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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

Wearable Triboelectric Nanogenerators Based on Printed Polyvinylidene Fluoride Films Incorporated with Cobalt-Based Metal-Organic Framework for Self-Powered Mobile Electronics

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Energy & Environmental Materials 2024年第4期7卷 396-403页

作者： Myeong-Hyeon kim Sang-joon Park Tae-Jun Ha Department of Electronic Materials Engineering Kwangwoon University

In this study,wearable triboelectric nanogenerators comprising bar-printed polyvinylidene fluoride (PVDF) films incorporated with cobalt-based metalorganic framework (Co-MOF) were *** enhanced output performance of the TENCs was attributed to the phase transition of PVDF from α-crystals to β-crystals,as facilitated by the incorporation of the MOF.

关键词： bar printing phase transition polyvinylidene fluoride incorporated with cobalt-based metal–organic framework self-powered mobile electronics wearable triboelectric nanogenerators

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

Nuclear receptor coactivator 6 is a critical regulator of NLRP3 inflammasome activation and gouty arthritis

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Cellular & Molecular Immunology 2024年第3期21卷 227-244页

作者： Kang-Gu Lee bong-Ki Hong Saseong Lee Naeun Lee Seung-Whan kim Donghyun kim Wan-Uk kim Center for Integrative Rheumatoid Transcriptomics and Dynamics The Catholic University of KoreaSeoul 06591Republic of Korea Department of Biomedicine&Health Sciences The Catholic University of KoreaSeoul 06591Republic of Korea Department of Pharmacology Asan Medical CenterUniversity of Ulsan College of MedicineSeoul 05505Republic of Korea Bio-Medical Institute of Technology University of UlsanSeoul 05505Republic of Korea Department of Microbiology and Immunology Seoul National University College of MedicineSeoul 03080Republic of Korea Institute of Infectious Diseases Seoul National University College of MedicineSeoul 03080Republic of Korea Division of Rheumatology Department of Internal MedicineThe Catholic University of KoreaSeoul 06591Republic of Korea

Transcriptional coactivators regulate the rate of gene expression in the *** receptor coactivator 6(NCOA6),a coactivator,has been implicated in embryonic development,metabolism,and cancer pathogenesis,but its role in innate immunity and inflammatory diseases remains ***,we demonstrated that NCOA6 was expressed in monocytes and macrophages and that its level was increased under proinflammatory ***,nuclear NCOA6 was found to translocate to the cytoplasm in activated monocytes and then become incorporated into the inflammasome with NLRP3 and ASC,forming cytoplasmic ***,NCOA6 associated with the ATP hydrolysis motifs in the NACHT domain of NLRP3,promoting the oligomerization of NLRP3 and ASC and thereby instigating the production of IL-1βand active *** note,Ncoa6 deficiency markedly inhibited NLRP3 hyperactivation caused by the Nlrp3^(R258W) gain-of-function mutation in *** ablation of Ncoa6 substantially attenuated the severity of two NLRP3-dependent diseases,folic-induced acute tubular necrosis and crystal-induced arthritis,in *** with these findings,NCOA6 was highly expressed in macrophages derived from gout patients,and NCOA6-positive macrophages were significantly enriched in gout macrophages according to the transcriptome profiling ***,NCOA6 is a critical regulator of NLRP3 inflammasome activation and is therefore a promising target for NLRP3-dependent diseases,including gout.

关键词： Nuclear receptor coactivator 6 Nuclear-to-cytoplasmic translocation NLRP3 inflammasome NACHT domain Gouty arthritis

Chemical and mechanical properties of stainless, environment-friendly, and nonflammable Mg alloys (SEN alloys): A review

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Journal of Magnesium and Alloys 2024年第3期12卷 841-872页

作者： Jong Un Lee Hyun Ji kim Sang-Cheol Jin Ye Jin kim Young Min kim bong Sun You Jun Ho Bae Sung Hyuk Park Advanced Metals Division Korea Institute of Materials ScienceChangwon 51508Republic of Korea Department of Materials Science and Metallurgical Engineering Kyungpook National UniversityDaegu 41566Republic of Korea Missile Research Institute Agency for Defense DevelopmentDaejeon 34060Republic of Korea

This review article provides overall understanding of stainless,environment-friendly,and nonflammable Mg alloys(SEN alloys)recently developed at the Korea Institute of Materials *** alloys are produced by adding small amounts of Ca and Y(each<1 wt%)into commercial Mg–Al based alloys,resulting in exceptional ignition and corrosion resistances and impressive mechanical *** main advantages of SEN alloys are as follows.(1)A dense multi-oxide layer of SEN alloys comprising MgO,CaO,and Y_(2)O_(3) impedes the outward dispersion of Mg vapor and the inward penetration of O_(2) during oxidation,thereby enhancing the oxidation and ignition resistances.(2)The presence of Ca-and Y-based second-phase particles in SEN alloys can enhance their corrosion resistance because Ca-containing particles prevent the spread of corrosion,and the replacement of Al-containing particles with less noble ones containing Y(e.g.,Al–Mn–Y or Al–Y particles)retards corrosion.(3)The addition of minor amounts of Ca and Y renders excellent mechanical properties due to improved strengthening *** enhanced properties are attributed to more pronounced dynamic recrystallization and grain refining behaviors caused by the second-phase particles during extrusion.(4)Despite the presence of various types of second-phase particles,the fatigue properties of SEN9 alloys are similar to those of commercial AZ91 alloys.(5)Simultaneous introduction of Ca and Y suppresses the formation of Mg17Al12 discontinuous precipitates during aging,leading to the enhanced elongation of aged SEN alloys.(6)Adding mischmetal into the SEN9 alloy leads to a six-fold enhancement in ***,the studies conducted on SEN alloys demonstrate their excellent ignition and corrosion resistances and mechanical properties,which broaden the industrial applications of Mg alloys by addressing their inherent weaknesses.

关键词： SEN magnesium alloy Corrosion resistance Ignition resistance Mechanical properties Extrudability.

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Stable immobilization of lithium polysulfides using three-dimensional ordered mesoporous Mn_(2)O_(3) 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

Microsphere-assisted hyperspectral imaging:super-resolution,non-destructive metrology for semiconductor devices

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Light(Science & Applications) 2024年第6期13卷 1098-1111页

作者： Jangryul Park Youngsun Choi Soonyang Kwon Youngjun Lee Jiwoong kim Jae-joon kim Jihye Lee Jeongho Ahn Hidong Kwak Yusin Yang Taeyong Jo Myungjun Lee Kwangrak kim Metrology and Inspection Equipment R&D Team Mechatronics ResearchSamsung Electronics Co.Ltd.1-1 Samsungjeonja-rohwaseong-siGyeonggi-do18848Republic of Korea Process Development Department DRAM Process Development TeamSemiconductor R&D CenterSamsung Electronics Co.Ltd.1-1 Samsungjeonja-rohwaseong-siGyeonggi-do18848Republic of Korea Process Development Department Semiconductor R&D CenterSamsung Electronics Co.Ltd.1-1 Samsungjeonja-rohwaseong-siGyeonggi-do18848Republic of Korea

As semiconductor devices shrink and their manufacturing processes advance,accurately measuring in-cell critical dimensions(CD)becomes increasingly *** test element group(TEG)measurements are becoming inadequate for representing the fine,repetitive patterns in cell *** non-destructive metrology technologies like optical critical dimension(OCD)are limited due to their large spot diameter of approximately 25μm,which impedes their efficacy for detailed in-cell structural ***,there is a pressing need for small-spot and non-destructive metrology *** address this limitation,we demonstrate a microsphere-assisted hyperspectral imaging(MAHSI)system,specifically designed for small spot optical metrology with *** microsphere-assisted super-resolution imaging,this system achieves an optical resolution of 66 nm within a field of view of 5.6μm×5.6μ*** approach effectively breaks the diffraction limit,significantly enhancing the magnification of the *** MAHSI system incorporating hyperspectral imaging with a wavelength range of 400–790 nm,enables the capture of the reflection spectrum at each camera *** achieved pixel resolution,which is equivalent to the measuring spot size,is 14.4 nm/pixel and the magnification is *** MAHSI system enables measurement of local uniformity in critical areas like corners and edges of DRAM cell blocks,areas previously challenging to inspect with conventional OCD *** our knowledge,this approach represents the first global implementation of microsphere-assisted hyperspectral imaging to address the metrology challenges in complex 3D structures of semiconductor devices.

关键词： metrology resolution enable

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

Enhancement of porcine in vitro embryonic development through luteolin‑mediated activation of the Nrf2/Keap1 signaling pathway

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Journal of Animal Science and Biotechnology 2024年第2期15卷 600-613页

作者： Se-Been Jeon Pil-Soo Jeong Min Ju kim Hyo-Gu Kang bong-Seok Song Sun-Uk kim Seong-Keun Cho Bo-Woong Sim Futuristic Animal Resource&Research Center(FARRC) Korea Research Institute of Bioscience and Biotechnology(KRIBB)Cheongju 28116Republic of Korea Department of Animal Science College of Natural Resources&Life SciencePusan National UniversityMiryang 50463Republic of Korea Department of Animal Science and Biotechnology College of Agriculture and Life ScienceChungnam National UniversityDaejeon 34134Republic of Korea Department of Functional Genomics University of Science and TechnologyDaejeon 34113Republic of Korea Department of Animal Science Life and Industry Convergence Research Institute(RICRI)College of Natural Resources&Life SciencePusan National UniversityMiryang 50463Republic of Korea

Background Oxidative stress,caused by an imbalance in the production and elimination of intracellular reactive oxygen species(ROS),has been recognized for its detrimental effects on mammalian embryonic ***(Lut)has been documented for its protective effects against oxidative stress in various ***,its specific role in embryonic development remains *** study aims to investigate the influence of Lut on porcine embryonic development and to elucidate the underlying *** After undergoing parthenogenetic activation(PA)or in vitro fertilization,embryos supplemented with 0.5μmol/L Lut displayed a significant enhancement in cleavage and blastocyst formation rates,with an increase in total cell numbers and a decrease in the apoptosis rate compared to the *** on D2 and D6 revealed that embryos with Lut supplementation had lower ROS levels and higher glutathione levels compared to the ***,Lut supplementation significantly augmented mitochondrial content and membrane ***,activation of the Nrf2/Keap1 signaling pathway was observed in embryos supplemented with Lut,leading to the upregulation of antioxidant-related gene transcription *** further validate the relationship between the Nrf2/Keap1 signaling pathway and effects of Lut in porcine embryonic development,we cultured PA embryos in a medium supplemented with brusatol,with or without the inclusion of *** positive effects of Lut on developmental competence were negated by brusatol *** Our findings indicate that Lut-mediated activation of the Nrf2/Keap1 signaling pathway contributes to the enhanced production of porcine embryos with high developmental competence,and offers insight into the mechanisms regulating early embryonic development.

关键词： Luteolin Mitochondrial function Nrf2/Keap1 signaling pathway Oxidative stress Porcine embryo development

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