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Dual-responsive nanovaccine for cytosolic delivery of antigens to boost cellular immune responses and cancer immunotherapy

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Asian Journal of Pharmaceutical Sciences 2022年第4期17卷 583-595页

作者： Yang Sui Ji Li Jiqiang Qu Ting Fang Hongyan Zhang Jian Zhang Zheran Wang mingyu xia Yinghui Dai Dongkai Wang Department of Pharmaceutics Shenyang Pharmaceutical UniversityShenyang 110016China Department of Traditional Chinese Medicine Shenyang Pharmaceutical UniversityShenyang 110016China Department of Mathematics and Statistics Auburn UniversityAuburnAL 36849USA School of Life Science and Biopharmaceutics Shenyang Pharmaceutical UniversityShenyang 110016China School of Pharmacy China Medical UniversityShenyang 110122China School of Pharmaceutical Sciences Zhejiang Chinese Medical UniversityHangzhou 310053China

Cancer vaccine contributing to the success of the treatment and prevention of tumors has attracted a huge attention as a strategy for tumor immunotherapy in recent years.A major challenge of cancer vaccine is to target cytosols of dendritic cells(DCs)in the lymph nodes(LNs)to enhance efficiency of antigen cross-presentation,which elicits high levels of cytotoxic T-lymphocytes to destruct tumor ***,we address this issue by conjugating ovalbumin(OVA)to PEG-PCL using disulfide bond(-ss-),and the degradable pH-responsive polymer-PEI-PCL as delivery *** addition,the mol ratio of PEG-PCL to PEI-PCL in the mixed micelles was tailored to deliver the OVA to ***,CpG ODN_(1826),a TLR-9 agonist,was further introduced into a mixed micelle of 30nm or less as a unique tumor ***,the results demonstrated the mixed micelles with 1:1mol of PCL-PEG and PCL-PEI can effectively migrate to distal LNs where antigen were efficiently captured by DCs,meanwhile,OVA was modified to the surface of mixed micelles via disulfide bonds(-ss-)for promotion efficiency of antigen *** surprisingly,combination of tumor vaccine with anti-PD-1,the therapy of ectopic melanoma(B16-OVA)and lung metastasis melanoma(B16-OVA)is excellent therapeutic *** together,our works offers a novel strategy for the cytosol delivery of antigens to achieve potent cancer immunotherapy.

关键词： Reducible Nanoparticles Vaccine Cross-presentation Immunotherapy Immune checkpoint blockade

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双城映像:宋元话本小说的空间书写

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明清小说研究 2020年第1期 192-203页

作者：夏明宇上海大学图书馆

宋元话本小说的叙事空间聚焦于两宋故都东京与杭州,透过神圣与凡俗两个维度的物象勾勒,再现了"双城"的世俗图景。宋元话本小说的双城空间书写,着重建构了双城"外部"漂泊不居的江湖空间,以及双城"内部"隔而不断的情色空间,细致入微地呈... 详细信息

宋元话本小说的叙事空间聚焦于两宋故都东京与杭州,透过神圣与凡俗两个维度的物象勾勒,再现了"双城"的世俗图景。宋元话本小说的双城空间书写,着重建构了双城"外部"漂泊不居的江湖空间,以及双城"内部"隔而不断的情色空间,细致入微地呈现出两宋都城的环境、风俗与普通市民的心灵生活;内涵着深厚的历史文化意蕴,开拓了白话小说的叙事技巧,对后代章回小说的空间建构影响深远。

关键词：宋元话本小说双城东京杭州空间

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细读、粗读与远读:从传统阅读到数字人文的范式演变

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图书与情报 2024年第1期 48-56页

作者：夏明宇上海大学图书馆上海200444

阅读是人类获取知识文化与接续文明的重要手段。技术、物质、思想等的瞬息万变,使得阅读主体、阅读载体及阅读媒介也发生变革,由此而引发了阅读方法的范式演变。在传统纸媒阅读时代,崇尚逐字逐句的“细读”,同时辅以概览式的“粗读”。... 详细信息

阅读是人类获取知识文化与接续文明的重要手段。技术、物质、思想等的瞬息万变,使得阅读主体、阅读载体及阅读媒介也发生变革,由此而引发了阅读方法的范式演变。在传统纸媒阅读时代,崇尚逐字逐句的“细读”,同时辅以概览式的“粗读”。但在屏幕阅读时代,随着计算技术的突飞猛进,开展大数据阅读的“远读”方法,不知不觉地影响了大众的阅读生活。文章拟就细读、粗读与远读的关系与内涵进行梳理与探讨,试图揭示阅读范式生成与演变的内在逻辑,以及如何在数字人文语境下理性应对阅读方法的时代变革。

关键词：细读粗读远读数字人文范式

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《西湖二集》的空间、结构与记忆

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明清小说研究 2022年第1期 226-241页

作者：夏明宇上海大学图书馆

《西湖二集》是一部以西湖地理空间命名的白话短篇小说集。小说集以“西湖-江南”地理空间为叙事的立足点,建构了以西湖为圆心、江南为辐射圈层的“同心圆”空间结构,同时运用时间附丽于空间的时空结构艺术,将“南宋-晚明”的时间伏线... 详细信息

《西湖二集》是一部以西湖地理空间命名的白话短篇小说集。小说集以“西湖-江南”地理空间为叙事的立足点,建构了以西湖为圆心、江南为辐射圈层的“同心圆”空间结构,同时运用时间附丽于空间的时空结构艺术,将“南宋-晚明”的时间伏线布设于同心圆空间结构之下,敷演南宋与明代等诸朝故事。《西湖二集》的时空结构与明代“以宋喻明”的社会心理“框架”暗相契合,体现了小说家关怀时局的叙事旨意,映射出晚明文人的集体记忆与家国情怀。

关键词：《西湖二集》空间结构记忆隐喻

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Synthesis of selective PAK4 inhibitors for lung metastasis of lung cancer and melanoma cells

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Acta Pharmaceutica Sinica B 2022年第6期12卷 2905-2922页

作者： Peilu Song Fan Zhao Dahong Li Jiqiang Qu Miao Yao Yuan Su Hanxun Wang Miaomiao Zhou Yujie Wang Yinli Gao Feng Li Dongmei Zhao Fengjiao Zhang Yu Rao mingyu xia Haitao Li Jian Wang Maosheng Cheng Key Laboratory of Structure-Based Drug Design&Discovery of Ministry of Education Shenyang Pharmaceutical UniversityShenyang 110016China MOE Key Laboratory of Protein Sciences School of Pharmaceutical SciencesMOE Key Laboratory of Bioorganic Phosphorus Chemistry Chemical BiologyTsinghua UniversityBeijing 100084China MOE Key Laboratory of Protein Sciences Beijing Advanced Innovation Center for Structural BiologyTsinghua-Peking Joint Center for Life SciencesSchool of Life Sciences and School of MedicineTsinghua UniversityBeijing 100084China School of Traditional Chinese Materia Medica Shenyang Pharmaceutical UniversityShenyang 110016China School of Life Science and Biopharmaceutics Shenyang Pharmaceutical UniversityShengyang 110016China Wuya College of Innovation Shenyang Pharmaceutical UniversityShenyang 110016China Department of Cell Biology Key Laboratory of Cell BiologyMinistry of Public Healthand Key Laboratory of Medical Cell BiologyMinistry of EducationChina Medical UniversityShenyang 110001China

The p21 activated kinase 4(PAK4) is serine/threonine protein kinase that is critical for cancer *** by X-ray crystallography and structure-based optimization,we report a novel subseries of C-3-substituted 6-ethynyl-1 H-indole derivatives that display high potential and specificity towards group Ⅱ *** these inhibitors,compound 55 exhibited excellent inhibitory activity and kinase selectivity,displayed superior anti-migratory and anti-invasive properties against the lung cancer cell line A549 and the melanoma cell line *** 55 exhibited potent in vivo antitumor metastatic efficacy,with over 80% and 90% inhibition of lung metastasis in A549 or B16-BL6 lung metastasis models,*** mechanistic studies demonstrated that compound 55 mitigated TGF-β1-induced epithelial-mesenchymal transition(EMT).

关键词： Anti-cancer PAK4 inhibitor Kinase selectivity Cocrystallization Lung metastasis EMT

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诗词吟诵与阅读推广——以上海大学图书馆诗词吟诵展演活动为例

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图书馆杂志 2018年第3期37卷 70-74页

作者：夏明宇上海大学图书馆

在文化强国战略与全民阅读的语境下,如何让阅读推广活动更好地担负起传承发展传统文化的使命,是对高校图书馆的一个挑战。本文介绍了上海大学图书馆阅读推广的成功案例"古韵新声——上海大学第一届古典诗词吟诵大会"活动,详细阐述了活... 详细信息

在文化强国战略与全民阅读的语境下,如何让阅读推广活动更好地担负起传承发展传统文化的使命,是对高校图书馆的一个挑战。本文介绍了上海大学图书馆阅读推广的成功案例"古韵新声——上海大学第一届古典诗词吟诵大会"活动,详细阐述了活动策划的主旨、目标、实施方式等,并总结了诗词吟诵阅读推广活动的绩效与启示。

关键词：高校图书馆诗词吟诵阅读推广传统文化

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Genomic Selection for Frogeye Leaf Spot Resistance in Soybean

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Journal of Northeast Agricultural University(English Edition) 2024年第1期31卷 11-19页

作者： Yao Lanning Chen Yizhi Li Haochen Zhang Yue xia mingyu Ning Shicheng Ning Hailong College of Arts and Sciences Northeast Agricultural UniversityHarbin 150030China College of Life Sciences Northeast Agricultural UniversityHarbin 150030China College of Economics and Management Northeast Agricultural UniversityHarbin 150030China College of Veterinary Medicine Northeast Agricultural UniversityHarbin 150030China Key Laboratory of Soybean Biology Ministry of EducationKey Laboratory of Soybean Biology and Breeding/GeneticsMinistry of AgricultureCollege of AgricultureNortheast Agricultural UniversityHarbin 150030China Zhongnongfa Wudalianchi Agricultural Technology Co. LtdWudalianchi 164100HeilongjiangChina

Soybean frogeye leaf spot(FLS) disease is a global disease affecting soybean yield, especially in the soybean growing area of Heilongjiang Province. In order to realize genomic selection breeding for FLS resistance of soybean, least absolute shrinkage and selection operator(LASSO) regression and stepwise regression were combined, and a genomic selection model was established for 40 002 SNP markers covering soybean genome and relative lesion area of soybean FLS. As a result, 68 molecular markers controlling soybean FLS were detected accurately, and the phenotypic contribution rate of these markers reached 82.45%. In this study, a model was established, which could be used directly to evaluate the resistance of soybean FLS and to select excellent offspring. This research method could also provide ideas and methods for other plants to breeding in disease resistance.

关键词： LASSO regression stepwise regression genomic selection model soybean frogeye leaf spot(FLS)disease

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Two New Indole Alkaloids from Toad Venom of Bufo bufo gargarizans

Two New Indole Alkaloids from Toad Venom of Bufo bufo gargar...

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中国化学会第十二届全国天然有机化学学术会议

作者： Yulin Chen Yinghui Dai mingyu xia Dongchun Liu Dong Wang School of Traditional Chinese Materia Medica Shenyang Pharmaceutical University School of Life Science and Biopharmaceutics Shenyang Pharmaceutical University

Toad venom(ChanSu in Chinese) is secreted by the skin or ear glands of giant toads,such as Bufo bufo gargarizans or *** was used as traditional Chinese medicine to treat tumor,carbuncle,scrofula and heart failures for a long *** order to investigate the water-soluble bioactive components in toad venom,two new indole alkaloids,Bufotenidine B(2)and Bufocarboline A(6),one new natural product 2-(5-hydroxy-1 H-indol-3-yl) ethyl) glycine,named N-carboxymethyl serotoin(5) along with seven known indole alkaloids(1,3-5,7-9) and three organic acids(10-12) were isolated from the water extract of toad *** compounds were elucidated on the basis of their 1 D,2 D NMR spectra and mass spectrometric *** structures were determined as bufotenine O-sulphate(1),dehydrobufothionine(3),6-hydroxy-1-methyltetrahydro-β-carboline-1-carboxylic acid(4),bufobutarginine(7),6-Hydroxy-2,3,4,9-tetrahydro-1 H-β-carboline-1-carboxylic acid(8),6-Hydroxy-1-oxo-3,4-dihydro-β-carboline(9),Pimelic acid(10),Suberic acid(11),and Azelaic acid(12).The absolute configuration of 4,6 and 8 was determined for the first time by electronic circular dichroism(ECD) *** cytotoxic activity of all compounds was tested against human malignant melanoma cells A375 by the MTT method,and no antitumor activity was observed.

关键词： Toad venom Bufotenidine B Bufocarboline A indole alkaloid cytotoxic activity

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Cloning,prokaryotic expression and function of the Bufo bufo gargarizans 3β-hydroxysteroid dehydrogenase(3βHSD) gene

Cloning,prokaryotic expression and function of the Bufo bufo...

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中国化学会第十二届全国天然有机化学学术会议

作者： Di Xu mingyu xia Dongchun Liu Yinghui Dai Bin Wu Dong Wang School of Traditional Chinese Materia Medica Shenyang Pharmaceutical University School of Life Science and Biopharmaceutics Shenyang Pharmaceutical University Shanghai Center for Drug Evaluation and Inspection

Bufadienolides,as the major active component in Bufonis venenum,has a significant physiological *** is the precursor in the biosynthesis of bufadienolides and3β-Hydroxysteroid dehydrogenase(3βHSD) might be an important enzyme,which catalyzes the conversion of cholesterol to 4-cholesten-3-one,to take part in the biosynthesis pathway of *** this study,Bbg-3βHSD cDNA was cloned from the ear-side gland of Bufo bufo gargarizans and was introduced into *** BL21 for prokaryotic ***-3βHSD has an open reading frame(ORF) of 1134 bp and encodes 377 amino acid *** speculated protein molecular weight is 42.8 kDa and its theoretical isoelectric point is *** acid sequence homologous analysis showed that Bbg-3βHSD was highly homologous to the 3βHSD protein of other *** tree showed the highest similarity between Bbg-3βHSD and3βHSD from Rana *** optimized express in conditions of recombinant Bbg-3βHSD are0.1 mmol·L IPTG at 15℃ for 20 *** activity in vitro shows that pregnenolone and dehydroepianaroesterone could be 3β-oxidized by Bbg-3βHSD when NAD was used as the *** properties showed that the optimum reaction temperature of recombinant Bbg-3βHSD was 40℃,the optimum pH was 8.5,and the optimum coenzyme concentration was1.5 mmol·L.

关键词： Bufo bufo gargarizans 3β-hydroxysteroid dehydrogenase prokaryotic expression enzyme activity

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浅水淘沙渐渐深——《重庆文理学院学报》创办三十年的回顾与思考

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重庆文理学院学报（社会科学版） 2013年第2期32卷 1-7页

作者：夏明宇重庆文理学院文化与传媒学院重庆永川402160

我校学报创办至今的三十年历程,是一个犹如浅水淘沙般在探索中渐渐深化的过程。理清我校学报创办三十年来的发展脉络,总结出一些可以称作"经验"和"感悟"的东西,是一件极有意义的事。

关键词：重庆文理学院学报三十年

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