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Development of a New High-throughput Screening Model for Human High Density Lipoprotein Receptor (CLA-1) Agonists

Biomedical and Environmental Sciences 2005年第4期18卷 265-272页

作者： DE-FENG TIAN BIN HONG shu-yi si Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China

To develop a new high-throughput screening model for human high-density lipoprotein （HDL） receptor （CD36 and LIMPⅡ analogous-1, CLA-1） agonists using CLA-1-expressing insect cells. Methods With the total RNA of human hepatoma cells BEL-7402 as template, the complementary DNA （cDNA） of CLA-1 was amplified by reverse transcription-polymerase chain reaction （RT-PCR）. Bac-to-Bac baculovirus expression system was used to express CLA-1 in insect cells. CLA-1 cDNA was cloned downstream of polyhedrin promoter of Autographa californica nuclear polyhedrosis virus （AcNPV） into donor vector pFastBacl and recombinant pFastBacl-CLA-1 was transformed into E. coli DH10Bac to transpose CLA-1 cDNA to bacrnid DNA. Recombinant bacrnid-CLA-1 was transfected into Spodopterafrugiperda Sf9 insect cells to produce recombinant baculovirus particles. Recombinant CLA- 1 was expressed on the membrane of Sf9 cells infected with the recombinant baculoviruses. A series of parameters of DiI-lipoprotein binding assays of CLA-1-expressing Sf9 cells in 96-well plates were optimized. Results Western blot analysis and DiI-lipoprotein binding assays confirmed that CLA-1 expressed in insect cells had similar immunoreactivity and ligand binding activity as its native counterpart. A reliable and sensitive in vitro cell-based assay was established to assess the activity of CLA-1 and used to screen agonists from different sample libraries. Conclusion Human HDL receptor CLA-1 was successfully expressed in Sf9 insect cells and a novel high-throughput screening model for CLA-1 agonists was developed. Utilization of this model allows us to identify potent and selective CLA-1 agonists which might possibly be used as therapeutics for atherosclerosis.

关键词： HDL SR-BI CLA-1 Insect cells High-throughput screening model Agonist

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THE IMPROVED XINANJIANG MODEL

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Journal of Hydrodynamics 2005年第6期17卷 746-751页

作者： LI Zhi-jia YAO Cheng KONG Xiang-guang College of Water Resources and Environment Hohai University Nanjing 210098 China yi shu si River Water Resources Bureau Xuzhou 221009 China

To improve the Xinanjiang model, the runoff generating from infiltration excess is added to the model. The another 6 parameters are added to Xinanjiang model. In prin ciple, the improved Xinanjiang model can be used to simulate runoff in the humid, semi-humid and also semi-arid regions. The application in yi River shows the improved Xinanjiang model could forecast discharge with higher acetrracy and can satisfy the practical requirements,It also shows thai the improved model is reasonable.

关键词： improved Xinanjiang model excess infiltration area of runoff model of infiltration

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A Cell-based High-throughput Screening Assay for Farnesoid X Receptor Agonists

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Biomedical and Environmental Sciences 2007年第6期20卷 465-469页

作者： ZHI-HUI ZHENG Guo-PING LV shu-yi si YUE-SHENG DONG BAO-HUA ZHAO HUA ZHANG JIAN-GONG HE Insitute of Medicinal Biotechnology Peking Union Medical College / Chinese Academy of Medical Sciences Beijing 100050 China College of Life Science Hebei Normal University Shijiazhuang 050016 Hebei China New Drug Research ＆ Development Center of North China Pharmaceutical Group Corporation National Microbial Medicine Engineering ＆ Research Center Shijiazhuang 050015 Hebei China

Objective To develop a high-throughput screening assay for Farnesoid X receptor （FXR） agonists based on mammalian one-hybrid system （a chimera receptor gene system） for the purpose of identifying new lead compounds for dyslipidaemia drug from the chemical library. Methods cDNA encoding the human FXR ligand binding domain （LBD） was amplified by RT-PCR from a human liver total mRNA and fused to the DNA binding domain （DBD） of yeast GAL4 of pBIND to construct a GAL4-FXR （LBD） chimera expression plasmid. Five copies of the GAL4 DNA binding site were synthesized and inserted into upstream of the SV40 promoter of pGL3-promoter vector to construct a reporter plasmid pG5-SV40 Luc. The assay was developed by transient co-transfection with pG5-SV40 Luc reporter plasmid and pBIND-FXR-LBD （189-472） chimera expression plasmid. Results After optimization, CDCA, a FXR natural agonist, could induce expression of the luciferase gene in a dose-dependent manner, and had a signal/noise ratio of 10 and Z＇ factor value of 0.65, Conclusion A stable and sensitive cell-based high-throughput screening model can be used in high-throughput screening for FXR agonists from the synthetic and natural compound library.

关键词： Farnesoid X receptor Agonist High-throughput screening Chimera

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NOX4 exacerbates Parkinson's disease pathology by promoting neuronal ferroptosis and neuroinflammation

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Neural Regeneration Research 2025年第7期20卷 2038-2052页

作者： Zhihao Lin Changzhou ying Xiaoli si Naijia Xue yi Liu Ran Zheng ying Chen Jiali Pu Baorong Zhang Department of Neurology The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina

Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra ***,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic ***,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely *** oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains *** aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what *** found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease *** oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic ***,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model ***,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic ***,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced *** findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.

关键词： dopaminergic neuron ferroptosis NADPH oxidase 4(NOX4) neuroinflammation Parkinson's disease

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Unraveling brain aging through the lens of oral microbiota

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Neural Regeneration Research 2025年第7期20卷 1930-1943页

作者： Qinchao Hu si Wang Weiqi Zhang Jing Qu Guang-Hui Liu State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong ProvinceChina Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders Xuanwu HospitalCapital Medical UniversityBeijingChina Aging Translational Medicine Center International Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijingChina CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences and China National Center for BioinformationBeijingChina University of Chinese Academy of Sciences BeijingChina Institute for Stem Cell and Regeneration Chinese Academy of SciencesBeijingChina Aging Biomarker Consortium BeijingChina State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijingChina Beijing Institute for Stem Cell and Regenerative Medicine BeijingChina

The oral cavity is a complex physiological community encompassing a wide range of *** of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative *** studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention *** this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and *** also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

关键词： Alzheimer's disease brain aging multiple sclerosis neurodegeneration neurodegenerative diseases oral microbiota Parkinson's disease periodontitis bacteria Porphyromonas gingivalis

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SENsiTIVE NUMERICAL siMULATION AND ANALYsiS OF RAINSTORM UsiNG NESTED WRF MODEL

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Journal of Hydrodynamics 2006年第5期18卷 578-586页

作者： WANG shu-chang HUANG si-xun LI yi Institute of Meteorology PLA University of Science and Technology Nanjing 211101 China

Nowadays, the nested grid model is widely used to increase the resolution of numerical model. An attempt to investigate the influence of the newly developed nesting technique of WRF model on the mesoscale numerical simulation of severe storm is described in this article. The results of sensitivity tests infer that the WRF model give more accurate and vivid prediction of severe storm with nesting scheme. As is shown in the tests, simulating value of the precipitation centers using nesting scheme are larger than those without using nesting scheme, which indicates that the simulating precipitation of nested storm is closer to the real rainfall. And there is obvious improvement of distribution of rain area and position of precipitation centers. According to the high resolution output data of the WRF model, deep and detailed analysis of characters of the mesoscale system that triggers the rainstorm is reported in this article, and the thermal and dynamical characters of this Meiyu front severe storm are also discussed.

关键词： WRF nesting numerical simulation mesoscale analysis

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Recycling of High Ferrous Bauxite Reducing Slag for Synthesis of CaAl_2si_2O_8-Al_2O_3-CaAl_(12)O_(19) Composite

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Journal of Iron and Steel Research International 2016年第12期23卷 1255-1261页

作者： ying-yi ZHANG Yuan-hong QI Zong-shu ZOU College of Materials Science and Engineering Chongqing University State Key Laboratory of Advanced Steel Processes and Products Central Iron and Steel Research Institute School of Metallurgy Northeastern University

CaAl2 si2 O8- Al2 O3- CaAl12 O19）（CAS2- Al2 O3 -CA6 ） composite was synthesized through reaction sintering alumina and bauxite reducing slag. The CAS2-Al2 O3-CA5 composite was mainly composed of α-Al2O3 , CAS2 , and CA6. Gehlenite （Ca2 Al2 siO7 , C2 AS） phase was effectively transformed to CASe and CA6 through high-temperature reaction sintering under weak oxidizing atmosphere at 1400 ℃for 4 h. SEM （scanning electron microscopy） and EDS （energy dispersive spectroscopy） analysis indicated that black and needle-shaped Al2O3, rhombic or irregular polygonal shaped FeAl2O4 , and glassy phase Ca2 Al2 siO7 disappeared after the reaction sintering. The light gray and flaky hexagon crystals of CaAl12 O19 （10 μm） and the grainy particles of Al2O3 （2-7 μm） were observed in the CASe-Al2 O3-CA6 composite. The gray crystals of CASe act as the binding phase and are distributed around CA6 and Al2O3. CAS2-Al2O3-CA6 composite exhibits high refractoriness and service temperature, which are 1 650 ℃ and 1 450 ℃, respectively. Reaction sintering of alumina and bauxite reducing slag is a feasible method for the synthesis of CAS2-Al2 O3-CA6 composite.

关键词： calcium hexaluminate composite reaction sintering bauxite reducing slag phase transformation

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High Fe‑Loading single‑Atom Catalyst Boosts ROS Production by Density Effect for Efficient Antibacterial Therapy

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Nano-Micro Letters 2025年第2期17卷 187-203页

作者： si Chen Fang Huang Lijie Mao Zhimin Zhang Han Lin Qixin Yan Xiangyu Lu Jianlin Shi Department of Cardiology Shanghai Tenth People’s HospitalSchool of MedicineTongji UniversityShanghai 200092People’s Republic of China Shanghai Institute of Ceramics Chinese Academy of SciencesShanghai 200050People’s Republic of China Shanghai Frontiers Science Center of Nanocatalytic Medicine School of MedicineTongji UniversityShanghai 200092People’s Republic of China

The current single-atom catalysts(SACs)for medicine still suffer from the limited active site ***,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with *** constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial ***,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading ***,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/*** addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)*** in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound *** work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.

关键词： Nanocatalytic medicine single-atom catalysts Reactive oxygen species(ROS) High metal loading Oxidase catalysis

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Yttrium-90 transarterial radioembolization versus conventional transarterial chemoembolization for patients with hepatocellular carcinoma：a systematic review and meta-analysis

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Cancer Biology & Medicine 2018年第3期15卷 299-310页

作者： yi Yang Tongguo si School of Medical Imaging Tianjin Medical University Tianjin 300203 China Department of Interventional Therapy Tianjin Medical University Cancer Institute and Hospital National Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin Tianjin's Clinical Research Center for Cancer Tianjin 300060 China

Objective: To compare the effects and safety of conventional transarterial chemoembolization(c TACE) and yttrium-90 transarterial radioembolization [TARE(90 Y)] for hepatocellular carcinoma(HCC)Methods: Nine high-quality observational studies, one low bias-risk randomized controlled trial(RCT), and one moderate biasrisk RCT included 1,652 patients [c TACE, 1,124; TARE(90 Y), 528], from whom data were extracted for this systematic review and ***: The extracted study outcomes included 1-year and 2-year overall survival(OS) rates, objective responses(ORs), and serious adverse events(AEs). 1-year OS rates: OR = 0.939, 95 % CI: 0.705-1.251, P = 0.66. 2-year OS rates: overall pooled OR =0.641, 95% CI: 0.382-1.075, P = 0.092; observational study subgroup OR = 0.575, 95% CI: 0.336-0.984, P = 0.043; RCT subgroup OR* = 0.641, 95% CI: 0.382-1.075, P = 0.346. OR: overall pooled OR = 0.781, 95% CI: 0.454-1.343, P = 0.371; m RECIST subgroup OR = 0.584, 95 % CI: 0.349-0.976, P = 0.040; WHO subgroup OR = 1.065; 95% CI: 0.500-2.268, P = 0.870. Serious AEs: overall pooled RR = 1.477, 95% CI: 0.864-2.526, P = 0.154; RCT subgroup RR = 0.680, 95% CI: 0.325-1.423, P = 0.306; observational study subgroup RR = 1.925; 95 % CI: 0.978-3.788, P = ***: TARE(90 Y) increased 2-year OS rates in the observational subgroup and resulted in better OR rates, according to m RECIST criteria, in comparison with c TACE. Furthermore, a lower risk of AEs was observed for TARE(90 Y) than for c TACE.

关键词： Hepatocellular carcinoma conventional transarterial chemoembolization transarterial radioembolization yttrium-90

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Cordyceps as potential therapeutic agents for atherosclerosis

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Journal of Integrative Medicine 2024年第2期22卷 102-114页

作者： yi Zhang si-jing Liu School of Marxism Chengdu University of Traditional Chinese MedicineChengdu 61137Sichuan ProvinceChina College of Medical Technology Chengdu University of Traditional Chinese MedicineChengdu 611137Sichuan ProvinceChina Chongqing Key Laboratory of sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases with Integrated Chinese and Western Medicine Chengdu University of Traditional Chinese MedicineChengdu 611137Sichuan ProvinceChina

Atherosclerosis is a leading cause of mortality and morbidity *** the challenges in managing atherosclerosis,researchers continue to investigate new treatments and complementary *** is a traditional Chinese medicine that has recently gained attention as a potential therapeutic agent for *** studies have demonstrated the effectiveness of cordyceps in treating atherosclerosis through various pharmacological actions,including anti-inflammatory and antioxidant activities,lowering cholesterol,inhibiting platelet aggregation,and modulating apoptosis or autophagy in vascular endothelial ***,the current misuse of the terms cordyceps and Ophiocordyceps sinensis has caused confusion among researchers,and complicated the current academic research on *** review focuses on the chemical composition,pharmacological actions,and underlying mechanisms contributing to the anti-atherosclerotic effects of cordyceps and the mycelium of Ophiocordyceps *** review provides a resource for the research on the development of new drugs for atherosclerosis from cordyceps.

关键词： Atherosclerosis Cordyceps Ophiocordyceps sinensis

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