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Polymyxin resistance caused by large-scale genomic inversion due to IS26 intramolecular translocation in Klebsiella pneumoniae

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药学学报:英文版 2023年第9期13卷 3678-3693页

作者： Haibin Li lang sun Han Qiao Zongti sun Penghe Wang Chunyang Xie Xinxin Hu Tongying Nie Xinyi Yang Guoqing Li Youwen Zhang Xiukun Wang Zhuorong Li Jiandong Jiang Congran Li Xuefu You Beijing Key Laboratory of Antimicrobial Agents Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Institute of Medicinal Biotechnology Chinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100050China State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100050China

Polymyxin B and polymyxin E(colistin)are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales,Acinetobacter baumannii,and Klebsiella *** resistance to this last-line drugs is a major public health threat and is rapidly *** S2(S2)is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and *** predict the possible resistant mechanism of S2for wide clinical application,we experimentally induced bacterial resistant mutants and studied the preliminary resistance ***-S,a resistant mutant of *** ATCC BAA-2146(Kpn2146)induced by S2,was analyzed by whole genome sequencing,transcriptomics,mass spectrometry and complementation ***,large-scale genomic inversion(LSGI)of approximately 1.1 Mbp in the chromosome caused by IS26mediated intramolecular transposition was found in Mut-S,which led to mgrB truncation,lipid A modification and hence *** resistance can be complemented by plasmid carrying intact *** same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146(Mut-B and Mut-E,respectively).This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in *** findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics.

关键词： Klebsiella pneumoniae Polymyxin resistance mgrB IS26 Whole genome sequencing Structural variation Inversion

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The clinical antiprotozoal drug nitazoxanide and its metabolite tizoxanide extend Caenorhabditis elegans lifespan and healthspan

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3266-3280页

作者： Wenfeng Li Shuming Chen Jing lang Jing Luo Jiahui Chen Liping Zhang Zhijie sun Deli Dong Department of Pharmacology China Pharmaceutical UniversityNanjing 210009China

The drugs extending healthspan in clinic have always been *** is an FDA-approved clinical antiprotozoal *** is rapidly metabolized to tizoxanide after absorption in *** previous studies find that nitazoxanide and its metabolite tizoxanide induce mild mitochondrial uncoupling and activate cellular AMPK,oral nitazoxanide protects against experimental hyperlipidemia,hepatic steatosis,and ***,we demonstrate that both nitazoxanide and tizoxanide extend the lifespan and healthspan of Caenorhabditis elegans through Akt/AMPK/sir 2.1/daf16 ***,both nitazoxanide and tizoxanide improve high glucose-induced shortening of *** *** has been a clinical drug with a good safety profile,we suggest that it is a novel anti-aging drug.

关键词： Nitazoxanide Tizoxanide C.elegans Healthspan Lifespan AMPK Akt Mitochondrial uncoupling

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Vulnerability and Conservation of Nearshore Cetaceans to Increasing Vessel Traffic:The Indo-Pacific Humpback Dolphin in the South China Sea

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Journal of Ocean University of China 2024年第4期23卷 1003-1014页

作者： LUO Dingyu GUO lang HUANG Nuoyan WANG Hongri ZENG Chen TANG Xikai XU Zhuo WU Yuping sun Xian School of Marine Sciences Zhuhai Key Laboratory of Marine Bioresources and EnvironmentGuangdong Provincial Key Laboratory of Marine Resources and Coastal EngineeringPearl River Estuary Marine Ecosystem Research Sta-tionMinistry of EducationSun Yat-Sen UniversitySouthern Marine Science and Engineering Guangdong Labora-tory(Zhuhai)Zhuhai 519082China

A comprehensive risk assessment to evaluate the vulnerability of the nearshore cetaceans to increasing marine traffic is *** this study,the risk to Indo-Pacific humpback dolphins(Sousa chinensis)in the main habitats in China was assessed based on a semiquantitative spatial vulnerability analysis.85%of the(sub)population which overlapped with the lanes of ferries and/or cargo vessels,with exposure scores of 1.23±0.31(calculated based on the proportion of sea routes that overlap the dolphin’s range).A combination of high exposure to the sea routes and sensitivity to marine traffic would render the(sub)populations to be highly vulnerable(EPRE:5.21 and XM:4.47).A low frequency of vessels and an awareness of the ecology assures a low vulnerability(SH:2.43,EZ:2.73).Uncertainty scores were commonly lower for the higher vulnerable populations,and higher for the lower vulnerable populations,suggesting additional field data and more monitoring are *** years of field data have been used to analyze the influences of various types of marine traffic on humpback dolphin *** and non-fishing vessels were significantly different(χ^(2)=65.19,p<0.01).The humpback dolphins were attracted by fishing vessels(83.1%)but avoided non-fishing vessels(95.2%).We recommend a management with seasonal and geographical constraints,to balance economic development and environmental conservation.

关键词： Indo-Pacific humpback dolphin vessel impacts risk analysis protection strategy

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Yuzaoea gen. nov., a new biraphid diatom(Bacillariophyceae)genus and its phylogenetic significance

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Acta Oceanologica Sinica 2024年第2期43卷 130-136页

作者： Honghan Liu Chenhong Li lang Li Xuesong Li Lin sun Junrong Liang Jun Zhang Yahui Gao Changping Chen Key Laboratory of Ministry of Education for Coastal and Wetland Ecosystems and School of Life Sciences Xiamen UniversityXiamen 361102China State Key Laboratory of Marine Environmental Science Xiamen UniversityXiamen 361102China Guangxi Key Laboratory of Marine Environmental Science Guangxi Academy of Marine SciencesGuangxi Academy of SciencesNanning 530007China Beibu Gulf Marine Industry Research Institute Fangchenggang 538000China

The flexed frustules in pennate diatoms are usually associated with monoraphid diatoms. Interestingly, we found a biraphid diatom species with flexed frustules in an offshore intertidal beach environment on Weizhou Island,Beihai City, Guangxi Zhuang Autonomous Region, China. Therefore, based on morphological characteristics, we described a new genus of diatoms Yuzaoea sinensis gen. et sp. nov. CH Li, HH Liu, YH Gao & CP Chen. The frustule of this genus is characterized by heterogeneous frustule with one concave valve and one convex valve,complete raphe on both valves, straight and moderately eccentric raphe, uniseriate striae and girdle bands with a single row of areolae. The most identifying feature of this genus was the flexed frustule, which is rare in biraphid diatoms and common in monoraphid diatoms. We compared the morphometric characteristics of genus Yuzaoea with genus Rhoikoneis and several genera within the family Rhoicospheniaceae, including Rhoicosphenia,Campylopyxis, and Cuneolus. Phylogenetic analyses based on SSU rRNA and rbc L showed that the genus Yuzaoea was the sister group to the clade of Rhoicosphenia with a high support value(bootstrap values = 100%), and the clade “Yuzaoea+Rhoicosphenia” was sister to the clade of monoraphid diatoms, in which the genera Achnanthidium, Planothidium and some Cocconeis with high support values(bootstrap = 100%).Morphologically, the genus Yuzaoea shares many morphological features with monoraphid diatoms like genera Achnanthidium and Planothidium and the members within the Rhoicospheniaceae. Therefore, based on a combined morphological studies and phylogenetic results we suggested that this branch may represented the evolution of one kind monoraphid diatoms, from biraphid diatoms(e.g. genus Yuzaoea), to incompleted biraphid diatoms(e.g. genera Rhoicosphenia, Campylopyxis), to monoraphid diatoms(e.g. genera Achnanthidium and Planothidium).

关键词： biraphid diatom marine new genus Rhoicospheniaceae taxonomy Yuzaoea

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Developing guanine base editors for G-to-T editing in rice

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Journal of Integrative Plant Biology 2024年第8期66卷 1557-1560页

作者： lang Liu Zhongming Zhang Chenyang Wang Fang Yan Wenxian sun Xueping Zhou Weiguo Miao Huanbin Zhou State Key Laboratory for Biology of Plant Diseases and Insect Pests Institute of Plant ProtectionChinese Academy of Agricultural SciencesBeijing 100193China Department of Plant Pathology China Agricultural UniversityBeijing 100193China Scientiﬁc Observing and Experimental Station of Crop Pests in Guilin Ministry of Agriculture and Rural AffairsGuilin 541399China School of Plant Protection Hainan UniversityHaikou 570228China State Key Laboratory of Rice Biology Institute of BiotechnologyZhejiang UniversityHangzhou 310058China Key Laboratory of Gene Editing Technologies Ministry of Agricultural and Rural AffairsSanya 572024China

Single nucleotide polymorphisms (SNPs) are widely present and related to desirable agronomic traits in *** regularly interspaced palindromic repeats(CRISPR)/CRISPR-associated nuclease 9 (Cas9)-mediated base editors have been frequently used to correct defective alleles and create novel alleles by artificial evolution for rapid crop genetic improvement (Ma et al.,2021).

关键词： alleles agronomic base

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Zeolite templated carbon nanodots for broadband ultrafast pulsed fiber laser generation

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Photonics Research 2019年第10期7卷 1182-1187页

作者： XINTONG XU JIAQI CHEN WENTAO SHI DALIN sun SHAOWEN CHU lang sun WENFEI ZHANG YANPING CHEN JIANPANG ZHAI SHUANGCHEN RUAN ZIKANG TANG Center for Advanced Material Diagnostic Technology College of Engineering PhysicsShenzhen Technology UniversityShenzhen 518118China Shenzhen Key Laboratory of Laser Engineering Shenzhen UniversityShenzhen 518060China College of New Materials and New Energies Shenzhen Technology UniversityShenzhen 518118China Institute of Applied Physics&Materials Engineering Faculty of Science and TechnologyUniversity of MacaoMacaoChina

Carbon nanodots(C-dots) with a uniform size of about 2 nm are synthesized via in situ pyrolysis of n-propylamine that is confined in the nanochannels of zeolite Linde Type A(LTA). The as-synthesized C-dots@LTA composite shows nonlinear optical saturable absorption properties in a broad wavelength band and can be used as saturable absorber(SA) to generate ultrafast pulsed fiber lasers. By inserting a zeolite LTA single crystal hosting C-dots into the fiber laser cavity, mode-locked fiber lasers with long-term operation stability at 1.5 μm and 1 μm are achieved. These results show that the C-dots@LTA are a promising SA material for ultrafast pulsed fiber laser generation in a broad wavelength band. To the best of our knowledge, this is the first demonstration of a C-dots@LTA-based mode-locked fiber laser.

关键词： fiber laser zeolite

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Sulfuric acid triggered cascade reaction of 3-（2-cyanophenyl）-propargylic alcohols to spiro [indene-1,1’-isoindolin]-3’-ones

Sulfuric acid triggered cascade reaction of 3-（2-cyanopheny...

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中国化学会第九届全国有机化学学术会议

作者： lang sun Peng Liu Ping Lu Yanguang Wang Department of Chemistry Zhejiang University

＜正＞Propargylic alcohols are versatile synthetic intermediates in modern organic *** can be easily accessed from terminal alkynes and carbonyl compounds through simple nucleophilic addition and can be readily converted into a variety of important compounds,such asα,β-unsaturated ketones,alleneamides,allenesulfonamides,allenephosphoramides,carbocycles,and

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CRISPR/Cas系统在抗细菌感染领域的应用现状与进展

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药学学报 2023年第9期58卷 2560-2568页

作者：孙宗倜孙琅游雪甫中国医学科学院、北京协和医学院医药生物技术研究所抗感染药物研究北京市重点实验室北京100050

CRISPR/Cas基因编辑技术是21世纪分子生物学领域的一次重大突破,该技术的便捷性、通用性、靶向性将其应用的范围推向各个领域。在目前细菌耐药形势严峻、耐药菌检测手段局限、抗感染药物研发缓慢的全球大背景下,CRISPR/Cas基因编辑技术... 详细信息

CRISPR/Cas基因编辑技术是21世纪分子生物学领域的一次重大突破,该技术的便捷性、通用性、靶向性将其应用的范围推向各个领域。在目前细菌耐药形势严峻、耐药菌检测手段局限、抗感染药物研发缓慢的全球大背景下,CRISPR/Cas基因编辑技术为抗细菌感染领域的发展提供了一些新的思路。一方面,CRISPR/Cas基因编辑技术有助于对细菌功能研究的展开,起到工具箱的作用,如利用Cas蛋白和外源修复系统实现高效、精准的基因编辑,nCas蛋白和脱氨酶系统实现无模板、单碱基精准编辑,dCas蛋白和反转录酶实现免修复基因编辑,以及dCas蛋白和改造后的sgRNA实现基因表达水平调控、基因功能解析。另一方面,它特异性识别基因、靶向切割DNA的特点可用于病原体检测、消除耐药菌及耐药基因,有望成为临床诊断和治疗的新策略。

关键词： CRISPR/Cas系统基因编辑细菌耐药治疗

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采用Gyrator变换的泰伯效应及图像去噪

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红外与激光工程 2014年第2期43卷 665-670页

作者：马媛花胡炳樑李然孙朗孙念王峥杰中国科学院西安光学精密机械研究所光谱成像技术实验室陕西西安710119 中国科学院大学北京100049

根据Gyrator变换原理,首先研究了Gyrator变换的自成像效应,即泰伯效应,讨论了实现Gyrator变换泰伯效应的条件,并指出了Gyrator变换的泰伯效应与传统意义上的泰伯效应不同,泰伯角度不是固定的,不同泰伯角度之间的分布也不是线性的,Gyrato... 详细信息

根据Gyrator变换原理,首先研究了Gyrator变换的自成像效应,即泰伯效应,讨论了实现Gyrator变换泰伯效应的条件,并指出了Gyrator变换的泰伯效应与传统意义上的泰伯效应不同,泰伯角度不是固定的,不同泰伯角度之间的分布也不是线性的,Gyrator变换的分数泰伯效应无法通过分数化泰伯角度得到。其次,应用Gyrator变换对图像减噪也进行了讨论,研究发现Gyrator变换不仅对双曲型噪声有较好的去除效果,而且对携带有双曲信号的噪声同样具有较好的去除效果。最后,还指出了研究的不足以及后续要开展的工作。不但深化了人们对Gyrator变换的认识,而且发展了图像的自成像和去噪等技术。

关键词：图像处理 Gyrator变换泰伯效应去噪

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Deformation,structure and potential hazard of a landslide based on InSAR in Banbar county,Xizang(Tibet)

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China Geology 2024年第2期7卷 203-221页

作者： Guan-hua Zhao Heng-xing Lan Hui-yong Yin lang-ping Li Alexander Strom Wei-feng sun Chao-yang Tian College of Earth Science and Engineering Shandong University of Science and TechnologyQingdao 266590China State Key Laboratory of Resources and Environmental Information System Institute of Geographic Sciences and Natural Resources ResearchChinese Academy of SciencesBeijing 100101China School of Geological Engineering and Geomatics Chang’an UniversityXi’an 710054China Key Laboratory of Ecological Geology and Disaster Prevention Ministry of Natural ResourcesXi’an 710054China University of Chinese Academy of Sciences Beijing 100049China JSC“Hydroproject Institute” Moscow 125993Russia

The Tibetan Plateau is characterized by complex geological conditions and a relatively fragile ecological *** recent years,there has been continuous development and increased human activity in the Tibetan Plateau region,leading to a rising risk of *** landslide in Banbar County,Xizang(Tibet),have been perturbed by ongoing disturbances from human engineering activities,making it susceptible to instability and displaying distinct *** this study,small baseline subset synthetic aperture radar interferometry(SBAS-InSAR)technology is used to obtain the Line of Sight(LOS)deformation velocity field in the study area,and then the slope-orientation deformation field of the landslide is obtained according to the spatial geometric relationship between the satellite’s LOS direction and the ***,the landslide thickness is inverted by applying the mass conservation *** results show that the movement area of the landslide is about 6.57×10^(4)m^(2),and the landslide volume is about 1.45×10^(6)m^(3).The maximum estimated thickness and average thickness of the landslide are 39 m and 22 m,*** thickness estimation results align with the findings from on-site investigation,indicating the applicability of this method to large-scale earth *** deformation rate of the landslide exhibits a notable correlation with temperature variations,with rainfall playing a supportive role in the deformation process and displaying a certain *** activities exert the most substantial influence on the spatial heterogeneity of landslide deformation,leading to the direct impact of several prominent deformation areas due to human ***,utilizing the long short-term memory(LSTM)model to predict landslide displacement,and the forecast results demonstrate the effectiveness of the LSTM model in predicting landslides that are in a continuous development and movement *** landslide is still active,and based

关键词： Landslide InSAR Human activity Deformation Structure LSTM model Engineering construction Thickness Neural network Machine learning Prediction and prevention Tibetan Plateau Geological hazards survey engineering

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