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NeoI represents a group of transcriptional repressors regulating the biosynthesis of multiple aminoglycosides

Science China Life Sciences 2024年

作者： Yue Li Xiangxi Meng Dong Li Xiulei Xia Jihui Zhang Yihua Chen Huarong Tan State Key Laboratory of Microbial Resources Institute of Microbiology Chinese Academy of Sciences University of Chinese Academy of Sciences

In general, the initiation or closure of antibiotic biosynthesis is determined by regulatory proteins, but most of their mechanisms of action remain unknown. The 2-deoxystreptamine-containing aminoglycosides（2-DOS AGs） form a unique category among antibiotics. Genomic analysis revealed that a group of hypothetical regulatory genes represented by neoI are widely distributed in the biosynthetic gene clusters（BGCs） of natural products from Streptomyces species, including several 2-DOS AGs. Only limited knowledge is available for the roles of NeoItype regulators although neomycin and some of the related AGs have been developed as therapeutic drugs for decades. This study focuses on the functional determination of neoI and its homologues situated in the BGCs of six AGs. We found that the yield of neomycin in neoI disruption mutant（ΔneoI） increased by 50% compared to the wild-type（WT） strain(（420.6±44.1） mg L-1), while it was partially restored by the complementation of neoI, demonstrating that NeoI acted as a repressor in neomycin biosynthesis. Further electrophoretic mobility shift assays（EMSAs） and DNase I footprinting assays indicated that NeoI could specifically bind to the promoter region between neoE and neoI with conserved nucleotides（5'-CVHYMRCHDKAGYGGACR-3'）, as determined by site-directed mutagenesis. Interestingly, cross-bindings of the NeoI homologues from the six different BGCs to their corresponding DNA targets were manifested, and the five exogenous NeoI homologues could complement NeoI function of repressing neomycin biosynthesis. Our results suggested that NeoI-type regulators represent widespread and conservative regulatory characteristics in the biosynthesis of 2-DOS AGs, which would be significant for optimizing the biosynthetic pathways of valuable commercialized aminoglycoside antibiotics.

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A flexible,modular and versatile functional part assembly toolkit for gene cluster engineering in Streptomyces

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Synthetic and Systems Biotechnology 2024年第1期9卷 69-77页

作者： Xuejin Zhao Yeqing Zong Qiuli Lou Chenrui Qin Chunbo Lou CAS Key Laboratory of Pathogenic microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing100101China CAS Key Laboratory of Microbial Physiological and Metabolic Engineering Institute of MicrobiologyChinese Academy of SciencesBeijing100101China Center for Cell and Gene Circuit Design Key Laboratory of Quantitative Synthetic BiologyShenzhen Institute of Synthetic BiologyShenzhen Institutes of Advanced TechnologyChinese Academy of Sciences1068 Xueyuan AvenueUniversity TownNanshanShenzhen518055China Peking-Tsinghua Joint Center for Life Sciences Peking UniversityBeijing100871China Center for Quantitative Biology Academy for Advanced Interdisciplinary StudiesSchool of PhysicsPeking UniversityBeijing100871China College of Life Sciences University of Chinese Academy of SciencesBeijing100149China

Streptomyces has enormous potential to produce novel natural products(NPs)as it harbors a huge reservoir of uncharacterized and silent natural product biosynthetic gene clusters(BGCs).However,the lack of efficient gene cluster engineering strategies has hampered the pace of new drug ***,we developed an easy-to-use,highly flexible DNA assembly toolkit for gene cluster *** DNA assembly toolkit is compatible with various DNA assembling approaches including Biobrick,Golden Gate,CATCH,yeast homologous recombination-based DNA assembly and homing endonuclease-mediated *** compatibility offers great flexibility in handling multiple genetic parts or refactoring large gene *** demonstrate the utility of this toolkit,we quantified a library of modular regulatory parts,and engineered a gene cluster(act)using characterized promoters that led to increased ***,this work provides a powerful part assembly toolkit that can be used for natural product discovery and optimization in Streptomyces.

关键词： Streptomyces Standard toolkit DNA assembly Gene cluster Synthetic biology

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Characterization of a pangolin SARS-CoV-2-related virus isolate that uses the human ACE2 receptor

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Science China(Life Sciences) 2024年第7期67卷 1502-1513页

作者： Luo-Yuan Xia Xue-Feng Wang Xiao-Ming Cui Yi-Ming Zhang Zhen-Fei Wang En-Tao Li Chang-Fa Fan Ke Song Yuan-Guo Li Run-Ze Ye Fang-Xu Li Dai-Yun Zhu Jie Zhang Zhuang-Zhuang Shi Ming-Zhu Zhang Liang-Jing Li Shi-Jing Shen Song Jin Ya-Wei Zhang Wei-Guang Fu Lin Zhao Wen-Hao Wang Tie-Cheng Wang You-Chun Wang Jia-Fu Jiang Yan-Ling Hu Na Jia Yu-Wei Gao Wu-Chun Cao Institute of EcoHealth School of Public HealthCheeloo College of MedicineShandong UniversityJinan 250012China Changchun Veterinary research Institute Changchun 130122China State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyBeijing 100071China Division of Animal Model research Institute for Laboratory Animal ResourcesNational Institutes for Food and Drug ControlBeijing 102629China National Institutes for Food and Drug Control Beijing 102629China Life Sciences Institute Guangxi Medical UniversityNanning 530020China College of Life Sciences Shandong Normal UniversityJinan 250014China research Unit of Discovery and Tracing of Natural Focus Diseases Chinese Academy of Medical SciencesBeijing 100071China

Various SARS-CoV-2-related coronaviruses have been increasingly identified in pangolins,showing a potential threat to *** we report the infectivity and pathogenicity of the SARS-CoV-2-related virus,PCoV-GX/P2V,which was isolated from a Malayan pangolin(Manis javanica).PCoV-GX/P2V could grow in human hepatoma,colorectal adenocarcinoma cells,and human primary nasal epithelial *** replicated more efficiently in cells expressing human angiotensin-converting enzyme 2(hACE2)as SARS-CoV-2 *** intranasal inoculation to the hACE2-transgenic mice,PCoV-GX/P2V not only replicated in nasal turbinate and lungs,but also caused interstitial pneumonia,characterized by infiltration of mixed inflammatory cells and multifocal alveolar *** population immunity established by SARS-CoV-2 infection and vaccination may not protect people from PCoV-GX/P2V *** findings further verify the hACE2 utility of PCoV-GX/P2V by in vivo experiments using authentic viruses and highlight the importance for intensive surveillance to prevent possible cross-species transmission.

关键词： pangolin SARS-CoV-2-related virus infectivity pathogenicity human cell lines human ACE2 receptor hACE2-transgenic mice

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Individualized anti-thrombotic therapy for acute myocardial infarction complicated with left ventricular thrombus: A case report

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World Journal of Clinical Cases 2024年第4期12卷 835-841页

作者： Yan Song Hua Li Xia Zhang Lei Wang Hong-Yan Xu Zhi-Chao Lu Xiao-Gang Wang Bo Liu Department of Clinical Pharmacy Zibo Municipal HospitalZibo 255400Shandong ProvinceChina Department of Cardiology Zibo Municipal HospitalZibo 255400Shandong ProvinceChina Department of Pharmacy Zibo Municipal HospitalZibo 255400Shandong ProvinceChina Department of Imaging Zibo Municipal HospitalZibo 255400Shandong ProvinceChina Department of Pulmonary and Critical Care Medicine Department of Clinical MicrobiologyZibo City Key Laboratory of Respiratory Infection and Clinical MicrobiologyZibo City Engineering Technology Research Center of Etiology Molecular DiagnosisZibo Municipal HospitalZibo 255400Shandong ProvinceChina

BACKGROUND Presently,there is no established standard anti-blood clot therapy for patients facing acute myocardial infarction(AMI)complicated by left ventricular thrombus(LVT).While vitamin K antagonists are the preferred choice for oral blood thinning,determining the best course of blood-thinning medication remains *** is unclear if non-vitamin K antagonist oral blood thinners have different effectiveness in treating *** study significantly contributes to the medical *** SUMMARY The blood-thinning treatment of a patient with AMI and LVT was *** blood-thinning therapy included daily enteric-coated aspirin tablets at 0.1 g,daily clopidogrel hydrogen sulfate at 75 mg,and dabigatran etexilate at 110 mg twice *** 15 d,the patient’s LVT did not decrease but instead *** pharmacists comprehensively analyzed the cases from the perspective of the patient’s disease status and drug *** drug regimen was reformulated for the patient,replacing dabigatran etexilate with warfarin,and was administered for six *** clinical pharmacist provided the patient with professional and standardized pharmaceutical *** patient’s condition was discharged after meeting the international normalized ratio value(2-3)*** patient fully complied with the follow-up,and the time in the therapeutic range was 78.57%,with no serious adverse effects during pharmaceutical *** Warfarin proves to be an effective drug for patients with AMI complicated by LVT,and its blood-thinning course lasts for six months.

关键词： Myocardial infarction Left ventricular thrombus Dabigatran etexilate Warfarin Clinical pharmacist Case report

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Mice with type I interferon signaling deficiency are prone to epilepsy upon HSV-1 infection

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Virologica Sinica 2024年第2期39卷 251-263页

作者： Wei Yang Chong-Yang Tang Dong-Ying Fan Yi-Song Wang Pei-Gang Wang Jing An Guo-Ming Luan Beijing Key Laboratory of Epilepsy Sanbo Brain HospitalCapital Medical UniversityBeijing100093China Beijing Institute for Brain Disorders Capital Medical UniversityBeijing100093China Department of Neurosurgery Epilepsy CenterSanbo Brain HospitalCapital Medical UniversityBeijing100093China Department of microbiology School of Basic Medical SciencesCapital Medical UniversityBeijing100069China Chinese Institute for Brain research Beijing102206China

Viral encephalitis continues to be a significant public health *** our previous study,we discovered a lower expression of antiviral factors,such as IFN-β,STING and IFI16,in the brain tissues of patients with Rasmussen's encephalitis(RE),a rare chronic neurological disorder often occurred in children,characterized by unihemispheric brain ***,a higher cumulative viral score of human herpes viruses(HHVs)was also found to have a significant positive correlation with the unihemispheric atrophy in *** I IFNs(IFN-I)signaling is essential for innate anti-infection response by binding to IFN-α/βreceptor(IFNAR).In this study,we infected WT mice and IFNAR-deficient A6 mice with herpes simplex virus 1(HSV-1)via periocular injection to investigate the relationship between IFN-I signaling and HHVs-induced brain *** all mice exhibited typical viral encephalitis lesions in their brains,HSV-induced epilepsy was only observed in A6 *** gene expression matrix,functional enrichment analysis and protein-protein interaction network revealed four gene models that were positively related with HSV-induced ***,ten key genes with the highest scores were *** together,these findings indicate that intact IFN-I signaling can effectively limit HHVs induced neural symptoms and brain lesions,thereby confirming the positive correlation between IFN-I signaling repression and brain atrophy in RE and other HHVs encephalitis.

关键词： IFN-I signaling Human herpes viruses(HHVs) Rasmussen's encephalitis(RE)

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Studies of polyol production by the yeast Yarrowia lipolytica growing on crude glycerol under stressful conditions

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Carbon Resources Conversion 2024年第3期7卷 17-31,F0004页

作者： Eleni-Stavroula Vastaroucha Nikolaos G.Stoforos George Aggelis Seraphim Papanikolaou Department of Food Science and Human Nutrition Agricultural University of Athens75 Iera Odos11855AthensGreece Unit of microbiology Department of BiologyUniversity of Patras26504 Rio PatrasGreece

Crude glycerol,the principal by-product of biodiesel production process,was employed as substrate by three wild-type Yarrowia lipolytica strains(ACA-YC 5030,LMBF 20 and NRRL Y-323).Stressful conditions(low pH value=2.0±0.3,low incubation temperature T=20±1℃,non-aseptic conditions)were ***-esting production of yeast biomass and polyols(***,mannitol and arabitol)was noted at pH=2.0±0.3 and T=20±1℃.Strains failed to produce significant quantities of cellular lipid,while variable quantities of intra-cellular polysaccharides were *** under previously pasteurized media supported significant biomass and polyols production for most of the tested strains,while only one strain(NRRL Y-323),managed to produce polyols at media that were not previously thermally treated at *** production of mannitol was favored at low initial glycerol(Glol0)concentrations,whereas higher Glol0 quantities favored the biosynthesis of *** the strain NRRL Y-323,highly aerated/agitated bioreactor trials showed different physiological profiles as compared to the respective flask ***,in flask experiments with the strain NRRL Y-323 at high Glol0 amounts(≈140 g/L)at low medium pH(=2.0±0.3),a significant production of polyols(=84.2 g/L)with the corresponding remarkable conversion yield on glycerol consumed=62%w/w was *** application:Renewable and biodegradable fuels,such as biodiesel,are safer and environmentally friendlier than the conventional petroleum *** is a cost-effective substrate obtained as the main side-product from biodiesel production process and is currently being employed in the realm of Industrial Microbi-ology and Biotechnology to produce metabolic products with added *** research focuses on using glycerol as a starting substrate for biotechnological conversions aiming at producing,amongst other compounds,polyols,microbial biomass,citric acid,*** selected strains of the Generall

关键词： Biomass Glycerol Polyols Yarrowia lipolytica

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Analysis of a diffusive two-strain malaria model with the carrying capacity of the environment for mosquitoes

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Infectious Disease Modelling 2024年第3期9卷 931-962页

作者： Jinliang Wang Wenjing Wu Yuming Chen Engineering research Center of Agricultural microbiology Technology Ministry of Education&Heilongjiang Provincial Key Laboratory of Ecological Restoration and Resource Utilization for Cold Region&School of Mathematical ScienceHeilongjiang UniversityHarbin150080PR China Department of Mathematics Wilfrid Laurier UniversityWaterlooOntarioN2L 3C5Canada

We propose a malaria model involving the sensitive and resistant strains,which is described by reaction-diffusion *** model reflects the scenario that the vector and host populations disperse with distinct diffusion rates,susceptible individuals or vectors cannot be infected by both strains simultaneously,and the vector population satisfies the logistic *** main purpose is to get a threshold type result on the model,especially the interaction effect of the two strains in the presence of spatial *** solve this issue,the basic reproduction number(BRN)R_(0)^(i)and invasion reproduction number(IRN)R_(0)^(i)of each strain(i=1 and 2 are for the sensitive and resistant strains,respectively)are ***,we investigate the influence of the diffusion rates of populations and vectors on BRNs and IRNs.

关键词： Threshold dynamics Two-strain malaria model Competition and coexistence Reproduction number

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A review on the parasitic isopod genus Notophryxus ***,1883(Crustacea:Isopoda),and first report of Notophryxus globularis ***,1885 from Lakshadweep Sea(Amini Island)

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Acta Oceanologica Sinica 2024年第8期43卷 142-153页

作者： Mukkattu Nazar Suhaana Jaime Gómez-Gutiérrez Paravanparambil Rajakumar Jayachandran Punnakkal Hari Praved Sivasankaran Bijoy Nandan Department of Marine Biology Microbiology and BiochemistrySchool of Marine SciencesCochin University of Science and TechnologyKochi-Kerala 682016India Departamento de Plancton y Ecología Marina Centro Interdisciplinario de Ciencias MarinasInstituto Politécnico NacionalLa Paz B.C.S.23096Mexico Applied research Centre for Environment and Marine Studies King Fahd University of Petroleum and MineralsDhahran 31261Saudi Arabia

Isopod crustaceans of the family Dajidae are exclusively marine *** genus Notophryxus ***,1883 currently includes nine nominal species,which are very rarely reported as the chances for encountering these specimens are *** comprehension of the taxonomy,biology,ecology,and life cycle of species belonging to the Notophryxus genus is notably *** nominal species of Notophryxus genus are reviewed here to obtain a comprehensive and integrative taxonomic understanding of this genus,in an attempt to address the *** paper also documents the rediscovery of an ectoparasitic isopod from the genus Notophryxus in Indian waters,after 55 *** isopod specimens obtained from the outer reefs of Amini Island in the Lakshadweep archipelago,Southeastern Arabian Sea,display morphological congruence to Notophryxus globularis ***,*** only previous report on this species dates back to 1885 from ***'description of *** as an ectoparasite on the euphausiid Thysanoessa gregaria ***,1883 in the North *** discovery represents a range extension of *** from the North Pacific to the Arabian *** cryptoniscid larvae and three adult females of ***(with dwarf males)were found attached to four adult mysid specimens of Siriella aequiremis Hansen,*** present study provides an improved diagnosis of *** with the aid of light microscopy images and line drawings which was not given in the original ***,1885 *** research also provides a concise description of cryptoniscid larvae from the same sampling location and same host which is most likely to be *** larvae.

关键词： Dajiidae Mysid cryptoniscan larvae Southeastern Arabian Sea Notophryxus

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Genetic diversity and occult hepatitis B infection in Africa: A comprehensive review

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World Journal of Hepatology 2024年第5期16卷 843-859页

作者： Michee M Bazie Mahamoudou Sanou Florencia Wendkuuni Djigma Tegwinde Rebeca Compaore Dorcas Obiri-Yeboah Benoît Kabamba Bolni Marius Nagalo Jacques Simpore Rasmata Ouédraogo Department of Medicine Transmissible Diseases LaboratoryUniversitéJoseph KI-ZERBOOuagadougou 0000Burkina Faso Department of Biochemistry and microbiology Molecular Biology and Genetics LaboratoryUniversity Joseph KI-ZERBOOuagadougou 0000Burkina Faso Infectious and parasitic disease Laboratory Health Sciences Research InstituteIRSS/CNRSTNational Center for Scientific and Technological ResearchOuagadougou 0000Burkina Faso Department of microbiology and Immunology School of Medical SciencesUniversity of Cape CoastPMBCape Coast 0000Ghana Department of Clinical Biology Virology LaboratoryCliniques Universitaires Saint LucUniversitéCatholique de LouvainBruxelles 0000Belgium Division of Hematology and Oncology Mayo ClinicAZ 0000United States

BACKGROUND Occult hepatitis B infection(OBI)is a globally prevalent infection,with its frequency being influenced by the prevalence of hepatitis B virus(HBV)infection in a particular geographic region,including *** can be transmitted th-rough blood transfusions and organ transplants and has been linked to the development of hepatocellular carcinoma(HCC).The associated HBV genotype influences the *** To highlight the genetic diversity and prevalence of OBI in *** This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and involved a comprehensive search on PubMed,Google Scholar,Science Direct,and African Journals Online for published studies on the prevalence and genetic diversity of OBI in *** The synthesis included 83 articles,revealing that the prevalence of OBI varied between countries and population groups,with the highest prevalence being 90.9%in patients with hepatitis C virus infection and 38%in blood donors,indicating an increased risk of HBV transmission through blood *** of OBI reactivation have been reported following *** D is the predominant,followed by genotypes A and *** This review highlights the prevalence of OBI in Africa,which varies across countries and population *** study also demonstrates that genotype D is the most prevalent.

关键词： Occult hepatitis B infection Blood transfusion Genetic diversity

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Expression and Prognostic Potential of ESR1 in Breast Cancer

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Proceedings of Anticancer research 2024年第5期8卷 146-158页

作者： Muhammad Akram Department of microbiology King Saud UniversitySaudi Arabia

This study aims to explore the potential of ESR1 as a biomarker in breast cancer(BRCA)using bioinformatics analysis *** up-regulation of ESR1 expression in BRCA was investigated using UALCAN and GEPIA2,illustrating its role in BRCA ***,analyses based on various variables such as gender,age,race,and pathological stages of BRCA patients revealed a consistent up-regulation of ESR1,emphasizing its role in the development and progression of ***,an analysis of ESR1 promoter methylation levels across various parameters revealed hypomethylation,affirming the inverse correlation between methylation and ESR1 *** analysis further indicated that overexpression of ESR1 is associated with poor overall survival,highlighting its potential as a prognostic biomarker in ***,genetic mutation analysis using cBioPortal disclosed a minor role of ESR1 genetic mutations in BRCA,with only 2.5%of genetic alterations *** STRING and DAVID tools were utilized to conduct pathway enrichment analysis,revealing diverse biological functions of ESR1 and its 10 interconnected ***,these results underscore the significance of understanding ESR1 up-regulation in BRCA and demonstrate its potential as a therapeutic,diagnostic,and prognostic biomarker.

关键词： Breast cancer ESR1 Biomarker Bioinformatics analysis

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