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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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Pd single atoms cooperate with S vacancies in ZnIn_(2)S_(4) nanosheets for photocatalytic pure-water splitting

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Science China Chemistry 2024年第3期67卷 855-861页

作者： Lin Sun Huiping Peng Fei Xue Shangheng Liu Zhiwei Hu Hongbo Geng Xiaozhi Liu Dong Su Yong Xu Xiaoqing Huang State Key Laboratory of Physical Chemistry of Solid Surfaces College of Chemistry and Chemical EngineeringXiamen UniversityXiamen 361005China Guangzhou Key Laboratory of Low-Dimensional Materials and Energy Storage Devices Collaborative Innovation Center of Advanced Energy MaterialsSchool of Materials and EnergyGuangdong University of TechnologyGuangzhou 510006China max planck institute for Chemical Physics of Solids Nothnitzer Strasse 40Dresden 01187Germany School of Materials Engineering Changshu Institute of TechnologyChangshu 215500China Beijing National Laboratory for Condensed Matter Physics institute of Physics Chinese Academy of SciencesBeijing 100190China Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(IKKEM) Xiamen 361005China

Photocatalytic water splitting has emerged as a new frontier for converting solar energy to green H_(2) and value-added ***,great challenges still remain for developing efficient photocatalysts for pure water splitting without sacrificial *** this work,we demonstrate that doping hexagonal ZnIn_(2)S_(4)(ZIS) with Pd single atoms(Pd_(0.03)/ZIS) can serve as a highly efficient photocatalyst for pure water splitting to simultaneously produce H_(2) and H_(2)O_(2) without any sacrificial *** from aberration-corrected high-angle annular dark field scanning transmission electron microscopy,X-ray fine spectroscopy,insitu electron paramagnetic resonance and diffuse Fourier transform infrared spectroscopy reveal that doping ZIS with Pd single atoms facilitates the formation of S vacancies(S_(v)),where the photogenerated electrons can transfer to Pd single atoms,as a result of enhanced separation of electron-hole pairs and improved photocatalytic ***,Pd_(0.03)/ZIS displays a stoichiometric ratio of H_(2) and H_(2)O_(2) with the productivity of 1,037.9 and 1,021.4μmol g^(-1)h^(-1),respectively,which has largely outperformed pure ZIS and other reported catalysts for pure water *** work provides an efficient photocatalyst for water splitting to produce H_(2) and H_(2)O_(2),which may attract rapid interest in materials science,chemistry,and heterogeneous catalysis.

关键词： ZnIn_(2)S_(4) Pd single atom S vacancy pure water splitting H_(2)O_(2)

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Direct amplification of femtosecond optical vortices in a single-crystal fiber

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Photonics Research 2024年第1期12卷 27-32页

作者： CHANGSHENG ZHENG TIANYI DU LEI ZHU ZHANXIN WANG KANGZHEN TIAN YONGGUANG ZHAO ZHIYONG YANG HAOHAI YU VALENTIN PETROV Jiangsu Key Laboratory of Advanced Laser Materials and Devices School of Physics and Electronic EngineeringJiangsu Normal UniversityXuzhou 221116China State Key Laboratory of Crystal Materials and institute of Crystal Materials Shandong UniversityJinan 250100China max Born institute for Nonlinear Optics and Short Pulse Spectroscopy 12489 BerlinGermany

Spatially twisted light with femtosecond temporal structure is of particular interest in strong-field physics and light–matter ***,present femtosecond vortex sources exhibit limited power handling capabilities,and their amplification remains an ongoing challenge particularly for high-order orbital angular momentum(OAM)states due to several inherent technical ***,we exploit a straightforward approach to directly amplify a femtosecond optical vortex(FOV,OAM=-8?)by using a two-stage single-crystal fiber(SCF)amplifier system without pulse stretching and compression in the time domain,delivering 23-W,163-fs pulses at a repetition rate of1 *** spatial and temporal features are well-conserved during the amplification,as well as the high modal purity(>96%).The results indicate that the multi-stage SCF amplifier system is particularly suited for direct amplification of high-order *** generated high-power femtosecond OAM laser beams are expected to help reveal complex physical phenomena in light–matter interactions and pave the way for practical applications in attoscience,laser plasma acceleration,and high-dimension micromachining.

关键词： fiber amplifier crystal

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Therapeutic Potential of Thunbergia laurifolia *** in Gestational Diabetes Mellitus:Insights from a Rat Model

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Chinese Journal of Integrative Medicine 2024年第9期30卷 788-798页

作者： Sasitorn Kerdsuknirund Arreeya Kosinan Panida Khunkaewla Pakanit Kupittayanant Ratchadaporn Oonsivilai Pattama Tongdee Porntip Nimkuntod Susan Wray Sajeera Kupittayanant School of Preclinical Sciences Institute of ScienceSuranaree University of TechnologyNakhon Ratchasima30000Thailand biochemistry-Electrochemistry Research Unit School of BiochemistryInstitute of ScienceSuranaree University of TechnologyNakhon Ratchasima30000Thailand School of Animal Technology and Innovation Institute of Agricultural TechnologySuranaree University of TechnologyNakhon Ratchasima30000Thailand School of Food Technology Institute of Agricultural TechnologySuranaree University of TechnologyNakhon Ratchasima30000Thailand School of Obstetrics and Gynecology Institute of MedicineSuranaree University of TechnologyNakhon Ratchasima30000Thailand School of Internal Medicine Institute of MedicineSuranaree University of TechnologyNakhon Ratchasima30000Thailand Harris-Wellbeing Preterm Birth Research Centre Department of Women and Children’s Healththe Institute of Lifecourse and Medical SciencesUniversity of LiverpoolLiverpoolUK

Objective:To assess the effects of Thunbergia laurifolia ***(TLE)on gestational diabetes mellitus(GDM)in a rat ***:Thunbergia laurifolin *** were subjected to ethanolic *** vivo study,50 pregnant rats were randomly divided into 5 groups(10 for each):non-GDM group,GDM induced by streptozotocin(STZ,60 mg/kg i.p.),metformin(MET)100 mg/kg,TLE 50,and 500 mg/kg *** was performed on gestation day 7 until term(day 21).The effects of TLE on blood glucose,insulin levels,lipid profiles,liver enzymes,and maternal performances were *** in vitro study,the effect of TLE was examined using the organ bath for uterine force ***:In in vivo study,TLE significantly reduced blood glucose as compared to GDM(Pmaximal inhibition concentration=1.2 mg/L).This inhibitory effect extended to potassium chloride depolarization and oxytocin-mediated *** combined with its major constituent,rosmarinic acid,TLE produced an enhanced inhibitory effect(P<0.05).Conclusions:TLE ameliorated blood glucose levels,enhanced uterine muscular structure,and improved maternal and fetal performance in *** also displayed tocolytic *** findings underscore the need for further explor

关键词： myometrium gestational diabetes mellitus tocolytic oxytocin Thunbergia laurifolia L.

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Nucleosynthesis in the little bang

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Nuclear Science and Techniques 2024年第8期35卷 1-4页

作者： Marcus Bleicher institute for Theoretical Physics Goethe-University FrankfurtMax‑von‑Laue‑Str.160438 FrankfurtGermany Helmholtz Research Academy Hesse for FAIR(HFHF) GSI HelmholtzzentrumCampusFrankfurtGermany

A new approach based on relativistic kinetic equations is proposed to solve the long-standing puzzle of light cluster formation, also called nucleosynthesis, in high-energy heavy-ion collisions. This method addresses the tension between STAR data and previous studies relying on either statistical equilibrium or coalescence approaches.

关键词： synthesis relativistic cluster

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Expanding through the Emerald Isle:exploration and spatial orientation of non-native bank voles in Ireland

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Current Zoology 2024年第3期70卷 320-331页

作者： Valeria Mazza Jana A.Eccard Animal Ecology Institute for Biochemistry and BiologyUniversity of PotsdamMaulbeerallee 114469PotsdamGermany and Department of Ecological and Biological Sciences University of TusciaLargo dell'Università10100 ViterboItaly

Whether introduced into a completely novel habitat or slowly expanding their current range,the degree to which animals can effciently explore and navigate new environments can be key to survival,ultimately determining population establishment and colonization *** tested whether spatial orientation and exploratory behavior are associated with non-native spread in free-living bank voles(Myodes glareolus,N=43)from a population accidentally introduced to Ireland a century *** measured spatial orientation and navigation in a radial arm maze,and behaviors associated to exploratory tendencies and risk-taking in repeated open-feld tests,at the expansion edge and in the source *** voles at the expansion edge re-visited unrewarded arms of the maze more,waited longer before leaving it,took longer to start exploring both the radial arm maze and the open feld,and were more risk-averse compared to conspecifcs in the source *** together,results suggest that for this small mammal under heavy predation pressure,a careful and thorough exploration strategy might be favored when expanding into novel environments.

关键词： animal personality biological invasions exploration behavior Myodes glareolus range expansion spatial orientation.

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In vivo femtosecond laser nanosurgery of the cell wall enabling patch-clamp measurements on filamentous fungi

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Microsystems & Nanoengineering 2024年第2期10卷 251-267页

作者： Tanja Pajić Katarina Stevanović Nataša V.Todorović Aleksandar J.Krmpot Miroslav Živić Svetlana Savić-Šević Steva M.Lević Marina Stanić Dejan Pantelić Brana Jelenković Mihailo D.Rabasović institute of Physiology and biochemistry“Ivan Djaja” Faculty of BiologyUniversity of BelgradeStudentski trg 1611158BelgradeSerbia institute for Biological Research“Siniša Stanković” University of BelgradeNational Institute of the Republic of SerbiaBulevar Despota Stefana 14211000BelgradeSerbia institute of Physics Belgrade University of BelgradeNational Institute of the Republic of SerbiaPregrevica 11811080BelgradeSerbia University of Belgrade Faculty of AgricultureNemanjina Street 611080BelgradeSerbia institute for Multidisciplinary Research University of BelgradeKneza Višeslava 111030BelgradeSerbia

Studying the membrane physiology of filamentous fungi is key to understanding their interactions with the environment and crucial for developing new therapeutic strategies for disease-causing ***,their plasma membrane has been inaccessible for a micron-sized patch-clamp pipette for pA current recordings due to the rigid chitinous cell ***,we report the first femtosecond IR laser nanosurgery of the cell wall of the filamentous fungi,which enabled patch-clamp measurements on protoplasts released from hyphae.A reproducible and highly precise(diffraction-limited,submicron resolution)method for obtaining viable released protoplasts was *** release from the nanosurgery-generated incisions in the cell wall was achieved from different regions of the *** plasma membrane of the obtained protoplasts formed tight and high-resistance(GΩ)contacts with the recording *** entire nanosurgical procedure followed by the patch-clamp technique could be completed in less than 1 *** to previous studies using heterologously expressed channels,this technique provides the opportunity to identify new ionic currents and to study the properties of the ion channels in the protoplasts of filamentous fungi in their native environment.

关键词： patch recording laser

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Caloric restriction,Sirtuins,and cardiovascular diseases

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Chinese Medical Journal 2024年第8期137卷 921-935页

作者： Ziyu Wei Bo Yang Huiyu Wang Shuangjie Lv Houzao Chen Depei Liu State Key Laboratory of Common Mechanism Research for Major Diseases Department of Biochemistry and Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China

Caloric restriction(CR)is a well-established dietary intervention known to extend healthy lifespan and exert positive effects on aging-related diseases,including cardiovascular ***,a family of nicotinamide adenine dinucleotide(NAD^(+))-dependent histone deacetylases,have emerged as key regulators of cellular metabolism,stress responses,and the aging process,serving as energy status sensors in response to ***,the mechanism through which CR regulates Sirtuin function to ameliorate cardiovascular disease remains *** review not only provided an overview of recent research investigating the interplay between Sirtuins and CR,specifically focusing on their potential implications for cardiovascular health,but also provided a comprehensive summary of the benefits of CR for the cardiovascular system mediated directly via *** has also been shown to have considerable impact on specific metabolic organs,leading to the production of small molecules that enter systemic circulation and subsequently regulate Sirtuin activity within the cardiovascular *** direct and indirect effects of CR offer a potential mechanism for Sirtuin modulation and subsequent cardiovascular *** the interplay between CR and Sirtuins will provide new insights for the development of interventions to prevent and treat cardiovascular diseases.

关键词： Caloric restriction Sirtuins Cardiovascular diseases Healthy lifestyle Dietary

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Efficient scar-free knock-ins of several kilobases in plants by engineered CRISPR-Cas endonucleases

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Molecular Plant 2024年第5期17卷 824-837页

作者： Tom Schreiber Anja Prange Petra Schafer Thomas Iwen Ramona Grutzner Sylvestre Marillonnet Aurelie Lepage Marie Javelle Wyatt Paul Alain Tissier Department of Cell and Metabolic Biology Leibniz Institute of Plant BiochemistryWeinberg 306120 Halle(Saale)Germany Limagrain Centre de RechercheRoute d’EnnezatCS 9012663720 ChappesFrance

In plants and mammals,non-homologous end-joining is the dominant pathway to repair DNA doublestrand breaks,making it challenging to generate knock-in *** this study,we identified two groups of exonucleases from the herpes virus and the bacteriophage T7 families that conferred an up to 38-fold increase in homology-directed repair frequencies when fused to Cas9/Cas12a in a tobacco mosaic virus-based transient assay in Nicotiana *** achieved precise and scar-free insertion of several kilobases of DNA both in transient and stable transformation *** Arabidopsis thaliana,fusion of Cas9 to a herpes virus family exonuclease led to 10-fold higher frequencies of knock-ins in the first generation of *** addition,we demonstrated stable and heritable knock-ins in wheat in 1%of the primary *** together,our results open perspectives for the routine production of heritable knock-in and gene replacement events in plants.

关键词： homology-directed repair knockin gene replacement CRISPR-Cas 50 exonuclease plants

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The effect of Laves phases and nano-precipitates on the electrochemical corrosion resistance of Mg-Al-Ca alloys under alkaline conditions

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Journal of Magnesium and Alloys 2024年第6期12卷 2447-2461页

作者： Markus Felten Veronika Chaineux Siyuan Zhang Ali Tehranchi Tilmann Hickel Christina Scheu Joshua Spille Marta Lipińska-Chwałek Joachim Mayer Benjamin Berkels Marcus Hans Imke Greving Silja Flenner Sandra Sefa Daniela Zander Chair of Corrosion and Corrosion Protection RWTH Aachen UniversityAachen 52072 Germany max-planck-Institut für Eisenforschung GmbH Düsseldorf 40237 Germany Central Facility for Electron Microscopy RWTH Aachen UniversityAachen 52074 Germany Ernst Ruska-Centre for Microscopy and Spectroscopy with Electrons Forschungszentrum Jülich GmbHJülich 52428Germany Mathematical Image and Signal Processing Aachen Institute for Advanced Study in Computational Engineering ScienceRWTH Aachen UniversityAachen 52062 Germany Materials Chemistry RWTH Aachen UniversityAachen 52074 Germany institute of Materials Physics Helmholtz-Zentrum HereonGeesthacht 21502 Germany

The electrochemical corrosion mechanisms of Mg alloys were extensively studied in previous investigations of different chemical com-positions,modified surface states and various electrolyte ***,recent research focused on the active state of Mg dissolution,leading to unresolved effects of secondary phases adjacent to a stableα-solid solution passive *** present study investigates the fundamental electrochemical corrosion mechanisms of three different Laves phases with varying phase morphologies and phase fractions in the passive state of Mg-Al-Ca *** microstructure was characterized by(transmission-)electron microscopy and synchrotron-based transmission X-ray *** electrochemical corrosion resistance was determined with a standard three-electrode setup and advanced in-situ flow cell measurements.A new electrochemical activity sequence(C15>C36>α-Mg>C14)was obtained,as a result of a stable passive layer formation on theα-solid ***,nm-scale Mg-rich precipitates were identified within the Laves phases,which tend to inhibit the corrosion kinetics.

关键词： Laves phase STEM Magnesium Corrosion Passive layer

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