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Alternative splicing and related RNA binding proteins in human health and disease

Signal Transduction and Targeted Therapy 2024年第3期9卷 839-871页

作者： Yining Tao Qi Zhang Haoyu Wang Xiyu Yang Haoran Mu department of Orthopedics Shanghai General HospitalShanghai Jiao Tong University School of Medicine200000 ShanghaiChina Shanghai Bone Tumor Institution 200000 ShanghaiChina department of Biochemistry and molecular cell biology Shanghai Key Laboratory for Tumor Microenvironment and InflammationShanghai Jiao Tong University School of Medicine200000 ShanghaiChina

Alternative splicing(AS)serves as a pivotal mechanism in transcriptional regulation,engendering transcript diversity,and modifications in protein structure and *** varying tissues,developmental stages,or under specific conditions,AS gives rise to distinct splice *** implies that these isoforms possess unique temporal and spatial roles,thereby associating AS with standard biological activities and *** these,AS-related RNA-binding proteins(RBPs)play an instrumental role in regulating alternative splicing *** physiological conditions,the diversity of proteins mediated by AS influences the structure,function,interaction,and localization of proteins,thereby participating in the differentiation and development of an array of tissues and *** pathological conditions,alterations in AS are linked with various diseases,particularly *** changes can lead to modifications in gene splicing patterns,culminating in changes or loss of protein *** instance,in cancer,abnormalities in AS and RBPs may result in aberrant expression of cancer-associated genes,thereby promoting the onset and progression of *** and RBPs are also associated with numerous neurodegenerative diseases and autoimmune ***,the study of AS across different tissues holds significant *** review provides a detailed account of the recent advancements in the study of alternative splicing and AS-related RNA-binding proteins in tissue development and diseases,which aids in deepening the understanding of gene expression complexity and offers new insights and methodologies for precision medicine.

关键词： organs alterations thereby

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Hydroxysafflor Yellow A Promotes HaCaT cell Proliferation and Migration by Regulating HBEGF/EGFR and PI3K/AKT Pathways and Circ_0084443

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Chinese Journal of Integrative Medicine 2024年第3期30卷 213-221页

作者： ZHANG Yue XIAO Yan-wei MA Jing-xin WANG Ao-xue department of Dermatology the Second Hospital of Dalian Medical UniversityDalianLiaoning Province116021China department of cell biology Dalian Medical UniversityDalianLiaoning Province116044China

Objective:To investigate the effect and possible mechanism of hydroxysafflor yellow A(HSYA) on human immortalized keratinocyte cell proliferation and ***:HaCaT cells were treated with *** proliferation was detected by the cell counting kit-8 assay,and cell migration was measured using wound healing assay and Transwell migration *** mRNA and protein expression levels of heparin-binding epidermal growth factor(EGF)-like growth factor(HBEGF),EGF receptor(EGFR),phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT),mammalian target of rapamycin(mTOR),and hypoxia-inducible factor-1α(HIF-1α) were detected by quantitative real-time polymerase chain reaction(qRT-PCR) and Western blot,***_0084443-overexpressing HaCaT cells and empty plasmid HaCaT cells were constructed using the lentiviral stable transfection and treated with *** expression of circ_0084443 was detected by ***:HSYA(800 μmol/L) significantly promoted HaCaT cell proliferation and migration(Pcell proliferation and migration via the HBEGF/EGFR and PI3K/AKT/m TOR signaling pathways(Pcells(Pcell migration(P>0.05).Conclusion:HSYA played an accelerative role in HaCaT cell proliferation and migration,which may be attributable to activating HBEGF/EGFR and PI3K/AKT signaling pathways,and had a particular inhibitory effect on the keratinocyte negative

关键词： hydroxysafflor yellow A circ_0084443 heparin-binding epidermal growth factor-like growth factor/epidermal growth factor receptor phosphatidylinositol 3-kinase/protein kinase B

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Host cyclophilin A facilitates SARS-CoV-2 infection by binding and stabilizing spike on virions

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Signal Transduction and Targeted Therapy 2024年第1期9卷 36-39页

作者： Xiangpeng Sheng Fang Zhu Hong Peng Fan Yang Yi Yang Cong Yang Zhen Wang Wei Chen Deyin Guo Ronggui Hu State Key Laboratory of molecular biology Center for Excellence in Molecular Cell ScienceShanghai Institute of Biochemistry and Cell BiologyUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghaiChina MOE Key Laboratory of Tropical Disease Control Centre for Infection and Immunity StudySchool of MedicineSun Yat-sen UniversityShenzhenChina ICU Longhua Hospital Shanghai University of Traditional Chinese MedicineShanghaiChina

Dear Editor,The novel coronavirus SARS-CoV-2 rapidly evolutes to increase its infectivity and transmissibility,facilitates its immune escape,impairs vaccine efficacy,and currently causes repeated infections in human,which is mainly determined by the accumulated mutations in spike(S).1 Transmembrane S is a heavily glycosylated protein on the surface of the virion as homotrimer,responsible for binding to human angiotensin-converting enzyme 2(hACE2)receptor.2 While the architecture of S trimers has been well studied,how the stability of S is regulated by potential host factors remains unknown.

关键词： ACE2 vaccine infection

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Intracellular redox potential-driven live-cell synthesis of CdSe quantum dots in Staphylococcus aureus

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Science China Chemistry 2024年第3期67卷 990-999页

作者： Cai-Qin Wu An-An Liu Xu Li Jia-Wei Tu Juan Kong Ling-Ling Yang Jian-Hong Jia Chuan Wang Bin Hu Zhi-Xiong Xie Dai-Wen Pang The Institute for Advanced Studies College of Chemistry and Molecular SciencesCollege of Life SciencesHubei Key Laboratory of Cell HomeostasisWuhan UniversityWuhan 430072China Research Center for Analytical Sciences College of ChemistryState Key Laboratory of Medicinal Chemical BiologyTianjin Key Laboratory of Biosensing and Molecular RecognitionFrontiers Science Center for New Organic MatterFrontiers Science Center for Cell Responsesand Haihe Laboratory of Sustainable Chemical TransformationsNankai UniversityTianjin 300071China

Biosynthesized semiconductor quantum dots(QDs) have bright fluorescence,adjustable particle sizes,and environmental friendliness,endowing them with convenience and potential for biological *** to the unclear mechanism of the cellular environment on the live-cell synthesis of QDs,it is still difficult to regulate their optical ***,the critical role of the intracellular redox environment in regulating the fluorescence properties of biosynthesized CdSe QDs in Staphylococcus aureus(***) has been *** glutathione peroxidase(GPx) activity directly affects the intracellular H_(2)O_(2) produced in the SeO_(3)^(2-) reduction,which further manipulates the glutathione redox cycle to determine the content of low-valence *** a result,the fluorescence intensity of the synthesized CdSe QDs increases by 60% in the GPx overexpressed *** cellular redox potential that is controlled by the GSH redox cycle provides the driving force for the reduction of SeO_(3)^(2-),facilitating the synthesis of CdSe QDs in *** *** proposed mechanism of the cellular redox state provides a new perspective for regulating the synthesis of semiconductor nanomaterials in live cells.

关键词： redox H_(2)O_(2) peroxidase quantum dot Staphylococcus aureus

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Impairment of Autophagic Flux After Hypobaric Hypoxia Potentiates Oxidative Stress and Cognitive Function Disturbances in Mice

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Neuroscience Bulletin 2024年第1期40卷 35-49页

作者： Shuhui Dai Yuan Feng Chuanhao Lu Hongchen Zhang Wenke Ma Wenyu Xie Xiuquan Wu Peng Luo Lei Zhang Fei Fei Zhou Fei Xia Li department of Neurosurgery Xijing HospitalFourth Military Medical UniversityXi'an 710000China National Translational Science Center for molecular Medicine and department of cell biology Fourth Military Medical UniversityXi'an 710000China department of Neurosurgery The Central Hospital of BaojiBaoji 721000China department of Ophthalmology Xijing HospitalFourth Military Medical UniversityXi'an 710000China

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude *** plays a critical role in ischemic brain injury,but its role in hypo-baric hypoxia(HH)remains *** we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain,and is partially responsible for HH-induced oxidative stress,neuronal loss,and brain *** autophagic agonist rapamycin only promotes the initiation of *** proteome analysis,a screen showed that protein dynamin2(DNM2)potentially regulates autophagic *** of DNM2 significantly increased the formation of autolysosomes,thus maintaining autophagic flux in combination with ***,the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH *** results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.

关键词： Autophagy-Proteomics Oxidative stress Hypobaric hypoxia-Brain injury

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γδT cells:Major advances in basic and clinical research in tumor immunotherapy

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Chinese Medical Journal 2024年第1期137卷 21-33页

作者： Yueqi Zhao Peng Dong Wei He Jianmin Zhang Hui Chen department of Immunology CAMS Key Laboratory for T Cell and ImmunotherapyState Key Laboratory of Medical Molecular BiologyInstitute of Basic Medical SciencesChinese Academy of Medical Sciences and School of Basic MedicinePeking Union Medical CollegeBeijing 100005China Changzhou Xitaihu Institute for Frontier Technology of cell Therapy ChangzhouJiangsu 213000China Haihe Laboratory of cell Ecosystem Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300020China

γδT cells are a kind of innate immune T *** have not attracted sufficient attention because they account for only a small proportion of all immune cells,and many basic factors related to these cells remain ***,in recent years,with the rapid development of tumor immunotherapy,γδT cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex(MHC)*** increasing number of basic studies have focused on the development,antigen recognition,activation,and antitumor immune response ofγδT ***,γδT cell-based immunotherapeutic strategies are being developed,and the number of clinical trials investigating such strategies is *** review mainly summarizes the progress of basic research and the clinical application ofγδT cells in tumor immunotherapy to provide a theoretical basis for further the development ofγδT cell-based strategies in the future.

关键词： Gamma-delta T-cells T cell receptor CD1a Tumor immunotherapy Receptors,chimeric antigen Vδ1 cells αβT cells

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Foraging valor linked with aggression:selection against completely abandoning aggression in the high-elevation ant Tetramorium alpestre?

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Insect Science 2024年第3期31卷 953-970页

作者： Marie-Luise Contala Patrick Krapf Florian M.Steiner Birgit C.Schlick-Steiner molecular Ecology Group Department of EcologyUniversitat InnsbruckInnsbruckAustria rganismal&Evolutionary biology Research Programme University of HelsinkiHelsinkiFinland

Aggression has multiple benefits and is often coupled with other behaviors("behavioral syndromes").The level of aggressiveness is influenced by an adaptive benefit-cost ratio suggesting that benefits should outweigh the costs of ***,we assess if several behaviors are coupled in two behaviorally different populations(aggressive,peaceful)of the high-elevation ant Tetramorium *** three weeks,we collected colony fragments and analyzed boldness,exploring,foraging,and risk-taking *** hypothesized that the aggressive population is bolder,more explorative and risk-prone,and forages more food than the peaceful *** test whether(a)the combination of experiments and parameters used yields a good setup,(b)populations differ behaviorally,and(c)populations display behavioral syndromes,we assessed(a)the frequency of repeatable behaviors of each experiment,(b)the behavioral means among populations,and(c)the behavioral repeatability,*** found that(a)boldness and exploring were most repeatable and represent a good experimental setup,(b)the aggressive population was bolder and more explorative and risk-prone than the peaceful population,(c)boldness and exploring behaviors were highly repeatable in both populations,thus corroborating our *** results suggest that boldness,exploring,and risk-taking but not foraging are presumably coupled with aggression and indicate the presence of behavioral syndromes in this *** specific ecological conditions,aggression may be coupled with other behaviors and important for finding *** is probably adaptive in ***,possibly indicating that selection favors aggression at least partially,which may counteract the complete loss of intraspecific aggression.

关键词： adaptive value behavioral syndromes boldness exploration repeatability trade-off

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Using microglia-derived extracellular vesicles to capture diversity of microglial activation phenotypes following neurological injury

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Neural Regeneration Research 2024年第8期19卷 1633-1634页

作者： Austyn D.Roseborough Nikita Ollen-Bittle Shawn NWhitehead Vulnerable Brain Laboratory Department of Anatomy&Cell BiologySchulich School of Medicine&DentistryLondonOHCanada

Microglia are one of the three glial cell populations in the central nervous system(CNS),along with astrocytes and *** microglia are unique among brain cells due to their hematologic origin and perform immune function... 详细信息

关键词： neurological cytes activation

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TabHLH27 orchestrates root growth and drought tolerance to enhance water use efficiency in wheat

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Journal of Integrative Plant biology 2024年第7期66卷 1295-1312页

作者： Dongzhi Wang Xiuxiu Zhang Yuan Cao Aamana Batool Yongxin Xu Yunzhou Qiao Yongpeng Li Hao Wang Xuelei Lin Xiaomin Bie Xiansheng Zhang Ruilian Jing Baodi Dong Yiping Tong Wan Teng Xigang Liu Jun Xiao Key Laboratory of Plant cell and Chromosome Engineering Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Center for Agricultural Resources Research Institute of Genetics and Developmental BiologyChinese Academy of SciencesShijiazhuang 050022China Key Laboratory of Crop biology College of Life SciencesShandong Agricultural UniversityTai'an 271018China State Key Laboratory of Crop Gene Resources and Breeding Institute of Crop SciencesChinese Academy of Agricultural SciencesBeijing 100081China Ministry of Education Key Laboratory of molecular and cellular biology Hebei Research Center of the Basic Discipline of Cell BiologyHebei Collaboration Innovation Center for Cell Signaling and Environmental AdaptationHebei Key Laboratory of Molecular and Cellular BiologyCollege of Life SciencesHebei Normal UniversityShijiazhuang 050024China Centre of Excellence for Plant and Microbial Science(CEPAMS) JIC‐CASBeijing 100101China

Cultivating high-yield wheat under limited water resources is crucial for sustainable agriculture in semiarid *** water scarcity,plants activate drought response signaling,yet the delicate balance between drought tolerance and development remains *** genome-wide association studies and transcriptome profiling,we identified a wheat atypical basic helix-loop-helix(b HLH)transcription factor(TF),Tab HLH27-A1,as a promising quantitative trait locus candidate for both relative root dry weight and spikelet number per spike in *** HLH27-A1/B1/D1 knockout reduced wheat drought tolerance,yield,and water use efficiency(WUE).Tab HLH27-A1 exhibited rapid induction with polyethylene glycol(PEG)treatment,gradually declining over *** activated stress response genes such as Ta CBL8-B1 and Ta CPI2-A1 while inhibiting root growth genes like Ta SH15-B1 and Ta WRKY70-B1 under short-term PEG *** distinct transcriptional regulation of Tab HLH27-A1 involved diverse interacting factors such as Ta ABI3-D1 and Tab *** variations of Tab HLH27-A1influence its transcriptional responses to drought stress,with Tab HLH27-A1^(Hap-II)associated with stronger drought tolerance,larger root system,more spikelets,and higher WUE in ***,the excellent Tab HLH27-A1^(Hap-II)was selected during the breeding process in China,and introgression of Tab HLH27-A1^(Hap-II)allele improved drought tolerance and grain yield,especially under water-limited *** study highlights Tab HLH27-A1's role in balancing root growth and drought tolerance,providing a genetic manipulation locus for enhancing WUE in wheat.

关键词： drought tolerance GWAS root growth wheat WUE

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Sciadopitysin exerts anticancer effects on HepG2 hepatocellular carcinoma cells by regulating reactive oxygen species-mediated signaling pathways

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BIOcell 2024年第7期48卷 1055-1069页

作者： YAN-NAN LI YUN-HONG XIU YAN-JUN TANG JING-LONG CAO WEN-SHUANG HOU AN-QI WANG TIAN-ZHU LI CHENG-HAO JIN department of Biochemistry and molecular biology Heilongjiang Bayi Agricultural UniversityDaqingChina Hemodialysis Center Daqing Oilfield General HospitalDaqingChina department of Food Science and Engineering Heilongjiang Bayi Agricultural UniversityDaqingChina department of molecular biology Chifeng UniversityChifengChina National Coarse Cereals Engineering Research Center DaqingChina

Objectives:Sciadopitysin(SP)is aﬂavonoid in Ginkgo biloba that exhibits various pharmacological *** study aimed to investigate its antitumor effects and the underlying molecular mechanism of SP in hepatocellular carcinoma(HCC)***:Network pharmacology was used for target prediction *** Counting Kit-8(CCK-8)assay was used to test the cell *** cytometry was used to test the cell cycle distribution,apoptosis status,and reactive oxygen species(ROS)*** and wound-healing assay was used to test the migration effect of SP on HepG2 *** Blot assay was used to test the expression levels of ***:Network pharmacology analysis results showed that the mitogen-activated protein kinase(MAPK)and other signaling pathways are involved in the SP anti-HCC biological ***-8 assay results demonstrated that SP showed an obvious killing effect on three types of HCC cells and low cytotoxic effect on normal *** Blot andﬂow cytometry results showed that SP regulated MAPK/signal transducer and activator of transcription 3(STAT3)/nuclear factor kappa-B(NF-κB)signaling pathway to induce mitochondrion-dependent apoptosis in HepG2 ***,SP can arrest the G0/G1 phase cell cycle via the protein kinase B(AKT)/p21/p27/cyclin-dependent kinase(CDK)/Cyclin signaling *** healing and transwell assays showed that SP inhibited cell motility and invasion through the AKT/glycogen synthase kinase3β(GSK-3β)/vimentin/β-catenin signaling ***:Theseﬁndings demonstrated that SP induced mitochondrion-dependent apoptosis,arrested cell cycle in the G0/G1 phase,and inhibited cell migration by regulating the ROS-mediated signaling pathway in HepG2 ***,SP could serve as a therapeutic agent for the treatment of human HCC.

关键词： Sciadopitysin Hepatocellular carcinoma Apoptosis cell cycle cell migration

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