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Auroramycin: A Potent Antibiotic from Streptomyces roseosporus by CRISPR-Cas9 Activation

CHEMBIOCHEM 2018年第16期19卷 1716-1719页

作者： Lim, Yee Hwee Wong, Fong Tian Yeo, Wan lin Ching, Kuan Chieh Lim, Yi Wee Heng, Elena Chen, shuwen Tsai, De-Juin Lauderdale, Tsai-ling Shia, Kak-Shan Ho, Ying Swan Hoon, Shawn Ang, Ee Lui Zhang, Mingzi M. Zhao, Huimin ASTAR Sci & Engn Inst MERL 31 Biopolis WayNanos 01-01 Singapore 138669 Singapore Univ Illinois Roger Adams Lab 215 Box C3600 South Mathews Ave Urbana IL 61801 USA ASTAR ICES Organ Chem 8 Biomed GroveNeuros 07-01-02-03 Singapore 138665 Singapore ASTAR Biomed Sci Inst MEL 61 Biopolis DrProteos 13-02 Singapore 138673 Singapore ASTAR BTI 20 Biopolis WayCtr 06-01 Singapore 138668 Singapore NHRI Natl Inst Infect Dis & Vaccinol DJT & TLL 35 Keyan Rd Zhunan Town 350 Miaoli County Taiwan NHRI Inst Biotechnol & Pharmaceut Res KSS 35 Keyan Rd Zhunan Town 350 Miaoli County Taiwan

Silent biosynthetic gene clusters represent a potentially rich source of new bioactive compounds. We report the discovery, characterization, and biosynthesis of a novel doubly glycosylated 24-membered polyene macrolactam from a silent biosynthetic gene cluster in Streptomyces roseosporus by using the CRISPR-Cas9 gene cluster activation strategy. Structural characterization of this polyketide, named auroramycin, revealed a rare isobutyrylmalonyl extender unit and a unique pair of amino sugars. Relative and absolute stereochemistry were determined by using a combination of spectroscopic analyses, chemical derivatization, and computational analysis. The activated gene cluster for auroramycin production was also verified by transcriptional analyses and gene deletions. Finally, auroramycin exhibited potent anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity towards clinical drug-resistant isolates.

关键词： biosynthesis genomics glycosylation lactams natural products

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咖啡酸抗人乳头瘤病毒感染的研究

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病毒学报 2018年第3期34卷 287-295页

作者：丁永桢温嘉泳赖宝龙刘叔文李琳南方医科大学药学院广东省新药筛选重点实验室广州市新发病毒防治药物研究重点实验室广州510515 中山大学附属第七医院药学部深圳518107

宫颈癌（Cervical cancer,CC）是妇科最常见的恶性肿瘤之一,而高危型人乳头瘤病毒（Human papillomavirus,HPV）的持续感染是诱导宫颈癌发生的重要危险因素。目前全球抗HPV药物极为匮乏,寻找新的高效、低毒、价廉的广谱抗病毒药物对HPV... 详细信息

宫颈癌（Cervical cancer,CC）是妇科最常见的恶性肿瘤之一,而高危型人乳头瘤病毒（Human papillomavirus,HPV）的持续感染是诱导宫颈癌发生的重要危险因素。目前全球抗HPV药物极为匮乏,寻找新的高效、低毒、价廉的广谱抗病毒药物对HPV感染的防治至关重要。本文研究发现,咖啡酸（Caffeic acid,CA）能有效抑制三株不同亚型的HPV感染（HPV-6、HPV-16及HPV-18）,其半数抑制浓度在12.1-16.5μg/mL之间。Time-of-addition结果证实,咖啡酸对病毒进入靶细胞的早期阶段具有一定抑制作用。Temperature shift实验发现,咖啡酸能一定程度抑制HPV病毒颗粒黏附于靶细胞表面。表面等离子共振分析表明,咖啡酸与HPV-16型病毒的主要衣壳蛋白L1具有极强的结合力。综上,咖啡酸具有较高的抗HPV活性,其作用机制可能是与病毒衣壳蛋白L1结合,从而阻止病毒黏附并进入靶细胞。咖啡酸具有安全、价廉、易得等优势,有望被开发成新型的抗HPV病毒感染的抑制剂,因其尚能同时抵抗多种性传播性病毒的感染,对HPV并发的多种性传播性疾病具有较好的预防作用,应用前景广泛。

关键词：人乳头瘤病毒(HPV) 咖啡酸病毒进入抑制剂病毒衣壳蛋白

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A Degraded Fragment of HIV-1 Gp120 in Rat Hepatocytes Forms Fibrils and Enhances HIV-1 Infection

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BIOPHYSICAL JOURNAL 2017年第7期113卷 1425-1439页

作者： Chen, Jinquan Ren, Ruxia Yu, Fei Wang, Chunyan Zhang, Xuanxuan Li, Wenjuan Tan, Suiyi Jiang, Shibo Liu, shuwen Li, lin Southern Med Univ Guangzhou Key Lab Drug Res Emerging Virus Prevent Sch Pharmaceut Sci Guangdong Prov Key Lab New Drug Screening Guangzhou Guangdong Peoples R China Jiangsu Food & Pharmaceut Sci Coll Jiangsu Prot Drug Engn Lab Huaian Peoples R China Agr Univ Hebei Coll Life Sci Baoding Peoples R China Fudan Univ Sch Basic Med Sci Key Lab Med Mol Virol MOE MOH Shanghai Peoples R China Southern Med Univ Nanfang Hosp Ctr Clin Lab Guangzhou Guangdong Peoples R China New York Blood Ctr Lindsley F Kimball Res Inst New York NY 10021 USA

Identification of the host or viral factors that enhance HIV infection is critical for preventing sexual transmission of HIV. Amyloid fibrils derived from human semen, including semen-derived enhancer of virus infection and semenogelins, enhance HIV-1 infection dramatically in vitro. In this study, we reported that a short-degraded peptide fragment 1 (DPF1) derived from native HIV-1 envelope protein gp120-loaded rat hepatocytes, formed fibrils by self-assembly and thus enhanced HIV-1 infection by promoting the binding of HIV-1 to target cells. Furthermore, DPF1-formed fibrils might be used as a crossing seed to accelerate the formation of semen-derived enhancer of virus infection and semenogelin fibrils. It will be helpful to clarify the viral factors that affect HIV-1 infection. DPF1 as an analog of gp120 containing the critical residues for CD4 binding might be useful for designing of HIV vaccines and developing HIV entry inhibitors.

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药理学课后小论文在提高药理学教学成绩中的研究

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中国高等医学教育 2018年第2期 110-111页

作者：姚新刚李琳刘叔文南方医科大学广东广州510515

药理学属于药学的专业知识,课程的理论内容较多、枯燥乏味,学生普遍反映药理学内容庞杂,难学、难记、易混淆,从而影响学生学习的积极性。本研究选取药学专业153和药学相关专业240名学生,以传统的教育理念和课后小论文撰写辅助教学后,对... 详细信息

药理学属于药学的专业知识,课程的理论内容较多、枯燥乏味,学生普遍反映药理学内容庞杂,难学、难记、易混淆,从而影响学生学习的积极性。本研究选取药学专业153和药学相关专业240名学生,以传统的教育理念和课后小论文撰写辅助教学后,对期末考试的客观题部分分值进行对比研究,结果表明课后小论文撰写对于药理学教学效果提高具有显著作用。

关键词：药理学小论文撰写教学效果

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华北板块南缘石人山岩块晚古生代陆内变形特征及侧向挤出构造

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地质论评 2019年第4期65卷 810-824页

作者：王静雅任升莲董树文李加好宋传中林寿发韩旭李振强张刚王莹杨青亮合肥工业大学资源与环境工程学院中国合肥230009 南京大学地球科学与工程学院中国南京230026 滑铁卢大学加拿大安大略省滑铁卢市N2L3G1

华北板块南缘在古生代时期经历了复杂的陆内变形过程。石人山岩块边界断裂发育大量平行于断裂带的A型褶皱和近水平的矿物生长线理,表明其经历了以走滑剪切变形为主的构造阶段。动力学研究表明石人山岩块具有南西向逆冲的运动学特征,其... 详细信息

华北板块南缘在古生代时期经历了复杂的陆内变形过程。石人山岩块边界断裂发育大量平行于断裂带的A型褶皱和近水平的矿物生长线理,表明其经历了以走滑剪切变形为主的构造阶段。动力学研究表明石人山岩块具有南西向逆冲的运动学特征,其南侧洛南—栾川断裂带(洛栾断裂带)以左行剪切变形为主,北东侧鲁山断裂带以北西向逆冲兼有右行剪切变形为特征,夹于其中的石人山岩块显示为向西、向上挤出的特征。选择典型岩石样品进行同位素测年来限定断裂活动的时代,其中,洛栾断裂带内同构造花岗岩脉的锆石U-Pb定年结果为413.6±7.4 Ma,鲁山断裂带内走滑剪切特征明显的构造透镜体内变形岩石的锆石定年结果为419.3±11.2 Ma。虽然洛栾断裂与鲁山断裂的运动方向不同,但是同位素年代学研究限定了两条断裂带发生走滑变形的时间都是晚古生代泥盆纪末期,从而共同构成了石人山岩块整体向西挤出的构造特征,同时也表明,相互碰撞的大陆在碰撞之后将很快转变为以平行造山带侧向挤出与走滑位移为主的陆内变形演化阶段。

关键词：华北板块南缘石人山岩块陆内变形侧向挤出洛栾断裂带鲁山断裂带

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Preparation and characterization of SrS: Eu²⁺_0.02, Dy³⁺_0.01/polyvinyl butyral composites

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OPTICAL ENGINEERING 2017年第6期56卷 067111-067111页

作者： Fu, Yu Wang, Zhiqiang Zhang, Jingjing Jiang, shuwen lin, Hai Dalian Polytech Univ Sch Text & Mat Engn Dalian Peoples R China

The SrS: Eu-0.02(2+), Dy-0.01(3+)/phosphors modified with stearic acid (SA) were compounded with the polyvinyl butyral (PVB) matrix to improve its chemical stability and luminescence properties. The structure and luminescence properties of modified and unmodified SrS: Eu-0.02(2+), Dy(0.01)(3+)and SrS: Eu-0.02(2+), Dy-0.01(3+)/PVB composites were studied. The results of x- ray diffraction showed that the crystalline of the modified SrS: Eu-0.02(2+), Dy-0.01(3+) phosphors (SrS: Eu-0.02(2+), Dy-0.01(3+)) has almost no change compared with SrS: Eu-0.02(2+), Dy-0.01(3+) phosphors. The infrared spectra indicated that the SA molecules were anchored onto the surface of the phosphors and -Sr-O-CO- bonds were formed. Microstructure of the samples was characterized by scanning electron microscopy. The investigation of fluorescence spectra reflected that the emission peak position of SrS: Eu-0.02(2+), Dy-0.01(3+)/PVB composites appeared at 611 nm with no migration, whereas the luminescence intensity increased. The results of waterresistant tests proved that SrS: Eu-0.02(2+), Dy-0.01(3+)/PVB materials had better chemical stability than SrS: Eu-0.02(2+), Dy-0.01(3+)/phosphors. (C) 2017 Society of Photo- Optical Instrumentation Engineers ( SPIE)

关键词： SrS: Eu-0.02(2+) Dy-0.01(3+)/PVB stearic acid composite materials

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Sensitivity-Enhanced Wearable Active Voiceprint Sensor Based on Cellular Polypropylene Piezoelectret

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ACS APPLIED MATERIALS & INTERFACES 2017年第28期9卷 23716-23722页

作者： Li, Wenbo Zhao, Sheng Wu, Nan Zhong, Junwen Wang, Bo lin, Shizhe Chen, shuwen Yuan, Fang Jiang, Hulin Xiao, Yongjun Hu, Bin Zhou, Jun Huazhong Univ Sci & Technol Wuhan Natl Lab Optoelect Wuhan 430074 Peoples R China

Wearable active sensors have extensive applications in mobile biosensing and human machine interaction but require good flexibility, high sensitivity, excellent stability, and self-powered feature. In this work, cellular polypropylene (PP) piezoelectret was chosen as the core material of a sensitivity-enhanced wearable active voiceprint sensor (SWAVS) to realize voiceprint recognition. By virtue of the dipole orientation control method, the air layers in the piezoelectret were efficiently utilized, and the current sensitivity was enhanced (from 1.98 pA/Hz to 5.81 pA/Hz at 115 dB). The SWAVS exhibited the superiorities of high sensitivity, accurate frequency response, and excellent stability. The voiceprint recognition system could make correct reactions to human voices by judging both the password and speaker. This study presented a voiceprint sensor with potential applications in noncontact biometric recognition and safety guarantee systems, promoting the progress of wearable sensor networks.

关键词： piezoelectret voiceprint active sensor wearable electronics self-powered

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液压挖掘机虚拟样机建模与作业过程动态仿真

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机械制造与自动化 2015年第5期44卷 105-107页

作者：罗君扬林述温福州大学机械工程及自动化学院福建福州350108

利用参数化设计软件Pro/E完成了液压挖掘机的参数化建模,对模型进行了虚拟装配,得到了虚拟样机模型,通过对液压挖掘机虚拟样机进行运动仿真分析,有助于理解和分析实际机械装置运动过程,并提供相应的改进机构设计的信息。

关键词：液压挖掘机参数化建模运动学仿真

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Relation of Transcriptional Factors to the Expression and Activity of Cytochrome P450 and UDP-Glucuronosyltransferases 1A in Human Liver: Co-Expression Network Analysis

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AAPS JOURNAL 2017年第1期19卷 203-214页

作者： Zhong, Shilong Han, Weichao Hou, Chuqi Liu, Junjin Wu, Lili Liu, Menghua Liang, Zhi lin, Haoming Zhou, Lili Liu, shuwen Tang, Lan Southern Med Univ Div Nephrol Natl Clin Res Ctr Kidney Dis State Key Lab Organ Failure Res Guangzhou Guangdong Peoples R China Guangdong Acad Med Sci Guangdong Gen Hosp Med Res Ctr Guangzhou 510080 Guangdong Peoples R China Southern Med Univ Sch Pharmaceut Sci Dept Biopharmaceut Guangdong Prov Key Lab New Drug Screening Guangzhou 510515 Guangdong Peoples R China Sun Yat Sen Univ Sun Yat Sen Mem Hosp Dept Hepatobiliary Surg Guangzhou 510120 Peoples R China

Cytochrome P450 (CYPs) and UDP-glucuronosyltransferases (UGTs) play important roles in the metabolism of exogenous and endogenous compounds. The gene transcription of CYPs and UGTs can be enhanced or reduced by transcription factors (TFs). This study aims to explore novel TFs involved in the regulatory network of human hepatic UGTs/CYPs. Correlations between the transcription levels of 683 key TFs and CYPs/UGTs in three different human liver expression profiles (n = 640) were calculated first. Supervised weighted correlation network analysis (sWGCNA) was employed to define hub genes among the selected TFs. The relationship among 17 defined TFs, CYPs/UGTs expression, and activity were evaluated in 30 liver samples from Chinese patients. The positive controls (e.g., PPARA, NR1I2, NR1I3) and hub TFs (NFIA, NR3C2, and AR) in the Grey(sWGCNA) Module were significantly and positively associated with CYPs/UGTs expression. And the cancer- or inflammation-related TFs (TEAD4, NFKB2, and NFKB1) were negatively associated with mRNA expression of CYP2C9/CYP2E1/UGT1A9. Furthermore, the effect of NR1I2, NR1I3, AR, TEAD4, and NFKB2 on CYP450/UGT1A gene transcription translated into moderate influences on enzyme activities. To our knowledge, this is the first study to integrate Gene Expression Omnibus (GEO) datasets and supervised weighted correlation network analysis (sWGCNA) for defining TFs potentially related to CYPs/UGTs. We detected several novel TFs involved in the regulatory network of hepatic CYPs and UGTs in humans. Further validation and investigation may reveal their exact mechanism of CYPs/UGTs regulation.

关键词： activity CYP450 sWGCNA TFs UGT1A1

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Electrospun polyetherimide electret nonwoven for bi-functional smart face mask

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NANO ENERGY 2017年 34卷 562-569页

作者： Cheng, Yongliang Wang, Chunya Zhong, Junwen lin, Shizhe Xiao, Yongjun Zhong, Qize Jiang, Hulin Wu, Nan Li, Wenbo Chen, shuwen Wang, Bo Zhang, Yingying Zhou, Jun Huazhong Univ Sci & Technol Wuhan Natl Lab Optoelect Wuhan 430074 Peoples R China Huazhong Univ Sci & Technol Sch Opt & Elect Informat Wuhan 430074 Peoples R China Tsinghua Univ Dept Chem Beijing 100084 Peoples R China Tsinghua Univ Ctr Nano & Micro Mech Beijing 100084 Peoples R China Hubei Engn Univ Sch Phys & Elect Informat Engn Xiaogan 432000 Peoples R China

Wearable healthcare devices with monitoring, treating and protecting applications can provide reliable and newfangled interactive service for people. Herein, a bi-functional smart face mask based on electrospun polyetherimide (PEI) electret nonwoven is developed. By virtue of the surplus charges maintained steadily in the PEI nonwoven, the smart face mask possesses bi-functions of removing the particulate matter and generating electricity. Moreover, the unique applications for dynamically monitoring the particulate matter removal ability and human's respiratory rates are demonstrated. Besides offering an unique air filter, this study will promisingly promote the progress of self-powered wearable electronics.

关键词： Self-powered Wearable electronics Smart face mask Electret

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