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Semi-synthesis of biotin-bearing activity-based ubiquitin probes through sequential enzymatic ligation,N-S acyl transfer and aminolysis reaction

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Chinese Chemical Letters 2023年第6期34卷 362-365页

作者： Yu Wang Qiong Xia Xiao Hua Yanyan Guo Jing Shi yi-ming li Department of Chemistry University of Science and Technology of ChinaHefei 230026China School of Food and Biological Engineering Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education InstitutesHefei University of TechnologyHefei 230009China

Activity-based Ubiquitin probes(Ub-ABPs)carrying a reporter group have emerged as effective tools for the investigation of deubiquitinating enzymes(DUBs),such as studying the molecular mechanism of DUBs,profiling new *** so far,the synthesis of commonly used biotin-bearing Ub-ABPs is a technical ***,we report a one-pot semi-synthetic strategy for the acquiring of Ub-ABPs carrying a biotin tag through sequential enzymatic ligation,N-S acyl transfer and aminolysis reaction without any purification *** probes enable to capture the different family of DUBs for enrichment and immunoblotting using the attached biotin tag.

关键词： Ubiquitination Deubiquitinating enzyme Activity-based ubiquitin probes Biotin tag Protein semi-synthesis

Numerical investigation of the interaction of the turbulent dual-jet and acoustic propagation

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Chinese Physics B 2017年第2期26卷 294-304页

作者： yi-ming li Bao-Kuan li Feng-Sheng Qi Xi-Chun Wang School of Metallurgy Northeastern University Shenyang 110819 China

In order to study the interaction between two independent jets, a three-dimensional（3D） transient mathematical model is developed to investigate the flow field and acoustic properties of the two-stream jets. The results are compared with those of the single-stream jet at Mach number 0.9 and Reynolds number 3600. The large eddy simulation（LES） with dynamic Smagorinsky sub-grid scale（SGS） approach is used to simulate the turbulent jet flow structure. The acoustic field is evaluated by the Ffowcs Williams–Hawkings（FW-H） integral equation. Considering the compressibility of high-speed gas jets, the density-based explicit formulation is adopted to solve the governing equations. Meanwhile, the viscosity is approximated by using the Sutherland kinetic theory. The predicted flow characteristics as well as the acoustic properties show that they are in good agreement with the existing experimental and numerical results under the same flow conditions available in the literature. The results indicate that the merging phenomenon of the dual-jet is triggered by the deflection mechanism of the Coanda effect, which sequentially introduces additional complexity and instability of flow structure. One of the main factors affecting the dual-jet merging is the aperture ratio, which has a direct influence on the potential core and surrounding flow fluctuation. The analysis on the noise pollution reveals that the potential core plays a fundamental role in noise emission while the additional mixing noise makes less contribution than the single jet noise. The overall sound pressure level（OASPL） profiles have a directive property, suggesting an approximate 25° deflection from the streamwise direction, however, shifting toward lateral direction of about 10° to 15° in the dual-jet. The conclusion obtained in this study can provide valuable data to guide the development of manufacturing-green technology in the multi-jet applications.

关键词： dual-jet jet entrainment acoustic characteristic Coanda effect

Racemic X-ray structure of L-type calcium channel antagonist Calciseptine prepared by total chemical synthesis

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Science China Chemistry 2018年第6期61卷 702-707页

作者： Chen-Chen Chen Shuai Gao Hua-Song Ai Qian Qu Chang-lin Tian yi-ming li High Magnetic Field Laboratory Chinese Academy of Sciences Hefei 230031 China School of life Sciences University of Science and Technology of China Hefei 230026 China School of Biological and Medical Engineering Hefei University of Technology Hefei 230009 China Department of Chemistry Tsinghua University Beijing 100084 China

Snake toxin Calciseptine as a natural antagonist of L-type calcium channel has potential drug values, but its structural information remains unknown. Here, we report the total chemical synthesis of Calciseptine by using hydrazide based native chemical ligation. The crystal structure of Calciseptine was determined by racemic protein crystallography technique. Compared to the structure of its homologous family protein, we found that Calciseptine is adopting a typical three-finger structure.

关键词： protein chemical synthesis calciseptine hydrazide based native chemical ligation racemic protein crystallography

Chemical synthesis and structural analysis of guanylate cyclase C agonist linaclotide

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Chinese Chemical Letters 2018年第7期29卷 1135-1138页

作者： Chenchen Chen Shuai Gao Qian Qu Pengcheng Mi Anjin Tao yi-ming li High Magnetic Field Laboratory Chinese Academy of Sciences School of life Sciences University of Science and Technology of China School of Biological and Medical Engineering Hefei University of Technology Hybio Pharmaceutical Co. Ltd.

Guanylate cyclase C(GC-C) is an important receptor protein expressed by intestinal epithelial cells, and its dysregulation leads to severe intestinal diseases. linaclotide is a 14-amino acid peptide approved by the FDA for the treatment of irritable bowel syndrome with constipation(IBS-C), which activates guanylate cyclase C to accelerate intestinal transit. Drug molecule design based on structural information plays a crucial role and the activity of linaclotide still need to improve, while the structure of linaclotide remains unknown. In this work, linaclotide and its D-enantiomer were obtained through Fmoc solid phase peptide synthesis method and co-crystalized through racemic crystallization. The crystal structure showed that linaclotide has a tight, three-beta turns structure immobilized by three pairs of disulfide bonds.

关键词： linaclotide Guanylyl cyclase Protein chemical synthesis Fmoc solid phase peptide synthesis Racemic crystallization

Use of a Removable Backbone Modification Strategy to Prevent Aspartimide Formation in the Synthesis of Asp Lactam Cyclic Peptides

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Chinese Journal of Chemistry 2021年第9期39卷 2517-2522页

作者： Tingting Cui Junyou Chen Rui Zhao Yanyan Guo JiahuiTang Yulei li yi-ming li Donald Bierer Lei liu School of Food and Biological Engineering Engineering Research Center of Bio-processMinistry of EducationHefei University of TechnologyHefeiAnhui 230009China Tsinghua-Peking Center for life Sciences Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical BiologyCenter for Synthetic and Systems BiologyDepartment of ChemistryTsinghua UniversityBeijing 100084China Department of Medicinal Chemistry Bayer AGAprather Weg 18A42096 WuppertalGermany Department of Chemistry University of Science and Technology of ChinaHefeiAnhui 230026China

The synthesis of an Asp lactam derivative of A-183,a selective inhibitor of Factor 7a with good anticoagulant and antithrombotic activity,is *** synthesis depends on the use of a removable backbone modification(RBM)strategy to prevent aspartimide formation,which thwarted all attempts to synthesize this target using direct solid-phase peptide *** of the RBM strategy in the synthesis of a second Asp lactam derivative was also *** RBM strategy is therefore proposed as a general method for the synthesis of Asp lactam cyclic peptides.

关键词： Peptides Solid-phase synthesis Synthetic methods Aspartimide Lactam cyclic peptides

Self-starting all-fiber PM Er:laser mode locked by a biased nonlinear amplifying loop mirror

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Chinese Physics B 2019年第12期28卷 160-164页

作者： Ke yin yi-ming li Yan-Bin Wang Xin Zheng Tian Jiang National Innovation Institute of Defense Technology Academy of Military Sciences PLA ChinaBeijing 100071China College of Advanced Interdisciplinary Studies National University of Defense TechnologyChangsha 410073China State Key Laboratory of High Performance Computing College of ComputerNational University of Defense TechnologyChangsha 410073China Luoyang Electronic Equipment Test Center of China Luoyang 471003China

A compact all-fiber polarization-maintaining Er:laser using a nonlinear amplifying loop mirror is reported. Fundamental single-pulse mode-locking operation can always self start, with a cavity round-trip decreased from ~ 4.7 m to~ 1.7 m. When the pulse repetition rate is 121.0328 MHz, output pulse is measured to have a center wavelength/3-d B spectral bandwidth/radio frequency signal to noise ratio(SNR)/pulse width of 1571.65 nm/18.70 nm/80 d B/477 fs, respectively. Besides, three states including the exponential growth, damping state, and steady state are investigated through the build-up process both experimentally and numerically. Excellent stability of this compact Er:laser is further evaluated,demonstrating that it can be an easy-fabrication maintenance-free ultrafast candidate for the scientific area of this kind.

关键词： ultrafast fiber laser single-mode polarization-maintaining Er:laser

DNA hypermethylation of COL4A1 in ultraviolet-Binduced age-related cataract models in vitro and in vivo

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International Journal of Ophthalmology(English edition) 2024年第10期17卷 1791-1799页

作者： li Wang Dan Zhu Yang Yang Yuan He Jing Sun yi-ming li Zi-Jing Wang Peng li Department of Optometry Xi’an Medical UniversityXi’an 710021Shaanxi ProvinceChina Department of Ophthalmology the Second Affiliated Hospital of Xi’an Medical UniversityXi’an 710038Shaanxi ProvinceChina Department of Ophthalmology Xijing 986 HospitalFourth Military Medical UniversityXi’an 710054Shaanxi ProvinceChina

AIM:To explore the DNA methylation of COL4A1 in ultraviolet-B(UVB)-induced age-related cataract(ARC)models in vitro and in ***:Human lens epithelium B3(HLEB3)cells and Sprague Dawley rats were exposure to UVB *** MTT assay was utilized to evaluate cell *** cytometry was employed for analysis of cell apoptosis and cell ***4A1 expression in HLEB3 cells and anterior lens capsules were assessed using Western blot and reverse transcription-polymerase chain reaction(RTPCR).The localization of COL4A1 in HLEB3 cells was determined by *** methylation status of CpG islands located in COL4A1 promoter was verified using bisulfite-sequencing PCR(BSP).DNMTs and TETs mRNA levels was examined by ***:UVB exposure decreased HLEB3 cells proliferation,while increased the apoptosis rate and cells were arrested in G0/G1 ***4A1 expression was markedly inhibited in UVB treated cells compared to the *** status was detected in the CpG islands within COL4A1 promoter in HLEB3 cells subjected to UVB *** of DNMTs including DNMT1/2/3 were elevated in UVB treated HLEB3 cells compared to that in the controls,while expressions of TETs including TET1/2/3 showed the opposite *** from the UVB treated rat model further confirmed the decreased expression of COL4A1,hypermethylation status of the CpG islands at promoter of COL4A1 and abnormal expression of DNMT1/2/3 and TET1/2/in UVB exposure ***:DNA hypermethylation of COL4A1 promoter CpG islands is correlated with decreased COL4A1 expression in UVB induced HLEB3 cells and anterior lens capsules of rats.

关键词： human lens epithelium cells age-related cataract COL4A1 hypermethylation ultraviolet-B rat

Clinical characteristics and in-hospital outcomes of patients receiving contemporary intensive cardiac care:retrospective study from a large centre in China

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Journal of Geriatric Cardiology 2021年第2期18卷 94-103页

作者： Fei CHEN yi-ming li Qi liU Bao-Tao HUANG Fang-Yang HUANG Yong PENG Mao CHEN Department of Cardiology West China HospitalSichuan UniversityChengduChina West China School of Medicine Sichuan UniversityChengduChina

BACKGROUND Few studies from developed countries have quantitatively characterized the clinical characteristics and outcomes of patients receiving contemporary intensive cardiac *** sought to investigate these data in patients admitted to a Chinese intensive cardiac care unit(ICCU).METHODS We conducted a retrospective study using data from 2,337 consecutive admissions to the ICCU at a large centre in China from June 2016 to May *** were captured after systematic inspection of individual medical records regarding current demographics,primary diagnosis,comorbidities,illnesses severity,and in-hospital *** The mean age was 65.6±14.2 years,and females accounted for 32.0%of *** Charlson Comorbidity Index and Oxford Acute Severity of Illness Score were 2.4±1.8 and 22.5±10.4,*** top reason for admission was ST-segment elevation myocardial infarction(32.0%),and nonischaemic heart diseases accounted for 31.2%of all primary *** diseases were prevalent in the ICCU population,including chronic illnesses and acute noncardiovascular critical illnesses(ANCIs);in particular,21.7%of patients were marked by acute respiratory failure(14.6%),acute kidney injury(13.7%),sepsis(4.2%),or gastrointestinal bleeding(3.3%).The median length of stay in the ICCU and hospital were 1.1 days[interquartile range(IQR):0.8–2.6 days]and 6.3 days(IQR:3.8−10.9 days),*** overall incidence of in-hospital death or discharge against medical advice under extremely critical conditions was 7.6%(n=177).Multivariate logistic regression analysis showed that the complexity of chronic illnesses and incident ANCIs were strong independent determinants for in-hospital *** Remarkable patient diversity and breadth of critical illnesses were observed in a Chinese ICCU ***,noncardiovascular diseases were prevalent and associated with adverse *** of organization and staffing practices may be

关键词： patients admitted centre

Semi-synthesis of Ubiquitin-propargylamide for identifying deubiquitinase targeting inhibitors

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Chinese Chemical Letters 2019年第3期30卷 743-746页

作者： Xiaodan Tan Jingsi Bai Shan Ding Yujing Ren Danning Hong Ziqing Mei yi-ming li School of Biological and Medical Engineering Hefei University of Technology Tsinghua-Peking Center for life Sciences Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical BiologyDepartment of Chemistry Tsinghua University Biotechnology Research Institute Chinese Academy of Agricultural Sciences School of Biological Science Beijing Institute of Technology

Ubiquitin-propargylamide(Ub-PA) is one of the most widely used activity-based probe to measure the activity of deubiquitinases(DUBs) and help validate DUBs targeting inhibitors. However, current synthetic route of Ub-PA is cumbersome. In this work, we report a novel semi-synthetic strategy to prepare Ub-PA in large-scale. Biochemical assays prove that semi-synthetic Ub-PA is an effective probe in identifying DUBs targeting inhibitors.

关键词： Deubiquitinase Activity-based probe Ubiquitin-propargylamide Protein semi-synthesis Inhibitor identification