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Chemo–immunotherapy for chemo-resistance and metastasis of triple-negative breast cancer by combination of iron-oxide nanoparticles and dual-targeting doxorubicin liposomes

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Chinese Chemical Letters 2023年第10期34卷 76-81页

作者： Heping Hu lijia yu Zhao Ding Jinsong Ding Yiguo Hu Zongning Yin Key Laboratory of Drug Targeting and Drug Delivery System of Ministry of Education West China School of PharmacySichuan UniversityChengdu 610041China Sichuan Huiyu Seacross Medical Technology Co. Ltd.Chengdu 610031China Sichuan Huiyu Pharmaceutical Co. Ltd.Neijiang 641000China Xiangya School of Pharmaceutical Sciences Central South UniversityChangsha 410013China State Key Laboratory of Biotherapy and Cancer Center West China HospitalSichuan Universityand Collaborative Innovation Center for BiotherapyChengdu 610044China

Triple-negative breast cancer(TNBC)lacks specific regimens for targeted *** chemotherapy promotes the evolution of TNBC into highly chemo-resistant tumors that metastasize to multiple organs ***,polyacrylic acid-coated ultrasmall superparamagnetic iron-oxide nanoparticles(PAA@IONs)and dual-targeting doxorubicin liposomes achieved chemo–immunotherapy through intermittent *** inhibited tumor-drug resistance and multiorgan-specific metastasis significantly by targeting tumors and the *** deciphered an immunosuppressive pre-metastatic niche and discovered that PAA@IONs could target tumors,tumor-draining lymph nodes(TDLNs),the liver,bone,and *** promoted the polarization of macrophages into M1 macrophages in these organs and *** action remodeled the immunosuppressive microenvironment and induced a sustained immune response,thereby reducing organ-specific *** the disadvantages of doxorubicin-induced cardiotoxicity as well as low tumor specificity,dual peptide-modified liposomes could target CD206 and CD13 simultaneously,and reverse *** properties resulted in a significant decrease in the numbers of myeloid-derived suppressor cells(MDSCs)and cancer stem cells(CSCs)in the liver,lungs,and bone,thereby reducing protein expression of Ki-67 in TDLNs,and dramatically increasing the number of cluster of differentiation(CD)8+T cells and CD8+T cell/T-regulatory-cell ratio in tumors and TDLNs(P<0.0001).Compared with the control(P<0.05 and P<0.01,respectively)or free drug(P<0.0001 and P<0.01,respectively),multi-organ metastases were suppressed significantly,tumor-growth rate reduced,and survival *** drug-delivery system overcame TNBC chemo-resistance and inhibited multiorgan-specific *** circumvents the lack of effective therapeutic targets,the problem of patient selection due to a low mutation rate,and can simultaneously offer the possibility of avoid

关键词： Multidrug resistance Multiorgan-specific metastases Immunogenic cell death Intermittent dosing Immunosuppressive tumor microenvironment Tumor-associated macrophages

基于热解吸-气相色谱质谱法测定呼出气中27种挥发性有机物浓度

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环境与职业医学 2024年第1期41卷 96-102页

作者：高汭彭方达何雅珍冯洁刘武宾于丽佳陈青松丁春光广东药科大学公共卫生学院广东广州510224 国家卫生健康委职业安全卫生研究中心/粉尘危害工程防护重点实验室北京102308 国家卫生健康委尘肺病重点实验室山西太原030001

[背景]呼出气中的挥发性有机物(VOCs)与呼吸系统疾病密切相关,与体内多种代谢反应存在联系,建立其分析方法可为疾病中VOCs的研究提供技术支持。[目的]建立呼出气中27种VOCs的热解吸-气相色谱质谱(TD-GC-MS)检测方法。[方法]呼出气中VOC... 详细信息

[背景]呼出气中的挥发性有机物(VOCs)与呼吸系统疾病密切相关,与体内多种代谢反应存在联系,建立其分析方法可为疾病中VOCs的研究提供技术支持。[目的]建立呼出气中27种VOCs的热解吸-气相色谱质谱(TD-GC-MS)检测方法。[方法]呼出气中VOCs使用Bio-VOC呼出气采样器进行采集,随后用Tenax TA热解吸管富集后进行TD-GC-MS分析。使用Tenax TA 60/80热解吸管采集标准气,对TD-GC-MS检测方法的热解吸条件和色谱、质谱条件进行优化:通过优化升温程序实现27种VOCs的分离,通过优化定量离子提高灵敏度,通过对热解吸时间和温度的优化提高VOCs解吸效率。采用空白气袋加标的方式对方法的检出限、定量限、准确度、精密度及稳定性进行检测,并采集20名健康志愿者呼出气样品进行方法的应用考察。[结果]本研究热解吸温度为280℃,解吸时间为6 min,选择VF-624ms色谱柱进行VOCs的分离,色谱柱升温程序:初始温度35℃,保持1 min;以3℃·min^(-1)升至100℃保持1 min;以28℃·min^(-1)升至210℃并保持5 min,选择单离子检测扫描(SIM)模式进行27种VOCs的定量分析。此检测条件下,27种VOCs在各自测定范围内线性良好,相关系数均>0.9990,方法检出限范围为0.01~0.13 nmol·mol^(-1),定量限范围为0.02~0.44 nmol·mol^(-1),方法加标回收率范围为80.1%~120.5%,批内、批间精密度分别≤18.8%、17.9%,所有VOCs在常温(23~28℃)条件下可保存7 d,在4℃条件下可保存14 d。应用本法对20名受试者呼出气样本进行检测,检出率≥80%(除反式-2-戊烯和癸烷),检出浓度范围为0.00~465.50 nmol·mol^(-1)。[结论]本研究建立的呼出气中挥发性有机物TD-GC-MS定量法,具有灵敏度高、准确度好的特点,适用于呼出气中VOCs的定量检测,可为呼出气VOCs研究提供技术支持。

关键词：呼出气挥发性有机物热解吸气相色谱-质谱

ACHIEVING OPTIMAL ADVERSARIAL ACCURACY FOR ADVERSARIAL DEEP LEARNING USING STACKELBERG GAMES

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Acta Mathematica Scientia 2022年第6期42卷 2399-2418页

作者：高小山刘爽于立佳 Academy of Mathematics and Systems Science Chinese Academy of SciencesUniversity of Chinese Academy of SciencesBeijing 100190China

The purpose of adversarial deep learning is to train robust DNNs against adversarial attacks,and this is one of the major research focuses of deep *** theory has been used to answer some of the basic questions about adversarial deep learning,such as those regarding the existence of a classifier with optimal robustness and the existence of optimal adversarial samples for a given class of *** most previous works,adversarial deep learning was formulated as a simultaneous game and the strategy spaces were assumed to be certain probability distributions in order for the Nash equilibrium to ***,this assumption is not applicable to practical *** this paper,we give answers to these basic questions for the practical case where the classifiers are DNNs with a given structure;we do that by formulating adversarial deep learning in the form of Stackelberg *** existence of Stackelberg equilibria for these games is ***,it is shown that the equilibrium DNN has the largest adversarial accuracy among all DNNs with the same structure,when Carlini-Wagner s margin loss is *** trade-off between robustness and accuracy in adversarial deep learning is also studied from a game theoretical perspective.

关键词： adversarial deep learning Stackelberg game optimal robust DNN universal adversarial attack adversarial accuracy trade-off result

A comparative study of assembly and disassembly process of dimeric and monomeric cyanine dyes with DNA templates

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Chinese Chemical Letters 2019年第3期30卷 694-697页

作者： lijia yu Qianfan Yang Yalin Tang National Center of Occupational Safety and Health State Administration of Work Safety College of Chemistry Sichuan University Beijing National Laboratory for Molecular Science Center for Molecular Science State Key Laboratory for Structural Chemistry for Unstable and State Species Institute of Chemistry Chinese Academy of Sciences

Cyanine dyes have attracted more and more interest due to their controllable assembly and disassembly process with biomolecular templates. The self-assembly of cyanine dye not only depend on the environment, but also on their structures. Here, we report assembly and disassembly of two cyanine dyes,a dimeric cyaine dye(TC-P4) and its corresponding monomer(TC). In PBS, these dyes could form aggregates. The parallel c-myc G-quadruplex as a template causes the transformation of TC-P4 from Haggregates to dimer and monomer; while duplex and single-stranded DNAs could not. The interaction between these DNAs motifs and TC could all induce the appearance of monomer band. Parallel c-myc Gquadruplex could enhance the fluorescence intensity of TC-P4 and TC. The self-assembly and disassembly of TC and TC-P4 could be regulated and used as probes for G-quadruplex recognition from duplex and single-stranded DNAs in solution.

关键词： Cyanine dye Supramolecular assembly DNA templates G-quadruplex c-myc

Linking coral fluorescence phenotypes to thermal bleaching in the reef-building Galaxea fascicularis from the northern South China Sea

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Marine Life Science & Technology 2024年第1期6卷 155-167页

作者： Sanqiang Gong Jiayuan Liang Gang Li lijia Xu Yehui Tan Xinqing Zheng Xuejie Jin Kefu yu Xiaomin Xia Key Laboratory of Tropical Marine Bio-Resources and Ecology&Guangdong Provincial Key Laboratory of Applied Marine Biology South China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou 510301China Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou) Guangzhou 510301China Coral Reef Research Center of China Guangxi UniversityNanning 53004China South China Institute of Environmental Sciences The Ministry of Ecology and Environment of PRCGuangzhou 510530China Third Institute of Oceanography Ministry of Natural ResourcesXiamen 361005China

Coral fluorescence phenotypes have been suggested as an adaptation to a broad range of environmental conditions,yet the mechanisms linking thermal bleaching tolerance in reef-building coral populations,associated with fluorescence phenotypes due to GFP-like proteins,remains *** this study,the relationship between the thermal sensitivity and phenotypic plasticity of corals was investigated using two phenotypes of Galaxea fascicularis,green and *** results reveal that brown *** was more susceptible to bleaching than green *** when exposed to a higher growth temperature of 32℃.Both phenotypes of *** were associated with the thermotolerant Symbiodiniaceae symbiont,Durusdinium ***,the brown *** showed a significant decrease in Symbiodiniaceae cell density and a significant increase in pathogenic bacteria abundance when the growth temperature was raised from 29 to 32℃.The physiological traits and transcriptomic profiles of Symbiodiniaceae were not notably affected,but there were differences in the transcriptional levels of certain genes between the two phenotype hosts of *** heat stress of 32℃,the gene encoding green fluorescent protein(GFP)-like and chromosome-associated proteins,as well as genes related to oxidative phosphorylation,cell growth and death showed lower transcriptional levels in the brown *** compared to the green ***,the results demonstrate that the green form of *** is better able to tolerate ocean warming and defend against pathogenic bacteria,likely due to higher gene transcription levels and defense ability.

关键词： Fluorescence phenotype Thermal bleaching Microbiome Galaxea fascicularis Ocean warming

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赵建军绘画中的隐喻性与时间性

美术 2023年第3期 50-53页

作者：于莉佳哈尔滨师范大学美术学院

绘画中的隐喻性和时间性是影响观众精神感官的两个要素,同时也是能较好地呈现作品精神内核的重要因素。赵建军在深厚的中国传统文化基础上,融入了有文本来源的图像隐喻、认同隐喻、并置映射、差异隐喻、多重元素交互作用隐喻,以及时间... 详细信息

绘画中的隐喻性和时间性是影响观众精神感官的两个要素,同时也是能较好地呈现作品精神内核的重要因素。赵建军在深厚的中国传统文化基础上,融入了有文本来源的图像隐喻、认同隐喻、并置映射、差异隐喻、多重元素交互作用隐喻,以及时间的静止、流淌、延伸或压缩等表现形式,创作出了具有诗性表达意味的中国画作品。

关键词：赵建军中国画隐喻性时间性

Immune function biomarker QuantiFERON-monitor is associated with infection risk in cirrhotic patients

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World Journal of Hepatology 2016年第35期8卷 1569-1575页

作者： Siddharth Sood lijia yu Kumar Visvanathan Peter William Angus Paul John Gow Adam Gareth Testro Department of Gastroenterology and Hepatology University of Melbourne Royal Melbourne Hospital Liver Transplant Unit Victoria University of Melbourne Innate Immune Laboratory University of Melbourne St Vincent’s Hospital

AIM To investigate whether a novel immune function biomarker Quanti FERON-Monitor(QFM) can identify cirrhotic patients at greatest risk of infection. METHODS Adult cirrhotic patients on the liver transplant waiting list were recruited for this observational cohort study from a tertiary liver transplant referral unit. The immune function biomarker, QFM was performed using the same method as the widely available Quantiferon-gold assay, and measures output in interferon gamma in IU/mL after dual stimulation of the innate and adaptive immune systems. Ninety-one cirrhotic patients were recruited, with 47(52%) transplanted on the day of their QFM. The remaining 44(48%) were monitored for infections until transplant, death, or census date of 1st February *** Cirrhotic patients express a median QFM significantly lower than healthy controls(94.5 IU/mL vs 423 IU/mL), demonstrating that they are severely *** factors including model for end stage liver disease, presence of hepatocellular carcinoma, bilirubin, international normalized ratio and haemoglobin were associated with QFM on univariate analysis. Disease aetiology did not appear to impact QFM. On multivariate analysis, only Child-Pugh score and urea were significantly associated with a patient's immune function as objectively measured by QFM. In the 44 patients who were not transplanted immediately after their blood test and could be monitored for subsequent infection risk, 13(29.5%) experienced a pre-transplant infection a median 20 d(range 2-182) post-test. QFM < 214 IU/mL was associated with HR = 4.1(P = 0.01) for infection. A very low QFM < 30 IU/mL was significantly associated(P = 0.003) with death in three patients who died while awaiting transplantation(HR = 56.6).CONCLUSION QFM is lower in cirrhotics, allowing objective determinations of an individual's unique level of immune dysfunction. Low QFM was associated with increased susceptibility to infection.

关键词：感染 Biomarker 有免疫力的机能障碍有免疫力的功能免疫力的抑制肝免疫系统肝硬化死亡

从自然的人化到人化的自然——赵龙“无人风景画”的创作历程

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艺术研究（哈尔滨师范大学艺术学报） 2023年第3期 17-19页

作者：于莉佳哈尔滨师范大学美术学院

“无人风景画”作为打破传统风景画创作风格的独特艺术画作形式,通过“无人之境”表达画中逸景之美,将艺术创作者的现实世界与内心体验完美融入到艺术画作中。本文旨在从城市景观、文人风骨、涅繁修炼、师法自然四个角度去系统分析赵龙... 详细信息

“无人风景画”作为打破传统风景画创作风格的独特艺术画作形式,通过“无人之境”表达画中逸景之美,将艺术创作者的现实世界与内心体验完美融入到艺术画作中。本文旨在从城市景观、文人风骨、涅繁修炼、师法自然四个角度去系统分析赵龙艺术创作从写实到写意的历程变化,探究赵龙“无人风景画”中所体现的人文精神和自然主义,浅析赵龙“无人风景画”中的情感表达和精神追求,了解以赵龙为代表的当代画家的艺术创作思想脉络。

关键词：自然风景画文人精神艺术创作

基于BP神经网络的输电线路电场屏蔽效果预测

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传感器与微系统 2022年第2期41卷 108-110,114页

作者：于利佳田瑾吴飞龚利上海工程技术大学电子电气工程学院上海201620 华东师范大学城市与区域科学学院上海200062

针对超高压(EHV)同塔双回交流(AC)输电线路下方工频电场,首先基于有限元法建立输电线路模型,通过架设屏蔽线研究屏蔽线数量、位置的变化与屏蔽效果之间关系,计算得到部分屏蔽线位置电场强度值作为训练值,对于未知位置对应的屏蔽效果,提... 详细信息

针对超高压(EHV)同塔双回交流(AC)输电线路下方工频电场,首先基于有限元法建立输电线路模型,通过架设屏蔽线研究屏蔽线数量、位置的变化与屏蔽效果之间关系,计算得到部分屏蔽线位置电场强度值作为训练值,对于未知位置对应的屏蔽效果,提出采用反向传播(BP)神经网络进行预测。结果表明:预测值与真实值之间最大误差仅为0.6%,具有良好的预测效果,可为交流超高压输电线路电场环境优化及建设提供参考依据。

关键词：输电线路有限元法屏蔽线反向传播神经网络