of immobilized ULam111, the enzyme activities immobilized on IB-S60S and those on IB-S60P remained at 40% and 30% respectively after the sixth trial. We selected IB-S60S as suitable beads for enzyme immobilization, and we attempted to construct a reactor system with ULam111 immobilized on IB-S60S beads. In this system, 1.2 - 1.9 g/L glucose was repeatedly produced from 30 mg/mL laminarin solutions after 20 hr when the reactor operation was repeated 10 times. We examined ethanol fermentation from the saccharified solutions with a marine-derived yeast (Saccharomyces cerevisiae C-19), and 0.51 - 0.58 g/L bioethanol was produced from the saccharified solution that contained 1.71 - 1.86 g/L of glucose.

Solubility of CO_(2) in nonaqueous system of 2-(butylamino)ethanol with 2-butoxyethanol:Experimental data and model representation

Nonaqueous amine-based system is an attractive solution to overcome high-energy-intensive CO_(2) capture process using the conventional aqueous amines.Advanced nonaqueous absorbent of 2-(butylamino)ethanol(BAE)with 2-butoxyethanol(2-BE)has been recently proposed for low-energyconsumption CO_(2) capture.In this work,Henry’s law constants of CO_(2) in the BAE/2-BE blend were obtained by N_(2)O/CO_(2) analogy,and correlated in the temperature range of(283–333)K.Vapor-liquid equilibrium(VLE)data for the BAE+CO_(2)+2-BE system at 65.4%(mass)BAE were also determined in a stirred equilibrium cell at temperatures of(313–393)K and CO_(2) partial pressures up to 275 kPa.A single apparent equilibrium constant KCO_(2);app was proposed for this system and correlated as a function of temperature,carbonated degree of amine and CO_(2) loading.Solubility data were well represented by the modified Kent-Eisenberg model with an average absolute relative deviation(AARD)of 13%.

Integrating network pharmacology and pharmacological evaluation for deciphering the mechanism of(-)-epigallocatechin-3-gallate alleviating ethanol-induced endothelial cells injury

Objective To investigate the potential therapeutic targets and pharmacological mechanism of(-)-epigallocatechin-3-gallate(EGCG)based on network pharmacology and experimental verification.METHODS The druggability of EGCG was measured by the traditional Chinese medicine systems pharmacology(TCMSP)server,and potential targets of EGCG were identified by Pharm Mapper and Drug Repositioning and Adverse drug Reaction via Chemical-Protein Interactome(DRAR-CPI).The potential targets were imported into GeneMANIA database to obtain the protein-protein direct interaction network,and target physical interaction,co-expression,prediction,genetic interaction,and shared protein domains.The biological process,molecular functions,cellular components and KEGG signaling pathways of potential targets were analyzed using DAVID database.For further study,ethanol was used to establish a model of endothelial injury in vitro.The cell viability was assayed by MTT method,the cellular apoptosis was stained by Annexin V/PI,and the expression levels of Bcl-2,Bax and cleved-caspase-3 were tested by Western blotting.Then,JC-1 and nuclear translocation of NF-κB experiments were used to study the mitochondrial membrane potential and nuclear translocation.RESULTS The oral availability of EGCG was 55.09%(≥30%)and drug-like index was 0.77(≥0.18),which were considered pharmacokinetically active.17 potential targetable proteins of EGCG were predicted by Pharm Mapper and DRAR-CPI.Further research showed that 68.13%displayed similar co-expression characteristics,26.11%physical interactions,and 2.74%shared the same protein domain.The depth network analysis results showed that the biofunctions of EGCG were mainly by regulating glutathione derivative biosynthetic process,glutathione metabolic process,nitrogen compound metabolic process etc..via drug binding,catalytic activity,glutathione transferase activity,anion binding etc..in sarcoplasmic reticulum,spindle pole,microtubule cytoskeleton and cytoplasm.KEGG enrichment analysis showed that Glutathione metabolism,IL^(-1)7 signaling pathway,EGFR tyrosine kinase inhibitor resistance,PI3K-Akt signaling pathway and other pathways were involves in the biofunction of EGCG.The above analyses indicated that EGCG exerts its biofunction through antioxidant and anti-inflammatory mechanisms.The experimental results showed that ethanol 20.0 mmol·L^(-1) decreased cell viability,Bcl-2 expression,and increased cell apoptosis,the intracellular ROS,as well as the expression of Bax and cleaved-caspase-3 of human endothelial cells.However,treatment of the cells with EGCG can significantly alleviate ethanol induced endothelial cells injury.Further study showed that EGCG significantly alleviates ethanol induced mitochondrial depolarization and nuclear translocation of NF-κB.CONCLUSIONS EGCG exerts pharmacological efficacies on ethanol induced endothelial cell injury through multi-target,multi-function and multi-pathway mode.Protective effect of EGCG on ethanol induced cell injury was mainly through alteration of mitochondrial function and NF-κB translocation.Therefore,EGCG have great potential in protecting against endothelial dysfunction of the persons who are chronically abuse of ethanol.This study also provides a new understanding of EGCG in clinical application on cardiovascular and cerebrovascular diseases.

Quantitative determination of residual 2-(2-chloroethoxy) ethanol (CEE) in quetiapine fumarate by gas chromatogaraphy

A simple and specific gas chromatographic method developed and validated for the determination of 2-(2-chloroethoxy) ethanol in Quetiapine Fumarate. The method is carried out with a flame ionization detector and DB-FFAP capillary column. The linearity was established over a range of 40-150 μg ml-1 and correlation coefficient is more than 0.999.

DFT-Comparison of Anti-Cancer Effect of Ibuprofen Drug Anions and Breast Cancer Treatment by Ethanolic Solution of Nitrobenzaldehyde in Two Hours

Focusing our DFT calculations on the carboxylic acid drugs such as ibuprofen drug (IBF), it has been concluded that the anions of these types of drugs have the spontaneous electron donor character to all the carcinogenic cells of electron deficiency in their nuclei. Due to the spontaneity of electron transfer of anions, it has been found clinically that ibuprofen drug cures cancers of colon, protostate, lung and breast. The breast cancer treatment of Matthew Gdovin group in two hours by injection of ethanolic solution of nitrobenzaldehyde in the breast tumor in presence of uv-irradiation has been studied from TD-DFT point of view;the excited states of these molecules in presence of uv-irradiation act as electron donors to the cancerous cells to compensate the electron deficiency. Finally, it has been concluded that the electron transfer is the main cause of the breast cancer treatment which is the most aggressive type of cancers and is one of the hardest to treat.

Quaternary phosphonium polymer-supported dual-ionically bound[Rh(CO)I_(3)]^(2-)catalyst for heterogeneous ethanol carbonylation

A single-Rh-site catalyst(Rh-TPISP)that was ionically-embedded on a P(V)quaternary phosphonium porous polymer was evaluated for heterogeneous ethanol carbonylation.The[Rh(CO)I_(3)]^(2-)unit was proposed to be the active center of Rh-TPISP for the carbonylation reaction based on detailed Rh L3-edge X-ray absorption near edge structure(XANES),X-ray photoelectron spectroscopy(XPS),and Rh extended X-ray absorption fine structure(EXAFS)analyses.As the highlight of this study,Rh-TPISP displayed distinctly higher activity for heterogeneous ethanol carbonylation than the reported catalytic systems in which[Rh(CO)_(2)I_(2)]^(-)is the traditional active center.A TOF of 350 h^(-1)was obtained for the reaction over[Rh(CO)I_(3)]^(2-),with>95%propionyl selectivity at 3.5 MPa and 468 K.No deactivation was detected during a near 1000 h running test.The more electron-rich Rh center was thought to be crucial for explaining the superior activity and selectivity of Rh-TPISP,and the formation of two ionic bonds between[Rh(CO)I_(3)]^(2-)and the cationic P(V)framework([P]^(+))of the polymer was suggested to play a key role in firmly immobilizing the active species to prevent Rh leaching.

改性ZSM-5上苯与乙醇烷基化反应条件的考察及再生评价

通过离子交换法制备出一种钛改性的分子筛,并在连续流动固定床反应器上对其进行了苯与乙醇烷基化反应条件和催化剂的失活再生评价。通过XRD、BET、NH3-TPD、Py-IR和ICP方法对催化剂进行了表征,结果表明,改性后催化剂的比表面积、微孔孔容和孔径均减少,B酸/L酸比值增加,改性元素含量8.56%。反应评价结果显示,改性后乙苯选择性略有降低,苯的转化率增加,乙醇利用率增加。改性催化剂的最佳反应条件:温度360～460℃,质量时空速3～5h-1,苯醇摩尔比3～5。催化剂4次再生评价效果良好,再生后酸性没有太大改变,是一种具有良好工业应用前景的催化剂。

不同HZSM-5催化剂上苯与乙醇的烷基化反应

以正丁胺为模板剂、水玻璃为硅源、硫酸铝为铝源，采用水热晶化法合成出晶粒大小不同的ZSM-5分子筛，通过XRD、BET、SEM、NH3-TPD和Py-IR方法对催化剂进行了表征，并在连续流动固定床反应器上对其进行了苯与乙醇烷基化反应性能评价。结果表明，ZSM-5催化剂的酸性质是影响苯与乙醇烷基化反应中苯转化率和乙苯选择性的重要因素，晶粒大小在一定程度上对乙苯的选择性有影响。酸性弱、酸量少的小晶粒ZSM-5催化剂乙苯选择性和苯的转化率能同时达到最优。考察了操作条件对催化性能较好的小晶粒HZSM-5催化剂上苯与乙醇烷基化反应苯的转化率和乙苯选择性的影响，得到该催化剂的最佳反应条件：反应温度380℃，苯／醇摩尔比3～5，质量空速3～5h。

檀香叶抽提物成分的Py-GC／MS分析

针对大量檀香叶被遗弃而造成巨大资源浪费的问题,采用热解-气相色谱/质谱(Py-GC/MS)技术研究檀香叶抽提物高品位资源化利用的前景.Py-GC/MS分析结果表明:檀香叶苯/醇抽提物主要包含16-三十烷酮(8.69%)、11,14,17-二十碳三烯酸甲酯(8.49%)、十六酸(5.38%)、吡嗪(4.01%)、环辛二十四烷(3.89%)、苯酚(3.19%)等118种化合物,檀香叶丙酮抽提物主要包含3-羽扇酮(39.35%)、蒲公英甾醇(7.60%)、β-谷甾醇(5.38%)、蒲公英萜醇(3.42%)、乙醛(2.37%)、(5α)-雄甾-6-酮(2.36%)等48种化合物.说明檀香叶抽提物富含名贵生物医药成分和名贵香料,副产物不仅可用于高档化妆品,而且可用作生物能源.

不同方法制备ZSM-11分子筛催化剂上乙醇和苯气相烷基化制乙苯

采用固定床反应器考察了在一定温度水热处理后无黏结剂、Al_2O_3和SiO_2黏结剂成型制备的强酸量相近ZSM-11分子筛催化剂催化乙醇和苯气相烷基化反应性能。采用X射线衍射(XRD)、N_2物理吸附-脱附、氨程序升温脱附(NH3-TPD)、吡啶吸附红外(Py-IR)和热重分析(TG)等技术手段对ZSM-11分子筛样品进行了表征。结果表明,Al_2O_3和SiO_2成型的ZSM-11催化剂(Cat-A、Cat-B)的微孔体积相近,无黏结剂ZSM-11分子筛催化剂(Cat-C)的BET比表面积最小,微孔体积最大;与Cat-A和Cat-B相比,Cat-C的强酸中Br9nsted酸/Lewis酸酸量比最高。在乙醇和苯气相烷基化反应中,乙醇未完全转化的情况下,Cat-A上苯和乙醇转化率最高。还考察了Cat-A分子筛催化剂上气相烷基化反应寿命,在500h的反应过程中,乙醇转化率可达99.9%,苯的转化率维持在12%,产物中烃类液体选择性达到98%～99%。

H-ZSM-5分子筛上苯与乙醇和乙烯烷基化反应的理论研究

采用ONIOM2(B3LYP/6-31G(d):UFF)计算方法研究了H-ZSM-5分子筛上苯与乙醇和乙烯烷基化反应历程.选取40T簇模型模拟了H-ZSM-5分子筛位于孔道交叉点的酸性位.从生成能和反应活化能角度分析并比较了苯与乙醇和乙烯烷基化反应机理.结果表明,苯与乙醇的烷基化按照分步机理进行,速控步骤的活化能为170.34kJ/mol.而乙烯作为烷基化剂与苯反应时同时存在联合机理和分步机理,且二者之间存在一定程度的竞争,其中联合机理的活化能为167.24kJ/mol,分步机理速控步骤的活化能为155.20kJ/mol.比较苯与乙醇和乙烯发生烷基化反应的机理可以看出,二者作为烷基化试剂对烷基化反应性能影响不大.

尾巨桉新旧木片苯/醇抽提物的Py-GC/MS分析

为解决尾巨桉木材成分抽提消耗大量的制浆漂白液及助剂、加重废水对环境的污染、造成巨大的抽提物天然资源浪费等问题,采用热解-气相色谱/质谱(Py-GC/MS)研究了尾巨桉新旧木片抽提物的主要化学成分.结果表明:尾巨桉新鲜木片苯/醇抽提物的成分为1,2,3,4,4a,9,10,10a-八氢-1,4a-二甲基-7-(1-甲乙叉)-1-菲酸甲酯(19.49%)、3,7-二羟基-9-甲氧基-1-甲基-6氢-二苯并[B,D]吡喃-6-酮(5.01%)、1,2,3,4,4a,9,10,10a-八氢-1,4a-二甲基-7-(1-甲乙叉)-1-菲酸(4.47%)、麦角甾-4,6,22-三烯-3β-醇(4.07%)、2,6-二甲氧基-苯酚(3.94%)、十六酸(2.96%)、乙酸(2.86%)、1-(3-甲氧基苯基)-乙酮(2.83%)、2-甲氧基-苯酚(2.47%)、日尔曼醇(2.00%)等145种化合物;陈旧木片苯/醇抽提物的成分为麦角甾-4,6,22-三烯-3β-醇(23.33%)、马钱子碱(9.61%)、(5β)-胆固醇-8(14)-烯-24-醇(6.86%)、油酸(6.14%)、2-甲基-苯酚(5.63%)、1-巯基-2-十七烷酮(4.06%)、2,4-二苄基-5,8-二甲氧基-6-甲基-1-萘酚(3.86%)、十六酸(3.65%)、β-谷甾醇(3.12%)、4-氯-2-氟苯胺(2.29%)、(3β,4α,5α)-4,14-二甲基-9,19-环麦角甾-24(28)-烯-3-醇(2.19%)、17-氯-7-十七烯(2.09%)等55种化合物.分析结果表明,尾巨桉新旧木片苯/醇抽提物在生物能源、生物医药、化妆品、护肤品及香料等领域有潜在的应用前景.