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Intranasal boosting with RBD-HR protein vaccine elicits robust mucosal and systemic immune responses

Genes & Diseases 2024年第4期11卷 327-339页

作者： Li Chen Wenyan Ren Hong Lei Jiayu Wang Haiying Que Dandan Wan Aqu Alu Dandan Peng Minyang Fu Weiqi Hong Yuhe Huang Xiangrong Song Guangwen Lu Xiawei Wei Laboratory of aging research and Cancer Drug Target State Key Laboratory of Biotherapy and Cancer CenterNational Clinical Research Center for GeriatricsWest China HospitalSichuan UniversityChengduSichuan 610041China

The emergence of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variants has decreased the efficacy of SARs-CoV-2 vaccines in containing coronavirus disease 2019(CoVID-19)over time,and booster vaccination strategies are urgently necessitated to achieve sufficient *** immunization can improvemucosal immunity,offer-ing protection against the infection and sustaining the spread of *** this study,an intranasal booster of the RBD-HR vaccine after two doses of the mRNA vaccine significantly increased the levels of specific binding antibodies in serum,nasal lavage fluid,and bronchoal-veolar lavage fluid compared with only two doses of mRNA *** intranasal boosting with the RBD-HR vaccine,the levels of serum neutralizing antibodies against prototype and variant strains of SARS-Cov-2 pseudoviruses weremarkedly higher than those in mice receiving mRNA vaccine alone,and intranasal boosting with the RBD-HR vaccine also inhibited the bind-ing of RBD to hACE2 ***,the heterologous intranasal immunization regimen promoted extensive memory T cell responses and activated CD103+dendritic cells in the respiratory mucosa,and potently enhanced the formation of T follicular helper cells and germinal center B cells in vital immune organs,including mediastinal lymph nodes,inguinal lymph nodes,and ***,these data infer that heterologous intranasal boosting with the RBD-HR vaccine elicited broad protective immunity against SARS-CoV-2 both locallyandsystemically.

关键词： Heterologous immunization Intranasal immunization mRNA vaccine SARS-CoV-2 Subunitprotein vaccine

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Mitochondrial DNA methylation and mitochondria-related epigenetics in neurodegeneration

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Neural Regeneration research 2024年第2期19卷 405-406页

作者： Fabio Coppedè Department of Translational research and of New Surgical and Medical Technologies Laboratory of Medical GeneticsUniversity of PisaPisaItaly、Interdepartmental Research Center of Biology and Pathology of AgingUniversity of PisaPisaItaly

Mitochondria are cytoplasmic organelles referred to as the powerhouse of the cell because they are primarily involved in oxidative phosphorylation and energy *** are particularly abundant in tissues with high energy demands,including muscle,liver,and brain,and mitochondrial dysfunction,oxidative mitochondrial DNA(mtDNA)damage,and impaired mitochondrial dynamics have often been associated with neurodegeneration.

关键词： impaired neurodegeneration oxidative

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Protein Arginine Methyltransferase 1 Ablation in Motor Neurons Causes Mitochondrial Dysfunction Leading to Age-related Motor Neuron Degeneration with Muscle Loss

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research 2024年第1期2023卷 637-649页

作者： Hyun-Kyung So Hyebeen Kim Jinwoo Lee Chang-Lim You Chae-Eun Yun Hyeon-Ju Jeong Eun-Ju Jin Yunju Jo Dongryeol Ryu Gyu-Un Bae Jong-Sun Kang Department of Molecular Cell Biology Sungkyunkwan University School of MedicineSuwonKorea Single Cell Network research center Sungkyunkwan University School of MedicineSuwonKorea research Institute of aging-Related Diseases AniMusCureInc.SuwonKorea Drug Information research Institute Muscle Physiome Research CenterCollege of PharmacySookmyung Women’s UniversitySeoulKorea

Neuromuscular dysfunction is tightly associated with muscle wasting that occurs with age or due to degenerative ***,the molecular mechanisms underlying neuromuscular dysfunction are currently *** studies have proposed important roles of Protein arginine methyltransferase 1(Prmt1)in muscle stem cell function and muscle *** the current study,we set out to determine the role of Prmt1 in neuromuscular function by generating mice with motor neuron-specific ablation of Prmt1(mnKO)using *** exhibited age-related motor neuron degeneration and neuromuscular dysfunction leading to premature muscle loss and ***1 deficiency also impaired motor function recovery and muscle reinnervation after sciatic nerve *** transcriptome analysis of aged mnKO lumbar spinal cords revealed alterations in genes related to inflammation,cell death,oxidative stress,and ***,mnKO lumbar spinal cords of sciatic nerve injury model or aged mice exhibited elevated cellular stress response in motor ***,Prmt1 inhibition in motor neurons elicited mitochondrial *** findings demonstrate that Prmt1 ablation in motor neurons causes agerelated motor neuron degeneration attributing to muscle ***,Prmt1 is a potential target for the prevention or intervention of sarcopenia and neuromuscular dysfunction related to aging.

关键词： degeneration impaired prevention

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Suspended particulate matter promotes epithelial-to-mesenchymal transition in alveolar epithelial cells via TGF-β1-mediated ROS/IL-8/SMAD3 axis

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Journal of Environmental Sciences 2024年第7期141卷 139-150页

作者： Shahrzad Molavinia Dian Dayer Mohammad Javad Khodayar Gholamreza Goudarzi Maryam Salehcheh Cellular and Molecular research center Medical Basic Sciences Research InstituteAhvaz Jundishapur University of Medical SciencesAhvazIran Department of Toxicology School of PharmacyAhvaz Jundishapur University of Medical SciencesAhvazIran Student research Committee Ahvaz Jundishapur University of Medical SciencesAhvazIran Toxicology research center Medical Basic Sciences Research InstituteAhvaz Jundishapur University of Medical SciencesAhvazIran Air Pollution and Respiratory Diseases research center Ahvaz Jundishapur University of Medical SciencesAhvazIran iranian Scientific Association of Clean Air TehranIran

Epidemiological evidence presents that dust storms are related to respiratory diseases,such as pulmonary fibrosis(PF).However,the precise underlying mechanisms of SPM-elicited adverse effects still need to be ***-mesenchymal transition(EMT)process is a characteristic of *** discussed whether suspended particulate matter(SPM)is involved in EMT induction via transforming growth factor-β1(TGF-β1).In this study,a detailed elemental analysis(55 elements),particle size,and morphology were *** investigate the toxicity of SPM,an MTT test was performed to detect cell ***,A549cells were exposed to selected concentrations of SPM(20 and 40μg/mL)for single and repeated *** DCFH-DA assay showed that exposure to SPM could produce reactive oxygen species(ROS).The ELISA assay demonstrated increased levels of interleukin-8(IL-8)and TGF-β1 in the *** blot was used to detect the expression of proteins associated with EMT and the SMAD3-dependent *** of western blot demonstrated that E-cadherin was reduced,whereas p-SMAD3,vimentin,andα-smooth muscle actin were *** findings indicated that SPM triggered EMT by induction of oxidative stress,inflammation,and the TGF-β1/SMAD3 pathway activation.

关键词： Particulate matter TGF-β1 Oxidative stress Epithelial-mesenchymal transition Pulmonary fibrosis Cells

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Ethical concerns in aging research: perspectives of global frontline researchers

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Science China Life Sciences 2024年第10期67卷 2149-2156页

作者： Yaojin Peng Lulu Ding Zhenyu Xiao Moshi Song Jianwei Lv Guang-Hui Liu Key Laboratory of Organ Regeneration and Reconstruction State Key Laboratory of Stem Cell and Reproductive BiologyInstitute of ZoologyChinese Academy of Sciences University of Chinese Academy of Sciences Beijing Institute for Stem Cell and Regenerative Medicine Institute for Stem Cell and Regeneration Chinese Academy of Sciences aging Biomarker Consortium (ABC) School of Life Science Beijing Institute of Technology School of Life Sciences Xiamen University Advanced Innovation center for Human Brain Protection and National Clinical research center for Geriatric Disorders Xuanwu HospitalCapital Medical University aging Translational Medicine center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical University

This study investigated the ethical landscape of aging research amid the increasing global focus on extending the human lifespan and health span. Our global survey of 180 researchers across 38 jurisdictions revealed divergent perceptions of aging, a consensus regarding the feasibility of delaying aging, and multiple perspectives regarding lifespan extension. The present findings underscore a paradigm shift toward inclusive and ethically sound research, emphasizing the need for an approach that strikes a balance between basic and clinical research. In addition, this study highlighted key ethical concerns in aging research, including the effects of misleading advertising, potential inequality in access to aging interventions, and risks pertaining to the extrapolation of research findings from lower-model organisms to humans. The insights presented in this paper call for an integrated approach for overcoming the complex ethical and societal challenges in aging research to ensure responsible and equitable advancements in this burgeoning field.

关键词： aging ethical landscape ethics surveys and questionnaires

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Identification of TMEM217 as a novel prognostic biomarker and potential therapeutic target in acute myeloid leukemia

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Genes & Diseases 2024年第4期11卷 90-93页

作者： Yunying Yao Zhizhou Xi Min Wu Bo Jiao Jiaming Gao Donghe Li Xi Xie Pengfei Xu Jiaoyang Li Lei Yan Ruibao Ren Ping Liu Shanghai Institute of Hematology State Key Laboratory for Medical GenomicsNational Research Center for Translational MedicineCollaborative Innovation Center of HematologyRuijin Hospital affiliated with Shanghai Jiao Tong University School of MedicineShanghai 200025China International center for aging and Cancer Hainan Medical UniversityHaikouHainan 570102China

Despite remarkable advances in molecular and cell biology of acute myeloid leukemia(AML),AML patients still frequently relapse and have low 5-year overall survival(OS)rates.1 It is worth noting that a recent study from the registry or clinical trial compilation has reported an improvement in the OS of adult AML patients,especially those under 60 years of age.

关键词： acute myeloid leukemia

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Simple procedure for assessing diffuse subarachnoid hemorrhage successfully created using filament perforation method in mice

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Animal Models and Experimental Medicine 2024年第1期7卷 77-81页

作者： Tatsushi Mutoh Ryota Tochinai Hiroaki Aono Masayoshi Kuwahara Yasuyuki Taki Tatsuya Ishikawa Department of Surgical Neurology Research Institute for Brain and Blood VesselsAkita Cerebrospinal and Cardiovascular CenterAkitaJapan Department of aging research and Geriatric Medicine Institute of DevelopmentAging and CancerTohoku UniversitySendaiJapan Department of Veterinary Pathophysiology and Animal Health Graduate School of Agriculture and Life SciencesThe University of TokyoTokyoJapan

The murine model of subarachnoid hemorrhage(SAH)is a valuable experimental tool for investigating molecular and cellular mechanisms,and the endovascular filament perforation technique can be used to simulate prominent pathophysiological features observed after human SAH;however,current validation methods for assessing an appropriate SAH model are ***,we introduce a simple procedure for se-lecting a mouse model of diffuse *** was induced in 24 mice using a standard filament perforation *** confirming survival at 24 h,SAH was scored 0-1 based on T2*-weighted images on whole-brain magnetic resonance imaging(MRI)and visual surveillance of the cisterna magna(CM)through the dura *** CM-based SAH grading correlated well with a reference parameter defined by extracted brain(r^(2)=0.53,p<0.0001).The receiver operating characteristic curve revealed a sensi-tivity of 85%and a specificity of 91%for detecting diffuse SAH,with a similar area under the curve(0.89±0.06[standard error of the mean])as the MRI-based grading(0.72±0.10,p=0.12).Our data suggest that confirming an SAH clot in the CM is a valuable way to select a clinically relevant diffuse SAH model that can be used in future experimental studies.

关键词： cisterna magna clot distribution filament perforation mouse model subarachnoid hemorrhage

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MgO-attached graphene nanosheet(MgO@GNS)reinforced magnesium matrix nanocomposite with superior mechanical,corrosion and biological performance

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International Journal of Minerals,Metallurgy and Materials 2024年第9期31卷 2062-2076页

作者： S.Abazari A.Shamsipur H.R.Bakhsheshi-Rad M.S.Soheilirad F.Khorashadizade S.S.Mirhosseini Department of Materials and Metallurgical Engineering Amirkabir University of TechnologyTehran ***Iran iranian National Standards Organization of Hormozgan HormozganIran Advanced Materials research center Department of Materials EngineeringNajafabad BranchIslamic Azad UniversityNajafabadIran Department of Materials and Metallurgical Engineering Iran University of Science and TechnologyTehranIran

Magnesium(Mg)alloys are gaining great consideration as body implant materials due to their high biodegradability and ***,they suffer from low corrosion resistance and antibacterial *** this research,semi-powder metallurgy followed by hot extrusion was utilized to produce the magnesium oxide@graphene nanosheets/magnesium(MgO@GNS/Mg)composite to improve mechanical,corrosion and cytocompatibility *** have revealed that the incorporation of MgO@GNS nanohybrids into Mg-based composite enhanced microhardness and compressive *** vitro,osteoblast cell culture tests show that using MgO@GNS nanohybrid fillers enhances osteoblast adhesion and apatite *** presence of MgO@GNS nanoparticles in the composites decreased the opening defects,micro-cracks and micro-pores of the composites thus preventing the penetration of the corrosive solution into the *** demonstrated that the MgO@GNS/Mg composite possesses excellent antibacterial properties because of the combination of the release of MgO and physical damage to bacterium membranes caused by the sharp edges of graphene nanosheets that can effectively damage the cell wall thereby facilitating penetration into the bacterial lipid ***,the MgO@GNS/Mg composite with high mechanical strength,antibacterial activity and corrosion resistance is considered to be a promising material for load-bearing implant applications.

关键词： metal matrix composites MgO@GNS nanohybrid strengthening mechanisms antibacterial activity biocompatibility

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Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

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Protein & Cell 2024年第1期15卷 36-51页

作者： Jinghui Lei Xiaoyu Jiang Daoyuan Huang Ying Jing Shanshan Yang Lingling Geng Yupeng Yan Fangshuo Zheng Fang Cheng Weiqi Zhang Juan Carlos Izpisua Belmonte Guang-Hui Liu Si Wang Jing Qu Advanced Innovation center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China aging Translational Medicine center Intermational Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration CASBeijing 100101China The Fifth People's Hospital of Chongqing Chongqing 400062China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China National Laboratory of Biomacromolecules CAs Center for Excellence in BiomacromoleculesInstitute of BiophysicsBeijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China China National center for Bioinformation Beijing 100101China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Sino-Danish center for Education and research Beijing 101408China aging Biomarker Consortium China Altos Labs San DiegoCA 92121United State

Hypoxia-inducible factor(HIF-1α),a core transcription factor responding to changes in cellular oxygen levels,is closely associated with a wide range of physiological and pathological ***,its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely ***,we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-ia-deficient human vascular cells including vascular endothelial cells,vascular smooth muscle cells,and mesenchymal stem cells(MsCs),as a platform for discovering cell type-specific hypox-ia-induced response *** comparative molecular profiling across cell types under normoxic and hypoxic conditions,we provide insight into the indispensable role of HIF-1αin the promotion of ischemic vascular *** found human MSCs to be the vascular cell type most susceptible to HIF-1a deficiency,and that transcriptional inactivation of ANKZF1,an effector of HIF-1a,impaired pro-angiogenic ***,our findings deepen the understanding of HIF-ia in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.

关键词： HIF-1 human ESC vascular cell regeneration

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An overview of the physiopathology and various treatment strategies for polycystic ovary syndrome

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生殖与发育医学(英文) 2024年第1期08卷 50-60页

作者： Rajabi Ayda Babaie Soraya Oskouei Behnaz Sadeghzadeh Mehdizadeh Amir Farshbaf-Khalili Azizeh Department of Reproductive Biology Faculty of Advanced Medical Sciences Hematology and Oncology research center Student research Committee 2. Department of Anatomy 3. Faculty of Medicine 4. Yasouj University of Medical Sciences 5. Yasouj 63614 6. Iran Physical Medicine and Rehabilitation research center aging research Institute 9. Tabriz University of Medical Sciences 10. Tabriz 51368

Polycystic ovary syndrome (PCOS), a common endocrine disorder with metabolic and reproductive consequences, affects a significant percentage of women of reproductive age. Because of its complexity and impact on the quality of life, PCOS requires timely diagnosis and screening for complications. The most common clinical manifestations of PCOS are hirsutism, hyperandrogenism, acne, irregular cycles, amenorrhea, and anovulation. Although PCOS has different clinical manifestations in women, hyperandrogenism, and anovulation are the most common symptoms. A good medical history, examination, blood tests, and ultrasound findings facilitate the diagnosis of PCOS. Novel treatments have also undergone clinical trials to improve the symptoms of PCOS. However, comprehensive review articles investigating the different communities of this disease are limited, and this review aimed to collect data on the different etiologies of PCOS along with the latest diagnostic methods and the most common and up-to-date treatments for this disease.

关键词： Polycystic ovary syndrome Endocrine disorder Hyperandrogenism Hyperinsulinemia Anovulation Amenorrhea

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