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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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Hyperreflective photonic crystals created by shearing colloidal dispersions at ultrahigh volume fraction

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Microsystems & Nanoengineering 2024年第1期10卷 161-173页

作者： Minji Kim Jong Bin Kim shin-hyun Kim Department of Chemical and Biomolecular Engineering Korea Advanced Institute of Science and Technology(KAIST)Daejeon 34141Republic of Korea

Colloidal crystallization serves as one of the most economic and scalable production methods for photonic ***,insufficient optical performance,nonuniformity and low reproducibility remain challenges for advanced high-value *** this study,we optimally formulate a photocurable dispersion of silica particles and apply shear flow to unify the orientation of the colloidal crystals,ensuring high optical performance and *** silica particles experience strong repulsion at ultrahigh volume fractions of 50%but demonstrate low mobility,leading to polycrystalline *** shear flow to the dispersions allows the silica particles to rearrange into larger crystalline domains with a unidirectional orientation along the *** shear-induced structural change produces absolute reflectivity at the stopband as high as 90%and a high transparency of 90%at off-resonant wavelengths with minimal diffusive ***,the strong interparticle repulsion ensures a uniform volume fraction of particles throughout the dispersion,reducing deviations in the optical *** intricately micropattern the photocurable dispersions using ***,the photonic films and patterns can be stacked to form multiple layers,displaying mixed structural colors and multiple reflectance peaks without sacrificing *** superior photonic materials hold promise for various optical applications,including optical components and anticounterfeiting patches.

关键词： properties. dispersion reflectivity

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Genetically encoded X-ray cellular imaging for nanoscale protein localization

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National Science Review 2020年第7期7卷 1218-1227页

作者： Huating Kong Jichao Zhang Jiang Li Jian Wang hyun-joon shin Renzhong Tai Qinglong Yan Kai Xia Jun Hu Lihua Wang Ying Zhu Chunhai Fan Bioimaging Center Shanghai Synchrotron Radiation FacilityZhangjiang Laboratory Shanghai Advanced Research Institute Chinese Academy of Sciences Division of Physical Biology CAS Key Laboratory of Interfacial Physics and Technology Shanghai Institute of Applied Physics Chinese Academy of Sciences Canadian Light Source Inc. University of Saskatchewan Pohang Accelerator Laboratory POSTECH School of Chemistry and Chemical Engineering Frontiers Science Center for Transformative Molecules and Shanghai Key Laboratory for Nucleic Acids Chemistry and NanomedicineInstitute of Molecular Medicine Renji Hospital School of Medicine Shanghai Jiao Tong University

Spatial resolution defines the physical limit of microscopes for probing biomolecular localization and interactions in cells. Whereas synchrotron-based X-ray microscopy(XRM) represents a unique approach for imaging a whole cell with nanoscale resolution due to its intrinsic nanoscale resolution and great penetration ability, existing approaches to label biomolecules rely on the use of exogenous tags that are multi-step and error-prone. Here, we repurpose engineered peroxidases as genetically encoded X-ray-sensitive tags(GXET) for site-specific labeling of protein-of-interest in mammalian cells. We find that 3,3-diaminobenzidine(DAB) polymers that are in-situ catalytically formed by fusion-expressed peroxidases are visible under XRM. Using this new tag, we imaged the protein location associated with the alteration of a DNA-methylation pathway with an ultra-high resolution of 30 nanometers. Importantly, the excellent energy resolution of XRM enables multicolor imaging using different peroxidase tags. The development of GXET enlightens the way to nanoscopic imaging for biological studies.

关键词： synchrotron-based X-ray microscopy cellular imaging nanoscale protein localization genetically encoded X-ray tags 3,3-diaminobenzidine polymers

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M1-polarized macrophage-derived cellular nanovesicle-coated lipid nanoparticles for enhanced cancer treatment through hybridization of gene therapy and cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3169-3183页

作者： Ha Eun shin Jun-Hyeok Han Seungyong shin Ga-hyun Bae Boram Son Tae-hyung Kim Hee Ho Park Chun Gwon Park Wooram Park Department of Integrative Biotechnology Sungkyunkwan University(SKKU)SuwonGyeonggi 16419Republic of Korea Deparment of Inteligent Precision Healthcare Convergence SKKUSuwonGyeonggi 16419Republic of Korea Department of MetaBioHealth SKKU Institute for ConvergenceSKKUSuwonGyeonggi 16419Republic of Korea Department of Bioengineering Hanyang UniversitySeoul 04763Republic of Korea Department of Integrative Engineering Chung-Ang UniversitySeoul 06974Republic of Korea Department of Biomedical Engineering SKKUSuwonGyeonggi 16419Republic of Korea Korea Institute of Science and Technology(KIST) Seoul 02792Republic of Korea

Optimum genetic delivery for modulating target genes to diseased tissue is a major obstacle for profitable gene *** nanoparticles(LNPs),considered a prospective vehicle for nucleic acid delivery,have demonstrated efficacy in human use during the COVID-19 *** study introduces a novel biomaterial-based platform,M1-polarized macrophage-derived cellular nanovesicle-coated LNPs(M1-C-LNPs),specifically engineered for a combined gene-immunotherapy approach against solid *** dual-function system of M1-C-LNPs encapsulates Bcl2-targeting siRNA within LNPs and immune-modulating cytokines within M1 macrophage-derived cellular nanovesicles(M1-NVs),effectively facilitating apoptosis in cancer cells without impacting T and NK cells,which activate the intratumoral immune response to promote granule-mediating killing for solid tumor *** retention within tumor was observed upon intratumoral administration of M1-C-LNPs,owing to the presence of adhesion molecules on M1-NVs,thereby contributing to superior tumor growth *** findings represent a promising strategy for the development of targeted and effective nanoparticle-based cancer genetic-immunotherapy,with significant implications for advancing biomaterial use in cancer therapeutics.

关键词： Genetic-immunotherapy M1 macrophage-derived cellular nanovesicles Lipid nanoparticles(LNPs) Gene therapy siRNA Cancer immunotherapy Solid tumor Tumor microenvironment(TME)

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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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Endoscopic radial incision and cutting method for adult congenital duodenal webs:A case report

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World Journal of Clinical Cases 2024年第18期12卷 3622-3628页

作者： hyun Deok shin Department of Internal Medicine Dankook University HospitalDankook University College of MedicineCheonan 31116ChungnamSouth Korea

BACKGROUND Congenital duodenal webs are rare in adults and can lead to various symptoms such as nausea,vomiting,and postprandial *** treatment for this disease is mostly *** treatment techniques have been developed and attempted for this *** radial incision and cutting(RIC)techniques are reportedly very effective in benign anastomotic *** case report highlights the effectiveness and safety of endoscopic RIC as a minimally invasive treatment for adult congenital duodenal *** SUMMARY A 23-year-old female patient with indigestion was referred to a tertiary *** patient complained of postprandial fullness in the epigastric *** physical examinations or blood tests indicated no *** tomography revealed an eccentric broad-based delayed-enhancing mass-like lesion in the second portion of the *** showed an enlarged gastric cavity and a significantly dilated duodenal bulb;a very small hole was observed in the distal part of the second portion,and scope passage was not *** upper gastrointestinal series was performed,revealing an intraduodenal barium contrast-filled sac with a curvilinear narrow radiolucent rim,a typical"windsock"*** RIC was performed on the duodenal *** patient recovered ***-up endoscopy showed a patent duodenal lumen without any residual *** patient reported complete resolution of symptoms at the 18-month *** Endoscopic RIC may be an effective treatment for congenital duodenal webs in adults.

关键词： Congenital duodenal web Endoscopic treatment Radial incision and cutting method Surgery Case report

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Capsosiphon fulvescens suppresses LPS-stimulated inflammatory responses by suppressing TLR4/NF-κB activation in RAW264.7 murine macrophages

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Asian Pacific Journal of Tropical Biomedicine 2024年第3期14卷 115-126页

作者： Seon Yeong Ji EunJin Bang hyun Hwangbo Min Yeong Kim Da Hye Kim Su hyun Hong shin-hyung Park Chang-Young Kwon Gi-Young Kim You-Jin Jeon Suengmok Cho Yung hyun Choi Department of Biochemistry Dong-eui University College of Korean MedicineBusan 47227Republic of Korea Basic Research Laboratory for the Regulation of Microplastic-Mediated Diseases and Anti-Aging Research Center Dong-eui UniversityBusan 47227Republic of Korea Department of Pathology Dong-eui University College of Korean MedicineBusan 47227Republic of Korea Department of Oriental Neuropsychiatry Dong-eui University College of Korean MedicineBusan 47227Republic of Korea Department of Marine Life Science Jeju National UniversityJeju 63243Republic of Korea Department of Food Science and Technology/Institute of Food Science Pukyong National UniversityBusan 48513Republic of Korea

Objective:To evaluate the effects of Capsosiphon fulvescens(***)ethanolic extract on inflammation in lipopolysaccharide(LPS)-induced RAW296.7 ***:The protective effects of *** ethanolic extract on LPS-induced inflammation in RAW264.7 macrophages were assessed using biochemical analysis,including enzyme-linked immunosorbent assay,quantitative reverse transcription-polymerase chain reaction,and Western blot *** examine reactive oxygen species(ROS)production,flow cytometry analysis,and immunofluorescence staining were ***,the modulatory effect of *** ethanolic extract on NF-κB activation was ***:*** ethanolic extract significantly attenuated LPS-induced levels of pro-inflammatory cytokines and notably reduced the secretion and mRNA levels of LPS-mediated matrix *** addition,*** ethanolic extract decreased ROS production and suppressed the TLR4/NF-κB signaling ***:*** ethanolic extract alleviates inflammation as well as oxidative stress by modulating the TLR4/NF-κB signaling in LPS-induced RAW264.7 *** can be used as a potential therapeutic agent to suppress inflammation and oxidative stress-associated diseases.

关键词： Capsosiphon fulvescens Inflammation Oxidative stress NF-κB Nrf2 TLR4

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Understanding the correlation between energy-state mismatching and open-circuit voltage loss in bulk heterojunction solar cells

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Carbon Energy 2024年第5期6卷 164-174页

作者： hyun-Seock Yang Danbi Kim Chang-Mok Oh Vellaiappillai Tamilavan Pesi MHangoma Hojun Yi Bo RLee Insoo shin In-Wook Hwang Sung Heum Park Pukyong National University BusanRepublic of Korea Clarendon Laboratory University of OxfordOxfordUK Institute of Energy Transport and Fusion Research Pukyong National UniversityBusanRepublic of Korea Advanced Photonics Research Institute Gwangju Institute of Science and TechnologyGwangjuRepublic of Korea Department of Chemical and Biomolecular Engineering Tandon School of EngineeringNew York UniversityBrooklynNew YorkUSA

Photoinduced intermolecular charge transfer(PICT)determines the voltage loss in bulk heterojunction(BHJ)organic photovoltaics(OPVs),and this voltage loss can be minimized by inducing efficient PICT,which requires energy-state matching between the donor and acceptor at the BHJ ***,both geometrically and energetically accessible delocalized state matching at the hot energy level is crucial for achieving efficient *** this study,an effective method for quantifying the hot state matching of OPVs was *** degree of energy-state matching between the electron donor and acceptor at BHJ interfaces was quantified using a mismatching factor(MF)calculated from the modified optical density of the ***,the correlation between the open-circuit voltage(Voc)of the OPV device and energy-state matching at the BHJ interface was investigated using the calculated *** OPVs with small absolute MF values exhibited high Voc *** result clearly indicates that the energy-state matching between the donor and acceptor is crucial for achieving a high Voc in *** the MF indicates the degree of energy-state matching,which is a critical factor for suppressing energy loss,it can be used to estimate the Voc loss in OPVs.

关键词： bulk heterojunction open circuit voltage organic photovoltaics photoinduced charge transfer voltage loss

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