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Synthetic lethal short hairpin RNA screening reveals that ring finger protein 183 confers resistance to trametinib in colorectal cancer cells

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Chinese Journal of Cancer 2017年第12期36卷 726-736页

作者： Rong Geng Xin Tan Zhixiang Zuo jiangxue wu Zhizhong Pan Wei Shi Ranyi Liu Chen Yao Gaoyuan Wang Jiaxin Lin Lin Qiu Wenlin Huang Shuai Chen State Key Laboratory of Oncology in South China Collaborative Innovation Center of Cancer MedicineSun Yat-sen University Cancer Center651 Dongfeng Road EastGuangzhou 510507GuangdongP.R.China Department of Experimental Research Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China Department of Colorectal Surgery Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China Guangdong Esophageal Cancer Institute Sun Yat-sen University Cancer CenterGuangzhou 510060GuangdongP.R.China Guangdong Provincial Key Laboratory of Tumor.Targeted Drugs and Guangzhou Enterprise Key Laboratory of Gene Medicine Guangzhou Doublle Bioproducts Co.Ltd.Guangzhou 510507GuangdongP.R.China

Background: The mitogen-activated extracellular signal-regulated kinase 1/2(MEK1/2) inhibitor trametinib has shown promising therapeutic effects on melanoma, but its efficacy on colorectal cancer(CRC) is limited. Synthetic lethality arises with a combination of two or more separate gene mutations that causes cell death, whereas individual mutations keep cells alive. This study aimed to identify the genes responsible for resistance to trametinib in CRC cells,using a synthetic lethal short hairpin RNA(shRNA) screening approach.Methods: We infected HT29 cells with a pooled lentiviral shRNA library and applied next-generation sequencing to identify shRNAs with reduced abundance after 8-day treatment of 20 nmol/L trametinib. HCT116 and HT29 cells were used in validation studies. Stable ring finger protein 183(RNF183)-overexpressing cell lines were generated by pcDNA4-myc/his-RNF183 transfection. Stable RNF 183-knockdown cell lines were generated by infection of lentiviruses that express RNF183 shRNA, and small interference RNA(siRNA) was used to knock down RNF183 transiently.Quantitative real-time PCR was used to determine the mRNA expression. Western blotting, immunohistochemical analysis, and enzyme-linked immunosorbent assay(ELISA) were used to evaluate the protein abundance. MTT assay,colony formation assay, and subcutaneous xenograft tumor growth model were used to evaluate cell proliferation.Results: In the primary screening, we found that the abundance of RNF183 shRNA was markedly reduced after treatment with trametinib. Trametinib induced the expression of RNF183, which conferred resistance to drug-induced cell growth repression and apoptotic and non-apoptotic cell deaths. Moreover, interleukin-8(IL-8) was a downstream gene of RNF183 and was required for the function of RNF183 in facilitating cell growth. Additionally, elevated RNF183 expression partly reduced the inhibitory effect of trametinib on IL-8 expression. Finally, xenograft tumor model showed the synergism of RNF183 knockdown and trametinib in repres

关键词： Synthetic lethal Colorectal cancer Ring finger protein 183 Mitogen-activated extracellular signalregulated kinase 1/2 Trametinib

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航空锂离子蓄电池组维护保障研究

化工时刊 2024年第2期38卷 1-4页

作者：钱陈吴江雪李艳峰 94783部队长兴313111 空军南京航空四站装备修理厂南京210042

针对航空锂离子蓄电池组的维护与管理需求,通过研究锂离子蓄电池工作原理、组成、功能结构,基于使用维护流程和要求,引入了一款信息化航空锂离子蓄电池组维护检测设备,重点介绍了维护检测设备的功能、结构、原理。加强航空蓄电池组的维... 详细信息

针对航空锂离子蓄电池组的维护与管理需求,通过研究锂离子蓄电池工作原理、组成、功能结构,基于使用维护流程和要求,引入了一款信息化航空锂离子蓄电池组维护检测设备,重点介绍了维护检测设备的功能、结构、原理。加强航空蓄电池组的维护管理,可有效延长蓄电池组的使用寿命,确保飞行安全。

关键词：航空锂离子蓄电池维护

粉煤灰不同掺加方式对再生骨料混凝土弹性模量的影响研究

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广东建材 2024年第7期40卷 9-12页

作者：何荣吴江雪周勇彭华程毕节市七星关区晶鑫建筑有限公司

为探究再生混凝土复掺矿粉和粉煤灰、单掺粉煤灰下弹性模量差异,文中就粉煤灰不同掺加方式对再生骨料混凝土弹性模量的影响展开研究。结果表明,掺入再生骨料的各组混凝土试件具有低于常规混凝土的弹性模量,单掺粉煤灰后混凝土弹性模量... 详细信息

为探究再生混凝土复掺矿粉和粉煤灰、单掺粉煤灰下弹性模量差异,文中就粉煤灰不同掺加方式对再生骨料混凝土弹性模量的影响展开研究。结果表明,掺入再生骨料的各组混凝土试件具有低于常规混凝土的弹性模量,单掺粉煤灰后混凝土弹性模量进一步降低。而复掺粉煤灰与矿渣后混凝土弹性模量与粉煤灰和矿渣掺入比例有关,其中粉煤灰掺量为10%、矿渣掺量为20%时试件具有较高弹性模量。对于复掺粉煤灰和矿渣的再生混凝土,其抗压强度与弹性模量之间具有良好相关性,并通过回归计算得到经验公式。

关键词：再生骨料混凝土粉煤灰弹性模量回归分析

Translational oncology toward benefiting cancer patients:the Sun Yat-sen University Cancer Center experience

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Science China(Life Sciences) 2016年第10期59卷 1057-1062页

作者： Mathilde Guerin Chaonan Qian Qian Zhong Qian Cui Yunmiao Guo Jinxin Bei Jianyong Shao Xiaofeng Zhu Wenlin Huang jiangxue wu Ranyi Liu Qiang Liu Jing Wang Weihua Jia Xiaohui Zheng Yixin Zeng Sun Yat-sen University Cancer Center Guangzhou 510060China

Cancer is a leading cause of death in China with an estimation of nearly 2 million deaths every year(Chen and Fu,2011b).Matter of a public health importance in China and worldwide,the scientific community is still facing

关键词：癌症患者中山大学肿瘤转化器官特异性多因子疾病公共卫生抗癌药物

A Hybrid Biofuel and Triboelectric Nanogenerator for Bioenergy Harvesting

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Nano-Micro Letters 2020年第4期12卷 53-64页

作者： Hu Li Xiao Zhang Luming Zhao Dongjie Jiang Lingling Xu Zhuo Liu Yuxiang wu Kuan Hu Ming‑Rong Zhang jiangxue Wang Yubo Fan Zhou Li Beijing Advanced Innovation Centre for Biomedical Engineering Key Laboratory for Biomechanics and Mechanobiology of Chinese Education MinistrySchool of Biological Science and Medical EngineeringBeihang UniversityBeijing 100083People’s Republic of China CAS Center for Excellence in Nanoscience Beijing Key Laboratory of Micro‑Nano Energy and SensorBeijing Institute of Nanoenergy and NanosystemsChinese Academy of SciencesBeijing 100083People’s Republic of China School of Nanoscience and Technology University of Chinese Academy of SciencesBeijing 100049People’s Republic of China School of Physical Education Jianghan UniversityWuhan 430056People’s Republic of China Center on Nanoenergy Research School of Physical Science and TechnologyGuangxi UniversityNanning 530004People’s Republic of China Department of Radiopharmaceuticals Development National Institute of Radiological SciencesNational Institutes for Quantum and Radiological Science and TechnologyChiba 263‑8555Japan

Various types of energy exist everywhere around us,and these energies can be harvested from multiple sources to power micro-/nanoelectronic system and even personal electronic products.In this work,we proposed a hybrid energy-harvesting system(HEHS)for potential in vivo applications.The HEHS consisted of a triboelectric nanogenerator and a glucose fuel cell for simultaneously harvesting biomechanical energy and biochemical energy in simulated body fluid.These two energy-harvesting units can work individually as a single power source or work simultaneously as an integrated system.This design strengthened the flexibility of harvesting multiple energies and enhanced corresponding electric output.Compared with any individual device,the integrated HEHS outputs a superimposed current and has a faster charging rate.Using the harvested energy,HEHS can power a calculator or a green light-emitting diode pattern.Considering the widely existed biomechanical energy and glucose molecules in the body,the developed HEHS can be a promising candidate for building in vivo self-powered healthcare monitoring system.

关键词： Self-powered Triboelectric nanogenerator Glucose fuel cell Hybrid energy harvester Bioenergy

Identification and characterization of mammaglobin-A epitope in heterogenous breast cancers for enhancing tumor-targeting therapy

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1778-1788页

作者： Zhiqiang Liu Xiqin Yang Cuimi Duan jiangxue Li Rongsheng Tong Yuting Fan Jiannan Feng Ruiyuan Cao wu Zhong Xiaoyan Feng Heqiu Zhang Lulu Cai Beijing Institute of Basic Medical Sciences 27 Taiping RoadHaidian DistrictBeijing 100850China Personalized Drug Therapy Key Laboratory of Sichuan Province Department of PharmacySichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 611731China Beijing Institute of Pharmacology and Toxicology 27 Taiping RoadHaidian DistrictBeijing 100850China

Although targeted therapy has been extensively investigated for breast cancers,a molecular target with broad application is currently unavailable due to the high heterogeneity of these cancers.Mammaglobin-A(Mam-A),which is overexpressed in most breast carcinomas,has been proposed as a promising target.However,the lack of specific targeting moieties due to uncertain binding epitopes hampers further translational study.Here,seven potential epitopes of Mam-A were disclosed,and a unique epitope was then identified in most types of breast cancers,despite the genotypic heterogeneity.With phage display technology,the epitope was determined to be N-terminal amino acids 42–51 of Mam-A(N42–51).Then,the N42–51 epitope-specific monoclonal antibody,mAb785,was conjugated to poly lactic-co-glycolic acid(PLGA)nanoparticles loaded with therapeutic agents,thereby enhancing the drug uptake and therapeutic efficacy in different genotypes of breast cancers.The computer simulation of the N42–51 epitope and the mAb785 structures,as well as their interactions,further revealed the specific targeting mechanism of the mAb785-conjugated nanoparticles to breast cancers.

关键词： breast cancers epitope

Expression of glucocorticoid receptor isoforms in cutaneous hemangiomas and vascular malformations

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Chinese Medical Journal 2005年第12期118卷 977-981页

作者： jiangxue-wu WANGGuang-huan LIJian-hong CHENZhong-xian HEFei DepartmentofPediatricSurgery SecondAffiliatedHospitalofShantouUniversityMedicalCollegeShantou515041China

Background Hemangiomas are the most common tumors in children. Some hemangiomas may require intervention because of their location, size, behavior, or potential for important complications. Pharmacological therapy with glucocorticoids is the mainstay treatment, but there is no consensus on therapeutic regimens or candidate selection, therapeutic efficacy vaires, and the mechanism mediating the beneficial effects of glucocorticoids remains unclear. This study was performed to investigate the expression patterns of the glucocorticoid receptor (GR) and its α isoform (GRα) in cutaneous hemangiomas and vascular malformations.Methods SP immunohistochemical technique was used to examine the expression of GR(e-20) (GR) and GR (p-20) (GRα) on vascular endothelial cells in 80 specimens that included 33 proliferating hemangiomas, 32 involuting hemangiomas, 7 vascular malformations as well as 8 normal skin tissues, all obtained from infants and children. GR and GRα expression in prepared tissue slides were examined using automated computer-assisted microscopic analysis. Mean gray scale values were compared among the various tumor types.Results The mean gray scale values of GR were 127.0±6.4 and 121.4±6.6 in hemangiomas and vascular malformations respectively, but this difference was not statistically significant ( P =0.104). However, these values were all markedly higher than that of normal skin, which was only 108.6±6.8 ( P =0.001 and P =0.000 for comparison with hemangiomas and vascular malformations respectively). The gray scale of GR in proliferation and involuting hemangiomas were 127.9±4.8 and 126.0±5.8 respectively, but this difference was not significant ( P =0.146). However, GRα expression in hemangiomas, vascular malformations and normal skin declined gradually in stepwise fashion (127.3±5.4, 120.4±6.1 and 109.9±5.3 respectively; P <0.001). GRα expression was higher in proliferating hemangiomas than in involuting hemangiomas (127.2±6.3 and 122.5±6.3; P =0.004).Conclusions GR and GRα are strongly expressed in hemang

关键词：糖皮质激素受体基因表达皮肤血管瘤血管畸形

制度内政治参与视域下铸牢中华民族共同体意识研究

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云南行政学院学报 2023年第6期25卷 1-13页

作者：吴开松马江雪中南民族大学公共管理学院湖北武汉430074 中南民族大学中国城市民族与宗教事务治理研究中心湖北武汉430074

铸牢中华民族共同体意识是实现民族团结、社会稳定繁荣的基础,也是推进中国式现代化,实现中华民族伟大复兴的重要保障。政治参与不仅与公民的利益诉求、民主权利有关,更关乎国家的民主政治建设。合法有序的制度内政治参与能提升公民社... 详细信息

铸牢中华民族共同体意识是实现民族团结、社会稳定繁荣的基础,也是推进中国式现代化,实现中华民族伟大复兴的重要保障。政治参与不仅与公民的利益诉求、民主权利有关,更关乎国家的民主政治建设。合法有序的制度内政治参与能提升公民社会治理参与的水平,也能够影响中华民族共同体意识的铸牢程度。本文基于CSS2019数据,系统分析了公民制度内政治参与对中华民族共同体意识的影响。研究结果表明:(1)制度内政治参与能显著提升公民中华民族共同体意识;(2)西部地区公民的制度内政治参与对铸牢中华民族共同体意识的影响作用强于中部和东部地区;(3)制度内政治参与主要通过政治效能感的培育影响公民中华民族共同体意识。据此,为全面铸牢中华民族共同体意识,有必要进一步完善相关政治参与机制,从而保障公民合法有序地扩大制度内政治参与行为。

关键词：制度内政治参与中华民族共同体意识政治效能感

长期施肥对不同深度稻田土壤团聚体磷素分配的影响

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农业资源与环境学报 2022年第6期39卷 1115-1123页

作者：柳开楼都江雪邬磊张文菊韩天富李文军施林林余喜初江西省红壤研究所国家红壤改良工程技术研究中心南昌330046 中国农业科学院农业资源与农业区划研究所北京100081 湖南文理学院资源环境与旅游学院湖南常德415000 苏州农业科学院江苏苏州215007

长期磷肥投入显著增加了耕层土壤各团聚体组分中磷素累积,而作为评判磷素是否向地下水迁移的重要指标,深层土壤团聚体磷素分配对长期磷肥投入的响应仍缺乏系统评估。本研究依托始于1981年红壤稻田长期定位试验,选取不施磷肥(NK)、氮磷... 详细信息

长期磷肥投入显著增加了耕层土壤各团聚体组分中磷素累积,而作为评判磷素是否向地下水迁移的重要指标,深层土壤团聚体磷素分配对长期磷肥投入的响应仍缺乏系统评估。本研究依托始于1981年红壤稻田长期定位试验,选取不施磷肥(NK)、氮磷钾化肥(NPK)和氮磷钾化肥配施有机肥(NPKM)处理,在长期试验40年后(2020年),分别采集0~20、20~40、40~60 cm深度的土壤样品,测定了全土和各团聚体组分的总磷和有效磷含量,并探讨了施肥-团聚体质量百分比-团聚体磷素之间的内在关系。结果表明,所有施肥处理均表现为>2 mm团聚体质量百分比随着土壤深度的增加而逐渐降低,与NK处理相比,磷肥施用显著提高了0~20 cm和20~40 cm全土和团聚体组分中有效磷含量,且NPKM处理的增幅最大。与NK处理相比,NPKM处理下0~20、20~40 cm和40~60 cm各团聚体总磷含量分别提高了2.14~2.60、1.39~2.80倍和27.03%~180%,各团聚体有效磷含量增幅分别为12.95~18.29、7.57~12.31倍和70.67%~709%。同时,NPKM处理总磷和有效磷的增幅呈现出随着团聚体粒径的增大而逐渐增加的趋势。水稻吸磷量和磷素盈余量也表现为NPKM处理最高,NPK处理次之,NK处理最低。进一步分析发现,团聚体总磷和有效磷含量主要受磷素盈余量的影响,且团聚体中的有效磷含量还受总磷含量的直接调控。研究表明,40年长期有机无机肥配施显著影响红壤稻田表层和深层团聚体磷素分配,且>2 mm团聚体组分中有效磷含量的响应最为敏感,通过调控磷素盈余可以显著影响团聚体中磷分配。

关键词：水稻土团聚体有效磷有机肥配施土壤深度