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Dual inhibition of EGFR at protein and activity level via combinatorial blocking of PI4KIla as anti-tumor strategy

Protein & Cell 2014年第6期5卷 457-468页

作者： Jiangmei Li Lunfeng Zhang zhen gao Hua Kang Guohua Rong Xu Zhang Chang Chen National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China Department of General Surgery Xuanwu Hospital Capital Medical University Beijing 100053 China Tianjin Research Center of Basic Medical Science Tianjin Medical University Tianjin 300070 China Beijing Institute for Brain Disorders Beijing 100069 China

Our previous studies indicate that phosphatidylinositol 4-kinase Ila can promote the growth of multi-malignant tumors via HER-2/PI3K and MAPK pathways. However, the molecular mechanisms of this pathway and its potential for clinical application remain unknown. In this study, we found that PI4KIla could be an ideal combinatorial target for EGFR treatment via regulating EGFR degradation. Results showed that PI4KIla knockdown reduced EGFR protein level, and the expression of Pi4KIla shows a strong correlation with EGFR in human breast cancer tissues （r= 0.77, P 〈 0.01）. PI4KIla knockdown greatly prolonged the effects and decreased the effective dosage of AG-1478, a specific inhibitor of EGFR. In addition, it significantly enhanced AG1478-induced inhibition of tumor cell survival and strengthened the effect of the EGFR-targeting anti-cancer drug Iressa in xenograft tumor models. Mechanistically, we found that PI4KIla suppression increased EGFR ligand-independent degradation. Quantitative proteomic analysis by stable isotope labeling with amino acids in cell culture （SlLAC） and LC-MS/MS suggested that HsPg0 mediated the effect of PI4KIla on EGFR. Furthermore, we found that combined inhibition of PI4KIla and EGFR suppressed both PI3K/AKT and MAPK/ERK pathways, and resulted in downregulation of multiple oncogenes like PRDX2, FASN, MTA2, ultimately leading to suppression of tumor growth. Therefore, we conclude that combined inhibition of PI4KIla and EGFR exerts a multiple anti-tumor effect. Dual inhibition of EGFR at protein and activity level via combinatorial blocking of PI4KIla presents a novel strategy to combat EGFR-dependent tumors.

关键词： phosphatidylinositol 4-kinase Ila (PI4KIla)EGFR dual inhibition enhanced anti-tumor effect breastcancer. Iressa

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Effect of cold-dryness on pulmonary and immunologic function in chronic obstructive pulmonary disease model rats

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Journal of Traditional Chinese Medicine 2014年第2期34卷 221-226页

作者： zhen gao Fengsen Li Halmurat Upur Jiang Min Wang Jing Jing Jing Dan Xu National Clinical Research Base of Traditional Chinese Medicine Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University Institute of Traditional Uighur Medicine Xinjiang Medical University

OBJECTIVE： To study the effects of cold-dryness on pulmonary and immunologic function of peripheral T-lymphocytes in chronic obstructive pulmonary disease （COPD） model rats, and to provide references for the prevention and treatment of cold-dryness COPD in the Xinjiang region. METHODS： The COPD model was established with an elastase drip into the trachea combined with smoking. The cold-dryness COPD model was developed by stressing with a cold-dry environment. Success of the model was determined by observation of pathologic lung sections. Rats were sacrificed by exsanguination from the femoral artery and changes of peripheral blood CD4＋, CD8＋, and CD4＋/CD8＋ were detected by flow cytometryo Data were analyzed with SAS 11.5 statistical software. RESULTS： On the ninetieth day after ending the ex- periment, Peak expiratory flow in the cold-dryness COPD group was lower than that in the COPD and normal control groups （P〈0.01）. The time of inspiration in the cold-dryness COPD group was higher than that in the COPD and normal groups （P〈0.05）. Time of expiration （Te） in the cold-dryness COPD group was higher than that in the COPD and normal groups （P〈0.01）. 50% tidal volume expiratory flow （EFS0） in the cold-dryness COPD group was lower than that in the COPD and normal groups （P〈 0.01）, and EFS0 in the COPD group was lower than that in the normal group （P〈0.05）. CD4＋ content of peripheral blood in the cold-dryness COPD group was lower than that in the COPD and the normal groups （P〈0.05）. CD8＋ content in the cold-dryness COPD and COPD groups was higher than that in the normal control group （P〈0.01）, and CD8＋ content in the cold-dryness COPD group was higher than that in the COPD group （P〈0.01）. CD4＋/CD8＋ in the cold-dryness COPD group and the COPD group was lower than that in the normal control group （P〈0.01）, and CD4＋/CD8＋ in the cold-dryness COPD group was lower than that in the COPD group （P〈0.05）. CONCLUSION： In the cold-dryness COPD model, CD8＋ increased and CD4＋/CD8＋ dec

关键词： Pulmonary disease, chronic obstructive T-lymphocytes CD4-CD8 ratio Cold-dryness

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Expression of airway mucus-associated proteins in rats with chronic obstructive pulmonary disease with a cold-dryness symptom pattern

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Journal of Traditional Chinese Medicine 2016年第5期36卷 671-677页

作者： gao zhen Halmurat Upur Wang Jing Jing Jing Li zheng Xu Dan Li Fengsen Post-doctoral Scientific Research Station of Tradi-tional Chinese Medicine Hospital affiliated to Xinjiang Medical University Urumqi 830000China National Clinical Research Base of Traditional Chinese Medicine Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical UniversityUrumqi 830000China

OBJECTIVE: To reveal the effects on expression of airway mucus-associated proteins in rats with chronic obstructive pulmonary disease(COPD) and a cold-dryness symptom pattern induced by elastase and ***: The COPD model was established with an elastase dose into the trachea combined with exposure to smoking; the COPD model cold-dryness symptom pattern was further developed by exposure to a cold, dry environment. After 90 days,pathologic lung sections, inflammatory cytokine levels(measured by enzyme linked immunosorbent assay), m RNA and protein expression of mucus-associated proteins and aquaporins(measured by real-time polymerase chain reaction and western blots) were ***: Cytokines interleukin-6(IL-6), interleukin-8(IL-8), and tumor necrosis factor-α(TNF-α) in the COPD and the cold-dryness symptom pattern COPD groups were all significantly higher than in controls(each P < 0.01). IL-6 and IL-8 levels were higher in the cold-dryness symptom pattern COPD group than in the COPD group(each P < 0.05). The AQP5 m RNA expression in the cold-dryness symptom pattern COPD and COPD groups was lower than in the control group(P < 0.01), and that in the cold-dryness symptom pattern COPD group was lower than the COPD group(P < 0.05). The expression of MUC5 AC and MUC5 B m RNAs in the cold-dryness symptom pattern COPD group and COPD group was higher than in the control group(each P < 0.01), and that in the cold-dryness symptom pattern COPD group was higher than the COPD group(P < 0.01, and P < 0.05, respectively).The ratio of MUC5 AC m RNA/MUC5 B m RNA was COPD group < the cold-dryness symptom pattern COPD group < the control group. AQP4 and AQP5 protein expression in the cold-dryness symptom pattern COPD group was lower than that in the COPD group which was lower again than in the control group. MUC5 AC and MUC5 B expression in the cold-dryness symptom pattern COPD group was higher than in the COPD group and higher again than in the control ***

关键词： Pulmonary disease chronic obstructive Cold-dryness syndrome Aquaporins Mucins

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Chemical weathering and chemical runoffs in the seashore granite hills in South China

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Science China Earth Sciences 2010年第8期53卷 1195-1204页

作者： gao QuanZhou & TAO zhen School of Geography and Planning, Sun Yat-sen University, Guangzhou 510275, China School of Geography and Planning Sun Yat-sen University Guangzhou China

Surface runoffs and the contents of major ions and dissolved silicon were surveyed and analyzed based on weekly sampling for one year in a granite watershed of Zhuhai City, Guangdong Province. The results demonstrated that the slope runoff played an essential role in feeding the rivulet during precipitation, whereas the groundwater was more important for the rivulet in the non-raining stages. Dissolved silicon, Na+, HCO3-, and Clions constituted the major chemical components of the rivulet water. Atmospheric CO2 and H2SO4 sourced from the oxidation of pyrite were the main erosive mediums in the natural chemical weathering. Natural chemical weathering, the wet and dry deposition of sea-salt, and acids precipitation contributed approximately equal shares of anions to the rivulet water. The ratio of NO3- to SO42- was more than 1.0 in the runoff of the studied seashore watershed, whereas it is less than 1.0 in the Xijiang River that is adjacent to the study area. This implied that the chemical composition of runoff is controlled mainly by the differences in atmospheric acid precipitation caused by human activities and lithology within the catchments under the same bio-climate zone. The CO2 flux consumed by the rock chemical weathering processes within the seashore granite watershed in South China was (0.35-1.37)×105 mol km-2 a-1.

关键词： chemical weathering granite ion sea-salt acid deposition CO2

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Cob color, an indicator of grain dehydration and agronomic traits in maize hybrids

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The Crop Journal 2022年第2期10卷 582-586页

作者： Xiao-Gui Liang zhen gao Si Shen Xue Zhao Li Zhang Shun-Li Zhou Key Laboratory of Crop Physiology Ecology and Genetic BreedingMinistry of Education/Jiangxi ProvinceJiangxi Agricultural UniversityNanchang 330045JiangxiChina College of Agronomy and Biotechnology China Agricultural UniversityBeijing 100193China Scientific Observation and Experimental Station of Crop High-Efficiency Use of Water in Wuqiao Ministry of Agriculture and Rural AffairsWuqiao 061802HebeiChina Innovation Center of Agricultural Technology for Lowland Plain of Hebei Wuqiao 061802HebeiChina

Screening for agronomic traits associated with grain moisture is important for mechanical grainharvesting of maize. Cob color as a visual indicator has received limited attention, though it has been subjected to artificial selection, and may have some association with threshability. To investigate the relationships between cob color and grain moisture and other agronomic traits, field experiments were conducted during 2016–2017 using 23 commercial hybrids with red or white cobs. Kernels of red-cob hybrids dehydrated faster, showing lower moisture content at harvest than white-cob hybrids. A cob color index(CCI) was established as a quantitative measure of cob color in the hybrid panel. Ranging from0(whitest) to 17.98(reddest), CCI correlated well with grain dehydration and other agronomic traits associated with growth ontogeny, plant morphology, and plant N content. Strong selection of red cob for recently released hybrids suitable for mechanical grain-harvesting indirectly validated the observed link between cob color and grain dehydration. We propose that cob color and CCI could be used in future selection of maize cultivars bred for mechanical grain-harvesting.

关键词： Maize hybrids Cob color Grain dehydration Agronomic traits Artificial selection

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Establishing motor disorder mouse models of Parkinson disease Comparison of 6-hydroxydompamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

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Neural Regeneration Research 2007年第10期2卷 611-616页

作者： Zhi hua Ren Jie gao Yan Chen zhen yu Lu Department of Medical Genetics Basic Medical CollegeShanghai JiaoTong UniversityShanghai200025China

At present, pathogenesis and mechanism of Parkinson disease （PD） are still unclear. Animal models of PD are essential tools in studies on etiology and therapy and should mimic the chronic pathological process, histological characteristics and motor behavior dysfunction. In recent years, transgenic mice have been widely utilized to study the mechanism of PD, and it has become imperative that a PD mouse model of motor behavioral dysfunction be established. OBJECTIVE： To compare the behavioral and histochemical characters of two neurotoxic mice model induced with 6-hydroxydopamine （6-OHDA） or 1-methyl-4-phenyl-1, 2, 3, 6 -tetrahydropyridine （MPTP）, and a better method to mimic Parkinson disease will be found out. DESIGN： Parallel experiment. SETTING： Laboratory of Molecular Genetics, Department of Medical Genetics, Shanghai Jiao Tohg University. MATERIALS： Sixty 129Sv/C57BL6J male wild mice, SPF grade, 8 - 12 weeks old, weighing 20 - 25 g, were provided by Experimental Animal Center, Shanghai Jiao Tong University. All the surgery operation was performed according to the rules of Shanghai Jiaotong University Animal Committee. METHODS： The experiment was carried out in the Laboratory of Molecular Genetics （National Key Laboratory）, Department of Medical Genetics, Shanghai Jiao Ttong University from March to August 2006. ①Thirty-two male mice were randomly divided into control group and drug treatment group with 16 mice in each group. Surgery was carried out and 6-OHDA was administrated to substantia nigra pars compacta （SNpc） and nigra-striatum pathway according to the different parameters with intoxication apparatus. Saline was injected to the other 16 mice according to the same paradigm. 1 mg/kg apomorphine was injected intraperitoneally 2 weeks later after surgery to induce the imbalanced rotation behavior for 40 minutes. ②Twenty-eight mice were randomly divided into 4 groups with 7 in each group, including low-dose, moderate-dose, high-dose groups and negative contr

关键词： Parkinson disease 6-hydroxydopamine 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine motor behavioral dysfunction

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Effect of Weight Loss on In Vitro Fertilization Treatment Outcome

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Reproductive and Developmental Medicine 2017年第4期1卷 210-215页

作者： Jing-Yan Song Shan Xiang zhen-gao Sun Department of Gynecology of Traditional Chinese Medicine The First Clinical CollegeShandong University of Traditional Chinese MedicineJinanShandong 250011China Reproductive Medicine Center of Integration of Traditional and Western Medicine The Affiliated Hospital of Shandong University of Traditional Chinese MedicineJinanShandong 250011China

Background:To assess the effect of weight loss in overweight and/or obese women on the in vitro fertilization(IVF)treatment outcome before IVF cycles by a systematic review and meta-analysis of clinical ***:Systematic review and meta-analysis of randomized controlled trials(RCTs)and cohort studies were *** literature searches were conducted,and all randomized trials that evaluated the impact of weight loss in IVF treatment cycles were included in the *** selection,quality estimation,and data extractions were performed independently and in ***:A total of 924 patients were enrolled in seven studies;the effects of weight loss on the IVF treatment outcome before the IVF treatment cycle were *** clinical pregnancy rate(risk ratio[RR]:1.61,95%confidence interval[CI]:1.15-2.27),miscarriage rate(RR:0.56,95%CI:0.34-0.93),and live birth rate(RR:1.86,95%CI:1.41-2.45)had a statistically significant difference between the intervention and control *** significant differences were observed in the number of oocytes retrieved(weighted mean difference[WMD]:0.84,95%CI:−0.12-1.79),gonadotropin consumption(WMD:2.59,95%CI:−6.61-1.42),or the duration of stimulation(WMD:−0.46,95%CI:−1.64-0.71).Conclusions:Before IVF treatment,obese and overweight women should lose weight by physical activity and/or dietary management because weight loss can improve pregnancy rate,reduce miscarriage rate,and meliorate live birth *** the same time,further prospective RCTs are required to establish which methods of weight loss are most suited to this purpose,as well as determining whether cut points for body mass index need to be recommended before accessing IVF.

关键词： Dietary Management In Vitro Fertilization Obesity Weight Loss

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基于改进遗传算法的印刷车间多AGV调度研究

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印刷与数字媒体技术研究 2024年第4期 268-275页

作者：许路李宏峰高振清刘玉琴宋鹏程刘景域北京印刷学院机电工程学院北京102600 北京印刷学院出版学院北京102600 北京起重运输机械设计研究院北京100007

针对当前印刷车间内印刷品依赖人工搬运、AGV利用率低且多AGV作业时会发生碰撞、死锁等问题,本研究提出了一种改进的遗传算法对AGV的任务分配进行优化。首先,结合印刷车间的实际环境,以AGV搬运任务总时间最少作为目标函数进行建模;其次... 详细信息

针对当前印刷车间内印刷品依赖人工搬运、AGV利用率低且多AGV作业时会发生碰撞、死锁等问题,本研究提出了一种改进的遗传算法对AGV的任务分配进行优化。首先,结合印刷车间的实际环境,以AGV搬运任务总时间最少作为目标函数进行建模;其次,利用加入了时间窗模型的改进双向A*算法对传统遗传算法进行优化,实现AGV的路径规划与调度管理;最后,利用MATLAB仿真软件对该算法进行仿真验证。对比传统遗传算法与改进遗传算法仿真结果,发现改进后的遗传算法得到的AGV调度结果搬运任务用时比传统遗传算法节省了13%,迭代次数比传统遗传算法减少了42%,因此改进后的遗传算法能更好的实现印刷车间内多AGV的无碰撞运行、路径规划与调度。

关键词：车间建模时间窗模型遗传算法任务调度路径规划

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Fault Tolerant Design of Large-Scale Digital Beam Forming in SRAM-FPGAs for Software Defined Satellite Platforms

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China Communications 2020年第7期17卷 67-79页

作者： zhen gao Jinhua Zhu Tong Yan Linghua Guo Xiangping Chen Yinqiao Li Xiaolei Wan School of Electrical and Information Engineering Tianjin UniversityTianjin 300072China China Academy of Space Technology Beijing 100094China

Large scale digital beamforming(LS-DBFs)are widely used in satellite communications for spectrum reuse and transmission ***-FPGAs are a popular option for software defined satellite platforms due to their rich computation resources and high ***,they are sensitive to soft errors,which limit their application in *** paper discusses the application of coding based fault tolerance schemes for the protection of LS-DBFs on software defined *** multiple FPGAs are usually needed to support the whole LS-DBFs system,different decomposition schemes are compared in terms of resource efficiency and reliability when the coding based scheme is applied to protect the DBFs on a *** analysis and hardware experiments shows that resource efficiency and reliability are a pair of contradictory requirements for decomposition *** protection with vertical decomposition could improve the reliability by 96%with 1.5x *** the protection with horizontal decomposition could improve the reliability by 85%with 1.2 x redundancy.

关键词： FPGAs payload hardware

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Traditional Chinese Medicine Pattern Classification and Herbal Medicine for COVID-19: A Comparative Study of Data from Different Sources

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World Journal of Traditional Chinese Medicine 2023年第1期9卷 81-93页

作者： zhen gao Ying-Ying Liu Ye-Meng Chen Jing-Cheng Dong Department of Integrative Medicine Huashan HospitalFudan UniversityShanghaiChina Institute of Basic Theory and Application Institutes of Integrative MedicineFudan UniversityShanghaiChina Department of Geriatrics and Retired Cadre Putuo HospitalShanghai University of Traditional Chinese MedicineShanghaiChina Dean's Office New York College of Traditional Chinese MedicineMineolaNYUSA

Background: Traditional Chinese medicine(TCM) plays a crucial role in the prevention and control of coronavirus disease 2019(COVID-19). Objective: The study aimed to reveal the distribution characteristics of COVID-19 TCM syndrome types and syndrome elements and the law of TCM treatment and medication. Methods: The TCM diagnosis and treatment protocol for COVID-19 and clinical research data were obtained through network retrieval, and Revman 5.3 and SPSS 23.0 were employed to analyze the composition of TCM syndromes and the situation of TCMs in meta and frequency. Results: The top three TCM syndromes of COVID-19 included damp-heat accumulation in the lung pattern, damp abundance due to spleen deficiency, and epidemic toxin invading the lung pattern, while the syndrome elements were dampness, heat, and toxin. Gypsum fibrosum, Pogostemonis herba, and Armeniacae semen were identified as the commonly used drugs. Different syndrome elements were identified at lung disease location: Forsythiae fructus, Glycyrrhizae radix, and Armeniacae semen can be used for “wind;” Glycyrrhizae radix, Armeniacae semen, and Scutellariae radix can be used for “Heat;” Armeniacae semen, Sheng Gypsum fibrosum, and Ephedrae herba can be used for “Toxin;” Ephedrae herba, Armeniacae semen, and Atractylodis rhizome can be used for “Damp;” Magnoliae officinalis Cortex, Ephedrae herba, and Zingiberis Rhizoma recens can be used for “cold;” and Armeniacae semen, Gypsum fibrosum, Ephedrae herba, and Lepidii/Descurainiae semen can be used for “epidemic.” Conclusion: The establishment of a treatment scheme based on the classification of disease syndrome elements should be considered for sudden infectious diseases, such as COVID-19. Pogostemonis herba, Armeniacae semen, Gypsum fibrosum, and Glycyrrhizae radix should be considered as effective drugs from TCM for the treatment of COVID-19.

关键词： COVID-19 diagnosis and treatment protocol for COVID-19 syndrome syndrome element traditional Chinese medicine traditional Chinese medicine syndrome investigation

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