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Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies

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Signal Transduction and Targeted Therapy 2024年第1期9卷 173-210页

作者： Md Entaz Bahar Hyun Joon kim Deok Ryong kim Department of Biochemistry and Convergence Medical Sciences and Institute of Medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea Department of Anatomy and Convergence Medical Sciences and Institute of Medical Science Gyeongsang National UniversityCollege of MedicineJinjuSouth Korea

Metastatic dissemination of solid tumors,a leading cause of cancer-related mortality,underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis,chemoresistance,and the mechanistic backgrounds of individuals whose cancers are prone to *** most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase(MAPK)pathway,encompassing the RAS–RAF–MAPK kinase(MEK)–extracellular signal-related kinase(ERK)*** kinase is a primary mediator of the MAPK pathway,responsible for the sequential activation of downstream targets,such as MEK and the transcription factor ERK,which control numerous cellular and physiological processes,including organism development,cell cycle control,cell proliferation and differentiation,cell survival,and *** in this signaling cascade are associated with diseases such as *** inhibitors(RAFi)combined with MEK blockers represent an FDAapproved therapeutic strategy for numerous RAF-mutant cancers,including melanoma,non-small cell lung carcinoma,and thyroid ***,the development of therapy resistance by cancer cells remains an important ***,an intracellular lysosome-dependent catabolic recycling process,plays a critical role in the development of RAFi resistance in ***,targeting RAF and autophagy could be novel treatment strategies for RAF-mutant *** this review,we delve deeper into the mechanistic insights surrounding RAF kinase signaling in tumorigenesis and ***,we explore and discuss the ongoing development of next-generation RAF inhibitors with enhanced therapeutic ***,this review sheds light on the functional interplay between RAF-targeted therapies and autophagy in cancer.

关键词： RAF insight mechanism

Rice breeding for low methane and high yields

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Plant Communications 2024年第5期5卷 94-96页

作者： Suvendu Das Pil Joo kim Institute of Agriculture and Life Sciences Gyeongsang National UniversityJinju 660-701South Korea Division of Applied Life Science Gyeongsang National UniversityJinju 660-701South Korea

Rice is the staple food for more than half of the world’s population,and the demand for rice is expected to increase by 28%by 2050(Jiang et al.,2017).However,rice production is one of the largest anthropogenic sources of the potent greenhouse gas methane(CH4),accounting for 22%of total agricultural CH4 emissions(Qian et al.,2023).Therefore,to achieve sustainable intensification of rice cultivation,it is necessary to increase yields while reducing CH4 *** management techniques to reduce CH4 emissions while maintaining high yields have been studied extensively over the past few decades,but crop breeding to reduce CH4 emissions without compromising yields has received less attention(Kwon et al.,2023).

关键词： breeding methane yields

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

α1-COP modulates plasmodesmata function through sphingolipid enzyme regulation

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Journal of Integrative Plant Biology 2024年第8期66卷 1639-1657页

作者： Arya Bagus Boedi Iswanto Minh Huy Vu Jong Cheol Shon Ritesh Kumar Shuwei Wu Hobin Kang Da-Ran kim Geon Hui Son Woe Yoen kim Youn-Sig Kwak Kwang Hyeon Liu Sang Hee kim Jae-Yean kim Division of Applied Life Science(BK21 FOUR Program) Plant Molecular Biology and Biotechnology Research CenterGyeongsang National UniversityJinju 52828Korea College of Pharmacy and Research Institute of Pharmaceutical Sciences Kyungpook National UniversityDaegu 702-701Korea Departement of Plant Medicine Gyeongsang National UniversityJinju 52828Korea Division of Life Science Gyeongsang National UniversityJinju 52828Korea

Callose,aβ-1,3-glucan plant cell wall polymer,regulates symplasmic channel size at plasmodesmata(PD)and plays a crucial role in a variety of plant ***,elucidating the molecular mechanism of PD callose homeostasis is *** screened and identified an Arabidopsis mutant plant with excessive callose deposition at PD and found that the mutated gene wasα1-COP,a member of the coat protein I(COPI)coatomer *** report that loss of function ofα1-COP elevates the callose accumulation at PD by affecting subcellular protein localization of callose degradation enzyme Pd *** process is linked to the functions of ERH1,an inositol phosphoryl ceramide synthase,and glucosylceramide synthase through physical interactions with theα1-COP ***,the loss of function ofα1-COP alters the subcellular localization of ERH1 and GCS proteins,resulting in a reduction of Glc Cers and Glc HCers molecules,which are key sphingolipid(SL)species for lipid raft *** findings suggest thatα1-COP protein,together with SL modifiers controlling lipid raft compositions,regulates the subcellular localization of GPI-anchored PDBG2 proteins,and hence the callose turnover at PD and symplasmic movement of *** findings provide the first key clue to link the COPI-mediated intracellular trafficking pathway to the callose-mediated intercellular signaling pathway through PD.

关键词： callose coatomer proteins membrane-bound vesicle plasmodesmata sphingolipid enzymes

Comparison of commercial silicon-based anode materials for the design of a high-energy lithium-ion battery

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Nano Research 2024年第6期17卷 5270-5277页

作者： Minhong Choi Eunhan Lee Jaekyung Sung Namhyung kim Minseong Ko Division of Convergence Materials Engineering Pukyong National UniversityBusan 48547Republic of Korea Department of Materials Engineering and Convergence Technology Gyeongsang National University501 Jinju-daeroJinju 52828Republic of Korea Department of Materials System Engineering Pukyong National UniversityBusan 48547Republic of Korea

Silicon(Si)is considered a potential alternative anode for next-generation Li-ion batteries owing to its high theoretical capacity and ***,the commercial use of Si anodes is hindered by their large volume expansion(~300%).Numerous efforts have been made to address this *** these efforts,Si-graphite co-utilization has attracted attention as a reasonable alternative for high-energy anodes.A comparative study of representative commercial Si-based materials,such as Si nanoparticles,Si suboxides,and Si−Graphite composites(SiGC),was conducted to characterize their overall performance in high-energy lithium-ion battery(LIB)design by incorporating conventional ***-Si was found to exhibit poor electrochemical performance,with severe volume expansion during *** suboxide provided excellent cycling stability in a full-cell evaluation with stable volume variation after 50 cycles,but had a large irreversible capacity and remarkable volume expansion during the first *** displayed a good initial Coulombic efficiency and the lowest volume change in the first cycle owing to the uniformly distributed nano-Si layer on graphite;however,its long-term cycling stability was relatively *** complement each disadvantage of Si suboxide and SiGC,a new combination of these Si-based anodes was suggested and a reasonable improvement in overall battery performance was successfully achieved.

关键词： silicon-based anode high-energy comparison lithium ion battery blended electrode

Changes in structural plasticity of hippocampal neurons in an animal model of multiple sclerosis

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Zoological Research 2024年第2期45卷 398-414页

作者： Poornima D.E.Weerasinghe-Mudiyanselage Sohi Kang Joong-Sun kim Sung-Ho kim Hongbing Wang Taekyun Shin Changjong Moon Department of Veterinary Anatomy and Animal Behavior College of Veterinary Medicine and BK21 FOUR ProgramChonnam National UniversityGwangju 61186Republic of Korea Department of Anatomy and Convergence Medical Science Institute of Health SciencesCollege of MedicineGyeongsang National UniversityJinju 52727Republic of Korea Department of Physiology and Neuroscience Program Michigan State UniversityEast LansingMI 48824USA Department of Veterinary Anatomy College of Veterinary Medicine and Veterinary Medical Research InstituteJeju National UniversityJeju 63243Republic of Korea

Structural plasticity is critical for the functional diversity of neurons in the *** autoimmune encephalomyelitis(EAE)is the most commonly used model for multiple sclerosis(MS),successfully mimicking its key pathological features(inflammation,demyelination,axonal loss,and gliosis)and clinical symptoms(motor and non-motordysfunctions).Recentstudieshave demonstrated the importance of synaptic plasticity in EAE *** the present study,we investigated the features of behavioral alteration and hippocampal structural plasticity in EAE-affected mice in the early phase(11 days post-immunization,DPI)and chronic phase(28DPI).EAE-affected mice exhibited hippocampus-related behavioral dysfunction in the open field test during both early and chronic *** complexity was largely affected in the cornu ammonis 1(CA1)and CA3 apical and dentate gyrus(DG)subregions of the hippocampus during the chronic phase,while this effect was only noted in the CA1 apical subregion in the early ***,dendritic spine density was reduced in the hippocampal CA1 and CA3 apical/basal and DG subregions in the early phase of EAE,but only reduced in the DG subregion during the chronic ***,mRNA levels of proinflammatory cytokines(Il1β,Tnfα,and Ifnγ)and glial cell markers(Gfap and Cd68)were significantly increased,whereas the expression of activity-regulated cytoskeletonassociated protein(ARC)was reduced during the chronic ***,exposure to the aforementioned cytokines in primary cultures of hippocampal neurons reduced dendritic complexity and ARC *** cultures of hippocampal neurons also showed significantly reduced extracellular signal-regulated kinase(ERK)phosphorylation upon treatment with proinflammatory ***,these results suggest that autoimmune neuroinflammation alters structural plasticity in the hippocampus,possibly through the ERK-ARC pathway,indicating that this alteration may be associated with hi

关键词： Activity-regulated cytoskeleton-associated protein Anxiety-like behavior Experimental autoimmune encephalomyelitis Hippocampal dysfunction Neuroinflammation

Methane Emission from Rice Fields:Necessity for Molecular Approach for Mitigation

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Rice science 2024年第2期31卷 159-178页

作者： Sujeevan RAJENDRAN Hyeonseo PARK Jiyoung kim Soon Ju PARK Dongjin SHIN Jong-Hee LEE Young Hun SONG Nam-Chon PAEK Chul Min kim Department of Horticulture Industry Wonkwang UniversityIksan 54538Korea Plant Molecular Biology and Biotechnology Research Center Gyeongsang National UniversityJinju 52828Korea Department of Southern Area Crop Science National Institute of Crop ScienceMiryang 50424Korea Department of Agricultural Biotechnology Seoul National UniversitySeoul 08826Korea Department of Plant Science Plant Genomics and Breeding InstituteResearch Institute of Agriculture and Life SciencesSeoul National UniversitySeoul 08826Korea

Anthropogenic methane emissions are a leading cause of the increase in global averagetemperatures,often referred to as global *** soils play a significant role in methaneproduction,where the anaerobic conditions promote the production of methane by *** fields contribute a considerable portion of agricultural methane emissions,as riceplants provide both factors that enhance and limit methane *** plants harbor both methaneproducingand methane-oxidizing *** from rice roots provide source for methaneproduction,while oxygen delivered from the root aerenchyma enhances methane *** haveshown that the diversity of these microorganisms depends on rice cultivars with some genes characterizedas harboring specific groups of microorganisms related to methane ***,there is still aneed for research to determine the balance between methane production and oxidation,as rice plantspossess the ability to regulate net methane *** agronomical practices,such as fertilizerand water management,have been employed to mitigate methane ***,studiescorrelating agronomic and chemical management of methane with productivity are ***,evidences for breeding low-methane-emitting rice varieties are scattered largely due to the absence ofcoordinated breeding *** has indicated that phenotypic characteristics,such as rootbiomass,shoot architecture,and aerenchyma,are highly correlated with methane *** reviewdiscusses available studies that involve the correlation between plant characteristics and *** emphasizes the necessity and importance of breeding low-methane-emitting rice varieties inaddition to existing agronomic,biological,and chemical *** review also delves into the idealphenotypic and physiological characteristics of low-methane-emitting rice and potential breeding techniques,drawing from studies conducted

关键词： methane emission rice breeding aerenchyma greenhouse gas radial oxygen loss

Anode surface engineering of zinc-ion batteries using tellurium nanobelt as a protective layer for enhancing energy storage performance

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Journal of Energy Chemistry 2024年第5期92卷 113-123页

作者： Soobeom Lee Yeonjin Je Boeun Seok Hyun Tae kim Yong-Ryun Jo Soong Ju Oh Byoungyong Im Dae Guen kim Sang-Soo Chee Geon-Hyoung An Department of Energy System Engineering Gyeongsang National UniversityJinju 52725Republic of Korea Nano Convergence Materials Center Korea Institute of Ceramic Engineering and Technology(KICET)Jinju 52851Republic of Korea Department of Materials Science and Engineering Korea UniversitySeoul 02841Republic of Korea School of Materials Science and Engineering Gyeongsang National UniversityJinju 52828Republic of Korea GIST Advanced Insitute of Instrumental Analysis(GAIA) Electron Microscopy LaboratoryGwangju Institute of Science and TechnologyGwangju 61005Republic of Korea Center for Advanced Materials and Processing Institute for Advanced EngineeringYongin 17180Republic of Korea Department of Energy Engineering Gyeongsang National UniversityJinju 52725Republic of Korea

Over the years,zinc-ion batteries(ZIBs)have attracted attention as a promising next-generation energy storage technology because of their excellent safety,long cycling performance,eco-friendliness,and high-power ***,issues,such as the corrosion and dissolution of the Zn anode,limited wet-tability,and lack of sufficient nucleation sites for Zn plating,have limited their practical *** introduction of a protective layer comprising of tellurium(Te)nanobelts onto the surface of Zn anode has emerged as a promising approach to overcome these limitations and improve the electrochemical behav-ior by enhancing the safety and wettability of ZIBs,as well as providing numerous nucleation sites for Zn *** the presence of a Te-based protective layer,the energy power density of the surface-engineered Zn anode improved significantly(ranging from 310 to 144 W h kg^(-1),over a power density range of 270 to 1,800 W kg^(-1)),and the lifespan capability was *** results demonstrate that the proposed strategy of employing Te nanobelts as a protective layer holds great promise for enhancing the energy storage performance of zIBs,making them even more attractive as a viable energy storage solution forthefuture.

关键词： Zn ion battery Anode Protective layer Tellurium Nanobelt

Sustainable Furfural Biomass Feedstocks Electrooxidation toward Value-Added Furoic Acid with Energy-Saving H_(2) Fuel Production Using Pt-Decorated Co_(3)O_(4) Nanospheres

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Energy & Environmental Materials 2024年第2期7卷 350-358页

作者： Talshyn Begildayeνa Jayaraman Theerthagiri Seung Jun Lee Ahreum Min Gyeong-Ah kim Siνakumar Manickam Myong Yong Choi Department of Chemistry(BK21 FOUR) Core-Facility Center for Photochemistry&NanomaterialsResearch Institute of Natural SciencesGyeongsang National UniversityJinju 52828South Korea Petroleum and Chemical Engineering Faculty of EngineeringUniversiti Teknologi BruneiJalan Tungku Link GadongBandar Seri Begawan BE1410Brunei Darussalam

Here,furfural oxidation was performed to replace the kinetically sluggish O_(2)evolution reaction(OER).Pt-Co_(3)O_(4)nanospheres were developed via pulsed laser ablation in liquid(PLAL)in a single step for the paired electrocatalysis of an H_(2)evolution reaction(HER)and furfural oxidation reaction(FOR).The FOR afforded a high furfural conversion(44.2%)with a major product of 2-furoic acid after a 2-h electrolysis at 1.55 V versus reversible hydrogen electrode in a 1.0-M KOH/50-mM furfural *** Pt-Co_(3)O_(4)electrode exhibited a small overpotential of 290 mV at 10 mA cm^(-2).As an anode and cathode in an electrolyzer system,the Pt-Co_(3)O_(4)electrocatalyst required only a small applied cell voltage of~1.83 V to deliver 10 mA cm^(-2),compared with that of the pure water electrolyzer(OER||HER,~1.99 V).This study simultaneously realized the integrated production of energy-saving H_(2)fuel at the cathode and 2-furoic acid at the anode.

关键词： biomass conversion electrochemical furfural oxidation overall water splitting Pt-Co_(3)O_(4)electrocatalyst pulsed laser ablation in liquid