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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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Intelligent structured nanocomposite adhesive for bioelectronics and soft robots

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Nano Research 2024年第2期17卷 534-549页

作者： Yeon soo Lee Min-Seok kim Da Wan kim Changhyun Pang School of Chemical Engineering Sungkyunkwan University(SKKU)Suwon 16419Republic of Korea Mechanical Metrology Group Korea Research Institute of Standards and ScienceDaejeon 34113Republic of Korea Department of Electronic Engineering Korea National University of TransportationChungbuk 27469Republic of Korea Samsung Advanced Institute for Health Sciences and Technology Sungkyunkwan University(SKKU)Suwon 16419Republic of Korea

The remarkable functionality of biological systems in detecting and adapting to various environmental conditions has inspired the design of the latest electronics and robots with advanced *** review focuses on intelligent bio-inspired strategies for developing soft bioelectronics and robotics that can accommodate nanocomposite adhesives and integrate them into biological *** underlying principles of the material and structural design of nanocomposite adhesives were investigated for practical applications with excellent functionalities,such as soft skin-attachable health care sensors,highly stretchable adhesive electrodes,switchable adhesion,and untethered soft *** addition,we have discussed recent progress in the development of effective fabrication methods for micro/nanostructures for integration into devices,presenting the current challenges and prospects.

关键词： biomimetics bio-adhesive switchable adhesion bioelectronics nanocomposite soft robotics

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Integration of earth-abundant cocatalysts for high-performance photoelectrochemical energy conversion

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Journal of Energy Chemistry 2024年第1期88卷 336-355,I0008页

作者： Joonhee Ma Sang Hyun Ahn soo Young kim Department of Materials Science and Engineering Korea UniversitySeoul 02841Republic of Korea School of Chemical Engineering and Materials Science Chung-Ang University84 Heukseok-roDongjak-guSeoul 06974Republic of Korea

Photoelectrochemical(PEC)energy conversion has emerged as a promising and efficient approach to sustainable energy harvesting and *** utilizing semiconductor photoelectrodes,PEC devices can harness solar energy and drive electrochemical reactions such as water splitting or carbon dioxide(CO_(2))reduction to generate clean fuels and value-added ***,PEC energy conversion faces several challenges such as high overpotential,sluggish reaction kinetics,charge carrier recombination,and stability issues,which limit its practical ***,significant research has been conducted to improve the overall conversion efficiency of PEC *** particularly promising approach is the use of cocatalysts,which involves introducing specific cocatalysts onto the photoelectrode surface to promote charge separation,improve reaction kinetics,and reduce the overpotential,thereby enhancing the overall performance of PEC energy *** review provides a comprehensive overview of the recent developments in the earth-abundant cocatalysts for PEC water splitting and CO_(2) *** main earth-abundant catalysts for the PEC water splitting include transition-metal dichalcogenide(TMD)-based materials,metal phosphides/carbides,and metal oxides/***,PEC-CO_(2)RR was divided into C_(1) and C_(2+)based on the final product since various products could be produced,focusing on diverse earth-abundant materials-based *** addition,we provide and highlight key advancements achieved in the very recent reports on novel PEC system design engineering with ***,the current problems associated with PEC systems are discussed along with a suggested direction to overcome these obstacles.

关键词： Solar energy Photo-electrochemical Water splitting CO_(2)reduction Cocatalysts

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Vacuum-free lamination via controlled polymer adhesion for selective photogeneration and photodetection

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Carbon Energy 2024年第7期6卷 205-218页

作者： Min soo kim Jihyun Lim Woongsik Jang Dong Hwan Wang Department of Intelligent Semiconductor Engineering Chung-Ang UniversitySeoulRepublic of Korea School of Integrative Engineering Chung-Ang UniversitySeoulRepublic of Korea

This study attempts to develop a reproducible thin-film formation technique called vacuum-free(VF)lamination,which transfers thin films using elastomeric polymer-based laminating ***,by controlling the interface characteristics of the mediator based on the work of adhesion,VF lamination is successfully performed for various thicknesses(from 20 to 240 nm)of a conjugated photoactive material composed of poly[(2,6-(4,8-bis(5-(2-ethylhexyl-3-fluoro)thiophen-2-yl)-benzo[1,2-b:4,5-bʹ]dithiophene))-alt-(5,5-(1ʹ,3ʹ-di-2-thienyl-5ʹ,7ʹ-bis(2-ethylhexyl)benzo[1ʹ,2ʹ-c:4ʹ,5ʹ-cʹ]dithiophene-4,8-dione)](a polymer donor)and 2,2ʹ-((2Z,2ʹZ)-((12,13-bis(2-butyloctyl)-3,9-diundecyl-12,13-dihydro-[1,2,5]thiadiazolo[3,4-e]thieno[2ʹʹ,3ʹʹ:4ʹ,5ʹ]thieno[2ʹ,3ʹ:4,5]pyrrolo[3,2-g]thieno[2ʹ,3ʹ:4,5]thieno[3,2-b]indole-2,10-diyl)bis(methanylylidene))bis(5,6-difluoro-3-oxo-2,3-dihydro-1H-indene-2,1-diylidene))dimalononitrile(a nonfullerene acceptor).Interestingly,the organic photovoltaic and photodetecting applications,prepared by the VF lamination process,showed superior performance compared to those of devices prepared by conventional *** is due to the overturned surface morphology,which led to enhanced charge transport ability and blocking of the externally injected ***,the reproducible VF lamination process,exploiting an adhesion-based elastomeric polymer mediator,is a promising thin-film formation technique for developing efficient next-generation organic optoelectronic materials consistent with the solution process.

关键词： conjugated nonfullerene acceptor photodetectors photovoltaics polymer vacuum-free lamination

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Retinal artery/arteriole occlusion risks after endovascular treatment for unruptured intracranial aneurysm

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Stroke & Vascular Neurology 2024年第3期9卷 295-305,I0251-I0263页

作者： Hae Rang kim Min Jeoung kim Sunyeup kim Myung soo Chang Dong Joon kim Byung Moon kim Keun Young Park Yong Bae kim Christopher Seungkyu Lee Suk Ho Byeon Sung soo kim Seung Won Lee Yong Joon kim Department of Ophthalmology CHA Bundang Medical CenterCHA University College of MedicineSeongnamKorea(the Republic of) Department of Neurosurgery Severance Stroke CenterSeverance HospitalYonsei University College of MedicineSeoulKorea(the Republic of) Department of Neurosurgery Uijeongbu St.Mary’s HospitalThe Catholic University of Korea College of MedicineUijeongbuKorea(the Republic of) Department of Medical AI Sungkyunkwan University School of MedicineSuwonKorea(the Republic of) Department of Ophthalmology Institute of Vision ResearchYonsei University College of MedicineSeoulKorea(the Republic of) Department of Radiology Severance Stroke CenterSeverance HospitalYonsei University College of MedicineSeoulKorea(the Republic of) Department of Precision Medicine Sungkyunkwan University School of MedicineSuwonKorea(the Republic of)

Background To evaluate the association between retinal artery/arteriole occlusion(RAO)and unruptured intracranial aneurysm(UIA).Methods Incident UIA patients from a nationwide cohort(n=253240)were categorised into three groups based on subsequent treatment:observation(n=208993),microsurgical clipping(n=14168)and endovascular treatment(EVT)groups(n=30079).The incidence and the incident time of RAO were *** of RAO and associated risk factors were ***,a hospital cohort comprising 2569 consecutive UIA patients treated at a tertiary hospital was analysed with detailed clinical information of *** In the nationwide cohort analysis,the incidence of RAO was significantly higher in EVT group than in observation and clipping groups,especially within 60 days(early RAO(within 60 days):HR=4.00,95%CI:2.44 to 6.56);delayed RAO(after 60 days:HR=1.74,95%CI:1.13 to 2.68).Multivariable analysis showed that the presence of chronic kidney disease(p=0.009)and use of a balloon microcatheter during the procedure(p=0.013)were associated with a higher risk of *** hospital cohort analysis,11(0.8%)cases of RAO occurred after EVT,whereas none occurred after microsurgical clipping(p<0.001).Patients with RAO were younger and received balloon microcatheters more frequently than their *** cases of RAO(90.9%)occurred in paraclinoid aneurysms,where EVT was preferred over microsurgical *** Performing EVT for UIA may increase the risk of subsequent *** should be taken when treating paraclinoid aneurysms with balloon microcatheters.

关键词： treatment nationwide balloon

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Vastly Synergistic Fe_(2)CuNiS_(4)-Nanoarchitectures Anchored 2D-Nano-Sandwich Derived from Flower-Like-CuFeS_(2)/N-Graphene and Cube-Like-NiFeS_(2)/N-CNTs for Water Oxidation and Nitrophenol Reduction

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Energy & Environmental Materials 2024年第6期7卷 274-289页

作者： Gopiraman Mayakrishnan Ramkumar Vanaraj Junpeng Xiong Muhammad Farooq Azeem Ullah Keqin Zhang Seong Cheol kim Ick soo kim Nano Fusion Technology Research Group Division of Molecules and PolymersInstitute for Fiber Engineering(IFES)Interdisciplinary Cluster for Cutting Edge Research(ICCER)Shinshu UniversityTokida 3-15-1UedaNagano 386-8567Japan School of Chemical Engineering Yeungnam UniversityGyeongsan 38541Korea Graduate School of Medicine Scienceand TechnologyShinshu UniversityTokida 3-15-1UedaNagano 386-8567Japan National Engineering Laboratory for Modern Silk College of Textile and Clothing EngineeringSoochow UniversitySuzhou 215123China

Surface area,pore properties,synergistic behavior,homogenous dispersion,and interactions between carbon matrix and metal-nanostructures are the key factors for achieving the better performance of carbon-metal based(electro)***,the traditional hydro-or solvothermal preparation of(electro)catalysts,particularly,bi-or tri-metallic nanostructures anchored graphene(G)or carbon nanotubes(CNTs),often pose to poor metal–support interaction,low synergism,and patchy *** first,bimetallic flower-like-CuFeS_(2)/NG and cube-like-NiFeS_(2)/NCNTs nanocomposites were prepared by solvothermal *** resultant bimetallic nanocomposites were employed to derive the 2D-nano-sandwiched Fe_(2)CuNiS_(4)/NGCNTs-SW(electro)catalyst by a very simple and green urea-mediated“mix-heat”*** desired physicochemical properties of Fe_(2)CuNiS_(4)/NGCNTs-SW such as multiple active sites,strong metal-support interaction,homogenous dispersion and enhanced surface area were confirmed by various microscopic and spectroscopic *** the best of our knowledge,this is the first urea-mediated“mix-heat”method for preparing 2D-nano-sandwiched carbon-metal-based(electro)*** Fe_(2)CuNiS_(4)/NGCNTs-SW was found to be highly effective for alkaline-mediated oxygen evolution reaction at low onset potential of 284.24 mV,and the stable current density of 10 mA cm^(−2) in 1.0 m KOH for 10 ***,the Fe_(2)CuNiS_(4)/NGCNTs-SW demonstrated excellent catalytic activity in the reduction of 4-nitrophenol with good kapp value of 87.71×10^(−2)s^(-1)and excellent reusability over five ***,the developed urea-mediated“mix-heat”method is highly efficient for the preparation of metal-nanoarchitectures anchored 2D-nano-sandwiched(electro)catalysts with high synergism,uniform dispersion and excellent metal-support interaction.

关键词： (electro)catalyst metal-sulfide nanoarchitectures mix-heat N-graphene/NCNTs synergistic effect urea

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Immediate secondary rhinoplasty using a folded dermofat graft for resolving complications related to silicone implants: A case report

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World Journal of Clinical Cases 2024年第14期12卷 2426-2430页

作者： Hoon kim Jong Hyup kim In Chang Koh soo Yeon Lim Department of Plastic and Reconstructive Surgery Konyang University HospitalUniversity of Konyang College of MedicineMyunggok Medical Research InstituteDaejeon 35365South Korea

BACKGROUND Various surgical techniques have been developed to enhance the nose shapes of Asian *** implant augmentation rhinoplasty is widely used because it is relatively easy to perform and often yields satisfactory ***,this technique may lead to complications,including ischemia,necrosis,and *** most appropriate management of these complications,including infection,is immediate implant removal and revision surgery once the accompanying inflammation has ***,the patient may experience distress from nasal deformities during the intervention *** SUMMARY Herein,we describe the case of a patient who underwent a secondary dorsal augmentation,with a folded dermofat graft harvested from the inguinal area and simultaneous implant removal,successfully preventing dimpling of the nasal *** This surgical method can effectively manage implant-related complications following augmentation rhinoplasty using a silicone implant and provide satis-factory patient outcomes.

关键词： Complications Nose deformities Acquired Rhinoplasty Dermofat Surgery Plastic Case report

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Evolution of nonmetallic inclusions in 80-t 9CrMoCoB large-scale ingots during electroslag remelting process

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International Journal of Minerals,Metallurgy and Materials 2024年第7期31卷 1525-1539页

作者： Shengchao Duan Min Joo Lee Yao Su Wangzhong Mu Dong soo kim Joo Hyun Park School of Mechanical and Materials Engineering North China University of TechnologyBeijing 100144China Department of Materials Science and Chemical Engineering Hanyang UniversityAnsan 15588Rep.of Korea Department of Materials Science and Engineering KTH Royal Institute of TechnologyBrinellvägen 23Stockholm 10044Sweden Department of Engineering Science and Mathematics Division of Materials ScienceLuleåUniversity of Technology97187 LuleåSweden Casting&Forging Business Unit Nuclear Business GroupDoosan EnerbilityChangwon 51711Rep.of Korea

In combination with theoretical calculations,experiments were conducted to investigate the evolution behavior of nonmetallic inclusions(NMIs)during the manufacture of large-scale heat-resistant steel ingots using 9CrMoCoB heat-resistant steel and CaF_(2)–CaO–Al_(2)O_(3)–SiO_(2)–B_(2)O_(3)electroslag remelting(ESR)-type slag in an 80-t industrial ESR *** main types of NMI in the consumable electrode comprised pure alumina,a multiphase oxide consisting of an Al_(2)O_(3)core and liquid CaO–Al_(2)O_(3)–SiO_(2)–MnO shell,and M_(23)C_(6)carbides with an MnS *** Al_(2)O_(3)and MnS inclusions had higher precipitation temperatures than the M_(23)C_(6)-type carbide under equilibrium and nonequilibrium solidification ***,inclusions can act as nucleation sites for carbide layer *** ESR process completely removed the liquid CaO–Al_(2)O_(3)–SiO_(2)–MnO oxide and MnS inclusion with a carbide shell,and only the Al_(2)O_(3)inclusions and Al_(2)O_(3)core with a carbide shell occupied the remelted *** M_(23)C_(6)-type carbides in steel were determined as Cr_(23)C_(6)based on the analysis of transmission electron microscopy *** substitution of Cr with W,Fe,or/and Mo in the Cr_(23)C_(6)lattice caused slight changes in the lattice parameter of the Cr_(23)C_(6)***,Cr_(21.34)Fe_(1.66)C_(6),(Cr_(19)W_(4)C_(6),Cr_(18.4)Mo_(4.6)C_(6),and Cr_(16)Fe_(5)Mo_(2)C_(6)can match the fraction pattern of Cr_(23)C_(6)*** Al_(2)O_(3)inclusions in the remelted ingot formed due to the reduction of CaO,SiO_(2),and MnO components in the liquid *** increased Al content in liquid steel or the higher supersaturation degree of Al_(2)O_(3)precipitation in the remelted ingot than that in the electrode can be attributed to the evaporation of CaF_(2)and the increase in CaO content in the ESR-type slag.

关键词： nonmetallic inclusion heat-resistant steel electroslag remelting M_(23)C_(6) carbide MnS inclusion supersaturation degree

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TonEBP expression is essential in the IL-1β–induced migration and invasion of human A549 lung cancer cells

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Oncology Research 2024年第1期32卷 151-161页

作者： HEE JU SONG TAEHEE kim HAN NA CHOI soo JIN kim SANG DO LEE Department of Physiology School of MedicineChungnam National UniversityDaejeon35015Korea

Lung cancer has the highest mortality rate among all cancers,in part because it readily *** tumor microenvironment,comprising blood vessels,fibroblasts,immune cells,and macrophages[including tumor-associated macrophages(TAMs)],is closely related to cancer cell growth,migration,and *** secrete several cytokines,including interleukin(IL)-1β,which participate in cancer migration and invasion.p21-activated kinase 1(PAK1),an important signaling molecule,induces cell migration and invasion in several ***responsive enhancer-binding protein(TonEBP)is also known to participate in cancer cell growth,migration,and ***,the mechanisms by which it increases lung cancer migration remain ***,in this study,we aimed to elucidate the mechanisms by which IL-1βand TonEBP affect lung cancer cell migration and *** found that A549 cocultured-MΦ-secreted IL-1βinduced A549 cell migration and invasion via the PAK1 *** deficiency reduced A549 cell migration and invasion and increased responsiveness to IL-1β–induced migration and ***1 phosphorylation,which was promoted by IL-1β,was reduced when TonEBP was *** results suggest that TonEBP plays an important role in IL-1βinduction and invasiveness of A549 cells via the PAK1 *** findings could be valuable in identifying potential targets for lung cancer treatment.

关键词： Lung cancer TonEBP Tumor microenvironment Tumor-associated macrophage IL-1β

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RUFY4 deletion prevents pathological bone loss by blocking endo-lysosomal trafficking of osteoclasts

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Bone Research 2024年第2期12卷 407-420页

作者： Minhee kim Jin Hee Park Miyeon Go Nawon Lee Jeongin Seo Hana Lee Doyong kim Hyunil Ha Taesoo kim Myeong Seon Jeong Suree kim Taesoo kim Han Sung kim Dongmin Kang Hyunbo Shim soo Young Lee Department of Life Science Ewha Womans UniversitySeoul 03760South Korea The Research Center for Cellular Homeostasis Ewha Womans UniversitySeoul 03760South Korea Department of Biomedical Engineering Yonsei UniversityWonju 26493South Korea KM Convergence Research Division Korea Institute of Oriental MedicineDaejeon 34054South Korea Chuncheon Center Korea Basic Science InstituteChuncheon 24341South Korea Fluorescence Core Imaging Center and Bioimaging Data Curation Center Ewha Womans UniversitySeoul 03760South Korea Multitasking Macrophage Research Center Ewha Womans UniversitySeoul 03760South Korea

Mature osteoclasts degrade bone matrix by exocytosis of active proteases from secretory lysosomes through a ruffled ***,the molecular mechanisms underlying lysosomal trafficking and secretion in osteoclasts remain largely ***,we show with GeneChip analysis that RUN and FYVE domain-containing protein 4(RUFY4)is strongly upregulated during *** lacking Rufy4 exhibited a high trabecular bone mass phenotype with abnormalities in osteoclast function in ***,deleting Rufy4 did not affect osteoclast differentiation,but inhibited bone-resorbing activity due to disruption in the acidic maturation of secondary lysosomes,their trafficking to the membrane,and their secretion of cathepsin K into the extracellular ***,RUFY4 promotes late endosome-lysosome fusion by acting as an adaptor protein between Rab7 on late endosomes and LAMP2 on primary ***,Rufy4-deficient mice were highly protected from lipopolysaccharide-and ovariectomy-induced bone ***,RUFY4 plays as a new regulator in osteoclast activity by mediating endo-lysosomal trafficking and have a potential to be specific target for therapies against bone-loss diseases such as osteoporosis.

关键词： osteoclast inhibited traffic

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