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CD8+T cell metabolic flexibility elicited by CD28-ARS2 axisdriven alternative splicing of PKM supports antitumor immunity

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Cellular & Molecular Immunology 2024年第3期21卷 260-274页

作者： G.Aaron Holling Colin A.Chavel Anand P.Sharda Mackenzie M.Lieberman Caitlin M.James Shivana M.Lightman Jason H.Tong Guanxi Qiao Tiffany R.Emmons Thejaswini Giridharan Shengqi Hou Andrew M.Intlekofer Richard M.Higashi Teresa W.M.Fan Andrew N.Lane Kevin H.Eng Brahm H.Segal Elizabeth A.Repasky Kelvin P.Lee Scott H.Olejniczak Department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Department of Medicine Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Center for Environmental Systems biochemistry Department of Toxicology and Cancer Biology and Markey Cancer CenterLexingtonKY 40536USA Department of Cancer Genetics and Genomics Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA present address:University of Colorado Boulder BoulderCO 80309USA present address:Dana Farber Cancer institute BostonMA 02215USA present address:Massachusetts institute of Technology BostonMA 02139USA present address:Melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA

Metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been *** this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T *** doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose ***2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing *** these effects,the CD28-ARS2 axis suppressed the expression of the M1 isoform of pyruvate kinase in favor of PKM2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector ***,PKM alternative splicing occurred independently of CD28-driven PI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.

关键词： Immunometabolism mRNA splicing CD8 T cells ARS2 PKM2

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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

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A Pan-Cancer Analysis of GAPDH as a Common Biomarker for Various Cancers

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Proceedings of Anticancer Research 2024年第5期8卷 105-120页

作者： Yasir Hameed Department of biotechnology Institute of BiochemistryBiotechnologyand BioinformaticsThe Islamia University of BahawalpurPakistan

Objective:To investigate the expression levels of glyceraldehyde-3-phosphate dehydrogenase(GAPDH)and explore its prognostic value across 24 different human *** investigation was conducted using comprehensive bioinformatics and in vitro approaches,incorporating multiple layers of ***:GAPDH expression and methylation levels were assessed using bioinformatics tools and validated in cell lines through RNA-seq and targeted bisulfite-seq *** potential prognostic significance of GAPDH was evaluated using the KM ***,cBioPortal was employed to investigate genetic alterations associated with this *** analysis was conducted using ***,a correlation analysis between GAPDH expression and CD8+T immune cells was performed using TIMER and ***,a gene-drug interaction network analysis was conducted using Cytoscape to examine the relationship between GAPDH and various ***:GAPDH was found to be commonly upregulated in 24 types of human cancers,with its upregulation significantly correlated with poor relapse-free survival(RFS)and overall survival(OS)in BLCA,CESC,HNSC,KIRP,LIHC,and *** suggests that GAPDH plays a significant role in the development of these *** upregulation was also associated with various clinicopathological features in patients with BLCA,CESC,HNSC,KIRP,LIHC,and *** analysis revealed GAPDH’s involvement in diverse ***,notable correlations were observed between GAPDH expression and its promoter methylation level,genetic alterations,and CD8+T immune cell ***,several regulatory drugs targeting GAPDH were identified,with the potential to modulate its expression and potentially prevent conditions such as BLCA,CESC,HNSC,KIRP,LIHC,and ***:Based on our findings,GAPDH emerges as a promising diagnostic and prognostic biomarker for BLCA,CESC,HNSC,KIRP,LIHC,and LUAD.

关键词： Cancer Expression GAPDH Biomarker

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Advancements and Challenges in Biomarkers for Colorectal Cancer Detection:A Comprehensive Review

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Proceedings of Anticancer Research 2024年第5期8卷 64-75页

作者： Yasir Hameed Department of biotechnology Institute of BiochemistryBiotechnologyand BioinformaticsThe Islamia University of BahawalpurPakistan

This study provides an overview of the current landscape of biomarkers for colorectal cancer(CRC)detection,focusing on genetic,proteomic,circulating microRNA(miRNA),and metabolomic *** remains a significant global health challenge,ranking among the most prevalent cancers worldwide and being a leading cause of cancer-related *** advancements in screening methods such as colonoscopy,sigmoidoscopy,and fecal occult blood tests(FOBT),the asymptomatic nature of early-stage CRC often results in late diagnoses,negatively impacting patient *** biomarkers like APC,KRAS,TP53,and microsatellite instability(MSI)play critical roles in CRC pathogenesis and *** biomarkers,detectable through polymerase chain reaction,next-generation sequencing,and other advanced techniques,guide early detection and personalized treatment *** biomarkers such as CEA,CA 19-9,and novel signatures offer insights into CRC’s physiological changes and disease status,aiding prognosis and treatment response assessments through enzyme-linked immunosorbent assay and mass *** miRNAs,including miR-21 and miR-92a,present promising non-invasive biomarkers that can be detected in blood and stool samples,reflecting CRC presence,progression,and therapeutic *** biomarkers,encompassing amino acids,lipids,and TCA cycle intermediates,provide further insights into CRC-associated metabolic alterations,which are crucial for early detection and treatment monitoring using mass spectrometry and nuclear magnetic *** these advancements,challenges such as biomarker validation,standardization,and clinical utility *** research directions include integrating multi-omics approaches and leveraging technologies like liquid biopsies and AI for enhanced biomarker discovery and clinical *** addressing these challenges and advancing research in biomarker development,CRC screening and management could pote

关键词： Colorectal cancer Biomarker Diagnosis Detection

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SARS-CoV-2 aberrantly elevates mitochondrial bioenergetics to induce robust virus propagation

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2702-2715页

作者： Hye Jin Shin Wooseong Lee Keun Bon Ku Gun Young Yoon Hyun-Woo Moon Chonsaeng Kim Mi-Hwa Kim Yoon-Sun Yi Sangmi Jun Bum-Tae Kim Jong-Won Oh Aleem Siddiqui Seong-Jun Kim Department of Convergent Research of Emerging Virus Infection Korea Research Institute of Chemical TechnologyDaejeon 34114Republic of Korea Gyeongnam Biohealth Research Center Gyeongnam Branch InstituteKorea Institute of ToxicologyJinju 52834Republic of Korea Center for Research Equipment Korea Basic Science InstituteCheongjuChungcheongbuk-do 28119Republic of Korea Department of biotechnology Yonsei UniversitySeoul 03722Republic of Korea Division of Infectious Diseases School of MedicineUniversity of CaliforniaSan DiegoLa JollaCA 92093USA present address:Department of Microbiology Chungnam National University School of MedicineDaejeon 35015Republic of Korea

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a‘highly transmissible respiratory pathogen,leading to severe multiorgan ***,knowledge regarding SARS-CoV-2-induced cellular alterations is *** this study,we report that SARSCoV-2 aberrantly elevates mitochondrial bioenergetics and activates the EGFR-mediated cell survival signal cascade during the early stage of viral ***-CoV-2 causes an increase in mitochondrial transmembrane potential via the SARS-CoV-2 RNAnucleocapsid cluster,thereby abnormally promoting mitochondrial elongation and the OXPHOS process,followed by enhancing ATP ***,SARS-CoV-2 activates the EGFR signal cascade and subsequently induces mitochondrial EGFR trafficking,contributing to abnormal OXPHOS process and viral *** EGFR inhibitors remarkably reduce SARS-CoV-2 propagation,among which vandetanib exhibits the highest antiviral *** of SARS-CoV-2-infected cells with vandetanib decreases SARS-CoV-2-induced EGFR trafficking to the mitochondria and restores SARS-CoV-2-induced aberrant elevation in OXPHOS process and ATP generation,thereby resulting in the reduction of SARS-CoV-2 ***,oral administration of vandetanib to SARS-CoV-2-infected hACE2 transgenic mice reduces SARS-CoV-2 propagation in lung tissue and mitigates SARS-CoV-2-induced lung *** also exhibits potent antiviral activity against various SARS-CoV-2 variants of concern,including alpha,beta,delta and omicron,in in vitro cell culture *** together,our findings provide novel insight into SARS-CoV-2-induced alterations in mitochondrial dynamics and EGFR trafficking during the early stage of viral infection and their roles in robust SARS-CoV-2 propagation,suggesting that EGFR is an attractive host target for combating COVID-19.

关键词： alterations aberrant thereby

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Constructing a biofunctionalized 3D-printed gelatin/sodium alginate/chitosan tri-polymer complex scaffold with improvised biological andmechanical properties for bone-tissue engineering

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Bio-Design and Manufacturing 2024年第1期7卷 57-73页

作者： Amit Kumar Singh Krishna Pramanik Amit Biswas Centre of Excellence in Tissue Engineering Department of Biotechnology and Medical EngineeringNational Institute of TechnologyRourkela 769008India

Sodium alginate(SA)/chitosan(CH)polyelectrolyte scaffold is a suitable substrate for tissue-engineering *** present study deals with further improvement in the tensile strength and biological properties of this type of scaffold to make it a potential template for bone-tissue *** experimented with adding 0%–15%(volume fraction)gelatin(GE),a protein-based biopolymer known to promote cell adhesion,proliferation,and *** resulting tri-polymer complex was used as bioink to fabricate SA/CH/GEmatrices by three-dimensional(3D)*** studies using scanning electron microscopy revealed the microfibrous porous architecture of all the structures,which had a pore size range of 383–419μm.X-ray diffraction and Fourier-transform infrared spectroscopy analyses revealed the amorphous nature of the scaffold and the strong electrostatic interactions among the functional groups of the polymers,thereby forming polyelectrolyte complexes which were found to improve mechanical properties and structural *** scaffolds exhibited a desirable degradation rate,controlled swelling,and hydrophilic characteristics which are favorable for bone-tissue *** tensile strength improved from(386±15)to(693±15)kPa due to the increased stiffness of SA/CH scaffolds upon addition of *** enhanced protein adsorption and in vitro bioactivity(forming an apatite layer)confirmed the ability of the SA/CH/GE scaffold to offer higher cellular adhesion and a bone-like environment to cells during the process of tissue *** vitro biological evaluation including the MTT assay,confocal microscopy analysis,and alizarin red S assay showed a significant increase in cell attachment,cell viability,and cell proliferation,which further improved biomineralization over the scaffold *** addition,SA/CH containing 15%gelatin designated as SA/CH/GE15 showed superior performance to the other fabricated 3D structures,demonstrating its pote

关键词： Scaffold Biomaterial Sodium alginate Chitosan Gelatin 3D printing Tissue engineering

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Exploring unconventional attributes of red blood cells and their potential applications in biomedicine

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Protein & Cell 2024年第5期15卷 315-330页

作者： Alkmini T.Anastasiadi Vasiliki-Zoi Arvaniti Krystalyn E.Hudson Anastasios G.Kriebardis Constantinos Stathopoulos Angelo D’Alessandro Steven L.Spitalnik Vassilis L.Tzounakas Department of biochemistry School of MedicineUniversity of Patras26504 PatrasGreece Department of Pathology and Cell Biology Columbia University Irving Medical CenterNew York CityNY 10032USA Laboratory of Reliability and Quality Control in Laboratory Hematology(HemQcR) Department of Biomedical SciencesSchool of Health&Caring SciencesUniversity of West Attica(UniWA)12243 EgaleoGreece Department of biochemistry and Molecular Genetics University of Colorado Anschutz Medical Campus13001 AuroraCOUSA present address:institute for Fundamental Biomedical Research(IFBR) Biomedical Sciences Research Center“Alexander Fleming”Vari11527 AthensGreece

We need to talk about red blood *** cells are defined as cells containing distinct nuclei and other membranous ***,red blood cells(RBCs)lack a nucleus and organelles—perhaps to limit the generation of reactive oxygen species(Zhang et al.,2011)—and are filled with hemoglobin(Hb).This oxygen carrier is limited to the cytosol by the cell membrane and cytoskeleton,which maintain cellular integrity and deformability as RBCs pass through narrow capillaries(Gratzer,1994)to perform their primary function of gas exchange.

关键词： membranous maintain

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The biosynthetic pathway of the hallucinogen mescaline and its heterologous reconstruction

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Molecular Plant 2024年第7期17卷 1129-1150页

作者： Paula Berman Luis Alejandro de Haro Ana-Rita Cavaco Sayantan Panda Younghui Dong Nikolay Kuzmich Gabriel Lichtenstein Yoav Peleg Hila Harat Adam Jozwiaki Jianghua Cai Uwe Heinig Sagit Meir Ilana Rogachev Asaph Aharoni Department of Plant and Environmental Sciences Weizmann Institute of ScienceRehovot 7610001Israel Life Sciences Core Facilities Weizmann Institute of ScienceRehovot 7610001Israel The Maurice and Vivienne Wohl institute for Drug Discovery Weizmann Institute of ScienceRehovot 7610001Israel present address:Department of Cell and Metabolic Biology Leibniz Institute of Plant BiochemistryWeinberg 306120 Halle(Saale)Germany Department of Molecular&Cellular Pharmacology University of Miami Miler School of MedicineMiamiFL 33136USA Department of Botany and Plant Sciences University of California RiversideRiversideCA 92521USA Laboratory of Plant Hormones and Development Regulation of Chongqing School of Life SciencesChongqing UniversityChongqing 401331China

Mescaline,among the earliest identified natural hallucinogens,holds great potential in psychotherapy ***,despite the existence of a postulated biosynthetic pathway for more than half a century,the specific enzymes involved in this process are yet to be *** this study,we investigated the cactus Lophophora williamsii(Peyote),the largest known natural producer of the phenethylamine *** employed a multi-faceted approach,combining de novo whole-genome and transcriptome sequencing with comprehensive chemical profiling,enzymatic assays,molecular modeling,and pathway engineering for pathway *** identified four groups of enzymes responsible for the six catalytic steps in the mescaline biosynthetic pathway,and an N-methyltransferase enzyme that N-methylates all phenethylamine intermediates,likely modulating mescaline levels in ***,we reconstructed the mescaline biosynthetic pathway in both Nicotiana benthamiana plants and yeast cells,providing novel insights into several challenges hindering complete heterologous mescaline *** together,our study opens up avenues for exploration of sustainable production approaches and responsible utilization of mescaline,safeguarding this valuable natural resource for future generations.

关键词： mescaline Lophophora williamsi Peyote biosynthetic pathway de novo genome sequencing mo-lecular modeling

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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

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Comprehensive Analysis of Estrogen Receptor 1 Dysregulation in Liver Hepatocellular Carcinoma: Implications for Prognosis and Therapeutic Targeting - A Secondary Publication

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Proceedings of Anticancer Research 2024年第3期8卷 51-59页

作者： Syed Hussain Raza Yasir Hameed Department of biochemistry and biotechnology The Islamia University of BahawalpurBahawalpurPakistan

The study investigates the expression pattern and regulatory mechanisms of estrogen receptor 1 (ESR1) in liver hepatocellular carcinoma (LIHC) through comprehensive bioinformatics analysis. Utilizing UALCAN and GEPIA2 databases, significant down-regulation of ESR1 expression is observed in LIHC samples compared to normal controls, indicating its potential role in tumor progression. Further analysis reveals consistent down-regulation across different clinical variables including patient age, gender, race, and various stages of LIHC, affirming the regulatory role of ESR1 in tumor development and progression. Additionally, promoter methylation analysis demonstrates hypermethylation of ESR1 in LIHC samples, negatively correlating with its expression. This association persists across different clinical parameters, emphasizing the inverse relationship between ESR1 methylation and expression levels. Survival analysis indicates that up- regulation of ESR1 is associated with better overall survival, suggesting its potential as a prognostic biomarker in LIHC. Furthermore, genetic mutation analysis using cBioPortal reveals a spectrum of alterations in ESR1, including amplification, missense mutation, deep deletion, splice mutation, and truncating mutation, highlighting the genetic complexity of ESR1 in LIHC. These findings collectively contribute to a deeper understanding of ESR1 dysregulation in LIHC and its clinical implications as a potential therapeutic target and prognostic marker.

关键词： Estrogen receptor 1 Liver hepatocellular carcinoma Biomarker Prognosis

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