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功能化纳米金介导的放疗-抗血管生成协同疗法用于肝癌治疗的研究
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作者 李春胤 吴梦琳 +3 位作者 李雪 王凌玮 李江 梁广立 《中国肿瘤临床》 北大核心 2025年第22期1135-1140,共6页
目的:构建具有内皮靶向作用的功能化纳米金放疗增敏剂(tAuNMs-siRNA),通过靶向肝癌血管生成活跃区域,增强该区域肝癌细胞的局部辐射剂量;同时通过定点释放血管内皮生长因子小干扰RNA(vascular endothelial growth factor small interfer... 目的:构建具有内皮靶向作用的功能化纳米金放疗增敏剂(tAuNMs-siRNA),通过靶向肝癌血管生成活跃区域,增强该区域肝癌细胞的局部辐射剂量;同时通过定点释放血管内皮生长因子小干扰RNA(vascular endothelial growth factor small interfering RNA,VEGF-siRNA),下调血管内皮生长因子(VEGF)表达以抑制肿瘤新生血管生成,实现放疗增敏与抗血管生成的有机结合。方法:以谷胱甘肽(GSH)、血管生成靶向肽(cNGR)和聚赖氨酸短肽(CK9)为模板,通过离子诱导法原位合成功能化纳米金(tAuNMs)。其中,金(Au)元素实现放疗增敏,cNGR用于识别肝癌血管生成活跃区域,CK9提供siRNA负载位点。tAuNMs通过负载VEGF-siRNA获得tAuNMs-siRNA。建立荷肝癌(H22)BALB/c小鼠皮下移植瘤模型,治疗期间对小鼠的生存状态、体重和肿瘤体积进行观察和测量,以此作为评判治疗疗效的依据。统计学分析采用单因素方差分析及独立样本t检验。结果:透射电镜显示tAuNMs呈规则球形,粒径约20 nm,大小均一。红外光谱显示t AuNMs已通过伯酰胺键成功偶联cNGR与CK9。琼脂糖凝胶电泳显示当tAuNMs与siRNA的质量比为10∶1时可完全负载VEGF-siRNA,此时伯胺基的红外特征双峰变成单峰,标志着tAuNMs-siRNA的成功构建。Western blot结果显示,与游离siRNA及商业化基因载体lipo2000相比,tAuNMssiRNA具有更显著的VEGF基因沉默效果。克隆实验结果显示,tAuNMs-siRNA处理后的细胞克隆形成率显著降低。动物实验结果显示,与空白对照组及单一治疗组相比,放疗增敏-抗血管生成协同治疗组对肿瘤具有显著的抑制作用(P<0.05)。结论:tAuNMs-siRNA介导的协同治疗一方面通过抑制DNA损伤修复,降低肝癌细胞对X射线的抵抗作用,另一方面通过下调VEGF表达抑制肿瘤新生血管生成,两者相结合可以显著抑制肿瘤生长。 展开更多
关键词 纳米放疗增敏剂 肿瘤血管生成 靶向治疗 放疗增敏-抗血管生成协同治疗
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Evaluation of N-acetylcysteine and glutathione as quenching agents for the analysis of halogenated disinfection by-products 被引量:2
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作者 Shunke Ding menglin wu +4 位作者 Rong Xiao Chao Fang Qi Wang Bin Xu Wenhai Chu 《Journal of Environmental Sciences》 SCIE EI CAS CSCD 2022年第7期71-79,共9页
Disinfection by-products(DBPs), formed from the reactions of disinfectants with natural organic matter and halides in drinking water, were considered to be cytotoxic and genotoxic, and might trigger various cancers. T... Disinfection by-products(DBPs), formed from the reactions of disinfectants with natural organic matter and halides in drinking water, were considered to be cytotoxic and genotoxic, and might trigger various cancers. The relatively low concentration of DBPs in finished water(low μg/L or even ng/L levels) and the interference from water matrix inhibited in situ determination of DBPs. Moreover, the further formation and degradation of DBPs by disinfectants during the holding time(several hours to several days) from sample collection to analysis could adversely affect the determination of DBPs. To obtain accurate, precise and reliable data of DBP occurrence and formation, robust and reliable sample preservation is indispensable. However, the commonly used quenching agents(e.g., sodium sulfite, sodium thiosulfate, and ascorbic acid) for sample preservation can decompose reactive DBPs by reductive dehalogenation. This study evaluated the performance of N-acetylcysteine(NAC) and glutathione(GSH) as quenching agents for the analysis of halogenated DBPs by investigating the stoichiometry of the disinfectant-quenching agent reaction, the formation of DBPs during chlor(am)ination of NAC or GSH, and the effects of NAC or GSH on the stability of 18 individual DBPs and total organic halogen(TOX). Based on the results of this study, NAC and GSH were considered to be ideal quenching agents for the analysis of most DBPs and TOX, except halonitromethanes. 展开更多
关键词 Disinfection by-products Total organic halogen Quenching agents N-ACETYLCYSTEINE GLUTATHIONE
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Artificial optical microfingerprints for advanced anticounterfeiting
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作者 Xueke Pang Qiang Zhang +7 位作者 Jingyang Wang Xin Jiang menglin wu Mingyue Cui Zhixia Feng Wenxin Xu Bin Song Yao He 《Nano Research》 SCIE EI CSCD 2024年第5期4371-4378,共8页
Artificial optical microfingerprints,known as physically unclonable functions(PUFs)offer a groundbreaking approach for anti-counterfeiting.However,these PUFs artificial optical microfingerprints suffer from a limited ... Artificial optical microfingerprints,known as physically unclonable functions(PUFs)offer a groundbreaking approach for anti-counterfeiting.However,these PUFs artificial optical microfingerprints suffer from a limited number of challenge-response pairs,making them vulnerable to machine learning(ML)attacks when additional error-correcting units are introduced.This study presents a pioneering demonstration of artificial optical microfingerprints that combine the advantages of PUFs,a large encoding capacity algorithm,and reliable deep learning authentication against ML attacks.Our approach utilizes the triple-mode PUFs,incorporating bright-field,multicolor fluorescence wrinkles,and the topography of surface enhanced Raman scattering in the mechanical and optical layers.Notably,the quaternary encoding of these PUFs artificial microfingerprints allows for an encoding capacity of 6.43×10^(24082) and achieves 100%deep learning recognition accuracy.Furthermore,the PUFs artificial optical microfingerprints exhibit high resilience against ML attacks,facilitated by generative adversarial networks(GAN)(with mean prediction accuracy of~85.0%).The results of this study highlight the potential of utilizing up to three PUFs in conjunction with a GAN training system,paving the way for achieving encoded information that remains resilient to ML attacks. 展开更多
关键词 artificial microfingerprints physically unclonable functions deep learning ANTI-COUNTERFEITING
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Glut3 promotes cellular O-GlcNAcylation as a distinctive tumorsupportive feature in Treg cells
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作者 Amit Sharma Garima Sharma +16 位作者 Zhen Gao Ke Li Mutong Li menglin wu Chan Johng Kim Yingjia Chen Anupam Gautam Hong Bae Choi Jin Kim Jung-Myun Kwak Sin Man Lam Guanghou Shui Sandip Paul Yongqiang Feng Keunsoo Kang Sin-Hyeog Im Dipayan Rudra 《Cellular & Molecular Immunology》 CSCD 2024年第12期1474-1490,共17页
Regulatory T cells(Tregs)establish dominant immune tolerance but obstruct tumor immune surveillance,warranting context-specific mechanistic insights into the functions of tumor-infiltrating Tregs(TIL-Tregs).We show th... Regulatory T cells(Tregs)establish dominant immune tolerance but obstruct tumor immune surveillance,warranting context-specific mechanistic insights into the functions of tumor-infiltrating Tregs(TIL-Tregs).We show that enhanced posttranslational O-linked N-acetylglucosamine modification(O-GlcNAcylation)of cellular factors is a molecular feature that promotes a tumor-specific gene expression signature and distinguishes TIL-Tregs from their systemic counterparts.We found that altered glucose utilization through the glucose transporter Glut3 is a major facilitator of this process.Treg-specific deletion of Glut3 abrogates tumor immune tolerance,while steady-state immune homeostasis remains largely unaffected in mice.Furthermore,by employing mouse tumor models and human clinical data,we identified the NF-κB subunit c-Rel as one such factor that,through Glut3-dependent O-GlcNAcylation,functionally orchestrates gene expression in Tregs at tumor sites.Together,these results not only identify immunometabolic alterations and molecular events contributing to fundamental aspects of Treg biology,specifically at tumor sites but also reveal tumor-specific cellular properties that can aid in the development of Treg-targeted cancer immunotherapies. 展开更多
关键词 Regulatory T cells TREG GLUT3 O-GLCNACYLATION Treg metabolism
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Insights into geminiviral pathogenesis:interaction betweenβC1 protein and GLABROUS1 enhancer binding protein(GeBP)in Solanaceae
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作者 Meisheng Zhao Mingjun Li +7 位作者 Liping Zhang Nan wu Xinyue Tang Xiaolong Yang Hussein Ghanem menglin wu Gentu wu Ling Qing 《Phytopathology Research》 2025年第1期405-420,共16页
Transcription factors(TFs)play crucial roles in plant development and pathogen defense.However,plant viruses can exploit TFs to facilitate their infection or transmission.In this study,we confirmed theβC1 proteins,en... Transcription factors(TFs)play crucial roles in plant development and pathogen defense.However,plant viruses can exploit TFs to facilitate their infection or transmission.In this study,we confirmed theβC1 proteins,encoded by tobacco curly shoot virus(TbCSV)-and tomato yellow leaf curl China virus(TYLCCNV)-associated betasatellites,interacted with GLABROUS1 enhancer binding protein(GeBP)TFs from solanaceous plants including Nicotiana benthamiana,Solanum lycopersicum,S.tuberosum,and Capsicum annuum.Further analysis verified the nuclear localization,homodimerization,and DNA-binding ability of the GeBP TFs,along with its interaction withβC1 in the nucleus.PVX-mediated overexpression of NbGeBP showed no effect on the accumulation of viral and betasatellite DNAs in N.benthamiana plants after infection with TbCSV and its heterologous betasatellite,malvastrum yellow vein virus associated betasatellite(MaYVB),or its homologous betasatellite,TbCSB.However,both TbCSV and MaYVV caused a decrease in NbGeBP expression during the early stages of infection,regardless of the presence of homologous or heterologous betasatellites,implying that NbGeBP might play a role in virus infection.TbCSV/TbCSB and TYLCCNV/TYLCCNB infect many solanaceous plants,and solanaceous GeBP proteins interact withβC1 proteins from TbCSB and TYLCCNB.The yeast two-hybrid and bimoleccular fluorescence complementation assays showed that AtGeBP from Arabidopsis thaliana could not interact with TbCSBβC1,revealing that the GeBP-βC1 interactions might only exist in GeBP proteins from solanaceous plants.Importantly,theβC1 protein from MaYVB,which was almost not reported on natural infection in solanaceous plants,could not interact with GeBP,suggesting the potential roles of GeBP in monopartite begomovirus infection of solanaceous plants. 展开更多
关键词 Geminivirus βC1 protein Transcription factor GLABROUS1 enhancer binding protein(GeBP) Nuclear localization Solanaceous plants Pathogen-host interaction
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