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Identification of anti-Gram-negative bacteria agents targeting the interaction between ribosomal proteins L12 and L10

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Acta Pharmaceutica Sinica B 2018年第5期8卷 772-783页

作者： Weiwei Wang Chao liu Ningyu Zhu Yuan Lin JiANDong Jiang yanchang Wang yan Li Shuyi Si Beijing Key Laboratory of Antimicrobial Agents Institute of Medicinal Biotechnology Peking Union Medical College and Chinese Academy of Medical Sciences State Key Laboratory of Bioactive Substances and Function of Natural Medicine Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Department of Biomedical Sciences College of Medicine Florida State University

Gram-negative bacteria have become the main pathogens and cause serious clinical problems with increased morbidity and mortality. However, the slow discovery of new antimicrobial agents is unable to meet the need for the treatment of bacterial infections caused by drug-resistant strains. The interaction of L12 and L10 is essential for ribosomal function and protein synthesis. In this study, a yeast two-hybrid system was established to successfully detect the interaction between L12 and L10 proteins from gram-negative bacteria Escherichia coli, which allows us to screen compounds that specifically disrupt this interaction. With this system, we identified two compounds IMB-84 and IMB-87 that block L12-L10 interaction and show bactericidal activity against E. coli. We used glutathione-S-transferase(GST) pull-down and surface plasmon resonance(SPR) assays to demonstrate that these compounds disrupt L12-L10 interaction in vitro and the target of compounds was further confirmed by the overexpression of target proteins. Moreover, protein synthesis and elongation factor G-dependent GTPase activities are inhibited by two compounds. Therefore, we have identified two antibacterial agents that disrupt L12-L10 interaction by using yeast two-hybrid system.

关键词： Yeast two-hybrid Escherichia coli Ribosome L12/L10 Antimicrobial agents

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Differences in MBUs induced by high-energy and medium-energy heavy ions in 28 nm FPGAs

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Nuclear Science and Techniques 2022年第9期33卷 28-36页

作者： Shuai Gao Jin-Hu yang Bing Ye Chang Cai Ze He Jie liu Tian-Qi liu Xiao-Yu yan You-Mei Sun Guo-Qing Xiao Institute of Modern Physics Chinese Academy of SciencesLanzhou 730000China University of Chinese Academy of Sciences Beijing 100049China State Key Laboratory of ASIC and System Fudan UniversityShanghai 201203China State Key Laboratory of Analog and Mixed-Signal VLSI University of MacaoMacao 999078China

Multiple-bit upsets(MBUs)have become a threat to modern advanced field-programmable gate arrays(FPGAs)applications in radiation ***,many investigations have been conducted using mediumenergy heavy ions to study the effects of MBU ***,high-energy heavy ions(HEHIs)greatly affect the size and percentage of MBUs because their ionizationtrack structures differ from those of medium-energy heavy *** this study,the different impacts of high-energy and medium-energy heavy ions on MBUs in 28 nm FPGAs as well as their mechanisms are thoroughly *** the Geant4 calculation,more serious energy effects of HEHIs on MBU scales were successfully *** addition,we identified worse MBU responses resulting from lowered *** MBU orientation effect was observed in the radiation of different *** broadened ionization tracks for tilted tests in different dimensions could result in different MBU *** results also revealed that the ionization tracks of tilted HEHIs have more severe impacts on the MBU scales than mediumenergy heavy ions with much higher linear energy ***,comprehensive radiation with HEHIs is indispensable for effective hardened designs to apply highdensity 28 nm FPGAs in deep space exploration.

关键词： FPGA High-energy heavy-ion radiation MBU Ionization track

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Dscam mutation leads to hydrocephalus and decreased motor function

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Protein & Cell 2011年第8期2卷 647-655页

作者： Yiliang Xu Haihong Ye yan Shen Qi Xu Li Zhu Jianghong liu Jane Y.Wu National Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Science and Peking Union Medical CollegeTsinghua UniversityBeijing 100084China The State Key Laboratory of Brain and Cognitive Science Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Department of Neurology Center of Genetic MedicineLurie Cancer CenterNorthwestern University Feinberg School of MedicineChicagoIL 60611USA

The nervous system is one of the most complicated organ systems in invertebrates and *** syndrome cell adhesion molecule(DSCAM)of the immunoglobulin(Ig)superfamily is expressed widely in the nervous system during embryonic *** studies in Drosophila suggest that Dscam plays important roles in neural development including axon branching,dendritic tiling and cell ***,the function of the mammalian DSCAM gene in the formation of the nervous system remains ***,we show that Dscam^(del17) mutant mice exhibit severe hydrocephalus,decreased motor function and impaired motor learning *** data indicate that the mammalian DSCAM gene is critical for the formation of the central nervous system.

关键词： Down syndrome cell adhesion molecule motor function motor learning hydrocephalus

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Immunity Genes and Susceptibility to Otitis Media:A Comprehensive Review

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Journal of Genetics and Genomics 2014年第11期41卷 567-581页

作者： Rahul Mittal Giannina Robalino Robert Gerring Brandon Chan Denise yan M'hamed Grati Xue-Zhong liu Department of Otolaryngology University of Miami Miller School of Medicine Department of Human Genetics University of Miami Miller School of Medicine Department of Biochemistry University of Miami Miller School of Medicine

Otitis media （OM） is a middle ear infection associated with inflammation and pain. This disease frequently afflicts humans and is the major cause of hearing loss worldwide. OM continues to be one of the most challenging diseases in the medical field due to its diverse host targets and wide range of clinical manifestations. Substantial morbidity associated with OM is further exacerbated by high frequency of recurrent infections leading to chronic suppurative otitis media （CSOM）. Children have greater susceptibility to, and thus, suffer most frequently from OM, which can cause significant deterioration in quality of life. Genetic factors have been demonstrated, in large part by twin and family studies, to be key determinants of OM susceptibility. In this review, we summarize the current knowledge on immunity genes and selected variants that have been associated with predisposition to OM. In particular, polymorphisms in innate immunity and cytokine genes have been strongly linked with the risk of developing OM. Future studies employing state-of-the-art technologies, including next-generation sequencing （NGS）, will aid in the identification of novel genes associated with susceptibility to OM. This, in turn, will open up avenues for identifying high-risk individuals and designing novel therapeutic strategies based on precise targeting of these genes.

关键词： Otitis media Genetics Innate immunity Cytokines

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Test of newly developed conceptual hydrological model for simulation of rain-on-snow events in forested watershed

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Water Science and Engineering 2013年第1期6卷 31-43页

作者： Si-min QU Han liu yan-ping CUI Peng SHI Wei-min BAO Zhong-bo YU State Key Laboratory of Hydrology-Water Resources and Hydraulic Engineering Hohai University College of Hydrology and Water Resources Hohai University Department of Forest Engineering Resources and ManagementOregon State UniversityCorvallisOR 97331USA

A conceptual hydrological model that links the Xin＇anjiang hydrological model and a physically based snow energy and mass balance model, described as the XINSNOBAL model, was developed in this study for simulating rain-on-snow events that commonly occur in the Pacific Northwest of the United States. The resultant model was applied to the Lookout Creek Watershed in the H. J. Andrews Experimental Forest in the western Cascade Mountains of Oregon, and its ability to simulate streamflow was evaluated. The simulation was conducted at 24-hour and one-hour time scales for the period of 1996 to 2005. The results indicated that runoffand peak discharge could be underestimated if snowpack accumulation and snowmelt under rain-on-snow conditions were not taken into account. The average deterministic coefficient of the hourly model in streamflow simulation in the calibration stage was 0.837, which was significantly improved over the value of 0.762 when the Xin＇anjiang model was used alone. Good simulation performance of the XINSNOBAL model in the WS 10 catchment, using the calibrated parameter of the Lookout Creek Watershed for proxy-basin testing, demonstrates that transplanting model parameters between similar watersheds can orovide a useful tool for discharge forecastin~, in un^au^ed basins.

关键词： Xin 'anjiang model " snow energy and mass balance model " rain-on-snow event " H. J.Andrews Experimental Forest

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Intestinal toxicity of deoxynivalenol is limited by supplementation with Lactobacillus plantarum JM113 and consequentially altered gut microbiota in broiler chickens

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Journal of Animal Science and Biotechnology 2019年第1期10卷 218-230页

作者： Shengru Wu yanli liu Yongle Duan Fangyuan Wang Fangshen Guo Fang yan Xiaojun yang Xin yang College of Animal Science and Technology Northwest A&F University College of animal science and Technology Hebei Agricultural University

Background: Limited research has focused on the effect of Lactobacillus on the intestinal toxicity of deoxynivalenol(DON).The present study was conducted to investigate the role of Lactobacillus plantarum(***) JM113 in protecting against the intestinal toxicity caused by ***: A total of 144 one-day-old healthy Arbor Acres broilers were randomly distributed into 3 treatments,including the CON(basal diet),the DON(extra 10 mg/kg deoxynivalenol),and the DL(extra 1 × 109 CFU/kg *** JM113 based on DON group) *** growth performance,organ indexes,intestinal morphology,pancreatic digestive enzymes,intestinal secreted immunoglobulin A(sIgA),jejunal transcriptome,and intestinal microbiota were ***: Compared with the CON and DL groups,the DON supplementation altered intestinal morphology,especially in duodenum and jejunum,where villi were shorter and crypts were deeper(P < 0.05).Meanwhile,the significantly decreased mRNA expression of jejunal claudin-1 and occludin(P < 0.05),ileal rBAT and jejunal GLUT1 of 21-day-old broilers(P < 0.05),as well as duodenal PepT1 and ileal rBAT of 42-day-old broilers were identified in the DON ***,supplementation with *** JM113 could increase duodenal expression of IL-10 and IL-12 of 21-dayold broilers,ileal s IgA of 42-day-old broilers,and the bursa of Fabricius index of 21-day-old *** jejunal transcriptome proved that the genes related to the intestinal absorption and metabolism were significantly reduced in the DON group but a significant increase when supplemented with extra *** ***,the bacteria related to nutrient utilization,including the Proteobacteria,Escherichia,Cc-115(P < 0.05),Lactobacillus and Prevotella(P < 0.1) were all decreased in the DON *** contrast,supplementation with *** JM113 increased the relative abundance of beneficial bacterium,including the Bacteroidetes,Roseburia,Anaerofustis,Anaerostipe,and Ruminococcus

关键词： Broiler chickens Deoxynivalenol Gut microbiota Lactobacillus plantarum JM113 mRNA sequencing 16S rRNA gene sequencing

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1 T moderate intensity static magnetic field affects Akt/mTOR pathway and increases the antitumor efficacy of m TOR inhibitors in CNE-2Z cells

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Science Bulletin 2015年第24期60卷 2120-2128页

作者： Lei Zhang Xingxing yang Juanjuan liu yan Luo Zhiyuan Li Xinmiao Ji Wenchao Wang Xin Zhang High Magnetic Field Laboratory Chinese Academy of Sciences University of Science and Technology of China

Static magnetic field （SMF） has been known to affect cell proliferation in a cell-type-dependent manner, while the mechanism still remains unclear. We found that 1 T moderate intensity SMF inhibits cell proliferation of nasopharyngeal carcinoma CNE-2Z cells and the Akt/ mTOR signaling pathway, which is upregulated in many cancers, roTOR inhibitors are potential chemodrugs, but their clinical effects are limited by the feedback reactiva- tion of other signaling components such as EGFR and Akt. We showed that 1 T SMF increases the antitumor efficacy of mTOR inhibitor Torin 2. In addition, 1 T SMF increases the inhibition efficiency on roTOR substrates phosphorylation and represses the mTOR inhibitor-induced feedback reactivation of EGFR and Akt. Our study not only demonstrates that mTOR/Akt pathway is one of the molecular targets of SMFs in cells, but also reveals the clinical potentials of combinations of roTOR inhibitors and SMFs in cancer treatment.

关键词： Static magnetic field - Cell proliferationmTOR mTOR inhibitor - Feedback reactivation

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variation in expression of small ubiquitin-like modifiers in injured sciatic nerve of mice

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Neural Regeneration Research 2019年第8期14卷 1455-1461页

作者： Dian-Ying Zhang Kai Yu Zhong yang Xiao-Zhi liu Xiao-Fang Ma yan-Xia Li Department of Orthopedics and Trauma People's Hospital Peking University Beijing China Department of Orthopedics Tianjin Fifth Central Hospital Tianjin China Central Laboratory Tianjin Fifth Central Hosp让al Tianjin China

Small ubiquitin-like modifiers (SUMOs) have been shown to regulate axonal regeneration, signal transduction, neuronal migration, and myelination, by covalently and reversibly attaching to the protein substrates during neuronal cell growth, development, and differentiation. It has not been reported whether SUMOs play a role in peripheral nerve injury and regeneration. To investigate any association between SUMOylation and potential neuroprotective effects during peripheral nerve injury and regeneration, C57/BL mice were randomly divided into sham and experimental groups. The sciatic nerve was exposed only in the sham group. The experimental group underwent neurotomy and epineurial neurorrhaphy. Real-time quantitative polymerase chain reaction and western blot assay results revealed different mRNA and protein expression levels of SUMO1, SUMO2, SUM03 and UBC9 in sciatic nerve tissue (containing both 5 mm of proximal and distal stumps at the injury site) at various time points after injury. Compared with the sham group, protein levels of SUM01 and SUMO2/3 increased in both their covalent and free states after sciatic nerve injury in the experimental group, especially in the covalent state. UBC9 protein levels showed similar changes to those of SUMO1 and SUMO2/3 in the covalent states. Immunohistochemical staining demonstrated that SUMO1 and SUMO2/3 immunopositivities were higher in the experimental group than in the sham group. Our results verified that during the repair of sciatic nerve injury, the mRNA and protein expression of SUMO1, SUMO2, SUMO3 and UBC9 in injured nerve tissues changed in varying patterns and there were clear changes in the expression of SUMO-related proteins. These findings reveal that SUMOs possibly play an important role in the repair of peripheral nerve injury. All animal protocols were approved by the Institutional Animal Care and Use Committee of Tianjin Fifth Central Hospital, China (approval No. TJWZXLL2018041) on November & 2018.

关键词： nerve regeneration peripheral nerve injury sciatic nerve SUMO1 SUMO2/3 UBC9 SUMOylation epineurial neurorrhaphy neural regeneration

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Effect and Safety of Acupuncture for Type 2 Diabetes Mellitus:A Systematic Review and Meta-analysis of 21 Randomised Controlled Trials

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Chinese Journal of Integrative Medicine 2022年第5期28卷 463-471页

作者： LI Shu-qing CHEN Jian-rong liu Mei-lu WANG yan-ping ZHOU Xu SUN Xin Evidence-Based Medicine Research Centre Jiangxi University of Traditional Chinese MedicineNanchang(330004)China Department of Endocrinology the First Affiliated Hospital of Nanchang UniversityNanchang(330006)China Department of Integrated Chinese and Western Medicine West China HospitalSichuan UniversityChengdu(610041)China Chinese Evidence-Based Medicine Centre West China HospitalSichuan UniversityChengdu(610041)China

Objective:To evaluate the effects of acupuncture on hypoglycaemic outcomes in type 2 diabetes mellitus(T2 DM).Methods:Pub Med,Embase,Cochrane Library,and Clinical *** were searched from inception up to July 2020,to identify randomised controlled trials(RCTs)that enrolled patients with T2 DM and compared acupuncture combined with antidiabetic drugs to antidiabetic drugs *** primary outcomes were haemoglobin A1 c(Hb A1 c)and fasting blood glucose(FBG).The secondary outcomes included 2-h blood glucose(2 h BG),fasting insulin(FINS),homeostatic model assessment for insulin resistance(HOMA-IR),and acupuncture-related adverse *** difference(MD)and 95%confidence interval(CI)were used as the effect measure in the *** quality of evidence was assessed using the Grading of Recommendations Assessment,Development and Evaluation ***:Twenty-one RCTs(n=1,188)were *** meta-analytic results showed that the acupuncture group had greater reductions in FBG(MD-6.46 mg/d L,95%CI-11.95 to-0.98;moderate-quality evidence)and HOMA-IR(MD-1.23,95%CI-2.16 to-0.31;low-quality evidence),but comparable changes in Hb A1 c(MD-0.39%,95%CI-0.84 to 1.61;very-low-quality evidence),2 h BG(MD-4.99 mg/d L,95%CI-20.74 to 10.76;low-quality evidence),and FINS(MD-1.32μIU/m L,95%CI-3.76 to 1.12;low-quality evidence).No data on the incidence of diabetic complications were *** acupuncture-related adverse events reported were ***:The current evidence suggests that acupuncture,as a complementary therapy to antidiabetic drugs,has a small but statistically significant effect on decreasing FBG and improving insulin *** effects of acupuncture on Hb A1 c,2 h BG,and FINS remain *** is generally safe in patients with mild *** evidence for the long-term effects of acupuncture on T2 DM is needed.(Registration ***42018115639)

关键词： acupuncture type 2 diabetes mellitus systematic review meta-analysis

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Response of carbon footprint to plastic film mulch application in spring maize production and mitigation strategy

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Journal of Integrative Agriculture 2021年第7期20卷 1933-1943页

作者： CHEN Bao-qing Shahar BARAM DONG Wen-yi HE Wen-qing liu En-ke yan Chang-rong Institute of Environment and Sustainable Development in Agriculture Chinese Academy of Agricultural SciencesBeijing 100081P.R.China Institute for Soil Water and Environmental SciencesAgricultural Research Organization(ARO)Volcani Research CenterBet Dagan 50250Israel

Producing more food with a lower environmental cost is one of the most crucial challenges worldwide. Plastic mulching has developed as one of the most dominant practices to improve crop yields, however its impacts on greenhouse gas(GHG) emissions during the production life cycle of a crop are still unclear. The objective of this work is to quantify the impacts of plastic film on GHG emissions and to reduce GHG emissions with innovative agronomic practices. Carbon footprint per unit of area(CFa), per unit of maize grain yield(CFy), and per unit of economic output(CFe) were evaluated for three maize cultivation systems: a no mulch system, a conventional plastic mulching system(PM) and a biennial plastic mulching pattern, namely a ’one film for 2 years’ system(PM2), during 2015–2018 in a maize field located on the Loess Plateau of China. The results suggested that PM induced a 24% improvement in maize yields during the four experimental years compared to a no-mulch treatment(NM). However, PM dramatically increased the CFa by 69%, 59% of which was created by the input of the plastic film material, and 10% was created by increases in the soil N2O emissions. The yield improvements from PM could not offset the increases in CFa, and CFy and CFe were both increased by 36%. Shifting from PM to PM2 did not reduce crop yields, but it led to a 21% reduction in CFa and 23% reductions in CFy and CFe due to the reduced input amount of plastic film, decreased soil N2O emissions, and less diesel oil used for tillage. Compared to NM, CFy and CFe were only 5% higher in PM2. This study highlights the necessity of reducing the amount of plastic film input in the development of low-carbon agriculture and shifting from conventional PM cultivation to PM2 could be an efficient option for mitigating GHG emissions while sustaining high crop yields in plastic mulched fields.

关键词： carbon footprint greenhouse gas plastic film maize

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