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

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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

Photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes to promote PD-L1 multivalent binding for effective immune checkpoint blockade therapy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1428-1440页

作者： Youngjoo Lee Sukyung Song Suah Yang Jinseong Kim Yujeong moon Nayeon Shim Hong Yeol yoon Sehoon Kim man Kyu Shim Kwangmeyung Kim KU-KIST Graduate School of Converging Science and Technology Korea UniversitySeoul 02841Republic of Korea medicinal materials Research Center Biomedical Research DivisionKorea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea College of Pharmacy Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoul 03760Republic of Korea Department of Bioengineering Korea UniversitySeoul 02841Republic of Korea

Immune checkpoint blockade(ICB)therapy targeting PD-L1 via monoclonal antibody(m Ab)has shown extensive clinical benefits in the diverse types of advanced ***,most patients are completely refractory to ICB therapy owing to the PD-L1 recycling ***,we propose photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes(immune checkpoint blockade liposomes;ICB-LPs)to promote PD-L1 multivalent binding for inducing lysosomal degradation of PD-L1 in tumor *** ICB-LPs are prepared by formulation of DC_(8,9)PC with photo-polymerized diacetylenic moiety,1,2-dipalmitoylphosphatidylcholine(DPPC)and anti-PD-L1peptide(D-form NYSKPTDRQYHF)-conjugated DSPE-PEG_(2k)(anti-PD-L1-DSPE-PEG_(2k))in a molar ratio of 45:45:10,followed by cross-linking of liposomal bilayer upon UV *** 10 mol% antiPD-L1-DSPE-PEG_(2k)incorporated ICB-LPs have a nano-sized lipid bilayer structure with an average diameter of 137.7±1.04 nm,showing a high stability in serum ***,the ICB-LPs efficiently promote the multivalent binding with PD-L1 on the tumor cell membrane,which are endocytosed with aim to deliver PD-L1 to the lysosomes,wherein the durable PD-L1 degradation is observed for72 h,in contrast to anti PD-L1 m Abs showing the rapid PD-L1 recycling within 9 *** in vitro coculture experiments with CD8^(+)T cells show that ICB-LPs effectively enhance the T cell-mediated antitumor immune responses against tumor cells by blocking the PD-L1/PD-1 *** ICB-LPs are intravenously injected into colon tumor-bearing mice,they efficiently accumulate within the targeted tumor tissues via both passive and active tumor targeting,inducing a potent T cell-mediated antitumor immune response by effective and durable PD-L1 ***,this study demonstrates the superior antitumor efficacy of crosslinked and anti-PD-L1 peptide incorporated liposome formulation that promotes PD-L1 multivalent binding for trafficking of PD-L1 toward

关键词： Cancer immunotherapy Immune checkpoint blockade PEGylated liposome Crosslinked lipid nanoparticles Anti-PD-L1 peptide Tumor-targeting PD-L1 multivalent binding Lysosomal PD-L1 degradation

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Advancing oxygen separation:insights from experimental and computational analysis of La_(0.7)Ca_(0.3)Co_(0.3)Fe_(0.6)m_(0.1)O_(3-δ)(m=Cu,Zn)oxygen transport membranes

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Frontiers of Chemical Science and Engineering 2024年第6期18卷 17-29页

作者： Guoxing Chen Wenmei Liu marc Widenmeyer Xiao Yu Zhijun Zhao Songhak yoon Ruijuan Yan Wenjie Xie Armin Feldhoff Gert Homm Emanuel Ionescu maria Fyta Anke Weidenkaff Fraunhofer Research Institution for materials Recycling and Resource Strategies IWKS Alzenau 63755Germany Electrochemistry Laboratory Paul Scherrer InstituteVilligen PSI 5232Switzerland Department of materials and Earth Sciences Materials and ResourcesTechnical University of DarmstadtDarmstadt 64287Germany Institute of Physical Chemistry and Electrochemistry Leibniz University HannoverHannover 30167Germany Institute for Computational Physics University of StuttgartStuttgart 70569Germany Computational Biotechnology RWTH AachenAachen 52074Germany

In this study,perovskite-type La_(0.7)Ca_(0.3)Co_(0.3)Fe_(0.6)m_(0.1)O_(3-δ)(m=Cu,Zn)powders were synthesized using a scalable reverse co-precipitation method,presenting them as novel materials for oxygen transport *** comprehensive study covered various aspects including oxygen permeability,crystal structure,conductivity,morphology,CO_(2) tolerance,and long-term regenerative durability with a focus on phase structure and *** membrane La_(0.7)Ca_(0.3)Co_(0.3)Fe_(0.6)m_(0.1)O_(3-δ)exhibited high oxygen permeation fluxes,reaching up to 0.88 and 0.64 mL·min^(−1)·cm^(−2) under air/He and air/CO_(2) gradients at 1173 K,*** 1600 h of CO_(2) exposure,the perovskite structure remained intact,showcasing superior CO_(2) resistance.A combination of first principles simulations and experimental measurements was employed to deepen the understanding of Cu/Zn substitution effects on the structure,oxygen vacancy formation,and transport behavior of the *** findings underscore the potential of this highly CO_(2)-tolerant membrane for applications in high-temperature oxygen *** enhanced insights into the oxygen transport mechanism contribute to the advancement of next-generation membrane materials.

关键词： perovskite oxygen permeation membrane oxygennionsdiffusiono xygen vacancy formation energy energy barrier

年龄相关的健康大腿肌群变化的多参数mR成像

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国际医学放射学杂志 2018年第3期 356-356页

作者： m.a.yoon S.J.Hong m.C.Ku C.H.Kang K.S.Ahn B.H.Kim 刘臻 Department of Radiology Korea University Guro Hospital Korea University College of Medicine

摘要目的应用多参数mR成像来评估和建立健康人大腿肌肉年龄相关的差异。材料与方法共纳入95例体质量指数均正常的受试者(男性47例,女性48例,平均年龄47

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扩散加权成像对预测软组织肉瘤筋膜受累的附加价值

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国际医学放射学杂志 2019年第3期 376-376页

作者：田恬 m.a.yoon C.G.Chee H.W.Chung J.S.Song J.S.Lee W.Kim Department of Radiology and Research Institute of Radiology University of Ulsan College of MedicineAsan Medical Center

摘要摘要目的本研究旨在评估扩散加权成像(DWI)对常规mRI预测靠近筋膜边界的软组织肉瘤的筋膜受累范围的附加价值。方法本回顾性研究纳入29例手术切除的软组织

关键词：加权成像软组织肉瘤附加价值

Chloride-Bridged Dimeric SalphenZr(IV) Cobaltate Catalyst Unleashes the Potential of Base-Free Carbonylative Polymerization for Biodegradable PHAs

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Chinese Journal of Chemistry 2023年第24期41卷 3560-3566页

作者： Vinothkumar Ganesan Sungho yoon Department of Chemistry Chung Ang University84 Heukseok-roDongjak-guSeoul06974 Republic of Korea

Poly(3-hydroxyalkanoates) (PHAs) are a promising class of biodegradable polymers,exhibiting properties comparable to traditional petroleum-based ***,the widespread commercialization of PHAs is hindered by the absence of an efficient and economically viable catalytic system,impeding their competitiveness against non-biodegradable *** an effort to address this challenge,we present a study on a newly developed chloro-bridged dimeric salphen zirconium cobaltate complex for the direct synthesis of PHAs via carbonylative polymerization of *** catalytic system demonstrates favorable activity under mild reaction conditions,enabling complete monomer conversion and an impressive 92% selectivity towards PHA *** meticulous control experiments and mechanistic studies,we have gained crucial insights into the polymerization ***,our findings challenge the prevailing notion of sequential ring-opening polymerization of in-situ generated β-lactones as the primary ***,we demonstrate that the polymerization predominantly proceeds through direct co-polymerization of epoxide and carbon monoxide,unveiling a unique and efficient mechanism for PHA synthesis.

关键词： C1 building blocks Chloro bridged salphenZr(IV)dimer Homogeneous catalysis Carbonylation Carbonylative polymerization Biodegradable polymer Poly(3-hydroxyalkanoates)

The role of emergency incident type in identifying first responders' health exposure risks

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Journal of Safety Science and Resilience 2023年第2期4卷 167-173页

作者： Emily J.Haas Katherine N.yoon Alexa Furek megan Casey Susan m.moore National Personal Protective Technology Laboratory(NPPTL) National Institute for Ocupational Safety and Health(NIOSH)PittsburghPA 15236United States National Personal Protective Technology Laboratory(NPPTL) National Institute forOccupational Safety and Health(NIOSH)MorgantownWV2605United States

Fire-based emergency management service(EmS)personnel are dispatched to various incidents daily,many of which have unique occupational *** fully understand the variability of incident types and how to best pre-pare and respond,an exploration of the *** system of incident types is *** study uses potential exposure to SARS-CoV-2 as a case example to understand if and how coding categories for incident call types may be updated to improve data standardization and emergency response decision *** received emergency response incident data generated by three fire department computer-aided dispatch(CAD)systems between march and September *** incident was labeled EmS,Fire,or *** the 162,766 incidents,approximately 8.1%(n=13,144)noted potential SARS-CoV-2 exposure within their narrative descriptions of which 86.3%were coded as EmS,9.9%as Fire,and 3.9%as *** assess coding variability across incident types,researchers used the original 3-incident type variable and a new 5-incident type variable reassigned by researchers into EmS,Fire,Other,Hazmat,and motor *** regressions compared differences in potential exposure using the 3-and 5-incident type *** evaluating the 3-incident type variable,those respond-ing to a Fire versus an EmS incident were 84%less likely to be associated with potential exposure to *** the 5-incident type variable,those responding to Fire incidents were 77%less likely to be associated with a potential exposure than those responding to EmS *** in potential exposure between the 3-and 5-incident type models show the need to understand how incident types are *** demonstrates the need for data standardization to accurately categorize incident types to improve emergency preparedness and *** have implications for incident type coding at fire department municipality and national levels.

关键词： Emergencymedical se Firefighter Incident type Surveillance Telecommunicator

Real-time porosity reduction during metal directed energy deposition using a pulse laser

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Journal of materials Science & Technology 2022年第21期116卷 214-223页

作者： Hoon Sohn Peipei Liu Hansol yoon Kiyoon Yi Liu Yang Sangjun Kim Department of Civil and Environmental Engineering Korea Advanced Institute of Science and Technology(KAIST)Daejeon 34141Republic of Korea Center for 3D Printing Nondestructive Testing Korea Advanced Institute of Science and Technology(KAIST)Daejeon 34141Republic of Korea Global R&D Center SQ EngineeringSeoul 05818Republic of Korea Department of Civil and Environmental Engineering The Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina

Porosity is a challenging issue in additive manufacturing and is detrimental to the quality of the additively manufactured *** this study,a real-time porosity reduction technique was developed by incorporating a pulse laser into a laser metal powder directed energy deposition(DED)*** incorporated pulse laser can accelerate fluid flow within the melt pool and facilitate the escape of pores before complete *** achieves this real-time porosity reduction by inducing accelerated and turbulent marangoni flow,ultrasonic waves,and shock waves into the melt *** uniqueness and advantages of the proposed technique include the following:(1)For a laser metal powder DED process,this study proposed a noncontact,nondestructive,and real-time porosity reduction technique at the melt pool level.(2)It was experimentally and numerically validated that the developed technique did not alter the geometry and the grain structure of the manufactured Ti-6Al-4V samples.(3)Because the porosity reduction is accomplished at the melt pool level,its application is not limited by the size,shape,or complexity of the printing target.(4)The developed technique can be readily incorporated into the existing DED systems without any modification of the original tool-path *** experimental results showed that the pore volume fraction decreased from 0.132%to 0.005%,no pores larger than 6×10^(4)μm^(3) were observed,and a 91%reduction in the total pore number was achieved when the pulse laser energy reached 11.5 mJ.

关键词： Real-time porosity reduction Pulse laser melt pool Directed energy deposition Ti-6Al-4V

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Accelerated identification of equilibrium structures of multicomponent inorganic crystals using machine learning potentials

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npj Computational materials 2022年第1期8卷 1027-1036页

作者： Sungwoo Kang Wonseok Jeong Changho Hong Seungwoo Hwang Youngchae yoon Seungwu Han Department of materials Science and Engineering Seoul National UniversitySeoul08826Korea

The discovery of multicomponent inorganic compounds can provide direct solutions to scientific and engineering challenges,yet the vast uncharted material space dwarfs synthesis *** the crystal structure prediction(CSP)may mitigate this frustration,the exponential complexity of CSP and expensive density functional theory(DFT)calculations prohibit material exploration at ***,we introduce SPINNER,a structure-prediction framework based on random and evolutionary *** speed and accuracy of neural network potentials(NNPs),the program navigates configurational spaces 10^(2)–10^(3) times faster than DFT-based ***,SPINNER incorporates algorithms tuned for NNPs,achieving performances exceeding conventional *** blind tests on 60 ternary compositions,SPINNER identifies experimental(or theoretically more stable)phases for~80%of *** benchmarked against data-mining or DFT-based evolutionary predictions,SPINNER identifies more stable phases in many *** developing a reliable and fast structure-prediction framework,this work paves the way to large-scale,open exploration of undiscovered inorganic crystals.

关键词： materials inorganic equilibrium