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The enzymatic biosynthesis of acylated steroidal glycosides and their cytotoxic activity

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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

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

New fast algorithm for hypercomplex decomposition and hypercomplex cross-correlation

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Journal of Systems Engineering and Electronics 2010年第3期21卷 514-519页

作者： Chunhui Zhu yi Shen qiang Wang School of Astronautics Harbin Institute of Technology Harbin 150001 E R. China

In order to calculate the cross-correlation of two color images treated as vector in a holistic manner,a rapid vertical/parallel decomposition algorithm for quaternion is *** calculation for decomposition is reduced from 21 times to 4 times real number multiplications with the same *** algorithm for cross-correlation of color images based on decomposition in time domain is put forward,in which some properties pointed out in this paper can be utilized to reduce the computational *** results show the effectiveness and superiority of the proposed method.

关键词： color image processing color image cross-correlation quaternion decomposition hypercomplex.

Collective effects in an incompressible electronic liquid

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National Science Review 2023年第6期10卷 168-182页

作者： jian-jian Miao Hui-Ke Jin yi Zhou Department of Physics The Chinese University of Hong Kong Department of Physics TQM Technische Universitat Munchen Institute of Physics Chinese Academy of Sciences Songshan Lake Materials Laboratory Kavli Institute for Theoretical Sciences & CAS Center for Excellence in Topological Quantum Computation University of Chinese Academy of Sciences

Starting from Landau’ s kinetic equation,we show that an electronic liquid in d=2,3 spatial dimensions depicted by a Landau-type effective theory will become incompressible on condition that the Landau parameters satisfy either(ⅰ) 1+F1s/d=0 or(ⅱ) F0s→+∞. Condition(ⅰ) is the Pomeranchuk instability in the current channel and suggests a quantum spin liquid(QSL) state with a spinon Fermi surface;while condition(ⅱ) means that the strong repulsion in the charge channel leads to a conventional charge and thermal *** the collisionless regime(ωτ>>1) and the hydrodynamic regime(ωτ<<1),the zero and first sound modes have been studied and classified by symmetries,including the longitudinal and transverse modes in d=2,3 and the higher angular momentum modes in d=*** sufficient(and/or necessary) conditions of these collective modes have been *** has been demonstrated that some of these collective modes will behave in quite different manners under incompressibility condition(ⅰ) or(ⅱ).Possible nematic QSL states and a hierarchy structure for gapless QSL states have been proposed in d=3.

关键词： quantum spin liquid Landau-type effective theory collective modes zero sound first sound

The influence of ultrasonic vibration on parts properties during incremental sheet forming

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Advances in Manufacturing 2021年第2期9卷 250-261页

作者： Yan-Le Li Zi-jian Wang Wei-Dong Zhai Zi-Nan Cheng Fang-yi Li Xiao-qiang Li Key Laboratory of High Efficiency and Clean Mechanical Manufacture Ministry of EducationSchool of Mechanical EngineeringShandong UniversityJinan 250061People’s Republic of China National Demonstration Center for Experimental Mechanical Engineering Education Shandong UniversityJinan 250061People’s Republic of China School of Mechanical Engineering and Automation Beihang UniversityBeijing 100083People’s Republic of China

The integration of ultrasonic vibration into sheet forming process can significantly reduce the forming force and bring benefits including the enhancement of surface quality,the enhancement of formability and the reduction of ***,the influencing mechanisms of the high-frequency vibration on parts properties during the incremental sheet forming(ISF)process are not well known,preventing a more efficient forming *** paper comprehensively investigates the effects of different process parameters(vibration amplitude,step-down size,rotation speed and forming angle)on the micro-hardness,minimum thickness,forming limit and residual stress of the formed ***,a series of truncated pyramids were formed with an experimental platform designed for the ultrasonic-assisted incremental sheet ***,microhardness tests,minimum thickness measurements and residual stress tests were performed for the formed *** results showed that the surface micro-hardness of the formed part was reduced since the vibration stress induced by the ultrasonic vibration within the material which eliminated the original internal *** superimposed University,Beijing 100083,People’s Republic of China ultrasonic vibration can effectively uniform the residual stress and thickness distribution,arid improve the forming limit in the case of the small deformation *** addition,through the tensile fracture analysis of the formed part,it is shown that the elongation of material is improved and the elastic modulus and hardening index are *** findings of the present work lay the foundation for a better integration of the ultrasonic vibration system into the incremental sheet forming process.

关键词： Incremental sheet forming(ISF) Ultrasonic vibration Residual stress Forming limit

Highly Soluble Polyimides Containing Di-tert-butylbenzene and Dimethyl Groups with Good Gas Separation Properties and Optical Transparency

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Chinese Journal of Polymer Science 2020年第7期38卷 759-768,I0007页

作者： Chen-yi Wang Cai-Rong jiang Bin Yu Xiao-Yan Zhao Zhao-Liang Cui jian Li qiang Ren jiangsu Collaborative Innovation Center of Photovoltaic Science and Engineering Jiangsu Key Laboratory of Environmentally Friendly Polymeric MaterialsSchool of Materials Science and EngineeringChangzhou UniversityChangzhou 213164China State Key Laboratory of Materials-Oriented Chemical Engineering College of Chemical EngineeringNanjing Tech UniversityNanjing 210009China

A rigid aromatic diamine monomer containing di-tert-butylbenzene and dimethyl groups,3,3'-dimethyl-4,4'-diaminophenyl-3",5"-di-tert-butyltoluene,was successfully synthesized by a simple coupling reaction using 3,5-di-tert-butylbenzaldehyde and o-toluidine as starting materials.A series of novel polyimides(PI 3a-3c)with large pendant groups were prepared with the obtained diamine monomer and three different commercial aromatic dianhydrides(3,3',4,4'-biphenyltetracarboxylic dianhydride,4,4'-oxydiphthalic anhydride,and 4,4'-(hexafluoroisopropylidene)diphthalic anhydride)by one-step high temperature *** prepared polyimides exhibited high solubility and good membrane forming ability:they could be dissolved not only in some high boiling solvents such as DMF,NMP,DMAc,and m-Cresol at room temperature,but also in some low boiling solvents such as CHCl3,CH2Cl2,and *** solubility in most solvents could exceed 10 wt%,and the flexible membranes could be obtained by casting their *** prepared membranes exhibited good gas separation *** permeability coefficients of PI 3c for CO2 and O2 were up to 124.6 and 42.8 barrer,respectively,and the selectivity coefficients for CO2/CH4 and O2/N2 were 14.7 and 3.3,*** membranes had light color and good optical *** optical transmittance at 450 nm wavelength was in the range of 67%-79%,and the cutoff wavelength was in the range of 310-348 *** also had good thermal properties with glass transition temperature(Tg)values in the range of 264-302℃.In addition,these membranes possessed good mechanical properties with tensile strength ranging between 77.8-87.4 MPa,initial modulus ranging between 1.69-1.82 GPa,and elongation at break ranging between 4.8%-6.1%.

关键词： Polyimides Di-tert-butyltoluene Gas separation performance Optical transparency

Immunotherapeutic strategies targeting B cell maturation antigen in multiple myeloma

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Military Medical Research 2021年第3期8卷 433-443页

作者： yi Fang jian Hou Department of Hematology Renji HospitalSchool of MedicineShanghai Jiao Tong University160 Pujian RoadShanghai 200127China

Multiple myeloma(MM) is the second most common hematologic malignancy, and is characterized by the clonal expansion of malignant plasma cells. Despite the recent improvement in patient outcome due to the use of novel therapeutic agents and stem cell transplantation, all patients eventually relapse due to clone evolution. B cell maturation antigen(BCMA) is highly expressed in and specific for MM cells, and has been implicated in the pathogenesis as well as treatment development for MM. In this review, we will summarize representative anti-BCMA immune therapeutic strategies, including BCMA-targeted vaccines, anti-BCMA antibodies and BCMA-targeted CAR cells. Combination of different immunotherapeutic strategies of targeting BCMA, multi-target immune therapeutic strategies, and adding immune modulatory agents to normalize anti-MM immune system in minimal residual disease(MRD) negative patients, will also be discussed.

关键词： B cell maturation antigen Multiple myeloma Vaccine Antibody CAR T-cells

Temperature-Aware Electromigration Analysis with Current-Tracking in Power Grid Networks

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Journal of Computer Science & Technology 2021年第5期36卷 1133-1144页

作者： Jing Wang yi-Ci Cai qiang Zhou Department of Computer Science and Technology Tsinghua UniversityBeijing 100084China

Electromigration(EM)is a severe reliability issue in power grid *** via array possesses special EM characteristics and suffers from Joule heating and current crowding,closely related to EM *** this study,a power grid EM analysis method was developed to solve temperature variation effects for the via array *** new method is based on the temperature-aware EM model,which considers the effects of self-heating and thermal coupling of interconnected lines in a power *** to the model,the proposed methodology introduces a locality-driven strategy and current tracking to perform full-chip EM assessment for multilayered power *** results show that temperature due to Joule heating indeed has significant impacts on the via EM *** results further demonstrate that the proposed method might reasonably improve efficiency while ensuring the accuracy of the analysis.

关键词： electromigration(EM) self-heating thermal coupling via

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