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Self-assembly of tau fragments as a key pathologic event in tauopathies

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Neural Regeneration Research 2024年第12期19卷 2565-2566页

作者： Ly Thi Huong Luu Le Jung Hoon Lee Min Jae Lee department of biochemistry and Molecular Biology Seoul National University College of MedicineSeoulKorea

Tau protein is encoded by the microtubuleassociated protein tau(MAPT)gene and stabilizes microtubules in the *** has unique biophysical properties that make it both highly water-soluble and positively *** tau is an intrinsically disordered protein lacking defined secondary structures,it can acquire highly organized-sheet structures and stack into a filamentous inclusion such as a paired helical filament(PHF).

关键词： tau pathologic assembly

A pipeline to characterize p53 effectors by integrative cistrome and transcriptome analysis in a genetically-defined organoid model

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Genes & Diseases 2024年第2期11卷 512-515页

作者： June-Ha Shin Hwa-Ryeon Kim Jae-Seok Roe department of biochemistry College of Life Science and BiotechnologyYonsei UniversitySeoul 120-749Republic of Korea

Tumor-protein 53(p53)is a transcription factor(TF)encoded by TP53(Trp53 in mice)and is a master regulator of tumor-suppressive programs'.Importantly,TP53 is the most frequently mutated gene in human cancer,and its loss of function contributes to tumor development,exemplified by variable p53 mutations detected in 50%-75%of pancreatic cancers.2 From these perceptions,a number of targets transcribed by p53 that confer tumor suppression have been ***,our understanding of how p53 prevents normal cells from initiating tumorigenesis is still *** complement this limitation,herein,we established a new approach to identify underlying effectors transcribed by p53 in normal physiology.

关键词： incomplete initiating herein

Erlotinib combination with a mitochondria-targeted ubiquinone effectively suppresses pancreatic cancer cell survival

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World Journal of Gastroenterology 2024年第7期30卷 714-726页

作者： Pui-Yin Leung Wenjing Chen Anissa N Sari Poojitha Sitaram Pui-Kei Wu Susan Tsai Jong-In Park department of biochemistry Medical College of WisconsinMilwaukeeWI 53226United States department of Surgery Medical College of WisconsinMilwaukeeWI 53226United States

BACKGROUND Pancreatic cancer is a leading cause of cancer-related *** activity of the epidermal growth factor receptor(EGFR)is often observed in pancreatic cancer,and the small molecule EGFR inhibitor erlotinib has been approved for pancreatic cancer therapy by the food and drug ***,erlotinib alone is ineffective and should be combined with other drugs to improve therapeutic *** previously showed that certain receptor tyrosine kinase inhibitors can increase mitochondrial membrane potential(Δψm),facilitate tumor cell uptake ofΔψm-sensitive agents,disrupt mitochondrial homeostasis,and subsequently trigger tumor cell *** has not been tested for this *** To determine whether erlotinib can elevateΔψm and increase tumor cell uptake ofΔψm-sensitive agents,subsequently triggering tumor cell ***Δψm-sensitive fluorescent dye was used to determine how erlotinib affectsΔψm in pancreatic adenocarcinoma(PDAC)cell *** viability of conventional and patient-derived primary PDAC cell lines in 2D-and 3D cultures was measured after treating cells sequentially with erlotinib and mitochondria-targeted ubiquinone(MitoQ),aΔψm-sensitive *** synergy between erlotinib and MitoQ was then analyzed using SynergyFinder *** preclinical efficacy of the twodrug combination was determined using immune-compromised nude mice bearing PDAC cell line *** Erlotinib elevatedΔψm in PDAC cells,facilitating tumor cell uptake and mitochondrial enrichment ofΔψm-sensitive *** triggered caspase-dependent apoptosis in PDAC cells in culture if used at high doses,while erlotinib pretreatment potentiated low doses of *** suggested that these drugs synergistically induced tumor cell *** with in vitro data,erlotinib and MitoQ combination suppressed human PDAC cell line xenografts in mice more effectively than single treatments of each *** Our findings suggest tha

关键词： Pancreatic cancer Erlotinib Mitochondria-targeted ubiquinone Mitochondria Combination therapy

Extended Deep Learning Algorithm for Improved Brain Tumor Diagnosis System

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Intelligent Automation & Soft Computing 2024年第1期39卷 33-55页

作者： M.Adimoolam K.Maithili N.M.Balamurugan R.Rajkumar S.Leelavathy Raju Kannadasan Mohd Anul Haq Ilyas Khan ElSayed M.Tag El Din Arfat Ahmad Khan department of Computer Engineering Government Polytechnic CollegeSevvapetTiruvallurTamil Nadu602025India department of Computer Science and Engineering KG Reddy College of Engineering and TechnologyHyderabadTelangana500075India department of Computer Science and Engineering Sri Venkateswara College of EngineeringSriperumbudurChennai602117India department of Computer Science and Engineering Annamalai UniversityChidambaramTamil Nadu608002India department of Computer Science and Engineering Aarupadai Veedu Institute of TechnologyVinayaka Mission Research FoundationPaiyanurTamil Nadu603104India department of Electrical and Electronics Engineering Sri Venkateswara College of EngineeringSriperumbudur602117India department of Computer Science College of Computer and Information SciencesMajmaah UniversityAl-Majmaah11952Saudi Arabia department of Mathematics College of Science Al-ZulfiMajmaah UniversityAl-Majmaah11952Saudi Arabia Electrical Engineering department Faculty of Engineering&TechnologyFuture University in EgyptNew Cairo11835Egypt department of Computer Science College of ComputingKhon Kaen UniversityKhon Kaen40002Thailand

At present,the prediction of brain tumors is performed using Machine Learning(ML)and Deep Learning(DL)*** various ML and DL algorithms are adapted to predict brain tumors to some range,some concerns still need enhancement,particularly accuracy,sensitivity,false positive and false negative,to improve the brain tumor prediction system ***,this work proposed an Extended Deep Learning Algorithm(EDLA)to measure performance parameters such as accuracy,sensitivity,and false positive and false negative *** addition,these iterated measures were analyzed by comparing the EDLA method with the Convolutional Neural Network(CNN)way further using the SPSS tool,and respective graphical illustrations were *** results were that the mean performance measures for the proposed EDLA algorithm were calculated,and those measured were accuracy(97.665%),sensitivity(97.939%),false positive(3.012%),and false negative(3.182%)for ten *** in the case of the CNN,the algorithm means accuracy gained was 94.287%,mean sensitivity 95.612%,mean false positive 5.328%,and mean false negative 4.756%.These results show that the proposed EDLA method has outperformed existing algorithms,including CNN,and ensures symmetrically improved *** EDLA algorithm introduces novelty concerning its performance and particular activation *** proposed method will be utilized effectively in brain tumor detection in a precise and accurate *** algorithm would apply to brain tumor diagnosis and be involved in various medical diagnoses *** the quantity of dataset records is enormous,then themethod’s computation power has to be updated.

关键词： Brain tumor extended deep learning algorithm convolution neural network tumor detection deep learning

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

Spatiotemporal dynamics of land use/land cover(LULC)changes and its impact on land surface temperature:A case study in New Town Kolkata,eastern India

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Regional Sustainability 2024年第2期5卷 26-48页

作者： Bubun MAHATA Siba Sankar SAHU Archishman SARDAR Laxmikanta RANA Mukul MAITY department of Geography Ravenshaw UniversityCuttack753003India department of Geography Sri Krushna Chandra Gajapati(Autonomous)CollegeParalakhemundi761200India

Rapid urbanization creates complexity,results in dynamic changes in land and environment,and influences the land surface temperature(LST)in fast-developing *** this study,we examined the impact of land use/land cover(LULC)changes on LST and determined the intensity of urban heat island(UHI)in New Town Kolkata(a smart city),eastern India,from 1991 to 2021 at 10-a intervals using various series of Landsat multi-spectral and thermal *** study used the maximum likelihood algorithm for image classification and other methods like the correlation analysis and hotspot analysis(Getis–Ord Gi^(*) method)to examine the impact of LULC changes on urban thermal *** study noticed that the area percentage of built-up land increased rapidly from 21.91%to 45.63%during 1991–2021,with a maximum positive change in built-up land and a maximum negative change in sparse *** mean temperature significantly increased during the study period(1991–2021),from 16.31℃to 22.48℃in winter,29.18℃to 34.61℃in summer,and 19.18℃to 27.11℃in *** result showed that impervious surfaces contribute to higher LST,whereas vegetation helps decrease *** ecological status has been found in built-up land,and excellent ecological status has been found in vegetation and water *** hot spot and cold spot areas shifted their locations every decade due to random LULC *** after New Town Kolkata became a smart city,high LST has been ***,this study indicated that urbanization and changes in LULC patterns can influence the urban thermal environment,and appropriate planning is needed to reduce *** study can help policy-makers create sustainable smart cities.

关键词： Urbanization Land use/land cover (LULC)changes Land surface temperature Urban heat island Hotspot analysis Smart city

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

Sporophytic control of tapetal development and pollen fertility by a mitogen-activated protein kinase cascade in rice

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Journal of Integrative Plant Biology 2024年第7期66卷 1500-1516页

作者： Jianguo Zeng Manman Duan Yiqing Wang Guangtao Li Yujing You Jie Shi Changhao Liu Jinyang Zhang Juan Xu Shuqun Zhang Jing Zhao department of Plant Pathology Nanjing Agricultural UniversityNanjing 210095China State Key Laboratory of Plant Physiology and biochemistry College of Life SciencesZhejiang UniversityHangzhou 310058China Division of biochemistry University of MissouriColumbia65211MOUSA

Tapetum,the innermost layer of the anther wall,provides essential nutrients and materials for pollen *** degradation of anther tapetal cells is a prerequisite for normal pollen development in flowering *** cells facilitate male gametogenesis by providing cellular contents after highly coordinated programmed cell death(PCD).Tapetal development is regulated by a transcriptional ***,the signaling pathway(s)involved in this process are poorly *** this study,we report that a mitogen-activated protein kinase(MAPK)cascade composed of OsYDA1/OsYDA2-OsMKK4-OsMPK6 plays an important role in tapetal development and male gametophyte *** of function of this MAPK cascade leads to anther indehiscence,enlarged tapetum,and aborted pollen *** cells in osmkk4 and osmpk6 mutants exhibit an increased presence of lipid body-like structures within the cytoplasm,which is accompanied by a delayed occurrence of *** of a constitutively active version of OsMPK6(CA-OsMPK6)can rescue the pollen defects in osmkk4 mutants,confirming that OsMPK6 functions downstream of OsMKK4 in this *** crosses also demonstrated that the MAPK cascade sporophyticly regulates pollen *** study reveals a novel function of rice MAPK cascade in plant male reproductive biology.

关键词： degradation MAPK cascade pollen fertility rice tapetum

Ionotropic receptors mediate olfactory learning and memory in Drosophila

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Insect Science 2024年第4期31卷 1249-1269页

作者： Md Zeeshan Ali Anushree Aarif Ahsan Mohammad Shamsul Ola Rizwanul Haque Jawaid Ahsan department of Biotechnology Central University of South BiharGayaBiharIndia department of Radiation Oncology University of MichiganAnn ArborMichiganUSA department of biochemistry College of ScienceKing Saud UniversityRiyadhSaudi Arabia

Phenylacetaldehyde(PAH),an aromatic compound,is present in a diverse range of fruits including overripe bananas and prickly pear cactus,the two major host fruits for Drosophila *** acts as a potent ligand for the ionotropic receptor 84a(IR84a)in the adult fruit fly and it is detected by the IR84a/IR8a heterotetrameric *** role in the male courtship behavior through IR84a as an environmental aphrodisiac is of additional *** ***,two distinct kinds of olfactory receptors,that is,odorant receptors(ORs)and ionotropic receptors(IRs),perceive the odorant *** display unique structural,molecular,and functional characteristics in addition to having different evolutionary ***,olfactory cues detected by the ORs such as ethyl acetate,1-butanol,isoamyl acetate,1-octanol,4-methylcyclohexanol,*** as aliphatic esters and alcohols have been employed in olfactory classical conditioning using fruit *** underlines the participation of OR-activated olfactory pathways in learning and memory *** study elucidates that likewise ethyl acetate(EA)(an OR-responsive odorant),PAH(an IR-responsive aromatic compound)too can form learning and memory when associated with an appetitive gustatory *** association of PAH with sucrose(PAH/SUC)led to learning and formation of the long-term memory(LTM).Additionally,the Orco^(1),Ir84a^(MI00501),and Ir8a^(1)mutant flies were used to confirm the exclusive participation of the IR84a/IR8a complex in PAH/SUC olfactory associative *** results highlight the involvement of IRs via an IR-activated pathway in facilitating robust olfactory behavior.

关键词： appetitive conditioning Drosophila melanogaster ethyl acetate ionotropic receptors learning and memory phenylacetaldehyde