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Modeling xeroderma pigmentosum associated neurological pathologies with patients-derived iPSCs

Protein & Cell 2016年第3期7卷 210-221页

作者： Lina Fu Xiuling Xu Ruotong Ren Jun Wu Weiqi Zhang Jiping Yang Xiaoqing Ren Si Wang Yang Zhao Liang Sun Yang Yu Zhaoxia Wang Ze Yang Yun Yuan Jie Qiao juan carlos izpisua belmonte Jing Qu Guang-Hui Liu National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China FSU-CAS Innovation Institute Foshan University Foshan 528000 China State Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Universidad Cato1ica San Antonio de Murcia (UCAIVI) Campus de los Jer6nimos N° 135 Guadalupe 30107 Murcia Spain Beijing Hospital of the Ministry of Health Beijing 100730 China Department of Gynecology and Obstetrics Peking University Third Hospital Beijing 100191 China Department of Neurology Peking University First Hospital Beijing 100034 China Beijing Institute for Brain Disorders Capital Medical University Beijing 100069 China University of Chinese Academy of Sciences Beijing 100049 China

Xeroderma pigmentosum （XP） is a group of genetic disorders caused by mutations of XP-associated genes, resulting in impairment of DNA repair. XP patients frequently exhibit neurological degeneration, but the underlying mechanism is unknown, in part due to lack of proper disease models. Here, we generated patientspecific induced pluripotent stem cells （iPSCs） harboring mutations in five different XP genes including XPA, XPB, XPC, XPG, and XPV. These iPSCs were further differentiated to neural cells, and their susceptibility to DNA damage stress was investigated. Mutation of XPA in either neural stem cells （NSCs） or neurons resulted in severe DNA damage repair defects, and these neural cells with mutant XPA were hyper-sensitive to DNA damage-induced apoptosis. Thus, XP-mutant neural cells represent valuable tools to clari the molecular mechanisms of neurological abnormalities in the XP patients.

关键词： xeroderma pigmentosum iPSC disease model neural stem cell. neuron

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Single-nucleus transcriptomic landscape of primate hippocampal aging

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Protein & Cell 2021年第9期12卷 695-716页

作者： Hui Zhang Jiaming Li Jie Ren Shuhui Sun Shuai Ma Weiqi Zhang Yang Yu Yusheng Cai Kaowen Yan Wei Li Baoyang Hu Piu Chan Guo-Guang Zhao juan carlos izpisua belmonte Qi Zhou Jing Qu Si Wang Guang-Hui Liu 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 Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China China National Center for Bioinformation Beijing 100101China Aging Translational Medicine Center Xuanwu HospitalCapital Medical UniversityBeijing 100053China Department of Neurosurgery Xuanwu HospitalCapital Medical UniversityBeijing 100053China Sino Danish CollegeUniversity of Chinese Academy of SciencesBeijing 101408China Sino Danish Center for Education and ResearchBeijing 101408China Department of Obstetrics and Gynecology Center for Reproductive MedicinePeking University Third HospitalBeijing 100191China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China Stem Cell Research Center Peking University Third HospitalBeijing 100191China Gene Expression Laboratory Salk Institute for Biological StudiesLa JollaCAUSA

The hippocampus plays a crucial role in learning and memory,and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative *** a systematic profiling of the aging effects on various hippocampal cell types in primates is still ***,we reported a variety of new aging-associated phenotypic changes of the primate *** include,in particular,increased DNA damage and heterochromatin erosion with time,alongside loss of proteostasis and elevated *** understand their cellular and molecular causes,we established the first single-nucleus transcriptomic atlas of primate hippocampal *** the 12 identified cell types,neural transiently amplifying progenitor cell(TAPC)and microglia were most affected by ***-depth dissection of gene-expression dynamics revealed impaired TAPC division and compromised neuronal function along the neurogenesis trajectory;additionally elevated pro-inflammatory responses in the aged microglia and oligodendrocyte,as well as dysregulated coagulation pathways in the aged endothelial cells may contribute to a hostile microenvironment for *** rich resource for understanding primate hippocampal aging may provide potential diagnostic biomarkers and therapeutic interventions against age-related neurodegenerative diseases.

关键词： aging hippocampus primate single-cell RNA sequencing

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Single-nucleus profiling unveils a geroprotective role of the Foxo3 in primate skeletal muscle aging

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Protein & Cell 2023年第7期14卷 499-514页

作者： Ying Jing Yuesheng Zuo Yang Yu Liang Sun Zhengrong Yu Shuai Ma Qian Zhao Guoqiang Sun Huifang Hu Jingyi Li Daoyuan Huang Lixiao Liu Jiaming Li Zijuan Xin Haoyan Huang juan carlos izpisua belmonte Weiqi Zhang Si Wang Jing Qu Guang-Hui Liu State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China China National Center for Bioinformation Beijing 100101China Aging Translational Medicine Center Intemational Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China Department of Obstetrics and Gynecology Center for Reproductive MedicinePeking University Third HospitalBeijing 100191China The Key Laboratory of Geriatrics Beijing Institute of GeriatricsInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing Hospital/National Center of Gerontology of National Health CommissionBeijing 100730China Clinical Stem Cell Research Center Peking University Third HospitalBeijing 100191China Department of Orthopaedics Peking University First HospitalBeijing 100034China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Sino-Danish Center for Education and Research Beijing 101408China Altos Labs Inc.San DiegoCA 94022USA The Fifth People's Hospital of Chongqing Chongqing 400062China

Age-dependent loss of skeletal muscle mass and function is a feature of sarcopenia,and increases the risk of many aging-related metabolic ***,we report phenotypic and single-nucleus transcriptomic analyses of non-human primate skeletal muscle aging.A higher transcriptional fluctuation was observed in myonuclei relative to other interstitial cell types,indicating a higher susceptibility of skeletal muscle fiber to *** found a downregulation of Foxo3 in aged primate skeletal muscle,and identi-fied FOxo3 as a hub transcription factor maintaining skeletal muscle *** the establishment of a complementary experimental pipeline based on a human pluripotent stem cell-derived myotube model,we revealed that silence of Foxo3 accelerates human myotube senescence,whereas genetic activation of endogenous FOxO3 alleviates human myotube ***,based on a combination of monkey skeletal muscle and human myotube aging research models,we unraveled the pivotal role of the FOxO3 in safeguarding primate skeletal muscle from aging,providing a comprehensive resource for the development of clinical diagnosis and targeted therapeutic interventions against human skeletal muscle aging and the onset of sarcopenia along with aging-relateddisorders.

关键词： single-nucleus RNA sequencing primate aging skeletal muscle FOxO3

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Opening up the black box of human cell plasticity

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The Innovation 2022年第5期3卷 13-14页

作者： Yusheng Cai juan carlos izpisua belmonte Jing Qu Guang-Hui Liu Weiqi Zhang 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 CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China China National Center for Bioinformation Beijing 100101China Gene Expression Laboratory Salk Institute for Biological StudiesLa JollaCA 92037USA Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China

Cell plasticity represents the ability of cells to acquire new *** plasticity can be reset in somatic cells via cellular reprogramming,a process that occurs in ***,cell plasticity occurs rarely in ***,Guan et *** cell plasticity in mature human cells,which they found to be essential for reprogramming human somatic cells to pluripotent stem cells using only small *** the first study demonstrates that chemical compounds can completely reprogram human somatic cells to a pluripotent state,it is a paradigm shift in developing pharmacological or therapeutic reprogramming approaches to control human cells.

关键词： al. plasticity programming

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A widely adaptable approach to generate integration-free iPSCs from non-invasively acquired human somatic cells

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Protein & Cell 2015年第5期6卷 386-389页

作者： Zhichao Ding Lina Sui Ruotong Ren Yanjun Liu Xiuling Xu Lina Fu Ruijun Bai Tingting Yuan Ying Hao Weiqi Zhang Huize Pan Wensu Liu Han Yu Concepcion Rodriguez Esteban Xiaobing Yu Ze Yang Jian Li Xiaomin Wang juan carlos izpisua belmonte Guang-Hui Liu Fei Yi Jing Qu National Laboratory of Biomacromolecules Institute of Biophysics University of the Chinese Academy of Sciences Chinese Acad- emy of Sciences Beijing 100101 China Department of Endocrinology 306th Hospital of PLA Beijing100101 China Science and Development Xtem Foshan 528000 China State Key Laboratory of Reproductive Biology Institute of ZoologyChinese Academy of Sciences Beijing 100101 China Beijing Hospital of the Ministry of Health Beijing 100073 China Beijing Institute for Brain Disorders Beijing 100069 China Gene Expression Laboratory Salk Institute for Biological Studies10010 North Torrey Pines Road La Jolla CA 92037 USA Center for Molecular and Translational Medicine Beijing 100101China Department of Molecular and Cellular Physiology StanfordUniversity School of Medicine Stanford CA 94305 USA

Dear Editor Human pluripotent stem cells including human embryonic stem cells （ESCs） and induced pluripotent stem cells （iPSCs） are cells displaying abilities of unlimited self-renewal and differentiation into any somatic cell type. These unique properties make them increasingly attractive for novel applications in disease modeling, drug discovery, and cell therapy （Buganim et al., 2014; Liu et al., 2011; Liu et al., 2012; Sanchez Alvarado and Yamanaka, 2014）. Moreover, iPSCs hold great potential for personalized cell therapy as they avoid some of the ethical concerns as well as the immunological rejection issues ascribed to ESCs.

关键词： iPSC dbcAMP Definitive Endoderm Cell Reprogram iPSC Line

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Mutations in foregut SOX2^+ cells induce efficient proliferation via CXCR2 pathway

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Protein & Cell 2019年第7期10卷 485-495页

作者： Tomoaki Hishida Eric Vazquez-Ferrer Yuriko Hishida-Nozaki Ignacio Sancho-Martinez Yuta Takahashi Fumiyuki Hatanaka Jun Wu Alejandro Ocampo Pradeep Reddy Min-Zu Wu Laurie Gerken Reuben J. Shaw Concepcion Rodriguez Esteban Christopher Benner Hiroshi Nakagawa Pedro Guillen Garcia Estrella Nunez Delicado Antoni Castells Josep M. Campistol Guang-Hui Liu juan carlos izpisua belmonte Gene Expression Laboratory Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Advaneed Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric Disorders Xuanwu Hospital Capital Medical University Beijing 100053 China National Laboratory of Biomacromolecules CAS Center for Excellence in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China University of the Chinese Academy of Sciences Beijing 100049 China Insitute for Stem Cell and Regeneration Chinese Academy of Sciences Beijing 100101 China Beijing Institute for Brain Disorder Beijing 100069 China Universidad Catolica San Antonio de Murcia Campus de los Jeronimos 135 Guadalupe 30107 Spain Molecular and Cell Biology Laboratory Dulbecco Center for Cancer Research Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Howard Hughes Medical Institute Dulbecco Center for Cancer Research Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Integrative Genomics Core Salk Institute for Biological Studies 10010 North Torrey Pines Road La Jolla CA 92037 USA Division of Gastroenterology Department of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104 USA Abramson Cancer Center University of Pennsylvania Philadelphia PA 19104 USA Department of Traumatology and Research Unit Clinica CEMTRO Av. Ventisquero de la Condesa 42 Madrid 28035 Spain Gastroenterology Department Hospital Clinic University of Barcelona IDIBAPS CIBEREHD Barcelona 08036 Spain

Identification of the precise molecular pathways involved in oncogene-induced transformation may help us gain a better understanding of tumor initiation and promotion. Here, we demonstrate that SOX2^+ foregut epithelial cells are prone to oncogenic transformation upon mutagenic insults, such as Kras^G12D and p53 deletion. GFP-based lineage-tracing experiments indicate that SOX2^+ cells are the cells-of-origin of esophagus and stomach hyperplasia. Our observations indicate distinct roles for oncogenic KRAS mutation and P53 deletion. p53 homozygous deletion is required for the acquisition of an invasive potential, and Kras^G12D expression, but not p53 deletion, suffices for tumor formation. Global gene expression analysis reveals secreting factors upregulated in the hyperplasia induced by oncogenic KRAS and highlights a crucial role for the CXCR2 pathway in driving hyperplasia. Collectively, the array of genetic models presented here demonstrate that stratified epithelial cells are susceptible to oncogenic insults, which may lead to a better understanding of tumor initiation and aid in the design of new cancer therapeutics.

关键词： Sox2 tumor CXCR2 stratified epithelia

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A human circulating immune cell landscape in aging and COVID-19

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Protein & Cell 2020年第10期11卷 740-770页

作者： Yingfeng Zheng Xiuxing Liu Wenqing Le Lihui Xie He Li Wen Wen Si Wang Shuai Ma Zhaohao Huang Jinguo Ye Wen Shi Yanxia Ye Zunpeng Liu Moshi Song Weiqi Zhang Jing-Dong J.Han juan carlos lzpisua belmonte Chuanle Xiao Jing Qu Hongyang Wang Guang-Hui Liu Wenru Su State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeiing 100101China National Center for Liver Cancer Second Military Medical UniversityShanghai 200433China Department of Critical Care Wuhan Hankou HospitalWuhan 430012China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Institute for Stem Cell and Regeneration CASBejjing 100101China University of Chinese Academy of Sciences Beijing 100049China Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China China National Center for Bioinformation Beijing 100101China Peking-Tsinghua Center for Life Sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology(CQB)Peking UniversityBeijing 100871China Gene Expression Laboratory Salk Institute for Biological StudiesLa JollaCAUSA

Age-associated changes in immune cells have been linked to an increased risk for ***,a global and detailed characterization of the changes that human circulating immune cells undergo with age is ***,we combined scRNA-seq,mass cytometry and sCATAC-seq to compare immune cell types in peripheral blood collected from young and old subjects and patients with *** found that the immune cell landscape was reprogrammed with age and was characterized by T cell polarization from naive and memory cells to effector,cytotoxic,exhausted and reg-ulatory cells,along with increased late natural killer cells,age-associated B cells,inflammatory monocytes and age-associated dendritic *** addition,the expression of genes,which were implicated in coron-avirus susceptibility,was upregulated in a cell subtype-specific manner with ***,COVID-19 promoted age-induced immune cell polarization and gene expression related to inflammation and cellular ***,these findings suggest that a dysreg-ulated immune system and increased gene expression associated with SARS-CoV-2 susceptibility may at least partially account for COVID-19 vulnerability in the elderly.

关键词： aging single-cell sequencing blood COVID-19 immune cells

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αKLOTHO and sTGFβR2 treatment counteract the osteoarthritic phenotype developed in a rat model

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Protein & Cell 2020年第3期11卷 219-226页

作者： Paloma Martinez-Redondo Isabel Guillen-Guillen Noah Davidsohn Chao Wang Javier Prieto Masakazu Kurita Fumiyuki Hatanaka Cuiqing Zhong Reyna Hernandez-Benitez Tomoaki Hishida Takashi Lezaki Akihisa Sakamoto Amy NNemeth Yuriko Hishida Concepcion Rodriguez Esteban Kensaku Shojima Ling Huang Maxim Shokhirev Estrella Nunez-Delicado Josep MCampistol Isabel Guillen-Vicente Elena Rodriguez-Inigo juan Manuel Lopez-Alcorocho Marta Guillen-Vicente George Church Pradeep Reddy Pedro Guillen-Garcia Guang-Hui Liu juan carlos izpisua belmonte Gene Expression Laboratory Salk Institute for Biological Studies10010 North Torrey Pines RoadLa JollaCA 92037USA Wyss Institute for Biologically Inspired Engineering Harvard UniversityCambridgeMA 02115USA Department of Genetics Harvard Medical SchoolBostonMA 02115USA Integrative Genomics and Bioinformatics Core Salk Institute for Biological Studies10010 North Torrey Pines RoadLa JollaCA 92037USA Universidad Catolica San Antonio de Murcia(UCAM) Campus de los JeronimosNo 1351230107 GuadalupeSpain Hospital Clinic of Barcelona Career Villarroel17008036 BarcelonaSpain Department of Traumatology and Research Unit Clinica CEMTRO28035 MadridSpain National Laboratory of Biomacromolecules CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem cell and Regeneration Chinese Academy of SciencesBeijing 100101China Translational Medical Center for Stem Cell Therapy Shanghai East HospitalTongji University School of MedicineShanghai 200120China

Dear Editor,Homeostasis and repair are critical biological processes that allow for tissue and organ preservation and function in multicellular *** regulation and extension vary drastically across the animal kingdom,and mammals show limited tissue-specific regenerative capacity that declines with *** aging,articular cartilage is one of the tissues that undergo substantial changes in the matrix structure,molecular composition,metabolic activity,and mechanical properties(Loeser et al.2016).

关键词： aging treatment critical

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Single-cell transcriptomic atlas of mouse cochlear aging

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Protein & Cell 2023年第3期14卷 180-201页

作者： Guoqiang Sun Yandong Zheng Xiaolong Fu Weiqi Zhang Jie Ren Shuai Ma Shuhui Sun Xiaojuan He QiaoranWang zhejun ji Fang Cheng KaowenYan Ziyi Liu juan carloszpisuaemonte Jing Qu Si Wang Renjie Chai Guang-Hui Liu State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Bioelectronics Jiangsu Province High-Tech Key Laboratory for Bio-Medical ResearchSchool of Life Sciences and TechnologySoutheast UniversityNanjing 211189China Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical University.Beijing100053China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China National Laboratory of Biomacromolecules CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital MedicalUniversityBeijing100053China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration CASBeijing 100101China China National Center for Bioinformation Beijing 100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China The Fifth People's Hospital of Chongqing Chongqing 400062China Gene Expression Laboratory Salk Institute for Biological StudiesLa JollaCA 92037USA Co-Innovation Center of Neuroregeneration Nantong UniversityNantong 226001China Shandong Provincial Hospital and School of Laboratory Animal Science Shandong First Medical UniversityJinan 250000China

Progressive functional deterioration in the cochlea is associated with age-related hearing loss(ARHL).However,the cellular and molecular basis underlying cochlear aging remains largely ***,we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging,in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time ***,our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging,highlights unexpected age-related transcriptional fluctuations in intermediate ceils localized in the stria vascularis(SV)and demonstrates that upregulation of endoplasmic reticulum(ER)chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with *** work suggests that targeting unfolded protein response pathways may help alleviate aging-related sVatrophyand hencedelay theprogressionofARHL.

关键词： single-cell transcriptomic atlas mouse cochlea aging

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Brent *** Texas Intermediate in the US petro derivatives price formation

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Petroleum Science 2024年第1期21卷 729-739页

作者： Alejandro Almeida Antonio A.Golpe juan Manuel Martín-Alvarez Jose carlos Vides Universidad Internacional de La Rioja Department of Quantitative Methods for Economics and BusinessLa RiojaSpain University of Huelva Department of Economics and Centro de Estudios Avanzados en FisicaMatematicas y Computacion and ICEIHuelvaSpain Complutense University of Madrid Department of Applied and Structural Economics and History and ICEIMadridSpain

In this paper,we apply the spatial panel model to explore the relationship between the dynamic of two types of crude oil prices(WTI and Brent crude oil)and their refined products over *** the turbulent months of 2011,when Cushing Oklahoma had reached capacity and the crude oil export ban removal in 2015 as breakpoints,we apply this method both in the full sample and the three resultant ***,results suggest our results show that both WTI and Brent display very similar behaviour with the refined ***,when attending to each regime,results derived from the first and third regimes are quite similar to the full sample ***,during the second regime,Brent crude oil became the benchmark in the petrol market,and it influenced the distillate ***,our model can let us determine the price-setters and price-followers in the price formation mechanism through refined *** results possess important considerations to policymakers and the market participants and the price formation.

关键词： Crude oil prices Spatial panel model Refined products Price formation

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