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

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

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Environmentally adaptive reshaping of plant photomorphogenesis by karrikin and strigolactone signaling

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Journal of Integrative Plant Biology 2024年第5期66卷 865-882页

作者： Young-joon Park Bo Eun Nam Chung-Mo Park Department of Smart Farm Science Kyung Hee UniversityYongin 17104Korea Departmentof Biological Sciences Seoul National UniversitySeoul 08826Korea Department of Chemistry Seoul National UniversitySeoul 08826Korea

Coordinated morphogenic adaptation of growing plants is critical for their survival and propagation under fluctuating *** morphogenic responses to light and warm temperatures,termed photomorphogenesis and thermomorphogenesis,respectively,have been extensively studied in recent *** photomorphogenesis,plants actively reshape their growth and developmental patterns to cope with changes in light ***,photomorphogenesis is closely associated with diverse growth hormonal ***,accumulating evidence indicates that light-directed morphogenesis is profoundly affected by two recently identified phytochemicals,karrikins(KARs)and strigolactones(SLs).KARs and SLs are structurally related butenolides acting as signaling molecules during a variety of developmental steps,including seed *** receptors and signaling mediators have been identified,and associated working mechanisms have been explored using gene-deficient mutants in various plant *** particular interest is that the KAR and SL signaling pathways play important roles in environmental responses,among which their linkages with photomorphogenesis are most comprehensively studied during seedling *** this review,we focus on how the phytochemical and light signals converge on the optimization of morphogenic *** also discuss molecular mechanisms underlying the signaling crosstalks with an aim of developing potential ways to improve crop productivity under climate changes.

关键词： karrikins morphogenic adaptation photomorphogenesis seedling establishment strigolactones

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Emission wavelength selection via anomalous polarized fluorescence in ZnO-C nanowires

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Nano Research 2024年第5期17卷 4489-4497页

作者： joon Kiat Kang Kim Yong Lim Chorng Haur Sow Department of Physics National University of SingaporeSingapore 117542Singapore

Defect fluorescence from high aspect ratio semiconductor nanowires typically displays a weak polarization parallel to the nanowire’s long axis due to dielectric mismatch in high aspect ratio ***,anomalous 2.2 eV defect fluorescence distinctly polarized perpendicular to the nanowire is observed and measured from carbon-incorporated zinc oxide *** observations are significant because polarized defect emissions with consistent polarization on a mesoscopic scale are *** a systematic study and comparison of experimental results with density functional theory calculations,an oriented defect complex comprising carbon substituting on an oxygen site and an oxygen vacancy(CO-VO)is deduced to be responsible for the anomalous yellow fluorescence,demonstrating a method for relating atomic-scale defect geometry to mesoscopic *** anomalous emission can appear in both green-and red-fluorescing nanowires grown with different carbon concentrations,verifying the independence and uniqueness of the 2.2 eV *** allows for polarization-dependent emission wavelength selection from a single nanowire.

关键词： anomalous polarization defects fluorescence zinc oxide carbon

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Callus proliferation-induced hypoxic microenvironment decreases shoot regeneration competence in Arabidopsis

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Molecular Plant 2024年第3期17卷 395-408页

作者： Dohee Koo Hong Gil Lee Soon Hyung Bae Kyounghee Lee Pil joon Seo Department of Chemistry Seoul National UniversitySeoul 08826Korea Plant Genomics and Breeding Institute Seoul National UniversitySeoul 08826Korea Research Institute of Basic Sciences Seoul National UniversitySeoul 08826Korea

Plants are aerobic organisms that rely on molecular oxygen for respiratory energy *** conditions,with oxygen levels ranging between 1%and 5%,usually limit aerobic respiration and affect plant growth and ***,we demonstrate that the hypoxic microenvironment induced by active cell proliferation during the two-step plant regeneration process intrinsically represses the regener-ation competence of the callus in Arabidopsis *** showed that hypoxia-repressed plant regener-ation is mediated by the RELATED TO APETALA2.12(RAP2.12)protein,a memberof the Ethylene Response Factor VIl(ERF-Vll)*** found that the hypoxia-activated RAP2.12 protein promotes salicylic acid(SA)biosynthesis and defense responses,thereby inhibiting pluripotency acquisition and de novo shoot regeneration in *** and genetic analyses revealed that RAP2.12 could bind directly to the SALICYLIC ACID INDUCTION DEFICIENT 2(SID2)gene promoter and activate SA biosynthesis,repressing plant regeneration possibly via a PLETHORA(PLT)-dependent ***,the rap2.12 mutant calli exhibits enhanced shoot regeneration,which is impaired by SA *** together,these find-ings uncover that the cell proliferation-dependent hypoxic microenvironment reduces cellular pluripotency and plant regeneration through the RAP2.12-SID2 module.

关键词： callus cell proliferation-induced hypoxia SID2 plant regeneration salicylic acid RAP2.12

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Durable hierarchical phosphorus‐doped biphase MoS_(2)electrocatalysts with enhanced H^(*)adsorption

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Carbon Energy 2024年第4期6卷 104-114页

作者： Yongteng Qian Jianmin Yu Zhiyi Lyu Qianwen Zhang Tae Hyeong Lee Huan Pang Dae joon Kang College of Pharmacy Jinhua PolytechnicJinhuaZhejiangChina Department of Physics Sungkyunkwan UniversitySuwonGyeonggi‐doRepublic of Korea International Collaborative Laboratory of 2D Materials for Optoelectronic Science and Technology of Ministry of Education Institute of Microscale OptoelectronicsShenzhen UniversityShenzhenGuangdongChina School of Chemistry and Chemical Engineering Yangzhou UniversityYangzhouJiangsuChina

Phase engineering is an efficient strategy for enhancing the kinetics of electrocatalytic ***,phase engineering was employed to prepare high‐performance phosphorous‐doped biphase(1T/2H)MoS_(2)(P‐BMS)nanoflakes for hydrogen evolution reaction(HER).The doping of MoS_(2)with P atoms modifies its electronic structure and optimizes its electrocatalytic reaction kinetics,which significantly enhances its electrical conductivity and structural stability,which are verified by various characterization tools,including X‐ray photoelectron spectroscopy,high‐resolution transmission electron microscopy,X‐ray absorption near‐edge spectroscopy,and extended X‐ray absorption fine ***,the hierarchically formed flakes of P‐BMS provide numerous catalytic surface‐active sites,which remarkably enhance its HER *** optimized P‐BMS electrocatalysts exhibit low overpotentials(60 and 72 mV at 10 mA cm^(−2))in H_(2)SO_(4)(0.5 M)and KOH(1.0 M),*** mechanism of improving the HER activity of the material was systematically studied using density functional theory calculations and various electrochemical characterization *** study has shown that phase engineering is a promising strategy for enhancing the H*adsorption of metal sulfides.

关键词： 1T/2H MoS_(2) density functional theory electrocatalysts phase engineering phosphorous doping

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Wireless sequential dual light delivery for programmed PDT in vivo

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Light(Science & Applications) 2024年第6期13卷 1047-1061页

作者： Jiayi Liu Bowen Sun Wenkai Li Han-joon Kim Shu Uin Gan John S.Ho Juwita Norasmara Bte Rahmat Yong Zhang Department of Oncology The Second Xiangya HospitalCentral South UniversityChangshaHunan410011China Department of Biomedical Engineering College of Design and EngineeringNational University of SingaporeSingapore117585Singapore Department of Mechanical Engineering College of Design and EngineeringNational University of SingaporeSingapore117576Singapore Department of Electrical and Computer Engineering College of Design and EngineeringNational University of SingaporeSingapore117583Singapore Department of Medical IT Convergence Engineering Kumoh National Institute of TechnologyGumi39253Republic of Korea Department of Surgery Yong Loo Lin School of MedicineNational University of SingaporeSingapore119228Singapore The N.1 Institute for Health National University of SingaporeSingapore117456Singapore Institute for Health Innovation and Technology National University of SingaporeSingapore119276Singapore Department of Biomedical Engineering College of EngineeringCity University of Hong KongKowloonHong Kong SARChina

Using photodynamic therapy(PDT)to treat deep-seated cancers is limited due to inefficient delivery of photosensitizers and low tissue penetration of *** nanocarriers are widely used for photosensitizer delivery,while the self-quenching of the encapsulated photosensitizers would impair the PDT ***,the generated short-lived reactive oxygen spieces(ROS)can hardly diffuse out of nanocarriers,resulting in low PDT ***,a smart nanocarrier system which can be degraded by light,followed by photosensitizer activation can potentially overcome these limitations and enhance the PDT efficacy.A light-sensitive polymer nanocarrier encapsulating photosensitizer(RB-M)was *** implantable wireless dual wavelength microLED device which delivers the two light wavelengths sequentially was developed to programmatically control the release and activation of the loaded *** transmitter coils with matching resonant frequencies allow activation of the connected LEDs to emit different wavelengths *** irradiation time,dose,and RB-M concentration were determined using an agent-based digital simulation *** vitro and in vivo validation experiments in an orthotopic rat liver hepatocellular carcinoma disease model confirmed that the nanocarrier rupture and sequential low dose light irradiation strategy resulted in successful PDT at reduced photosensitizer and irradiation dose,which is a clinically significant event that enhances treatment safety.

关键词： PDT overcome hardly

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Tailoring local structures of atomically dispersed copper sites for highly selective CO_(2) electroreduction

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Carbon Energy 2024年第4期6卷 79-90页

作者： Kyung‐Jong Noh Byoung joon Park Ying Wang Yejung Choi Sang‐Hoon You Yong‐Tae Kim Kug‐Seung Lee Jeong Woo Han Department of Chemical Engineering Pohang University of Science and Technology(POSTECH)PohangGyeongbukRepublic of Korea Department of Materials Science and Engineering Pohang University of Science and Technology(POSTECH)PohangGyeongbukRepublic of Korea Pohang Accelerator Laboratory(PAL) Beamline DivisionPohangGyeongbukRepublic of Korea

Atomically‐dispersed copper sites coordinated with nitrogen‐doped carbon(Cu–N–C)can provide novel possibilities to enable highly selective and active electrochemical CO_(2) reduction ***,the construction of optimal local electronic structures for nitrogen‐coordinated Cu sites(Cu–N_(4))on carbon remains ***,we synthesized the Cu–N–C catalysts with atomically‐dispersed edge‐hosted Cu–N_(4) sites(Cu–N_(4)C_(8))located in a micropore between two graphitic sheets via a facile method to control the concentration of metal ***‐hosted Cu–N_(4)C_(8) catalysts outperformed the previously reported M–N–C catalysts for CO_(2)‐to‐CO conversion,achieving a maximum CO Faradaic efficiency(FECO)of 96%,a CO current density of–8.97 mA cm^(–2) at–0.8 V versus reversible hydrogen electrode(RHE),and over FECO of 90%from–0.6 to–1.0 V versus *** studies revealed that the micropore of the graphitic layer in edge‐hosted Cu–N_(4)C_(8) sites causes the d‐orbital energy level of the Cu atom to shift upward,which in return decreases the occupancy of antibonding states in the*COOH *** research suggests new insights into tailoring the locally coordinated structure of the electrocatalyst at the atomic scale to achieve highly selective electrocatalytic reactions.

关键词： atomic local structure density functional theory electrochemical CO_(2)reduction metal nitrogen‐doped carbon single‐atom catalyst

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Body-Shaping Membrane to Regenerate Breast Fat by Elastic Structural Holding

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Research 2024年第1期2023卷 165-180页

作者： Hye-Seon Kim Jeongeun Park Hyun-Su Ha Sewoom Baek Chan Hee Lee Kyubae Lee Suji Park Jueun Kim Se Won Yi Hak-joon Sung Department of Medical Engineering Graduate School of Medical ScienceBrain Korea 21 ProjectYonsei University College of MedicineSeoul 03722Republic of Korea TMD LAB Co.Ltd. 6th Floor31Gwangnaru-ro 8-gilSeongdong-guSeoul 04799Republic of Korea

Tissue regeneration requires structural holding and movement support using tissue-type-specific aids such as bone casts,skin bandages,and joint ***,an unmet need exists in aiding breast fat regeneration as the breast moves following continuous body motion by exposing the breast fat to dynamic ***,the concept of elastic structural holding is applied to develop a shape-fitting moldable membrane for breast fat regeneration(“adipoconductive”)after surgical defects are *** membrane has the following key characteristics:(a)It contains a panel of honeycomb structures,thereby efficiently handling motion stress through the entire membrane;(b)a strut is added into each honeycomb in a direction perpendicular to gravity,thereby suppressing the deformation and stress concentration upon lying and standing;and(c)thermo-responsive moldable elastomers are used to support structural holding by suppressing large deviations of movement that occur *** elastomer became moldable upon a temperature shift above T_(m).The structure can then be fixed as the temperature *** a result,the membrane promotes adipogenesis by activating mechanotransduction in a fat miniature model with pre-adipocyte spheroids under continuous shaking in vitro and in a subcutaneous implant placed on the motion-prone back areas of rodents in vivo.

关键词： thereby shaking Elastic

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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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Stable immobilization of lithium polysulfides using three-dimensional ordered mesoporous Mn2O3 as the host material in lithium-sulfur batteries

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Carbon Energy 2024年第6期6卷 99-112页

作者： Sung joon Park Yun Jeong Choi Hyun-seung Kim Min Joo Hong Hongjun Chang Janghyuk Moon Young-Jun Kim Junyoung Mun Ki Jae Kim Department of Energy Science Sungkyunkwan UniversitySuwonGyeonggi-doRepublic of Korea Department of Energy Engineering Konkuk UniversitySeoulRepublic of Korea Advanced Batteries Research Center Korea Electronic Technology InstituteSeongnamRepublic of Korea Department of Future Energy Engineering Sungkyunkwan UniversitySuwonRepublic of Korea Department of Energy Systems Engineering Chung-Ang UniversitySeoulRepublic of Korea SKKU Advanced Institute of Nanotechnology Sungkyunkwan UniversitySuwonGyeonggi-doRepublic of Korea SKKU Institute of Energy Science and Technology(SIEST) Sungkyunkwan UniversitySuwonRepublic of Korea School of Advanced Materials Science and Engineering Sungkyunkwan UniversitySuwonRepublic of Korea

Lithium-sulfur batteries(LSBs)have drawn significant attention owing to their high theoretical discharge capacity and energy ***,the dissolution of long-chain polysulfides into the electrolyte during the charge and discharge process(“shuttle effect”)results in fast capacity fading and inferior electrochemical *** this study,Mn_(2)O_(3)with an ordered mesoporous structure(OM-Mn_(2)O_(3))was designed as a cathode host for LSBs via KIT-6 hard templating,to effectively inhibit the polysulfide shuttle ***-Mn_(2)O_(3)offers numerous pores to confine sulfur and tightly anchor the dissolved polysulfides through the combined effects of strong polar-polar interactions,polysulfides,and sulfur chain *** OM-Mn_(2)O_(3)/S composite electrode delivered a discharge capacity of 561 mAh g-1 after 250 cycles at 0.5 C owing to the excellent performance of OM-Mn_(2)O_(3).Furthermore,it retained a discharge capacity of 628mA h g-1 even at a rate of 2 C,which was significantly higher than that of a pristine sulfur electrode(206mA h g-1).These findings provide a prospective strategy for designing cathode materials for high-performance LSBs.

关键词： host material lithium-sulfur battery ordered mesoporous structure shuttle effect transition-metal oxides

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