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HIF-1α signaling: Essential roles in tumorigenesis and implications in targeted therapies

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Genes & Diseases 2024年第1期11卷 234-251页

作者： Yan Zhao Cheng Xing Yating Deng can ye Hongling Peng Department of Hematology The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China Hunan Key Laboratory of Tumor Models and Individualized Medicine The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China Hunan Engineering Research Center of Cell Immunotherapy for Hematopoietic Malignancies The Second Xiangya HospitalCentral South UniversityChangshaHunan 410011China

The hypoxic microenvironment is an essential characteristic of most malignant ***,hypoxia-inducible factor-1 alpha(HIF-1a)is a key regulatory factor of cellular adaptation to hypoxia,and many critical pathways are correlated with the biological activity of organisms via *** the intra-tumoral hypoxic environment,HIF-1αis highly expressed and contributes to the malignant progression of tumors,which in turn results in a poor prog-nosis in ***,it has been indicated that HiF-1αinvolves in various critical pro-cesses of life events and tumor development via regulating the expression of HiF-1a target genes,such as cell proliferation and apoptosis,angiogenesis,glucose metabolism,immune response,therapeutic resistance,*** from solid tumors,accumulating evidence has re-vealed that HiF-1αis also closely associated with the development and progression of hemato-logical malignancies,such as leukemia,lymphoma,and multiple *** inhibition of HiF-1a can facilitate an increased sensitivity of patients with malignancies to relevant ther-apeutic *** the review,we elaborated on the basic structure and biological functions of HIF-1a and summarized their current role in various *** is expected that they will have future potential fortargeted therapy.

关键词： Angiogenesis Hematological malignancies Hypoxia-inducible factor-1 alpha(HIF-1α) Immune escape Targeted therapy

Proton transfer-mediated GPCR activation

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Protein & Cell 2015年第1期6卷 12-17页

作者： Xuejun C. Zhang can Cao ye Zhou Yan Zhao National Laboratory of Macromolecules National Center of Protein Science--Beijing Institute of Biophysics ChineseAcademy of Sciences Beijing 100101 China

G-protein coupled receptors （GPCRs） play essential roles in signal transduction from the environment into the cell. While many structural features have been elu- cidated in great detail, a common functional mechanism on how the ligand-binding signal is converted into a conformational change on the cytoplasmic face result- ing in subsequent activation of downstream effectors remain to be established. Based on available structural and functional data of the activation process in class-A GPCRs, we propose here that a change in protonation status, together with proton transfer via conserved structural elements located in the transmembrane region, are the key elements essential for signal trans- duction across the membrane.

关键词： GPCR activation protonation membranepotential

MicroRNA-132 in the Adult Dentate Gyrus is Involved in Opioid Addiction Via Modifying the Differentiation of Neural Stem Cells

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Neuroscience Bulletin 2019年第3期35卷 486-496页

作者： Meng Jia Xuewei Wang Haolin Zhang can ye Hui Ma Mingda Yang Yijing Li Cailian Cui Department of Neurobiology School of Basic Medical Sciences Key Laboratory for Neuroscience of the Ministry of Education and National Health and Family Planning Commission Neuroscience Research Institute Peking University

MicroRNA-132(miR-132), a small RNA that regulates gene expression, is known to promote neurogenesis in the embryonic nervous system and adult *** exposure to psychoactive substances can increase miR-132 expression in cultured neural stem cells(NSCs)and the adult brain of rodents, little is known about its role in opioid addiction. So, we set out to determine the effect of miR-132 on differentiation of the NSCs and whether this effect is involved in opioid addiction using the rat morphine self-administration(MSA) model. We found that miR-132 overexpression enhanced the differentiation of NSCs in vivo and in vitro. Similarly, speci?c overexpression of miR-132 in NSCs of the adult hippocampal dentate gyrus(DG) during the acquisition stage of MSA potentiated morphine-seeking behavior. These ?ndings indicate that miR-132 is involved in opioid addiction,probably by promoting the differentiation of NSCs in the adult DG.

关键词： miR-132 Opioid addiction Neural stem cell Dentate gyrus

The levels, sources and reactivity of volatile organic compounds in a typical urban area of Northeast China

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Journal of Environmental Sciences 2019年第5期31卷 121-134页

作者： Zhuobiao Ma Chengtang Liu Chenglong Zhang Pengfei Liu can ye Chaoyang Xue Di Zhao Jichen Sun Yiming Du Fahe Chai Yujing Mu Research Center for Eco-Environmental Sciences Chinese Academy of Sciences University of Chinese Academy of Sciences Center for Excellence in Regional Atmospheric Environment Institute of Urban Environment Chinese Academy of Sciences Shenyang Academy of Environmental Sciences Shenyang Environmental Monitoring Centre Chinese Research Academy of Environmental Sciences

Air concentrations of volatile organic compounds(VOCs) were continually measured at a monitoring site in Shenyang from 20 August to 16 September 2017. The average concentrations of alkanes, alkenes, aromatics and carbonyls were 28.54, 6.30, 5.59 and9.78 ppbv, respectively. Seven sources were identified by the Positive Matrix Factorization model based on the measurement data of VOCs and CO. Vehicle exhaust contributed the most(36.15%) to the total propene-equivalent concentration of the measured VOCs,followed by combustion emission(16.92%), vegetation emission and secondary formation(14.33%), solvent usage(10.59%), petrochemical industry emission(9.89%), petrol evaporation(6.28%), and liquefied petroleum gas(LPG) usage(5.84%). Vehicle exhaust, solvent usage and combustion emission were found to be the top three VOC sources for O_3 formation potential, accounting for 34.52%, 16.55% and 11.94%, respectively. The diurnal variation of the total VOCs from each source could be well explained by their emission characteristics,e.g., the two peaks of VOC concentrations from LPG usage were in line with the cooking times for breakfast and lunch. Wind rose plots of the VOCs from each source could reveal the possible distribution of the sources around the monitoring site. The O_3 pollution episodes during the measurement period were found to be coincident with the elevation of VOCs, which was mainly due to the air parcel from the southeast direction where petrochemical industry emission was found to be dominant, suggesting that the petrochemical industry emission from the southeast was probably a significant cause of O_3 pollution in Shenyang.

关键词： Volatile organic compounds Source apportionment Photochemical ozone formation Field measurement

Pollution levels, composition characteristics and sources of atmospheric PM2.5 in a rural area of the North China Plain during winter

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Journal of Environmental Sciences 2020年第9期32卷 172-182页

作者： Xiaoxi Zhao Xiujuan Zhao Pengfei Liu can ye Chaoyang Xue Chenglong Zhang Yuanyuan Zhang Chengtang Liu Junfeng Liu Hui Chen Jianmin Chen Yujing Mu Research Center for Eco-Environmental Sciences Chinese Academy of SciencesBeijing 100085China Institute of Urban Meteorology Chinese Meteorological AdministrationBeijing 100089China Center for Excellence in Urban Atmospheric Environment Institute of Urban EnvironmentChinese Academy of SciencesXiamen 361021China University of Chinese Academy of Sciences Beijing 100049China Shanghai Key Laboratory of Atmospheric Particle Pollution and Prevention Department of Environmental Science and EngineeringFudan UniversityShanghai 200433China Key Laboratory of Atmospheric Chemistry China Meteorological AdministrationBeijing 100081China

The pollution levels,composition characteristics and sources of atmospheric PM2.5 were investigated based on field measurement at a rural site in the North China Plain(NCP) from pre-heating period to heating period in winter of *** hourly average concentrations of PM2.5 frequently exceeded 150 μg/m3 and even achieved 400 μg/m3,indicating that the PM2.5pollution was still very serious despite the implementation of stricter control measures in the rural *** with the pre-heating period,the mean concentrations of organic carbon(OG),element carbon(EC) and chlorine ion(Cl-) during the heating period increased by 20.8%,36.6% and 38.8%,accompanying with increments of their proportions in PM2.5from 37.5%,9.8% and 5.5% to 42.9%,12.7% and 7.2%,*** significant increase of both their concentrations and proportions during the heating period was mainly ascribed to the residential coal *** proportions of sulfate,nitrate and ammonium respectively increased from 9.9%,10.9% and 9.0% in nighttime to 13.8%,16.2% and 11.1% in daytime,implying that the daytime photochemical reactions made remarkable contributions to the secondary inorganic *** simulation results from WRF-Chem revealed that the emission of residential coal combustion in the rural area was underestimated by the current emission *** sources identified by positive matrix factorization(PMF) based on the measurement were residential coal combustion,secondary formation of inorganic aerosols,biomass burning,vehicle emission and raising dust,contributing to atmospheric PM2.5 of 40.5%,21.2%,16.4%,10.8%,8.6% and 2.5%,respectively.

关键词： pollution winter characteristics

Activity maintenance of the excised branches and a case study of NO_2 exchange between the atmosphere and *** branches

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Journal of Environmental Sciences 2019年第6期31卷 316-326页

作者： Chun Chen Yuzheng Wang Yuanyuan Zhang Xiaoxiu Lun Chengtang Liu Yujing Mu Chenglong Zhang Pengfei Liu Chaoyang Xue Min Song can ye Junfeng Liu Research Center for Eco-Environmental Sciences Chinese Academy of Sciences University of Chinese Academy of Sciences Center for Excellence in Urban Atmospheric Environment Institute of Urban Environment Chinese Academy of Sciences College of Environmental Science & Engineering Beijing Forest University

The efficient maintenance of the activity of excised branches is the powerful guarantee to accurately determine gas exchange flux between the detached branches of tall trees and the atmosphere. In this study, the net photosynthetic rate(NPR) of the excised branches and branches in situ were measured simultaneously by using two photosynthetic instruments to characterize the activity of the excised branches of Phyllostachys nigra. The ratio of normalized NPR of excised branches to NPR in situ was used to assess the photosynthetic activity of detached branches. Based on photosynthetic activity, an optimal hydroponics protocol for maintaining activity of excised P. nigra branches was presented:1/8 times the concentration of Gamborg B5 vitamin mixture with p H = 6. Under the best cultivation protocol, photosynthetic activity of excised P. nigra branches could be maintained more than 90% within 6 hr in the light intensity range of 200–2000 μmol/(m2·sec) and temperature range of 13.4–28.7°C. The nitrogen dioxide(NO2) flux differences between in situ and in vitro branches and the atmosphere were compared using double dynamic *** on the maintenance method of excised branches, the NO2 exchange flux between the excised P. nigra branches and the atmosphere(from-1.01 to-2.72 nmol/(m2·sec) was basically consistent with between the branches in situ and the atmosphere(from-1.12 to-3.16 nmol/(m2 sec)) within 6 hr. Therefore, this study provided a feasible protocol for in vitro measurement of gas exchange between tall trees and the atmosphere for a period of time.

关键词： Excised branches Activity maintenance NO2 exchange flux Hydroponics Dynamic chamber

Effect of potential HONO sources on peroxyacetyl nitrate(PAN)formation in eastern China in winter

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Journal of Environmental Sciences 2020年第8期32卷 81-87页

作者： Jingwei Zhang Yitian Guo Yu Qu Yong Chen Ruipeng Yu Chaoyang Xue Rui Yang Qiang Zhang Xingang Liu Yujing Mu Jing Wang can ye Haihan Zhao Qiangqiang Sun Ziwen Wang Junling An State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry(LAPC) Institute of Atmospheric Physics(IAP)Chinese Academy of SciencesBeijing 100029China College of Earth Science University of Chinese Academy of SciencesBeijing 100049China College of Resources and Environmental Sciences China Agricultural UniversityBeijing 100193China Research Center for Eco-Environmental Sciences Chinese Academy of SciencesBeijing 100085China Guangzhou Meteorological Observatory Guangzhou 511430China Ministry of Education Key Laboratory for Earth System Modeling Department of Earth System ScienceTsinghua UniversityBeijingChina Collaborative Innovation Center for Regional Environmental Quality BeijingChina State Key Laboratory of Water Environment Simulation School of EnvironmentBeijing Normal UniversityBeijing 100875China Center for Excellence in Urban Atmospheric Environment Institute of Urban EnvironmentChinese Academy of SciencesXiamen 361021China College of Land Science and Technology China Agricultural UniversityBeijing 100193China Qinghai Climate Center Qinghai Meteorological BureauXiningQinghai 810001China

As an important secondary photochemical pollutant,peroxyacetyl nitrate(PAN)has been studied over decades,yet its simulations usually underestimate the corresponding observations,especially in polluted *** observations in north China found unusually high concentrations of PAN during wintertime heavy haze events,but the current model still cannot reproduce the observations,and researchers speculated that nitrous acid(HONO)played a key role in PAN *** the first time we systematically assessed the impact of potential HONO sources on PAN formation mechanisms in eastern China using the Weather Research and Forecasting/Chemistry(WRF-Chem)model in February of *** results showed that the potential HONO sources significantly improved the PAN simulations,remarkably accelerated the RO x(sum of hydroxyl,hydroperoxyl,and organic peroxy radicals)cycles,and resulted in 80%–150%enhancements of PAN near the ground in the coastal areas of eastern China and 10%–50%enhancements in the areas around 35–40°N within 3 km during a heavy haze *** direct precursors of PAN were aldehyde and methylglyoxal,and the primary precursors of PAN were alkenes with C>3,xylenes,propene and *** above results suggest that the potential HONO sources should be considered in regional and global chemical transport models when conducting PAN studies.

关键词： Nitrous acid(HONO) Peroxyacetyl nitrate(PAN) WRF-Chem model Winter haze RO x cycles

Sudden extramedullary and extranodal Philadelphia-positive anaplastic large-cell lymphoma transformation during imatinib treatment for CML:A case report

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World Journal of Clinical Cases 2022年第28期10卷 10339-10345页

作者： Qiong Wu Yong Kang Jing Xu Wen-can ye Zhen-Jiang Li Wen-Feng He Yuan Song Qing-Ming Wang Ai-Ping Tang Ting Zhou Department of Clinical Laboratory The Second Affiliated Hospital of Nanchang UniversityNanchang 330006Jiangxi ProvinceChina Department of Hematology The Second Affiliated Hospital of Nanchang UniversityNanchang 330006Jiangxi ProvinceChina Department of Hematology Pingxiang People's hospitalPingxiang 337000Jiangxi ProvinceChina Department of Hematology The First Affiliated Hospital of Gannan Medical UniversityGanzhou 341001Jiangxi ProvinceChina Key laboratory of Molecular Medicine of Jiangxi The Second Affiliated Hospital of Nanchang UniversityNanchang 330006Jiangxi ProvinceChina Department of Pathology The Second Affiliated Hospital of Nanchang UniversityNanchang 330006Jiangxi ProvinceChina

BACKGROUND Chronic myeloid leukemia(CML)is a malignant hematologic malignancy that can progress to blast phase with a myeloid or lymphoid *** patients with CML can also progress to blast crisis phase;however,the transformation of CML into Philadelphia-positive lymphoma is extremely *** SUMMARY We present a patient with CML who experienced a sudden transformation to anaplastic large-cell lymphoma(ALCL)after 7 mo of treatment with imatinib,during which she had achieved partial cytogenetic response as well as early molecular *** patient noticed a mass in her left shoulder,the biopsy data of which were consistent with ALCL;moreover,her lymphoma cells exhibited BCR-ABL gene *** patient was diagnosed with Philadelphia-positive ALCL that progressed from CML,and was thus treated with the second generation tyrosine kinase inhibitor *** months later,the mass had totally disappeared and the BCR-ABL fusion gene was undetectable in the peripheral *** our knowledge,this is the first patient known to have developed Philadelphia-positive ALCL transformed from *** Unexplained lymphadenopathy or an extramedullary mass in a patient with CML may warrant a biopsy and testing for BCR-ABL fusion.

关键词： Chronic myeloid leukemia BCR-ABL fusion gene Imatinib mesylate Anaplastic large-cell lymphoma Philadelphia-positive Nilotinib Case report

Analysis of the 5' flanking sequence of the human norepinephrine transporter gene

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Cell Research 1998年第2期8卷 143-149页

作者： HUANG FANG JIAN FEI SHUN KAI MA LI HUAZHU ZHAO PING LIU GUO QIANG CAI ZEN can ye LI HE GUO (Shanghai Institute of Cell Biology, Chinese Academy of Sciences, Shanghai 200031, China ) Shanghai Institute of Cell Biology Chinese Academy of Sciences Shanghai 200031 China

The human norepinephrine transporter(NET) gene was cloned and structurally analyzed. The far 5' fragment containing exon 1 (a non-coding exon) and exon 2 was sequenced. The transcription start site of the gene in human brain stem tissue was determined by primer extension analysis. It was found that the gene could be transcribed from multiple starting points. The 5' flanking sequence contains a proximal G-C rich region, one possible GSG elemeflt and several SP1 sites. However it does not contain TATA box and CAAT box motifS. Gel shift analysis with nuclear extracts from different tissues of mouse shows that the G-C rich region may be involved in tissue specific expression of the gene.

关键词： Norepinephrine transporter gene primer extension transcription regulation