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The enzymatic biosynthesis of acylated steroidal glycosides and their cytotoxic activity

Acta Pharmaceutica Sinica B 2018年第6期8卷 981-994页

作者： Ming liu Jian-qiang Kong State Key Laboratory of Bioactive Substance and Function of Natural Medicines & Ministry of Health Key Laboratory of Biosynthesis of Natural Products Institute of Materia Medica Chinese Academy of Medical Sciences & Peking Union Medical College

Herein we describe the discovery and functional characterization of a steroidal glycosyltransferase(SGT) from Ornithogalum saundersiae and a steroidal glycoside acyltransferase(SGA) from Escherichia coli and their application in the biosynthesis of acylated steroidal glycosides(ASGs). Initially,an SGT gene, designated as OsSGT1, was isolated from O. saundersiae. OsSGT1-containing cell free extract was then used as the biocatalyst to react with 49 structurally diverse drug-like compounds. The recombinant OsSGT1 was shown to be active against both 3β-and 17β-hydroxyl steroids. Unexpectedly,in an effort to identify OsSGT1, we found the bacteria lacA gene in lac operon actually encoded an SGA,specifically catalyzing the acetylations of sugar moieties of steroid 17β-glucosides. Finally, a novel enzymatic two-step synthesis of two ASGs, acetylated testosterone-17-O-β-glucosides(AT-17β-Gs) and acetylated estradiol-17-O-β-glucosides(AE-17β-Gs), from the abundantly available free steroids using OsSGT1 and EcSGA1 as the biocatalysts was developed. The two-step process is characterized by EcSGA1-catalyzed regioselective acylations of all hydroxyl groups on the sugar unit of unprotected steroidal glycosides(SGs) in the late stage, thereby significantly streamlining the synthetic route towards ASGs and thus forming four monoacylates. The improved cytotoxic activities of 30-acetylated testosterone17-O-β-glucoside towards seven human tumor cell lines were thus observable.

关键词： Steroidal glycosyltransferase Steroidal glycoside acyltransferase Ornithogalum saundersiae Acylated steroidal glycosides LacA

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Characterization and degradation of β-Sn particles in thermal aged Pb-rich solder joint for low-temperature co-fired ceramic(LTCC)applications

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Rare Metals 2024年第10期43卷 5346-5361页

作者： Jin-Hong liu Zhe Zhu qiang-qiang Nie Jun-Fu liu Peng He Shu-Ye Zhang State Key Laboratory of Advanced Welding and Joining Harbin Institute of TechnologyHarbin 150001China Anhui Key Laboratory of Microsystem East China Research Institute of MicroelectronicsHefei 230088China School of Materials Science and Engineering Hefei University of TechnologyHefei 230009China

High-lead solder joints are still playing an indispensable role in military and space ***,in-depth characterization of high-lead solder joints and the underlying degradation mechanisms remain *** research first performed aging tests on Sn10Pb90 solder joints,the shear strength at room and elevated temperatures gradually reduced,and the resistance ***,a two-layered Ni-Sn intermetallic compound(IMC)structure was identified using transmission electron microscopy(TEM),which could be attributed to the change of Sn content in the ***,the internal annealing twin of a Sn particle was discovered,which could be attributed to creeping induced by thermal expansion coefficient(CTE)difference between Sn and *** analysis of partial and whole annealing twins was conducted through high-resolution TEM(HRTEM).Finally,four degradation mechanisms were *** of the IMC layer would result in increased brittleness and *** particle coarsening,apart from diminishing the ductility and toughness of the solder joint,it would also accelerate the creeping rate by weakening the phase boundary *** voids and cracks induced by phase boundary sliding,wedgeshaped cracking and pore-shaped cracking were discovered and their formation was *** importantly,the consumption of Sn resulted in a depletion of wettable layer,leading to the formation of Pb streams and isolated IMC islands,also known as the spalling and delamination of *** diffusion followed a spiral path,which was mutually influenced by orientation misfit and concentration gradient.A technique to prevent cracking was *** research is expected to provide significant technical references for high-lead solder joints.

关键词： High-lead solder joints Aging TEM characterization Degradation mechanisms Properties

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Recent advances in visible-light-driven organic reactions

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National Science Review 2017年第3期4卷 359-380页

作者： qiang liu Li-Zhu Wu State Key Laboratory of Applied Organic Chemistry Lanzhou University Key Laboratory of Photochemical Conversion and Optoelectronic Materials Technical Institute of Physics and ChemistryChinese Academy of Sciences

In recent years, visible-light-driven organic reactions have been experiencing a significant renaissance in response to topical interest in environmentally friendly green chemical synthesis. The transformations using inexpensive, readily available visible-light sources have come to the forefront in organic chemistry as a powerful strategy for the activation of small molecules. In this review, we focus on recent advances in the development of visible-light-driven organic reactions, including aerobic oxidation, hydrogen-evolution reactions, energy-transfer reactions and asymmetric reactions. These key research topics represent a promising strategy towards the development of practical, scalable industrial processes with great environmental benefits.

关键词： visible light catalysis synthesis photocatalyst aerobic oxidation hydrogen evolution energy transfer asymmetric photoreaction

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基于SHOX2和RASSF1A甲基化水平的机器学习算法预测早期肺腺癌病理类型

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中国胸心血管外科临床杂志 2025年第1期32卷 67-72页

作者：黄润棋强光亮刘益飞史加海南通大学附属医院临床研究中心南通大学医学院江苏南通226001 北京大学第三医院胸外科北京100191 南通大学附属医院病理科江苏南通226001 南通大学附属医院胸心外科江苏南通226001

目的探讨基于SHOX2和RASSF1A甲基化水平的机器学习算法预测早期肺腺癌病理类型的准确性。方法回顾性分析2021年1月—2023年1月在南通大学附属医院接受肺部肿瘤切除手术患者的石蜡包埋(formalin-fixed paraffin-embedded,FFPE)标本。... 详细信息

目的探讨基于SHOX2和RASSF1A甲基化水平的机器学习算法预测早期肺腺癌病理类型的准确性。方法回顾性分析2021年1月—2023年1月在南通大学附属医院接受肺部肿瘤切除手术患者的石蜡包埋(formalin-fixed paraffin-embedded,FFPE)标本。根据肿瘤的病理学分类,将患者分为3组:良性肿瘤/原位腺癌(benign tumor/adenocarcinoma in situ,BT/AIS)组、微浸润腺癌(minimally invasive adenocarcinoma,MIA)组和浸润性腺癌(invasive adenocarcinoma,IA)组。使用LungMe试剂盒通过甲基化特异性PCR(MS-PCR)测量FFPE标本的SHOX2和RASSF1A甲基化水平。以SHOX2和RASSF1A的甲基化水平为预测变量,采用机器学习算法(包括逻辑回归、XGBoost、随机森林、朴素贝叶斯)预测不同的肺腺癌病理类型,并构建网络服务器供临床使用。结果共纳入272例患者,BT/AIS组、MIA组和IA组患者的平均年龄分别为57.97岁、61.31岁和63.84岁;女性患者占比分别为55.38%、61.11%和61.36%。基于SHOX2和RASSF1A甲基化水平建立的早期肺腺癌预测模型中,随机森林与XGBoost模型在预测各病理类型时表现良好。随机森林模型的C统计量在BT/AIS组、MIA组和IA组分别为0.71、0.72和0.78。XGBoost模型的C统计量在BT/AIS组、MIA组和IA组分别为0.70、0.75和0.77。朴素贝叶斯模型仅在IA组表现较为稳健,C统计量为0.73,具有一定的预测能力。逻辑回归模型在各组中的表现最差,对各组均无预测能力。通过决策曲线分析,随机森林模型在BT/AIS和MIA病理类型的预测中展示了较高的净收益,表明其在临床应用中具有潜在价值。结论基于SHOX2和RASSF1A甲基化水平的机器学习算法预测早期肺腺癌病理类型具有较高的准确性。

关键词：肺腺癌 SHOX2 RASSF1A 甲基化侵袭性

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Steroids hydroxylation catalyzed by the monooxygenase mutant 139-3 from Bacillus megaterium BM3

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Acta Pharmaceutica Sinica B 2017年第4期7卷 510-516页

作者： Xing liu Jian-qiang Kong State Key Laboratory of Bioactive Substance and Function of Natural Medicines&Ministry of Health Key Laboratory of Biosynthesis of Natural Products Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

The search of new substrates with pharmaceutical and industrial potential for biocatalysts including cytochrome P450 enzymes is always challenging. Cytochrome P450 BM3 mutant 139-3, a versatile biocatalyst, exhibited hydroxylation activities towards fatty acids and alkanes. However, there were limited reports about its hydroxylation activity towards steroids. Herein, an Escherichia coli-based whole-cell extract containing the recombinant 139-3 protein was used as the biocatalyst to screen 13 steroids. Results revealed that 139-3 was able to specifically hydroxylate androstenedione (1) at 1α-position, generating a hydroxylated steroid 1α-OH-androstenedione (1a). To investigate whether C-1α hydroxylation catalyzed by BM3 mutant 139-3 could be industrially used, an optimization of catalyzing conditions was performed. Accordingly, the BM3 mutant 139-3 enzyme was observed to display maximum activity at 37 °C, under pH 7.0 for 4 h, with 37% transformation rate. Moreover, four 139-3 variants were generated by random mutagenesis with the aim of improving its activity and expanding substrate scope. Surprisingly, these mutants, sharing a common mutated site R379S, lost their activities towards androstenedione (1). These data clearly indicated that arginine residue located at site 379 played key role in the hydroxylation activities of 139-3. Overall, these new findings broadened the substrate scope of 139-3 enzyme, thereby expanding its potential applications as a biocatalyst on steroids hydroxylation in pharmaceutical industry.

关键词： Cytochrome P450 BM3 139-3 Steroids hydroxylation 1α-OH-androstenedione Biocatalyst

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Highly inhibited transport of dissolved thallium(I) in manganese oxide-coated sand: Chemical condition effects and retention mechanisms

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Journal of Environmental Sciences 2023年第7期129卷 104-114页

作者： Xiaoliu Huangfu Ziqiang liu Hainan Wang qiang He Hongxia liu Caihong liu Key Laboratory of Eco-Environments in Three Gorges Reservoir Region Ministry of EducationCollege of Environment and EcologyChongqing UniversityChongqing 400044China State Key Laboratory of Pollution Control and Resource Reuse School of EnvironmentNanjing UniversityNanjing 210023China

Thallium contamination in water can cause great danger to the *** this study,we synthesized manganese oxide-coated sand(MOCS)and investigated the transport and retention behaviors of Tl(I)in MOCS under different *** methods combined with a two-site nonequilibrium transport model were applied to explore the *** results showed that Tl(I)mobility was strongly inhibited in MOCS media,and the retention capacity calculated from the fitted model was 510.41 mg/g under neutral *** retention process included adsorption and oxidative precipitation by the manganese oxides coated on the sand *** with the same concentration of Mn(II)led to halving Tl(I)retention due to competition for reactive *** Tl(I)retention was observed under alkaline conditions,as increasing pH promoted electronegativity on the media ***,the competitive cation Ca^(2+)significantly weakened Tl(I)retention by occupying adsorption *** findings provide new insights into understanding Tl(I)transport behavior in water-saturated porous media and suggest that manganese oxide-coated sand can be a cost-effective filter media for treating Tl-contaminated water.

关键词： Thallium(I) Manganese oxide-coated sand Transport and retention Adsorption Oxidative precipitation

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Identifying the sensitive areas in targeted observation for predicting the Kuroshio large meander path in a regional ocean model

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Acta Oceanologica Sinica 2022年第2期41卷 3-14页

作者： Xia liu qiang Wang Mu Mu School of Mathematics Zhengzhou University of AeronauticsZhengzhou 450046China Key Laboratory of Marine Hazards Forecasting of Ministry of Natural Resources Hohai UniversityNanjing 210098China College of Oceanography Hohai UniversityNanjing 210098China Institute of Atmospheric Sciences Fudan UniversityShanghai 200438China

With the Regional Ocean Modeling System(ROMS),this paper investigates the sensitive areas in targeted observation for predicting the Kuroshio large meander(LM)path using the conditional nonlinear optimal perturbation *** identify the sensitive areas,the optimal initial errors(OIEs)featuring the largest nonlinear evolution in the LM prediction are first calculated;the resulting OIEs are localized mainly in the upper 2500 m over the LM upstream region,and their spatial structure has certain similarities with that of the optimal triggering *** on this spatial structure,the sensitive areas are successfully identified,located southeast of Kyushu in the region(29°–32°N,131°–134°E).A series of sensitivity experiments indicate that both the positions and the spatial structure of initial errors have important effects on the LM prediction,verifying the validity of the sensitive ***,the effect of targeted observation in the sensitive areas is evaluated through observing system simulation *** targeted observation is implemented in the identified sensitive areas,the prediction errors are effectively reduced,and the prediction skill of the LM event is improved *** provides scientific guidance for ocean observations related to enhancing the prediction skill of the LM event.

关键词： Kuroshio large meander targeted observation sensitive areas ROMS

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Ceramic membrane separation technique for washing nano-sized ceramic powder precursors

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Particuology 2011年第5期9卷 492-496页

作者： qiang Dong Xingqin liu Tianshu Zhang Department of Chemistry ＆ Materials Engineering. Hefei University Hefei 230022 China USTC Lab for Solid State Chemistry and Inorganic Membranes Department of Materials Science ＆ Engineering University of Science ＆ Technology of China Hefei 230026 China School of Materials Science and Engineering The University of New South Wales Sydney NSW2052 Australia

Washing using ceramic micro-filtration membranes was studied in the preparation of nano-sized TiO2 and A1203 powder precursors obtained by wet chemical methods. The key parameters for the washing process, such as operation pressure, cross-flow velocity, and slurry concentration, were examined and optimized. The shape and size of particles influenced the structure of the filter cake, leading to different permeation flux for different systems. The results demonstrated that washing using ceramic membranes is superior to the traditional plate-and-frame filtration and could be considered an advanced technique for ultra-fine powder preparation by wet-chemical method.

关键词： Nano-sized ceramic powder Wet-chemical method Ceramic membrane Washing Filtration

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Experimental study on geochemical characteristic of methane hydrate formed in porous media

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Journal of Natural Gas Chemistry 2009年第2期18卷 217-221页

作者： qiang Chen Changling liu Yuguang Ye Qingdao Institute of Marine Geology the Ministry of Land and Resources Qingdao 266071 Shandong China The key Laboratory of Marine Hydrocarbon Resources and Environment Resources the Ministry of Land and Resources Qingdao 266071 Shangdong China

The natural occurrence of methane hydrates in marine sediments has been intensively studied over the past decades, and geochemical charac-teristic of hydrate is one of the most attractive research fields. In this paper, we discussed the geochemical anomaly during hydrate formation in porous media. By doing so, we also investigated the temperature influence on hydrate formation under isobaric condition. It turns out that sub-cooling is an important factor to dominate hydrate formation. Larger subcooling provides more powerful driving force for hydrate formation. During the geochemical anomaly research, six kinds of ions and the total dissolved salt （TDS） were measured before and after the experiment in different porous media. The result is that all kinds of ionic concentration increased after hydrate formation which can be defined as salting out effect mainly affected by gas consumption. But the variation ratio of different ions is not equal. Ca^2＋ seems to be the most significantly influenced one, and its variation ratio is up to 80%. Finally, we theoretically made a model to calculate the TDS variation, the result is in good accordance with measured one, especially when gas consumption is large.

关键词： hydrate formation porous media subcooling salting out effect geochemical anomaly

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Multicolored Bipartite Ramsey Numbers of Large Cycles

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Acta Mathematicae Applicatae Sinica 2024年第2期40卷 347-357页

作者： Shao-qiang liu Yue-jian PENG College of Mathematics and Statistics Hanshan Normal UniversityChaozhou 521041China School of Mathematics Hunan UniversityChangsha 410082China

For an integer r≥2 and bipartite graphs Hi,where 1≤i≤r,the bipartite Ramsey number br(H1,H2,…,Hr)is the minimum integer N such that any r-edge coloring of the complete bipartite graph KN;N contains a monochromatic subgraph isomorphic to Hi in color i for some 1≤i≤*** show that if r≥3;α1,α2>0,αj+2≥[(j+2)!-1]Σi=1^(j+1)α1 for j=1,2…r-2,then br(C2[α1n],C2[α2n],…,C2[αrn]=(Σ=j=1^(r)a j+o(1))n.

关键词： ramsey number bipartite ramsey number regularity lemma

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