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ZD7288, a selective hyperpolarization-activated cyclic nucleotide-gated channel blocker, inhibits hippocampal synaptic plasticity

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Neural Regeneration Research 2016年第5期11卷 779-786页

作者： xiao-xue zhang xiao-chun Min Xu-lin Xu Min Zheng Lian-jun Guo Department of Laboratory Medicine Affiliated Pu'ai Hospital Tongji Medical College Huazhong University of Science and Technology Department of Pharmacology School of Basic Medical Sciences Tongji Medical College Huazhong University of Science and Technology School of Biomedical Engineering Hubei University of Science and Technology

The selective hyperpolarization-activated cyclic nucleotide-gated（HCN） channel blocker 4-（N-ethyl-N-phenylamino）-1,2-dimethyl-6-（methylamino） pyrimidinium chloride（ZD7288） blocks the induction of long-term potentiation in the perforant path-CA3 region in rat hippocampus in vivo. To explore the mechanisms underlying the action of ZD7288, we recorded excitatory postsynaptic potentials in perforant path-CA3 synapses in male Sprague-Dawley rats. We measured glutamate content in the hippocampus and in cultured hippocampal neurons using high performance liquid chromatography, and determined intracellular Ca2＋ concentration（[Ca2＋]i） using Fura-2. ZD7288 inhibited the induction and maintenance of long-term potentiation, and these effects were mirrored by the nonspecific HCN channel blocker cesium. ZD7288 also decreased glutamate release in hippocampal tissue and in cultured hippocampal neurons. Furthermore, ZD7288 attenuated glutamate-induced rises in [Ca2＋]i in a concentration-dependent manner and reversed 8-Br-c AMP-mediated facilitation of these glutamate-induced [Ca2＋]i rises. Our results suggest that ZD7288 inhibits hippocampal synaptic plasticity both glutamate release and resultant [Ca2＋]i increases in rat hippocampal neurons.

关键词： nerve regeneration ZD7288 Ih, channels perforant path-CA3 synapse long-term potentiation field excitatory postsynaptic potentials glutamate release neural regeneration

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Mechanism of Wnt/β-catenin signaling pathway in enhanced malignant phenotype of non-small cell lung cancer induced by antiangiogenesis therapy

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Asian Pacific Journal of Tropical Medicine 2016年第1期9卷 55-59页

作者： xiao-xue zhang Ling-Ling zhang Huan-Lian Yang Xiu-Wen Wang Shandong University School of Medicine Department of Oncology Binzhou People's Hospital Department of Oncology Qilu Hospital of Shandong University

Objective:To study the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of A549 cells of human non-small cell lung cancer induced by the antiangiogenesis ***:The siRNA technique was employed to inhibit the expression of vascular endothelial growth factor(VEGF) in A549 cells and simulate the clinical course of anti-angiogencsis ***-time PCR and western-blot were used to study the change in the expression of Wnt/β-catenin signaling molecules at the mRNA and protein level respectively,as well as the effect on the epithelial mesenchymal transition in A549 *** proliferation and invasion abilities of tumor cells were detected to discuss the mechanism of Wnt/β-catenin signaling pathway in the enhanced malignant phenotype of non-small cell lung cancer induced by the anti-angiogenesis ***:The specific siRNA could significantly inhibit the expression of VEGF in cells to simulate the anti-angiogenesis *** the action of 50 nM VEGF siRNA,the proliferation ability of A549 significantly increased(P<0.05).After being treated with VEGF siRNA,the invasion ability of cells ***-four hours after the transcription of 50 nM siRNA into cells,the number of cells that come through the membrane was278.3 ± *** with the Ctrl siRNA group,when VEGF was inhibited,the expression ofβ-catenin and Cyclin D1 increased by 86%and 55%***,the expression of E-cadherin decreased,while the one of vimentin ***:siRNA can significantly inhibit the expression of *** the anti-angiogencsis therapy,the inhibited expression of VEGF can activate the Wnt/β-catenin signaling pathway to cause the epithelial mesenchymal transition and then the enhanced malignant phenotype of non-small cell lung cancer.

关键词： Anti-angiogenesis Wnt 1 β-catenin Epithelial mesenchymal transition Proliferation and invasion

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Role of transforming growth factor-beta signaling pathway in pathogenesis of benign biliary stricture

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World Journal of Gastroenterology 2008年第31期14卷 4949-4954页

作者： Zhi-Min Geng Jian-Bao Zheng xiao-xue zhang Jie Tao Lin Wang Department of Hepatobiliary Surgery First Affiliated Hospital Medical College Xi'an Jiaotong University Xi'an 710061. Shaanxi Province China Department of General Surgery Firs Affiliated Hospital Medical College Xi'an Jiaotong University Xi'an 710061 Shaanxi Province China

AIM: To characterize the expression of members of the transforming growth factor-beta (TGF-β)/Smad/ connective tissue growth factor (CTGF) signaling pathway in the tissue of benign biliary stricture, and to investigate the effect of TGF-β signaling pathway in the pathogenesis of benign biliary stricture. METHODS: Paraffin embedded materials from 23 cases of benign biliary stricture were analyzed for members of the TGF-β/Smad/CTGF signaling pathway. TGF-β_1, TβRⅠ, TβRⅡ, Smad4, Smad7 and CTGF protein were detected by immunohistochemical strepto-advidinbiotin complex method, and CTGF mRNA was evaluated by hybridization in situ, while 6 cases of normal bile duct served as controls. The percentages of positive cells were counted. The correlation between TGF-β_1, Smad4 and CTGF was analyzed. RESULTS: The positive expression ratios of TGF-β_1, TβRⅠ , TβRⅡ , Smad4, CTGF and CTGF mRNA in 23 cases with benign biliary stricture were 91.3%, 82.6%, 87.0%, 78.3%, 82.6% and 65.2%, respectively, signifi cantly higher than that in 6 cases of normal bile duct respectively (vs 33.3%, 16.7%, 50.0%, 33.3%, 50.0%, 16.7%, respectively, P 0.05). There was a positive correlation between positive expression of TGF-β_1, Smad4 and CTGF in cases with benign biliary stricture. CONCLUSION: The high expression of TGF-β/Smad/ CTGF signaling pathway plays an important role in the pathogenesis of benign biliary stricture.

关键词： Biliary stricture Transforming growth factor-beta 1 Smad Connective tissue growth factor TβR

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Whole-genome resequencing reveals molecular imprints of anthropogenic and natural selection in wild and domesticated sheep

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Zoological Research 2022年第5期43卷 695-705页

作者： De-Yin zhang xiao-xue zhang Fa-Di Li Lv-Feng Yuan xiao-Long Li Yu-Kun zhang Yuan Zhao Li-Ming Zhao Jiang-Hui Wang Dan Xu Jiang-Bo Cheng xiao-Bin Yang Wen-Xin Li Chang-Chun Lin Bu-Bo Zhou Wei-Min Wang State Key Laboratory of Grassland Agro-Ecosystems Key Laboratory of Grassland Livestock Industry InnovationMinistry of Agriculture and Rural AffairsEngineering Research Center of Grassland IndustryMinistry of EducationCollege of Pastoral Agriculture Science and TechnologyLanzhou UniversityLanzhouGansu 730020China College of Animal Science and Technology Gansu Agricultural UniversityLanzhouGansu 730070China Engineering Laboratory of Sheep Breeding and Reproduction Biotechnology in Gansu Province MinqinGansu 733300China Lanzhou Veterinary Research Institute Chinese Academy of Agricultural SciencesLanzhouGansu 730046China

The abundance of domesticated sheep varieties and phenotypes is largely the result of long-term natural and artificial selection. However, there is limited information regarding the genetic mechanisms underlying phenotypic variation induced by the domestication and improvement of sheep. In this study, to explore genomic diversity and selective regions at the genome level, we sequenced the genomes of 100 sheep across 10 breeds and combined these results with publicly available genomic data from 225 individuals, including improved breeds, Chinese indigenous breeds,African indigenous breeds, and their Asian mouflon ancestor. Based on population structure, the domesticated sheep formed a monophyletic group,while the Chinese indigenous sheep showed a clear geographical distribution trend. Comparative genomic analysis of domestication identified several selective signatures, including IFI44 and IFI44L genes and PANK2 and RNF24 genes, associated with immune response and visual *** genomic analysis of improvement demonstrated that candidate genes of selected regions were mainly associated with pigmentation,energy metabolism, and growth ***, the IFI44 and IFI44L genes showed a common selection signature in the genomes of 30domesticated sheep breeds. The IFI44 c. 54413058C>G mutation was selected for genotyping and population genetic validation. Results showed that the IFI44 polymorphism was significantly associated with partial immune traits. Our findings identified the population genetic basis of domesticated sheep at the whole-genome level, providing theoretical insights into the molecular mechanism underlying breed characteristics and phenotypic changes during sheep domestication and improvement.

关键词： Sheep Whole-genome resequencing Selection signature analysis Immunity IFI44 gene

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Blockade of HCN2 Channels Provides Neuroprotection Against Ischemic Injury via Accelerating Autophagic Degradation in Hippocampal Neurons

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Neuroscience Bulletin 2020年第8期36卷 875-894页

作者： Cheng Chen Li Liu Ya-Qiao Shu Ping Jing Yun Lu xiao-xue zhang Xian-Gang Zong Lian-Jun Guo Chang-Jun Li Department of Pharmacology School of Basic Medical SciencesTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Neurology The Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Office of Academic Research The Central Hospital of WuhanTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Pharmacy Zhongnan Hospital of Wuhan UniversityWuhan 430030China Department of Clinical Laboratory Wuhan PuAi HospitalWuhan 430033China Key Laboratory of Drug Target Research and Pharmacodynamic Evaluation Wuhan 430030China Center for Integrated Protein Science and Zentrum fur Pharmaforschung Department PharmazieLudwig-Maximilians-Universitat Miinchen80539 MunichGermany

In the central nervous system,hyperpolarizationactivated cyclic nucleotide-gated(HCN)channels are essential to maintain normal neuronal *** studies have shown that HCN channels may be involved in the pathological process of ischemic brain injury,but the mechanisms remain *** is activated in cerebral ischemia,but its role in cell death/survival remains *** this study,our results showed that the HCN channel blocker ZD7288 remarkably decreased the percentage of apoptotic neurons and corrected the excessive autophagy induced by oxygen-glucose deprivation followed by reperfusion(OGD/R)in hippocampal HT22 ***,in the OGD/R group,p-mTOR,p-ULK1(Ser757),and p62 were significantly decreased,while p-ULK1(Ser317),atg5,and beclin1 were remarkably ***7288 did not change the expression of p-ULK1(Ser757),ULK1(Ser317),p62,Beclin1,and atg5,which are involved in regulating autophagosome ***,we found that OGD/R induced a significant increase in Cathepsin D expression,but not *** with ZD7288 at 10μmol/L in the OGD/R group did not change the expression of cathepsin D and ***,chloroquine(CQ),which decreases autophagosome-lysosome fusion,eliminated the correction of excessive autophagy and neuroprotection by ***,shRNA knockdown of HCN2 channels significantly reduced the accumulation of LC3-Ⅱand increased neuron survival in the OGD/R and transient global cerebral ischemia(TGCI)models,and CQ also eliminated the effects of ***,we found that the percentage of LC3-positive puncta that co-localized with LAMP-1-positive lysosomes decreased in Con-shRNAtransfected HT22 neurons exposed to OGD/R or *** HCN2-shRNA-transfected HT22 neurons,the percentage of LC3-positive puncta that co-localized with LAMP-1-positive lysosomes increased under OGD/R;however,the percentage was significantly decreased by the addition of CQ to HCN2-shRNA-transfected HT22 *** present re

关键词： HCN2 channel Autophagy Neuroprotection Oxygen-glucose deprivation/reperfusion Transient global cerebral ischemia

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Carotid-subclavian bypass and endovascular aortic repair of Kommerell’s diverticulum with aberrant left subclavian artery:A case report

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World Journal of Clinical Cases 2023年第33期11卷 8038-8043页

作者： Wajeehullahi Akilu Yi Feng xiao-xue zhang Shi-Liang Li Xian-Tao Ma Min Hu Cai Cheng Division of Cardiothoracic Surgery and Vascular Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030Hubei ProvinceChina

BACKGROUND Kommerell’s diverticulum(KD)with aberrant left subclavian artery is a rare congenital deformity and also has very little research literature about it(35%of case study).There are three types of aortic arch *** literature concerning the treatment options are *** SUMMARY We present a case report of a 50-year-old male with KD in the right aortic arch with aberrant left subclavian *** conducted a total endovascular repair procedure,which is innovative and will spread more light in the medical *** patient has no past medical history and is a non-smoker and *** presented with shortness of breath,chest pain and dizziness for six *** tests were done and computerized tomography(CT)angiogram of the chest confirmed the diagnosis,illustrating showed a 3.9 cm *** Day 1,the CT angiogram showed mild dilatation of the thoracic aorta,adjacent esophagus,trachea was compressed and *** was planned as the treatment ***-Subclavian artery bypass and endovascular aortic repair was *** used prolene 5-0 C1 sutures to precisely anastomose a 6-mm Dacron graft to the left subclavian *** was secured and wounds were *** was administered and patient was shifted to intensive care ***-operative,patient responded favorably and was *** follow-up is *** The procedure we performed is *** will help the cardio-thoracic surgeons a better insight about the full procedures we conducted,thereby bringing more light and better treatment options in managing KD with aberrant subclavian artery.

关键词： Kommerell’s diverticulum Left common carotid artery Aberrant left subclavian artery Carotid-subclavian bypass Medtronic stent catheter endovascular repair Case report

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RING finger and WD repeat domain 3 regulates proliferation and metastasis through the Wnt/β-catenin signalling pathways in hepatocellular carcinoma

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World Journal of Gastroenterology 2022年第27期28卷 3435-3454页

作者： Ruo-Peng Liang xiao-xue zhang Jie Zhao Qin-Wei Lu Rong-Tao Zhu Wei-Jie Wang Jian Li Kai Bo Chi-Xian zhang Yu-Ling Sun Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina Department of Physical Examination The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052Henan ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC)exhibits high invasiveness and mortality rates,and the molecular mechanisms of HCC have gained increasing research *** abnormal DNA damage response has long been recognized as one of the important factors for tumor occurrence and *** studies have shown the potential of the protein RING finger and WD repeat domain 3(RFWD3)that positively regulates p53 stability in response to DNA damage as a therapeutic target in *** To investigate the relationship between HCC and RFWD3 in vitro and in vivo and explored the underlying molecular signalling transduction *** RFWD3 gene expression was analyzed in HCC tissues and adjacent normal *** was used to stably knockdown RFWD3 expression in HCC cell *** verifying the silencing efficiency,Celigo/cell cycle/apoptosis and MTT assays were used to evaluate cell proliferation and ***,cell migration and invasion were assessed by wound healing and transwell *** addition,transduced cells were implanted subcutaneously and injected into the tail vein of nude mice to observe tumor growth and ***,we used lentiviral-mediated rescue of RFWD3 shRNA to verify the ***,the microarray,ingenuity pathway analysis,and western blot analysis were used to analyze the regulatory network underlying *** Compared with adjacent tissues,RFWD3 expression levels were significantly higher in clinical HCC tissues and correlated with tumor size and TNM stage(P<0.05),which indicated a poor prognosis ***3 silencing in BEL-7404 and HCC-LM3 cells increased apoptosis,decreased growth,and inhibited the migration in shRNAi cells compared with those in shCtrl cells(P<0.05).Furthermore,the in vitro results were supported by the findings of the in vivo experiments with the reduction of tumor cell invasion and ***,the rescue of RFWD3 shRNAi resulted in the resumption of invasion and metastasis

关键词： RING finger and WD repeat domain 3 Hepatocellular carcinoma Invasion Proliferation Metastasis Wnt/β-catenin signaling pathways

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Rosuvastatin escape in a Chinese elderly with hyperlipidemia

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Chinese Medical Journal 2013年第18期126卷 3578-3579页

作者： CHEN Xu-jiao CHENG Lei CHU Jiao-jiao CHEN Jia TANG xiao-fang zhang xue-feng Department of Geriatrics Zhejiang Hospital Hangzhou Zhejiang 310013 China

Statin is being used widely in patients who have ＇hyperlipidemia, coronary arterial disease （CAD）or other atherosclerosis diseases. Analysis shows that lowering plasma low density lipoprotein cholesterol C （LDL-C） level depends on the dose and various statins treated. LDL-C will achieve the maximal effects after 7-10 days administration.1＇2 Rosuvastatin is a hydrophilic statin, does not metabolize depending on cytochrome P 450 3A4, meaning less drug-drug interactions in cases of multipharmacy. 3 It shows to be the most potent of the available statins, with the greatest effect of lowering LDL-C in the Mercury I and II trials and the STELLAR trial,a＇5 decreasing LDL-C levels at approximately 50% of dose of atorvastatin.5 The recommended starting dose of rosuvastatin is 5-10 mg, according the individual patient＇s baseline LDL-C. Most patients get effective treatment after rosuvastatin therapy. However, few patients fail to get to the target range of LDL-C. One of possible mechanisms is statin escape.

关键词： rosuvastain escape elderly hyperlipidemia genetic polymorphism

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Separation of alumina and silica from metakaolinite by reduction roasting-alkaline leaching process: Effect of CaSO_(4) and CaO

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Transactions of Nonferrous Metals Society of China 2022年第3期32卷 999-1009页

作者： Hong-yang WANG xiao-xue zhang Si-yuan YANG Cheng LIU Li-qun LUO School of Resources and Environmental Engineering Wuhan University of TechnologyWuhan 430070China Hubei Key Laboratory of Mineral Resources Processing and Environment Wuhan University of TechnologyWuhan 430070China

Limestone(CaCO3),which could promote sulfur fixation,was added to coal gangue during roasting in a circulating fluidized bed(CFB)*** and CaSO_(4) were the main Ca-bearing minerals while metakaolinite was the major Al-bearing mineral in CFB *** effect of CaSO_(4) and CaO on the separation of alumina and silica from metakaolinite by reduction roasting−alkaline leaching process was *** showed that metakaolinite was completely converted into hercynite and silica solid solutions(i.e.,quartz and cristobalite solid solutions)by reduction roasting with *** than 95%of silica in the reduced specimen was removed by alkaline *** addition of CaSO_(4) and CaO remarkably decreased the separation efficiency of alumina and silica in metakaolinite,which could be attributed to the formation of Si-bearing minerals:(1)Fayalite and anorthite were formed during the reduction roasting process;(2)Fayalite was stable while anorthite was converted into sodalite and wollastonite during the alkaline leaching *** study demonstrates that sulfur in coal gangue should be fixed by treating the exhaust gas instead of controlling the combustion process of CFB to achieve the comprehensive recovery of silica and alumina from the CFB slag.

关键词： circulating fluidized bed slag metakaolinite Ca-bearing minerals reduction roasting alkaline leaching

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Solar X-ray and EUV imager on board the FY-3E satellite

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Light(Science & Applications) 2022年第12期11卷 2939-2951页

作者： Bo Chen xiao-Xin zhang Ling-Ping He Ke-Fei Song Shi-Jie Liu Guang-Xing Ding Jin-Ping Dun Jia-Wei Li Zhao-Hui Li Quan-Feng Guo Hai-Feng Wang xiao-Dong Wang Yun-Qi Wang Hong-Ji zhang Guang zhang Zhen-Wei Han Shuang Dai Pei-Jie zhang Liang Sun Yang Liu software engineer Peng Wang Kun Wu Chen Tao Shi-Lei Mao Gui Mei Liang Yang Li-Heng Chen Chun-Yang Han Bin Huang Yang Liu mechanical engineer Shuai Ren Peng Zhou Ze-XiWei xiao-xue zhang Yue zhang Xin Zheng Yang Wang Ya Chen Jing-Jiang Xie Fei He Qiao Song Wei-Guo Zong Xiu-Qing Hu Peng zhang Jing-Song Wang Zhong-Dong Yang Changchun Institute of Optics Fine Mechanics and PhysicsChinese Academy of SciencesChangchunChina State Key Laboratory of Applied Optics Chinese Academy of SciencesChangchunChina National Satellite Meteorological Center China Meteorological AdministrationBeijingChina Key Laboratory of Space Weather National Center for Space WeatherChina Meteorological AdministrationBeijingChina Innovation Center for Fengyun Meteorological Satellite(FYSIC) BeijingChina Key Laboratory of Earth and Planetary Physics Institute of Geology and GeophysicsChinese Academy of SciencesBeijingChina

The solar X-ray and Extreme Ultraviolet Imager(X-EUVI),developed by the Changchun Institute of Optics,Fine Mechanics and Physics,Chinese Academy of Sciences(CIOMP),is the first space-based solar X-ray and Extreme ultraviolet(EUV)imager of China loaded on the Fengyun-3E(FY-3E)satellite supported by the China Meteorological Administration(CMA)for solar *** started work on July 11,2021,X-EUVI has obtained many solar *** instrument employs an innovative dual-band design to monitor a much larger temperature range on the Sun,which covers 0.6-8.0 nm in the X-ray region with six channels and 19.5 nm in the EUV region.X-EUVI has a field of view of 42′,an angular resolution of 2.5″per pixel in the EUV band and an angular resolution of 4.1″per pixel in the X-ray *** instrument also includes an X-ray and EUV irradiance sensor(X-EUVS)with the same bands as its imaging optics,which measures the solar irradiance and regularly calibrates the solar *** radiometric calibration of X-EUVS on the ground has been completed,with a calibration accuracy of 12%.X-EUVI is loaded on the FY-3E satellite and rotates relative to the Sun at a uniform ***-field calibration is conducted by utilizing successive rotation solar *** agreement between preliminarily processed X-EUVI images and SDO/AIA and Hinode/XRT images indicates that X-EUVI and the data processing algorithm operate properly and that the data from X-EUVI can be applied to the space weather forecast system of CMA and scientific investigations on solar activity.

关键词： image instrument Solar

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