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Spatio-temporal delivery of both intra-and extracellular toll-like receptor agonists for enhancing antigen-specific immune responses

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Acta Pharmaceutica Sinica B 2022年第12期12卷 4486-4500页

作者： nannan Wang Yueyue Zuo Shengjie Wu Chenlu huang Linhua Zhang Dunwan Zhu Tianjin Key Laboratory of Biomedical Materials Key Laboratory of Biomaterials and Nanotechnology for Cancer ImmunotherapyInstitute of Biomedical EngineeringChinese Academy of Medical Sciences&Peking Union Medical CollegeTianjin 300192China

For cancer immunotherapy,triggering toll-like receptors(TLRs)in dendritic cells(DCs)can potentiate antigen-based immune responses.Nevertheless,to generate robust and long-lived immune responses,a well-designed nanovaccine should consider different locations of TLRs on DCs and co-deliver both antigens and TLR agonist combinations to synergistically induce optimal antitumor immunity.Herein,we fabricated lipid-polymer hybrid nanoparticles(LPNPs)to spatio-temporally deliver model antigen ovalbumin(OVA)on the surface of the lipid layer,TLR4 agonist monophosphoryl lipid A(MPLA)within the lipid layer,and TLR7 agonist imiquimod(IMQ)in the polymer core to synergistically activate DCs by both extra-and intra-cellular TLRs for enhancing adaptive immune responses.LPNPs-based nanovaccines exhibited a narrow size distribution at the mean diameter of 133.23 nm and zeta potential of−2.36 mV,showed a high OVA loading(around 70.83μg/mg)and IMQ encapsulation efficiency(88.04%).Our data revealed that LPNPs-based nanovaccines showed great biocompatibility to immune cells and an excellent ability to enhance antigen internalization,thereby promoting DCs maturation and cytokines production.Compared to Free OVA,OVA-LPNPs promoted antigen uptake,lysosome escape,depot effect and migration to secondary lymphatic organs.In vivo immunization showed that IMQ-MPLA-OVA-LPNPs with dual agonists induced more powerful cellular and humoral immune responses.Moreover,prophylactic vaccination by IMQ-MPLA-OVA-LPNPs effectively suppressed tumor growth and increased survival efficacy.Hence,the nanovaccines we fabricated can effectively co-deliver antigens and different TLR agonists and realize coordinated stimulation of DCs in a spatio-temporal manner for enhanced immune responses,which provides a promising strategy for cancer immunotherapy.

关键词： Lipid-polymer hybrid nanoparticles TLR agonist combinations Ovalbumin Monophosphoryl lipid AImiquimod Nanovaccine Spatio-temporal manner Cancer immunotherapy

Sanguinarine suppresses cell proliferation, migration and invasion in nasopharyngeal carcinoma via inhibiting mTOR signaling

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Journal of Traditional Chinese Medicine 2022年第5期42卷 687-692页

作者： YANG Mengzhe ZHANG Beibei LIANG Zhenqiang CHENG nannan LüAnqiao YANG Jianyu GUO Xingzhe BAI Xianyu huang Yuanjiao JIAO Aijun XU Ning School of Basic Medical Sciences Guangxi Medical UniversityNanning 530021China Institute of Biomedical Research Yunnan UniversityKunming 650500China Department of Otolaryngology-Head and Neck Surgery the Affiliated Tumor Hospital of Guangxi Medical UniversityNanning 530021China Life Science Institute Guangxi Medical UniversityNanning 530021China Pharmaceutical College Guangxi Medical UniversityNanning 530021China Department of Neurology the Fifth Affiliated Hospital of Guangxi Medical UniversityNanning 530021China

OBJECTIVE: To confirm the anti-NPC effect of sanguinarine(SA) through a series of wet experiments.METHODS: NPC cell viability was determined by proliferation experiment. Cell clone formation experiment, cell scratch test, transwell migration and invasion experiment and flow cytometry-based cell apoptosis assay were further performed. In addition, Western blotting was performed to investigate the cell signaling pathway. All the relevant experimental data were statistically processed using SPSS 16.0 software.RESULTS: The results showed that sanguinarine represented a time and dose dependent inhibition effects on NPC cell proliferation including the low differentiated CNE2 cells and high metastatic 5-8F cells, along with the cell cloning ability reduction. In addition, sanguinarine has a certain inhibitory effect on the invasion and migration of NPC cells. Mechanistically, sanguinarine displayed the anti-NPC effects mainly involved into the suppression of m TOR signaling and cell apoptosis, which is closely associated with the tumor growth and metastatic malignancy. CONCLUSIONS: Collectively, we discover that sanguinarine is a new high-efficiency anti-NPC monomer of Chinese medicine, with a value for the follow-up preclinical research.

关键词： nasopharyngeal carcinoma sanguinarine TOR serine-threonine kinases apoptosis

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长白山人参包装的五感体验设计研究

工业设计 2023年第3期 79-81页

作者：黄南南吉林化工学院机电工程学院吉林吉林132022

调研分析鲜人参、保鲜参、干人参三种人参的常见包装形式;归纳礼品包装、等级包装等六种人参包装的设计策略,以五感体验的内涵为理论依据,秉持视觉主导及多感官综合体验的原则,深入探讨长白山人参包装的五感体验设计思路。通过研究发现... 详细信息

调研分析鲜人参、保鲜参、干人参三种人参的常见包装形式;归纳礼品包装、等级包装等六种人参包装的设计策略,以五感体验的内涵为理论依据,秉持视觉主导及多感官综合体验的原则,深入探讨长白山人参包装的五感体验设计思路。通过研究发现人参包装的五感体验设计可以让消费者切实感受长白山人参的野、奇、香、鲜、趣之美,激发消费者购买欲望,引导互动美妙的人参使用过程,推进长白山人参文化的传承与发展。

关键词：长白山人参包装五感体验设计

Activation of the wnt/β-catenin/CYP1B1 pathway alleviates oxidative stress and protects the blood-brain barrier under cerebral ischemia/reperfusion conditions

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Neural Regeneration Research 2024年第7期19卷 1541-1547页

作者： Xingyong Chen nannan Yao Yanguang Mao Dongyun Xiao Yiyi huang Xu Zhang Yinzhou Wang Department of Neurology Fujian Provincial HospitalShengli Clinical Medical College of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology Cangzhou Central HospitalCangzhouHebei ProvinceChina Fujian Academy of Medical Science FuzhouFujian ProvinceChina Key Testing Laboratory of Fujian Province FuzhouFujian ProvinceChina

Accumulating evidence suggests that oxidative stress and the Wnt/β-catenin pathway participate in stroke-induced disruption of the blood-brain barrier.However,the potential links between them following ischemic stroke remain largely unknown.The present study found that cerebral ischemia leads to oxidative stress and repression of the Wnt/β-catenin pathway.Meanwhile,Wnt/β-catenin pathway activation by the pharmacological inhibito r,TWS119,relieved oxidative stress,increased the levels of cytochrome P4501B1(CYP1B1)and tight junction-associated proteins(zonula occludens-1[ZO-1],occludin and claudin-5),as well as brain microvascular density in cerebral ischemia rats.Moreove r,rat brain microvascular endothelial cells that underwent oxygen glucose deprivation/reoxygenation displayed intense oxidative stress,suppression of the Wnt/β-catenin pathway,aggravated cell apoptosis,downregulated CYP1B1and tight junction protein levels,and inhibited cell prolife ration and migration.Overexpression ofβ-catenin or knockdown ofβ-catenin and CYP1B1 genes in rat brain mic rovascular endothelial cells at least partly ameliorated or exacerbated these effects,respectively.In addition,small interfering RNA-mediatedβ-catenin silencing decreased CYP1B1 expression,whereas CYP1B1 knoc kdown did not change the levels of glycogen synthase kinase 3β,Wnt-3a,andβ-catenin proteins in rat brain microvascular endothelial cells after oxygen glucose deprivatio n/reoxygenation.Thus,the data suggest that CYP1B1 can be regulated by Wnt/β-catenin signaling,and activation of the Wnt/β-catenin/CYP1B1 pathway contributes to alleviation of oxidative stress,increased tight junction levels,and protection of the blood-brain barrier against ischemia/hypoxia-induced injury.

关键词： blood-brain barrier CYP1B1 oxidative stress oxygen glucose deprivation/reoxygenation tight junction vascular endothelial cells Wnt/β-catenin pathway β-catenin

生态系统服务价值评价中的效益转移:进展与挑战

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中国人口·资源与环境 2022年第3期32卷 159-168页

作者：亢楠楠黄季焜北京大学现代农学院中国农业政策研究中心北京100871

正确评价生态系统服务中蕴含的经济价值是促进生态产品价值实现的重要保障。“难识别、难度量”导致的生态系统服务价值数据匮乏,仍是政策制定者面临的一个现实难题。效益转移法利用二手数据,将已有研究融入待评估的地点当中来,避免了... 详细信息

正确评价生态系统服务中蕴含的经济价值是促进生态产品价值实现的重要保障。“难识别、难度量”导致的生态系统服务价值数据匮乏,仍是政策制定者面临的一个现实难题。效益转移法利用二手数据,将已有研究融入待评估的地点当中来,避免了初始评价研究中数据获取时间长、成本高的难题,在生态系统服务价值评价领域备受青睐。资金、时间预算有限的条件下,能够帮助管理者迅速解决生态系统服务价值数据的缺口,是这种评价技术的核心优势。鉴于该方法在实践应用中的广阔前景,对其评价结果有效性和可靠性的关注也比其他方法更为迫切。但其理论背景决定了不可避免地会带来一系列估值偏差。因此,围绕近年来国内外学者在该领域的研究现状,文章首先梳理了三种常见的效益转移形式,进一步总结了对转移效度进行检验的方法;然后,重点厘清了该方法面临的挑战,探讨了研究文献中减小效益转移偏差的最新共识。可概括为:①初始研究的选择,应该考虑与研究地点的匹配性,降低“跨环境”的泛化误差。②谨慎辨别生态系统服务特征,避免中间服务和最终服务的重复性计算。③加入地理信息变量,评估生态系统服务价值的空间格局变化。④模型中保留时间维度,检验生态系统服务价值的时间稳定性。此外,高效的效益转移还离不开足够数量且优质的初始研究。因此,作者最后从操作规范、初始研究数据库的支持两个视角,建议中国跨学科的专家们应该联合制定一套指导方针,用以提高生态系统服务价值评价中的效益转移效率。

关键词：效益转移生态系统服务价值评价

DNA hybridization chain reaction and DNA supersandwich self-assembly for ultrasensitive detection

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Science China Chemistry 2017年第3期60卷 311-318页

作者： nannan Liu Fujian huang Xiaoding Lou Fan Xia Key Laboratory of Carbon Materials of Zhejiang Province College of Chemistry & Materials EngineeringWenzhou UniversityWenzhou 325027China Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica School of Chemistry and Chemical EngineeringHuazhong University of Science and Technology CAS Key Laboratory of Soft Matter Chemistry Department of Polymer Science and EngineeringUniversity of Science and Technology of China

The fabrication of sensitive sensors with high selectivity is highly desirable for the detection of some important biomarkers,such as nucleic acids,proteins,small molecules and ions.DNA hybridization chain reaction(HCR) and DNA supersandwich self-assembly(SSA) are two prevalent enzyme-free signal amplification strategies to improve sensitivity of the sensors.In this review,we firstly describe the characteristics about DNA HCR and DNA SSA,and then summarize the advances in the one-dimensional DNA nanostructures assisted by HCR and SSA.This review has been divided into three parts according to the two signal amplification methods and highlights recent progress in these two strategies to improve the detection sensitivity of proteins,nucleic acids,small molecules and ions.

关键词： signal amplification method hybridization chain reaction supersandwich self-assembly ultrasensitive detection

平台企业政府事务部门专门化与政企关系发展--基于国家制度环境的分析

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社会学研究 2022年第6期37卷 59-80,227页

作者：黄冬娅杜楠楠中山大学中国公共管理研究中心中山大学政治与公共事务管理学院

平台企业崛起是否意味着政企关系新发展?与传统民营企业个人化和地方化的政企关系不同,平台企业政府事务部门专门化成为普遍现象。本文揭示了国家制度环境影响企业内部组织的双重逻辑,即国家监管制度形塑下平台企业商业模式的需要,以及... 详细信息

平台企业崛起是否意味着政企关系新发展?与传统民营企业个人化和地方化的政企关系不同,平台企业政府事务部门专门化成为普遍现象。本文揭示了国家制度环境影响企业内部组织的双重逻辑,即国家监管制度形塑下平台企业商业模式的需要,以及国家监管力度强化下企业内外部组织资源的争夺。中国平台经济的成长展现了与传统民营经济部门不同的政治经济结构,国家权力与资本力量正式遭遇,将政企关系放在了全国性舞台。

关键词：平台企业组织社会学平台监管政商关系

Taxonomic status of Chinese blue sheep(Pseudois nayaur):new evidence of a distinct subspecies

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Integrative Zoology 2020年第3期15卷 202-212页

作者： Hui GAO nannan LI Yongjie huang Fujie QIAO Junle LI Zongzhi LI Yanxiang LI Zhenghuan WANG Liwei TENG Zhensheng LIU College of Wildlife and Protected Area Northeast Forestry UniversityHarbinChina Forestry Science and Technology Research Institute of Greater Hinggan in Inner Mongolia YakeshiChina School of Ecology and Nature Conservation Beijing Forestry UniversityBeijingChina School of Life Sciences Lvliang UniviersityLvliangChina School of Life Sciences East China Normal UniversityShanghaiChina Key Laboratory of Conservation Biology National Forestry and Grassland AdministrationHarbinChina

The blue sheep is an endemic species to the Qinghai-Tibet Plateau and surrounding regions.It has been regarded as having 2 subspecies:Pseudois nayaur nayaur and P.n.szechuanensis.However,such a classification remains controversial.Herein,we analyze 10 microsatellite loci and part of the mitochondrial control region for clarification in such taxonomic debates.We use samples from 168 individuals from 6 geographic populations covering almost all the distribution areas of the species in China to carry out comparisons.Phylogenetic trees derived from both the microsatellite and mitochondrial markers combined with the discriminant analysis of principal components(DAPC)and the STRUCTURE analysis reveal that the individuals in the Helan Mountains are well grouped with a distinct evolutionary lineage and are significantly different from the other populations of P.n.szechuanensis according to Fst values,implying that this isolated population should be categorized as a valid subspecies;namely,Pseudois nayaur alashanicus.The isolation-by-distance(IBD)analysis shows a significant positive relationship between genetic and geographical distances among the populations.

关键词： blue sheep isolation by distance microsatellite mtDNA control region taxonomy

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光固化技术制备聚氨酯人造大理石研究

陶瓷学报 2013年第4期34卷 425-429页

作者：黄南南吉林化工学院吉林吉林132022

开发了一种新型的聚氨酯丙烯酸酯类人造大理石制备方法,聚酯中不含有石英砂等无机类填料,仅混以炭黑和白炭黑,同时作为填料和颜料;采用UV光固化工艺,将传统的成型过程及表面处理环节整合为一步法,极大的简化了生产工艺。聚氨酯丙烯酸酯... 详细信息

开发了一种新型的聚氨酯丙烯酸酯类人造大理石制备方法,聚酯中不含有石英砂等无机类填料,仅混以炭黑和白炭黑,同时作为填料和颜料;采用UV光固化工艺,将传统的成型过程及表面处理环节整合为一步法,极大的简化了生产工艺。聚氨酯丙烯酸酯本身具有较高的耐擦伤性能和强度,以及优越的光学性能和耐候性能,掺混的炭黑和白炭黑结构粒子在增加涂层强度和抗冲击性能方面起到了显著的作用。采用炭黑和白炭黑作为基本色,通过调配比例来调配所需的灰度时,涂层的基本性能并不会受比例变化而发生较大的影响。涂膜平整、光滑、饱满,耐干热性优良,具有良好的耐化学腐蚀性和耐污染性。

关键词：紫外光固化人造大理石聚氨酯丙烯酸酯炭黑