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SARS-CoV-2 aberrantly elevates mitochondrial bioenergetics to induce robust virus propagation

Signal Transduction and Targeted Therapy 2024年第6期9卷 2702-2715页

作者： Hye Jin Shin Wooseong Lee Keun Bon Ku Gun Young Yoon Hyun-Woo Moon Chonsaeng kim mi-Hwa kim Yoon-Sun Yi Sangmi Jun Bum-Tae kim Jong-Won Oh Aleem Siddiqui Seong-Jun kim Department of Convergent Research of Emerging Virus Infection Korea Research Institute of Chemical TechnologyDaejeon 34114Republic of Korea Gyeongnam Biohealth Research Center Gyeongnam Branch InstituteKorea Institute of ToxicologyJinju 52834Republic of Korea Center for Research Equipment Korea Basic Science InstituteCheongjuChungcheongbuk-do 28119Republic of Korea Department of Biotechnology Yonsei UniversitySeoul 03722Republic of Korea Division of Infectious Diseases School of MedicineUniversity of CaliforniaSan DiegoLa JollaCA 92093USA Present address:Department of microbiology Chungnam National University School of MedicineDaejeon 35015Republic of Korea

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a‘highly transmissible respiratory pathogen,leading to severe multiorgan ***,knowledge regarding SARS-CoV-2-induced cellular alterations is *** this study,we report that SARSCoV-2 aberrantly elevates mitochondrial bioenergetics and activates the EGFR-mediated cell survival signal cascade during the early stage of viral ***-CoV-2 causes an increase in mitochondrial transmembrane potential via the SARS-CoV-2 RNAnucleocapsid cluster,thereby abnormally promoting mitochondrial elongation and the OXPHOS process,followed by enhancing ATP ***,SARS-CoV-2 activates the EGFR signal cascade and subsequently induces mitochondrial EGFR trafficking,contributing to abnormal OXPHOS process and viral *** EGFR inhibitors remarkably reduce SARS-CoV-2 propagation,among which vandetanib exhibits the highest antiviral *** of SARS-CoV-2-infected cells with vandetanib decreases SARS-CoV-2-induced EGFR trafficking to the mitochondria and restores SARS-CoV-2-induced aberrant elevation in OXPHOS process and ATP generation,thereby resulting in the reduction of SARS-CoV-2 ***,oral administration of vandetanib to SARS-CoV-2-infected hACE2 transgenic mice reduces SARS-CoV-2 propagation in lung tissue and mitigates SARS-CoV-2-induced lung *** also exhibits potent antiviral activity against various SARS-CoV-2 variants of concern,including alpha,beta,delta and omicron,in in vitro cell culture *** together,our findings provide novel insight into SARS-CoV-2-induced alterations in mitochondrial dynamics and EGFR trafficking during the early stage of viral infection and their roles in robust SARS-CoV-2 propagation,suggesting that EGFR is an attractive host target for combating COVID-19.

关键词： alterations aberrant thereby

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The SARS-CoV-2 spike protein induces lung cancer migration and invasion in a TLR2-dependent manner

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Cancer Communications 2024年第2期44卷 273-277页

作者： mi-Jeong kim Ji Young kim Ji Hye Shin Juhee Son Yeeun Kang Soo-Kyung Jeong Duk-Hwan kim Kyun-Hwan kim Eunyoung Chun Ki-Young Lee Department of Immunology Samsung Biomedical Research InstituteSungkyunkwan University School of MedicineSuwonRepublic of Korea Research and Development Center CHA Vaccine InstituteSeongnam-siRepublic of Korea Department of Molecular Cell Biology Sungkyunkwan University School of MedicineSuwonRepublic of Korea Department of Precision Medicine Sungkyunkwan University School of MedicineSuwonRepublic of Korea Department of Health Sciences and Technology Samsung Advanced Institute for Health Sciences&TechnologySamsung Medical CenterSungkyunkwan UniversitySeoulRepublic of Korea

Dear editor,Severe acute respiratory syndrome coronavirus2(SARS-CoV-2)infection can lead to severe outcomes in patients with cancer[1].It has been reported that patients with lung cancers disproportionately manifest severe COVID-19 with a high rate of hospitalization and death[2].Notably,the SARS-CoV-2 Spike(S)protein can induce hyper-inflammation in both epithelial cells and macrophages through toll-like receptor(TLR)1/TLR2 or TLR2/6-dependent nuclear factor-kappaB(NF-κB)path-way[3].However,molecular and cellular evidence on whether the SARS-CoV-2 virus affects the severity of lung cancer patients through TLR1/2 or TLR2/6 signaling remains unclear.

关键词： lung TLR2 invasion

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Visible-light-activated N-doped CQDs/g-C3N4/Bi2WO6 nanocomposites with different component arrangements for the promoted degradation of hazardous vapors

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Journal of Materials Science & Technology 2020年第5期40卷 168-175页

作者： mi Gyeong kim Wan-Kuen Jo Department of Environmental Engineering Kyungpook National University 80 University RoadBukguDaegu702-701Republic of Korea

To investigate whether the arrangement of componentsin multi-composite photocatalysts may affect their photocatalytic properties,due to different charge-transfer routes,two ternary-nanocomposite photocatalysts with different component arrangements,comprising N-doped carbon quantum dots(NCQDs),g-C3N4(CN),and Bi2WO6(BWO)(hereafter referred to as NCQDs/CN/BWO),were developed,and the photocatalytic degradation of model hazardous vapors under visible-light illumination was *** I NCQDs/CN/BWO,which was developed by the combination of NCQDs/BWO and CN,exhibited photocatalytic ability superior to that of type II NCQDs/CN/BWO,which was developed by the combination of CN/BWO and NCQDs;the superior photocatalytic ability corresponded to the dual properties of NCQDs:charge mediation and upconversion ***,the photocatalytic ability of NCQDs/CN/BWO was greater than those of the reference catalysts;in addition,this photocatalyst exhibited outstanding photochemical ***,the effects of CN/(BWO+CN)weight ratio of the CN/BWO dual nanocomposites and the NCQDs/(BWO+CN+NCQDs)weight percentage of NCQDs/CN/BWO ternary nanocomposites on the pollutant removal efficiency were *** plausible mechanisms over the two NCQDs/CN/BWO photocatalysts for the degradation of hazardous vapors were *** component arrangement approach proposed herein afforded a technique toward the perceptive development of novel multi-component heterostructures for the photocatalytic degradation of hazardous vapors.

关键词： Component arrangement Charge-transfer route NCQDs dual role Charge mediator Upconversion photoluminescence

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Insulinotrophic and hypolipidemic effects of Ecklonia cava in streptozotocin-induced diabetic mice

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Asian Pacific Journal of Tropical Medicine 2012年第5期5卷 374-379页

作者： mi-Ja kim Hye Kyung kim Department of Food and Biotechnology Hanseo UniversitySeosan 356-706Republic of Korea Department of Pharmacology school of MedicineKyunghee UniversitySeoul 130-701Republic of Korea

Objective:To explore the anti-diabetic activity of Ecklonia cava(EC) in streptozotocin(STZ)-induced diabetic ***:Diabetes was induced by a single intraperitoneal injection of STZ(90 mg/kg).Normal and diabetic mice were treated with 0%,3%,and 5%EC diet for 4 weeks. Serum glucose and insulin concentrations,serum lipid profile,oral glucose tolerance test,and liver and pancreaticβ-cell histopathological observations were *** addition,in vitro glucose-induced insulin secretion was determined using pancreaticβ-islet ***:EC supplementation significantly and dose-dependently decreased serum glucose concentration, and improved glucose homeostasis in diabetic mice by preventing loss ofβ-cell mass resulting in increase of insulin *** triglyceride and total cholesterol concentrations in the serum and liver were markedly reduced by EC treatment in STZ-diabetic ***,LDL-,and HDL-cholesterol levels were ameliorated in EC supplemented diabetic *** steatosis induced by STZ was ameliorated by EC ***,in vitro insulinotrophic effect of EC extract was observed in pancreaticβ-***:This study demonstrated that EC is a potent and efficacious hypoglycemic and hypolipidemic agent,and prevents the loss ofβ-cell mass resulting in increase of insulin secretary capacity.

关键词： Diabetes Streptozotocin Insulin Lipid profile Pancreaticβ-cell

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Brain-derived neurotrophic factor mediates macrophage migration inhibitory factor to protect neurons against oxygen-glucose deprivation

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Neural Regeneration Research 2020年第8期15卷 1483-1489页

作者： Su Hwan Bae mi Ran Yoo Ye Yeong kim In Kyung Hong mi Hee kim Seung Hak Lee Dae Yul kim Department of Rehabilitation Medicine Asan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea Asan Institute for Life Sciences Asan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea

Macrophage migration inhibitory factor(miF)is a chemokine that plays an essential role in immune system *** studies suggested that miF protects neurons in ischemic ***,few studies are reported on the role of miF in neurological recovery after ischemic *** purpose of this study is to identify the molecular mechanism of neuroprotection mediated by *** neuroblastoma cells were incubated in Dulbecco’s modified Eagle’s medium under oxygen-glucose deprivation(OGD)for 4 hours and then returned to normal aerobic environment for reperfusion(OGD/R).30 ng/mL miF recombinant(30 ng/mL)or ISO-1(miF antagonist;50μM)was administered to human neuroblastoma *** cell cultures were assigned to one of four groups:control,OGD/R,OGD/R with miF,OGD/R with *** viability was analyzed using WST-1 *** levels of brain-derived neurotrophic factor(BDNF),microtubule-associated protein 2(MAP2),Caspase-3,Bcl2,and Bax were detected by western blot assay and immunocytochemistry in each group to measure apoptotic ***-1 assay results revealed that compared to the OGD/R group,cell survival rate was significantly higher in the OGD/R with miF group and lower in the OGD/R with ISO-1 *** blot assay and immunocytochemistry results revealed that expression levels of BDNF,Bcl2,and MAP2 were significantly higher,and expression levels of Caspase-3 and Bax were significantly lower in the miF group than in the OGD/R *** levels of BDNF,Bcl2,and MAP2 were significantly lower,and expression levels of Caspase-3 and Bax were significantly higher in the ISO-1 group than in the OGD/R *** administration promoted neuronal cell survival and induced high expression levels of BDNF,MAP2,and Bcl2(anti-apoptosis)and low expression levels of Caspase-3 and Bax(pro-apoptosis)in an OGD/R *** results suggest that miF administration is effective for inducing expression of BDNF and leads to neuroprotection of neuronal cells

关键词： apoptosis brain-derived neurotrophic factor hypoxia in vitro ischemic stroke macrophage migration inhibitory factor nerve regeneration neuroprotective effect reperfusion

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CRISPR-Mediated Engineering across the Central Dogma in Plant Biology for Basic Research and Crop Improvement

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Molecular Plant 2021年第1期14卷 127-150页

作者： Dibyajyoti Pramanik Rahul Mahadev Shelake mi Jung kim Jae-Yean kim Division of Applied Life Science(BK21 Four Program) Plant Molecular Biology and Biotechnology Research CenterGyeongsang National UniversityJinju 52828Korea These authors contributed equally to this article

The central dogma(CD)of molecular biology is the transfer of genetic information from DNA to RNA to *** CD processes governing genetic flow include the cell cycle,DNA replication,chromosome packaging,epigenetic changes,transcription,posttranscriptional alterations,translation,and posttranslational *** CD processes are tightly regulated in plants to maintain genetic integrity throughout the life cycle and to pass genetic materials to next *** of various CD processes involved in gene regulation will accelerate crop improvement to feed the growing world *** technology enables programmable editing of CD processes to alter DNA,RNA,or protein,which would have been impossible in the ***,an overview of recent advancements in CRISPR tool development and CRISPR-based CD modulations that expedite basic and applied plant research is ***,CRISPR applications in major thriving areas of research,such as gene discovery(allele mining and cryptic gene activation),introgression(de novo domestication and haploid induction),and application of desired traits beneficial to farmers or consumers(biotic/abiotic stress-resilient crops,plant cell factories,and delayed senescence),are ***,the global regulatory policies,challenges,and prospects for CRISPR-mediated crop improvement are discussed.

关键词： central dogma CRISPR crop improvement gene regulation genome editing

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Cytochrome P450 endoplasmic reticulumassociated degradation(ERAD): therapeutic and pathophysiological implications

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Acta Pharmaceutica Sinica B 2020年第1期10卷 42-60页

作者： Doyoung Kwon Sung-mi kim Maria Almira Correia Department of Cellular and Molecular Pharmacology University of California San FranciscoSan FranciscoCA 94158-2517USA Pharmaceutical Chemistry University of California San FranciscoSan FranciscoCA 94158-2517USA Bioengineering and Therapeutic Sciences University of California San FranciscoSan FranciscoCA 94158-2517USA The Liver Center University of California San FranciscoSan FranciscoCA 94158-2517USA

The hepatic endoplasmic reticulum(ER)-anchored cytochromes P450(P450s)are mixedfunction oxidases engaged in the biotransformation of physiologically relevant endobiotics as well as of myriad xenobiotics of therapeutic and environmental relevance.P450 ER-content and hence function is regulated by their coordinated hemoprotein syntheses and proteolytic *** P450 proteolytic turnover occurs through a process known as ER-associated degradation(ERAD)that involves ubiquitindependent proteasomal degradation(UPD)and/or autophagic-lysosomal degradation(ALD).Herein,on the basis of available literature reports and our own recent findings of in vitro as well as in vivo experimental studies,we discuss the therapeutic and pathophysiological implications of altered P450 ERAD and its plausible clinical *** specifically(i)describe the P450 ERAD-machinery and how it may be repurposed for the generation of antigenic P450 peptides involved in P450 autoantibodypathogenesis in drug-induced acute hypersensitivity reactions and liver injury,or viral hepatitis;(ⅱ)discuss the relevance of accelerated or disrupted P450-ERAD to the pharmacological and/or toxicological effects of clinically relevant P450 drug substrates;and(ⅲ)detail the pathophysiological consequences of disrupted P450 ERAD,contributing to non-alcoholic fatty liver disease(NAFLD)/non-alcoholic steatohepatitis(NASH)under certain synergistic cellular conditions.

关键词： Cytochromes P450 Endoplasmic reticulumassociated degradation CHIP E3 ubiquitin ligase gp78/AMFR E3 ubiquitin ligase JNK1 AMPK1 Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis

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Comparison of excyclotorsion following graded inferior oblique recession for primary versus secondary inferior oblique overaction

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International Journal of Ophthalmology(English edition) 2020年第8期13卷 1281-1286页

作者： Donghun Lee Won Jae kim Myung mi kim Department of Ophthalmology Catholic University of Daegu School of MedicineDaegu 42472Republic of Korea Department of Ophthalmology Yeungnam University Medical CenterDaegu 42415Republic of Korea Nune Eye Hospital Daegu 2179Republic of Korea

AIM:To compare the changes in excyclotorsion after inferior oblique(IO)recession in patients with primary and secondary inferior oblique overaction(IOOA).METHODS:We retrospectively analyzed the data obtained from patients with IOOA who underwent graded IO *** patients were followed up for at least 3 mo after *** photographs were taken preand postoperatively,and the sum of the angles of torsion in both eyes was used to analyze changes in *** were divided into two groups:those diagnosed with primary IOOA were enrolled in the 1’IOOA group,and those diagnosed with secondary IOOA caused by superior oblique palsy(SOP)were enrolled in the 2’IOOA *** before and after surgery were compared between the two ***:A total of 78 patients were enrolled in this study:34 eyes in the 1’IOOA group and 44 eyes in the 2’IOOA *** the 78 patients,torsional angle significantly decreased from 15.31°±7.40°to 12.11°±6.53°after IO recession(P<0.001).Mean preoperative torsional angle was larger in the 2’IOOA group than in the 1’IOOA group(P=0.03).In both groups,excyclotorsion significantly decreased after IO recession(P=0.001 and P<0.001,respectively);however,there was no significant difference in the amounts of changes in excyclotorsion between the two ***:Excyclotorsion is significantly larger in secondary IOOA than in primary IOOA,and a significant decrease in the torsional angle occurs after IO recession in both types of IOOA.

关键词： inferior oblique overaction inferior oblique recession ocular excyclotorsion strabismus

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Genome-Wide Analysis and Molecular Characterization of Heat Shock Transcription Factor Family in Glycine max

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Journal of Genetics and Genomics 2013年第3期40卷 127-135页

作者： Eunsook Chung Kyoung-mi kim Jai-Heon Lee BK21 Center for Silver-Bio Industrialization College of Natural Resources and Life Science Dong-A University

Heat shock transcription factors （Hsfs） play an essential role on the increased tolerance against heat stress by regulating the expression of heat-responsive genes. In this study, a genome-wide analysis was performed to identify all of the soybean （Glycine max） GmHsfgenes based on the latest soybean genome sequence. Chromosomal location, protein domain, motif organization, and phylogenetic relationships of 26 non-redundant GmHsf genes were analyzed compared with AtHsfs （Arabidopsis thaliana Hsfs）. According to their structural features, the predicted members were divided into the previously defined classes A-C, as described for AtHsfs. Transcript levels and subcellular localization of five GmHsfs responsive to abiotic stresses were analyzed by real-time RT-PCR. These results provide a fundamental clue for understanding the complexity of the soybean GmHsfgene family and cloning the functional genes in future studies.

关键词： Abiotic stress Arabidopsis thaliana Expression patterns Glycine max Heat shock transcription factor Phylogenetic analysis

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Effect of expanding nanocellulose sponge on nasal mucosal defects in an animal model

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Regenerative Biomaterials 2020年第1期7卷 47-52页

作者： JiWon kim Kyungbae Woo Jeong mi kim mi Eun Choi Young-Mo kim Su-Geun Yang Bong Sup Shim Jeong-Seok Choi Department of Otorhinolaryngology Inha UniversityCollege of Medicine27 Inhang-roJung-guIncheon 22332Republic of Korea Department of Chemical Engineering Inha University100 InharoMichuholguIncheon 22212Republic of Korea Department of New Drug Development Inha UniversityCollege of MedicineB-308Chungsuk Bldg.366Seohae-DaeroJung-GuIncheon 22332Republic of Korea

Nanocellulose has emerged for a wide range of applications in biomedical engineering because of its water absorption capacity,appropriate *** investigated the hemostatic and regenerative abilities of an expanding polyvinyl alcohol(PVA)-nanocellulose sponge on nasal mucosal defects.A 3 mm-diameter nasal defect was made in experimental *** were divided into four groups with control,vaseline,PVA and PVA-nanocellulose packing *** the defect was created,bleeding times and amounts were *** materials were removed on experimental day(ED)*** ED 3,7 and 14,histological analysis and immunohistochemical study for neutrophils were *** cells were counted and epithelial thicknesses were *** amounts and times in the vaseline packing group were smaller than in the PVA ***-nanocellulose group showed less neutrophils than in the other groups on ED *** epithelium thickness in the PVA-nanocellulose group was significantly smaller than in the control group at ED 7,but at ED 14,there was no significant intergroup *** group had a significant lower inflammatory cell count than the control group on ED ***-nanocellulose sponge applied to nasal mucosal defects can significantly enhance mucosal regeneration during early wound healing.

关键词： polyvinyl alcohol nasal mucosa nanocellulose

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