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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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Depolarization mitigated in ferroelectric Hf_(0.5)Zr_(0.5)O_(2)ultrathin films(<5 nm)on Si substrate by interface engineering

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Journal of Advanced Ceramics 2024年第3期13卷 282-292页

作者： Se hyun Kim Younghwan Lee Dong hyun Lee Geun Hyeong Park hyun woo Jeong Kun Yang Yong Hyeon Cho Young Yong Kim Min Hyuk Park Department of Materials Science and Engineering College of EngineeringSeoul National UniversitySeoul 08826Republic of Korea Research Institute of Advanced Materials College of EngineeringSeoul National UniversitySeoul 08826Republic of Korea Inter-university Semiconductor Research Center College of EngineeringSeoul National UniversitySeoul 08826Republic of Korea Pohang Accelerator Laboratory Pohang University of Science&TechnologyPohang 790784Republic of Korea

(Hf,Zr)O_(2)offers considerable potential for next-generation semiconductor devices owing to its nonvolatile spontaneous polarization at the ***,scaling this material to sub-5 nm thickness poses several challenges,including the formation of an interfacial layer and high trap *** particular,a low-k SiO_(2)interfacial layer is naturally formed when(Hf,Zr)O_(2)films are directly grown on a Si substrate,leading to high depolarization fields and rapid reduction of the remanent *** address these issues,we conducted a study to significantly improve ferroelectricity and switching endurance of(Hf,Zr)O_(2)films with sub-5 nm thicknesses by inserting a TiO_(2)interfacial *** deposition of a Ti film prior to Hf_(0.5)Zr_(0.5)O_(2)film deposition resulted in a high-k TiO_(2)interfacial layer and prevented the direct contact of Hf_(0.5)Zr_(0.5)O_(2)with *** findings show that the high-k TiO_(2)interfacial layer can reduce the SiO_(2)/Si interface trap density and the depolarization field,resulting in a switchable polarization of 60.2μC/cm^(2)for a 5 nm thick Hf_(0.5)Zr_(0.5)O_(2)***,we propose that inserting a high-k TiO_(2)interfacial layer between the Hf_(0.5)Zr_(0.5)O_(2)film and the Si substrate may offer a promising solution to enhancing the ferroelectricity and reliability of(Hf,Zr)O_(2)grown on the Si substrate and can pave the way for next-generation semiconductor devices with improved performance.

关键词： ferroelectric charge trapping hafnia depolarization

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Increasing concentrations of dietary threonine,tryptophan,and glycine improve growth performance and intestinal health with decreasing stress responses in broiler chickens raised under multiple stress conditions

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Animal Nutrition 2024年第3期18卷 145-153页

作者： hyun woo Kim Jong Hyuk Kim Gi Ppeum Han Dong Yong Kil Department of Animal Science and Technology Chung-Ang UniversityAnseong-siGyeonggi-do 17546Republic of Korea Department of Animal Science Chungbuk National UniversityCheongju 28644Republic of Korea

The current study aimed to compare the effects of increasing concentrations of dietary threonine(Thr),tryptophan(Trp),and glycine(Gly)on growth performance,stress biomarkers,and intestinal function in broiler chickens under multiple stress *** hundred sixty broiler chickens at 21 d old were randomly allotted to 5 treatments with 8 *** in a positive control(PC)treatment were raised under low stock density(16.9 birds/m2 per cage)with recommended environmental conditions,whereas birds in 4 treatments were subjected to multiple stress conditions:a cyclic heat stress of 30±0.3°C for 10 h and 23±0.2°C for 14 h per day with high stock density(25.3 birds/m2 per cage).A basal diet was assigned to both PC and negative control(NC)*** additional diets were individually formulated to contain double concentrations of digestible Thr,Trp,or Gly+Ser compared with their concentrations in the basal *** experiment lasted for 14 *** showed that NC treatment had less growth performance(P<0.001),jejunal goblet cell counts(P=0.018),and trans-epithelial electrical resistance(TEER;P<0.001),but greater(P=0.026)feather corticosterone(CORT)concentrations than PC *** treatment showed the least(P<0.001)feed conversion ratio(FCR)among treatments under multiple stress ***,Trp,and Gly treatments had less(P=0.026)feather CORT concentrations,but had greater(P<0.001)TEER than NC *** conclusion,increasing concentrations of dietary Thr,Trp,or Gly improve the growth performance and intestinal health in broiler chickens with decreasing stress response under multiple stress conditions.

关键词： Broiler chicken Glycine Multiple stress Threonine Tryptophan

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Bone-targeted lipoplex-loaded three-dimensional bioprinting bilayer scaffold enhanced bone regeneration

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Regenerative Biomaterials 2024年第4期3卷 138-148页

作者： woo-Jin Kim Jeong-hyun Ryu Ji Won Kim Ki-Tae Kim Hye-Rim Shin Heein Yoon hyun-Mo Ryoo Young-Dan Cho Department of Molecular Genetics School of Dentistry and Dental Research InstituteSeoul National UniversitySeoul03080Republic of Korea Department of Periodontology School of Dentistry and Dental Research InstituteSeoul National University and Seoul National University Dental HospitalSeoul03080Republic of Korea

Clinical bone-morphogenetic protein 2(BMP2)treatment for bone regeneration,often resulting in complications like soft tissue inflammation and ectopic ossification due to high dosages and non-specific delivery systems,necessitates research into improved biomaterials for better BMP2 stability and *** tackle this challenge,we introduced a groundbreaking bone-targeted,lipoplex-loaded,three-dimensional bioprinted bilayer scaffold,termed the polycaprolactone-bioink-nanoparticle(PBN)scaffold,aimed at boosting bone *** encapsulated BMP2 within the fibroin nanoparticle based lipoplex(Fibroplex)and functionalized it with DSS6 for bone tissue-specific targeting.3D printing technology enables customized,porous PCL scaffolds for bone healing and soft tissue growth,with a two-step bioprinting process creating a cellular lattice structure and a bioink grid using gelatin-alginate hydrogel and DSS6-Fibroplex,shown to support effective nutrient exchange and cell growth at specific pore *** PBN scaffold is predicted through in silico analysis to exhibit biased BMP2 release between bone and soft tissue,a finding validated by in vitro osteogenic differentiation *** PBN scaffold was evaluated for critical calvarial defects,focusing on sustained BMP2 delivery,prevention of soft tissue cell infiltration and controlled fiber membrane pore size in *** PBN scaffold demonstrated a more than eight times longer BMP2 release time than that of the collagen sponge,promoting osteogenic differentiation and bone regeneration in a calvarial defect *** findings suggest that the PBN scaffold enhanced the local concentration of BMP2 in bone defects through sustained release and improved the spatial arrangement of bone formation,thereby reducing the risk of heterotopic ossification.

关键词： 3D bioprinting bone-targeting lipoplex BMP2 bone regeneration

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Factor analysis of recent major heatwaves in East Asia

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Geoscience Frontiers 2024年第1期15卷 374-383页

作者： Arim Yoon Jeongwon Kim Jooyeop Lee hyun Min Sung Je-woo Hong Seung-Ki Min Junhong Lee Jinkyu Hong Ecosystem-Atmosphere Process Laboratory Department of Atmospheric SciencesYonsei UniversitySeoul 03722Republic of Korea National Institute of Meteorological Sciences Jeju 63568Republic of Korea Korea Adaptation Center for Climate Korea Environment InstituteSejong 30121Republic of Korea Division of Environmental Science and Engineering Pohang University of Science and TechnologyPohang 37673Republic of Korea Max Planck Institute for Meteorology Hamburg 20146Germany Institute for Convergence Research and Education in Advanced Technology Yonsei UniversitySeoulRepublic of Korea

Heatwaves(HWs)present a major hazard to our society and more extreme heatwaves are expected with future climatic ***,it is important to improve our understanding of the underlying processes that drive HWs,in order to boost our socioeconomic-ecological *** this study,we quantified the influences of key driving factors(large-scale atmospheric circulation,soil moisture,and sea surface temperature)and their synergies on recent heatwaves in East *** conducted a factor separation analysis for three recent HW events by constraining the key factors in the regional Weather Research and Forecasting model with their climatologies or pseudo-observations in different *** study showed distinct spatial variations in the HW-controlling factors in East *** synergistic interaction of large-scale circulation and soil moisture was the most important factors in the 2013 Chinese *** the 2018 HWs in Korea and Japan,the same stagnant large-scale atmospheric circulation played a dominant role in driving the HW *** land-atmosphere coupling via soil moisture,its interaction with circulation,and SST exhibited stronger influences during the Korean HW than the Japanese *** analysis also revealed temporal variations in the factors driving Korean and Chinese HWs due to typhoon passage and other multiple processes over heterogeneous surfaces(i.e.,topographically induced Foehn winds,large-scale warm advection from the warm ocean,spatial differences in soil moisture).Our findings suggest that future heatwave-related studies should consider interactive contributions of key factors,their interplay with surface heterogeneities of complex terrain.

关键词： Heatwave East Asia Large-scale circulation Soil moisture Sea surface temperature Synergistic impacts

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Two distinct subpopulations of marginal zone B cells exhibit differential antibody-producing capacities and radioresistance

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Cellular & Molecular Immunology 2024年第4期21卷 393-408页

作者： Sujin Lee Yeunjung Ko hyun woo Lee Won Joon Oh Hun Gi Hong Dinuka Ariyaratne Se Jin Im Tae Jin Kim Department of Immunology Graduate School of Basic Medical ScienceSungkyunkwan University School of MedicineSuwon16419Republic of Korea Department of Immunology and Molecular Medicine Faculty of Medical SciencesUniversity of Sri JayewardenepuraNugegodaSri Lanka Present address:Immunology and Microbiology Graduate Program Baylor College of MedicineHoustonTX77030USA

Marginal zone(MZ)B cells,which are splenic innate-like B cells that rapidly secrete antibodies(Abs)against blood-borne pathogens,are composed of heterogeneous ***,we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression ***80^(high)MZ B cells exhibited greater Ab-producing,proliferative,and IL-10-secreting capacities than did CD80^(low)MZ B ***,CD80^(high)MZ B cells survived 2-Gy whole-body irradiation,whereas CD80^(low)MZ B cells were depleted by irradiation and then repleted with one month after *** of CD80^(low)MZ B cells led to accelerated development of type II collagen(CII)-induced arthritis upon immunization with bovine ***80^(high)MZ B cells exhibited higher expression of genes involved in proliferation,plasma cell differentiation,and the antioxidant ***80^(high)MZ B cells expressed more autoreactive B cell receptors(BCRs)that recognized double-stranded DNA or CII,expressed more immunoglobulin heavy chain sequences with shorter complementarity-determining region 3 sequences,and included more clonotypes with no N-nucleotides or with B-1a BCR sequences than CD80^(low)MZ B *** transfer experiments showed that CD21^(+)CD23^(+)transitional 2 MZ precursors preferentially generated CD80^(low)MZ B cells and that a proportion of CD80^(low)MZ B cells were converted into CD80^(high)MZ B cells;in contrast,CD80^(high)MZ B cells stably remained CD80^(high)MZ B *** summary,MZ B cells can be divided into two subpopulations according to their CD80 expression levels,Ab-producing capacity,radioresistance,and autoreactivity,and these findings may suggest a hierarchical composition of MZ B cells with differential stability and BCR specificity.

关键词： Marginal Zone B Cell CD80 Autoreactivity Radioresistance

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Acute cholangitis with Achromobacter xylosoxidans bacteremia after endoscopic retrograde cholangiopancreatography in hilar cholangiocarcinoma:A case report

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World Journal of Clinical Cases 2024年第20期12卷 4377-4383页

作者： Ik hyun Jo Sung woo Ko Department of Internal Medicine St.Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSeoul 16471South Korea Department of Internal Medicine Eunpyeong St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoul 03312South Korea

BACKGROUND Achromobacter xylosoxidans is a Gram-negative opportunistic aerobe,usually causing nosocomial infections in immunocompromised patients with manifestations including bacteremia,pneumonia,and catheter-related ***,*** have not yet been reported to cause biliary system *** SUMMARY A 72-year-old woman presented to the outpatient department of our hospital with a chief complaint of *** tomography of her abdomen revealed the presence of a mass of approximately 2.4 cm in the hilar portion of the common hepatic duct,consistent with hilar *** performed endoscopic retrograde cholangiopancreatography(ERCP)to decompress the obstructed left and right intrahepatic ducts(IHDs)and placed 10 cm and 11 cm biliary stents in the left and right IHDs,***,the day after the procedure,the patient developed post-ERCP cholangitis as the length of the right IHD stent was insufficient for proper bile *** blood culture of the patient tested positive for *** measures included the replacement of the right IHD stent(11 cm)with a longer one(12 cm)and administering culturedirected antibiotic therapy,solving the cholangitis-related *** the cholangitis had resolved,the patient underwent surgery for hilar cholangiocarcinoma and survived for 912 d without *** ***-induced biliary system infections are extremely *** awareness of physicians and endoscopists is required as this rare pathogen might cause infection after endoscopic procedures.

关键词： Achromobacter xylosoxidans Bacteremia Cholangitis Endoscopic retrograde cholangiopancreatography Malignant biliary stricture Cholangiocarcinoma Case report

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Generation of double knockout cattle via CRISPR-Cas9 ribonucleoprotein(RNP)electroporation

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Journal of Animal Science and Biotechnology 2024年第1期15卷 456-462页

作者： Gyeong-Min Gim Kyeong-Hyeon Eom Dong-Hyeok Kwon Dae-Jin Jung Dae-hyun Kim Jun-Koo Yi Jae-Jung Ha Ji-hyun Lee Seong-Beom Lee woo-Jae Son Soo-Young Yum Won-Wu Lee Goo Jang Laboratory of Theriogenology and Biotechnology Department of Veterinary Clinical ScienceCollege of Veterinary Medicine and the Research Institute of Veterinary ScienceSeoul National UniversitySeoulRepublic of Korea LARTBio Co. Ltd.SeoulRepublic of Korea Gyeongsangbukdo Livestock Research Institute YeongjuRepublic of Korea Comparative Medicine Disease Research Center Seoul National UniversitySeoulRepublic of Korea

Background Genome editing has been considered as powerful tool in agricultural ***,genome editing progress in cattle has not been fast as in other mammal species,for some disadvantages including long gestational periods,single pregnancy,and high raising ***,technically demanding methods such as microinjection and somatic cell nuclear transfer(SCNT)are needed for gene editing in *** this point of view,electroporation in embryos has been risen as an *** First,editing efficiency of our electroporation methods were tested for *** of mutation on embryo was confirmed by T7E1 *** first combination,mutation rates for MSTN and PRNP were 57.6%±13.7%and 54.6%±13.5%,*** case of MSTN/BLG,mutation rates were 83.9%±23.6%for MSTN,84.5%±18.0%for ***,the double-KO embryos were transferred to surrogates and mutation rate was identified in resultant calves by targeted deep *** recipients were transferred for MSTN/PRNP,4 calves were delivered,and one calf underwent an induction for double *** surrogates were given double-KO embryos for MSTN/BLG,and four of the six calves that were born had mutations in both *** These data demonstrated that production of genome edited cattle via electroporation of RNP could be effectively ***,MSTN and PRNP from beef cattle and MSTN and BLG from dairy cattle have been born and they will be valuable resources for future precision breeding.

关键词： Beta-lactoglobulin Cattle CRISPR-Cas9 Electroporation Knockout MSTN PRNP

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Recent trends in the epidemiology and clinical outcomes of inflammatory bowel disease in South Korea,2010-2018

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World Journal of Gastroenterology 2024年第9期30卷 1154-1163页

作者： Seulji Kim hyun Jung Lee Seung woo Lee Sanghyun Park Seong-Joon Koh Jong Pil Im Byeong Gwan Kim Kyung-Do Han Joo Sung Kim Department of Internal Medicine Korea Institute of Radiological and Medical SciencesSeoul 01812South Korea Department of Internal Medicine and Liver Research Institute Seoul National University College of MedicineSeoul 03080South Korea Department of Statistics and Actuarial Science Soongsil UniversitySeoul 06978South Korea

BACKGROUND Inflammatory bowel disease(IBD)was previously regarded as a Western disease;however,its incidence is increasing in the *** epidemiology of IBD in Asia differs significantly from the patterns in the *** To comprehensively investigate the epidemiology of IBD in South Korea,inclu-ding its incidence,prevalence,medication trends,and *** We analyzed claims data from the Health Insurance Review and Assessment Service and Rare and Intractable Diseases(RIDs),operated by the National Health Insurance Service of South *** with IBD were identified based on the International Classification of Diseases,Tenth Revision,and RID diagnostic codes for Crohn’s disease(CD)and ulcerative colitis(UC)from 2010 to *** In total,14498 and 31409 patients were newly diagnosed with CD and UC,respectively,between 2010 and *** annual average incidence of CD was 3.11 cases per 105 person-years,and that of UC was 6.74 cases per 10^(5) *** 2014,the incidence rate of CD has been stable,while that of UC has steadily increased,shifting the peak age group from 50-year-olds in 2010 to 20-year-olds in *** CD and UC prevalence increased consistently over the study period;the use of 5-aminosali-cylates and corticosteroids gradually decreased,while that of immunomodulators and biologics steadily increased in both CD and *** clinical outcomes of IBD,such as hospitalization and surgery,decreased during the study *** The CD incidence has been stable since 2014,but that of UC has increased with a shift to a younger age at peak incidence between 2010 and *** clinical outcomes improved over time,with increased use of immunomodu-lators and biologics.

关键词： Inflammatory bowel disease Crohn’s disease Ulcerative colitis Incidence Prevalence

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Effect of smoking on the risk of gastrointestinal cancer after cholecystectomy: A national population-based cohort study

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World Journal of Gastrointestinal Surgery 2024年第9期16卷 2796-2807页

作者： Minseob Kim Kyung-Do Han Seung-hyun Ko Yoonkyung woo Jae hyun Han Department of Surgery Graduate School of MedicineThe Catholic University of KoreaSeoul 06591South Korea Department of Statistics and Actuarial Science Soongsil UniversitySeoul 06978South Korea Division of Endocrinology and Metabolism Department of Internal MedicineSt Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSuwon 16247South Korea Division of Hepatobiliary-Pancreas Surgery and Liver Transplantation Department of SurgerySt Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSuwon 16247South Korea

BACKGROUND The role of smoking in the incidence of colorectal cancer(CRC)or gastric cancer(GC)in populations undergoing cholecystectomy has not been *** To evaluate the effect of smoking on CRC or GC development in cholecystectomy *** A total of 174874 patients who underwent cholecystectomy between January 1,2010 and December 31,2017 were identified using the Korean National Health Insurance Service claims *** patients were matched 1:1 with mem-bers of a healthy population according to age and *** or GC risk after cholecystectomy and the association between smoking and CRC or GC risk in cholecystectomy patients were evaluated using adjusted hazard ratios(HRs)and 95%*** The risks of CRC(adjusted HR:1.15;95%CI:1.06-1.25;P=0.0013)and GC(adjusted HR:1.11;95%CI:1.01-1.22;P=0.0027)were significantly higher in cholecystectomy *** the population who underwent cholecystectomy,both CRC and GC risk were higher in those who had smoked compared to those who had never *** both cancers,the risk tended to increase in the order of non-smokers,ex-smokers,and current *** addition,a positive correlation was observed between the amount of smoking and the risks of both CRC and *** Careful follow-up and screening should be performed,focusing on the increased risk of gastrointestinal cancer in the cholecystectomy group,particularly considering the individual smoking habits.

关键词： Cholecystectomy Smoking,Gastric cancer Colon cancer Risk factor Hazard ratio

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