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Natural long-chain saturated fatty acids doped LNPs enabling spleen selective mRNA translation and potent cancer immunotherapy

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Nano Research 2024年第3期17卷 1804-1817页

作者： fazhan wang Meng Zhang Meiling Tian Jia Lou Longze Pan Xiaoke Gao Lijing Zhang Xiaohan Lou Linyu Zhu Yuqiao Sheng Ming wang Rui Xue Wenjing Deng Shuai Shao Zhihai Qin Medical Research Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Translational Medical Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Department of Neuro-Intensive Care Unit The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Academy of Medical Sciences Zhengzhou UniversityZhengzhou 450052China

Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA *** expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA *** by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered *** the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA *** mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in *** with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma *** natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.

关键词： mRNA vaccine lipid nanoparticles spleen long-chain saturated fatty acid cancer immunotherapy

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改善大学生学业拖延劝导设计研究

设计 2024年第12期37卷 100-103页

作者：敖游林王发展西安建筑科技大学艺术学院

从劝导设计的角度研究大学生学业拖延行为改善的方法,帮助他们养成良好的学习习惯行为,并为拖延问题的研究提供更广泛的思路。运用问卷调查及数据分析法调查大学生学业拖延的现状及后果,得出导致学业拖延的拖延因子。接着通过分析Fogg... 详细信息

从劝导设计的角度研究大学生学业拖延行为改善的方法,帮助他们养成良好的学习习惯行为,并为拖延问题的研究提供更广泛的思路。运用问卷调查及数据分析法调查大学生学业拖延的现状及后果,得出导致学业拖延的拖延因子。接着通过分析Fogg行为表格下用户学习行为及Hooked模型行为四机制,运用案例分析法分析21种案例,得出203条劝导措施,再将劝导措施归纳总结,提炼出劝导设计要素。提出改善大学生学业拖延的习惯行为养成的劝导设计模型。文章为劝导设计在改善学业拖延行为的应用上提供了新的思路和方法,提出的劝导设计模型也可用于其他拖延行为及领域。

关键词：学业拖延大学生劝导设计行为引导习惯行为养成

Research on knowledge acquisition method about the IF/THEN rules based on rough set theory

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Journal of Systems Engineering and Electronics 2008年第3期19卷 628-634,F0003页

作者： Liu Daohua Yuan Sicong Zhang Xiaolong wang fazhan School of Mechanical & Electronic Engineering Xi'an Univ. of Architecture & Technology Xi'an 710055 P. R. China Dept. of Computer Science Xinyang Normal Univ. Xinyang 464000 P. R. China

The basic principles of IF/THEN rules in rough set theory are analyzed first, and then the automatic process of knowledge acquisition is given. The numerical data is qualitatively processed by the classification of membership functions and membership degrees to get the normative decision table. The regular method of relations and the reduction algorithm of attributes are studied. The reduced relations are presented by the multi-representvalue method and its algorithm is offered. The whole knowledge acquisition process has high degree of automation and the extracted knowledge is true and reliable.

关键词： rough set theory knowledge's automatic gain IF/THEN rule attribute reduction multi-dimensionalrepresentative value.

Semi-elastic core-shell nanoparticles enhanced the oral bioavailability of peptide drugs

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Chinese Chemical Letters 2020年第5期31卷 1147-1152页

作者： Shengnan Zhao Jinhua Li fazhan wang Ting Yu Yang Zhou Lili He Yi Zhang jian Yang School of Applied Chemistry and Biological Technology Shenzhen PolytechnicShenzhen 518055China Department of Pancreatic Surgery West China HospitalSichuan University.Chengdu 610041China College of Pharmacy Southwest Minzu UniversityChengdu 610041China

The rigidity of nanoparticles was newly reported to influence their oral ***-elastic nanoparticles can enhance the penetration in mucus and uptake by epithelial ***,it is still challenging and unclear that the semi-elastic core-shell nanoparticles can enhance the oral bioavailability of peptide *** study was for the first time to validate the semi-elastic coreshell poly(lactic-co-glycolic acid)(PLGA)-lipid nanoparticles(LNPs)as the carrier of the oral peptide *** antihypertensive peptide Val-Leu-Pro-Val-Pro(VP5)loaded LNPs(VP5-LNPs)were prepared by a modified thin-film ultrasonic dispersion *** experiment was performed in Caco-2 and HT-29 cells and monito red by high content screening(HCS)and flow cyto metric(FCM).Pharmacokinetics of VP5-LNPs was carried out in Sprague-Dawley(SD)rats and analyzed by DAS *** optimal VP5-LNPs had an average particle size of 247.3±3.8 nm,zeta potential of-6.57±0.45 mV and excellent entrapment efficiency(EE)of 89.88%±1.23%.Transmission electron microscope(TEM)and Differential scanning calorimeter(DSC)further confirmed the core-shell ***5-LNPs could increase the cellular uptake in vitro and have a 2.55-fold increase in AUC0-72 h,indicating a great promotion of the o ral *** semi-elastic LNPs remarkably improved the oral availability of peptide and could be a promising oral peptide delivery system for peptide drugs in the future.

关键词： Semi-elastic nanoparticles Oral bioavailability Lipid nanoparticles Antihypertensive peptide Pharmacokinetics

Core-shell lipid-polymer nanoparticles as a promising ocular drug delivery system to treat glaucoma

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Chinese Chemical Letters 2020年第2期31卷 494-500页

作者： Yang Zhou Aiping Fang fazhan wang Huili Li Quansheng Jin Lingjing Huang Chunmei Fu Jun Zeng Zhaohui Jin Xiangrong Song State Key Laboratory of Biotherapy and Cancer Center/Department of Pharmacy West China Hospitaland Collaborative Innovation Center for BiotherapySichuan UniversityChengdu 610041China West China School of Pharmacy Sichuan UniversityChengdu 610041China

Nowadays,tremendous researches have been focused on the core-shell lipid-polymer nanoparticles(LPNs) due to the advantages of both liposomes and polymer *** this work,LPNs were applied to encapsulate brinzolamide(Brz-LPNs) for achieving sustained drug release,improving drug corneal permeation and enhancing drug topical therapeutic *** structure of Brz-LPNs was composed of poly(lactic-co-glycolic) acid(PLGA) nanocore which encapsulated Brz(Brz-NPs) and lipid shell around the ***-LPNs were prepared by a modified thin-film dispersion *** the parameters optimization of Brz-LPNs,optimal Brz-LPNs showed an average particle size of151.23±1.64 nm with a high encapsulation efficiency(EE) of 86.7%±2.28%.The core-shell structure of Brz-LPNs were confirmed by transmission electronic microscopy(TEM).Fourier transformed infrared spectra(FTIR) analysis proved that Brz was successfully entrapped into ***-LPNs exhibited obvious sustained release of Brz,compared with AZOPT^■ and ***,the corneal accumulative permeability of Brz-LPNs significantly increased compared to the commercial available formulation(AZOPT^■) in ***,Brz-LPNs(1 mg/mL Brz) showed a more sustained and effective intraocular pressure(IOP) reduction than Brz-LPs(1 mg/mL) and AZOPT^■(10 mg/mL Brz) in *** conclusion,Brz-LPNs,as promising ocular drug delivery systems,are well worth developing in the future for glaucoma treatment.

关键词： Core-shell lipid-polymer nanoparticles Ocular drug delivery system Sustained release Corneal permeation Intraocular pressure

Inhibiting collagen Ⅰ production and tumor cell colonization in the lung via miR-29a-3p loading of exosome-/liposome-based nanovesicles

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Acta Pharmaceutica Sinica B 2022年第2期12卷 939-951页

作者： Yan Yan Cancan Du Xixi Duan Xiaohan Yao Jiajia Wan Ziming Jiang Zhongyu Qin Wenqing Li Longze Pan Zhuoyu Gu fazhan wang Ming wang Zhihai Qin Medical Research Center the First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Academy of Medical Sciences Zhengzhou UniversityZhengzhou 450052China Department of Urology the First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhou 450052China Changzhi Medical College Changzhi 046000China Institute of Biophysics Chinese Academy of SciencesBeijing 100101China

The lung is one of the most common sites for cancer *** in the lung provide a permissive microenvironment that supports the colonization and outgrowth of disseminated tumor ***,down-regulating the production of collagens may contribute to the inhibition of lung *** has been suggested that mi R-29 exhibits effective anti-fibrotic activity by negatively regulating the expression of ***,our clinical lung tumor data shows that mi R-29 a-3 p expression negatively correlates with collagen I expression in lung tumors and positively correlates with patients’***,suitable carriers need to be selected to deliver this therapeutic mi RNA to the *** this study,we found that the chemotherapy drug cisplatin facilitated mi R-29 a-3 p accumulation in the exosomes of lung tumor cells,and this type of exosomes exhibited a specific lung-targeting effect and promising collagen *** scale up the preparation and simplify the delivery system,we designed a lung-targeting liposomal nanovesicle(by adjusting the molar ratio of DOTAP/cholesterol-mi RNAs to 4:1)to carry mi R-29 a-3 p and mimic the *** liposomal nanovesicle delivery system significantly down-regulated collagen I secretion by lung fibroblasts in vivo,thus alleviating the establishment of a pro-metastatic environment for circulating lung tumor cells.

关键词： Lung metastasis miR-29a-3p CollagenⅠ Liposomal nanovesicle Exosomes Fibroblasts Pre-metastatic niche

AN EXPLANATION ON FOUR NEW DEFINITIONS OF FRACTIONAL OPERATORS

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Acta Mathematica Scientia 2024年第4期44卷 1271-1279页

作者： Jiangen LIU fazhan GENG School of Mathematics and Statistics Changshu Institute of TechnologyChangshu 215500China Qin Institute of Mathematics Shanghai Hanjing Centre for Science and TechnologyShanghai 201609China

Fractional calculus has drawn more attentions of mathematicians and engineers in recent years.A lot of new fractional operators were used to handle various practical *** this article,we mainly study four new fractional operators,namely the CaputoFabrizio operator,the Atangana-Baleanu operator,the Sun-Hao-Zhang-Baleanu operator and the generalized Caputo type operator under the frame of the k-Prabhakar fractional integral ***,the theory of the k-Prabhakar fractional integral is regarded as a much broader than classical fractional ***,we firstly give a series expansion of the k-Prabhakar fractional integral by means of the k-Riemann-Liouville ***,a connection between the k-Prabhakar fractional integral and the four new fractional operators of the above mentioned was shown,*** terms of the above analysis,we can obtain this a basic fact that it only needs to consider the k-Prabhakar fractional integral to cover these results from the four new fractional operators.

关键词： k-Prabhakar fractional operator Caputo-Fabrizio operator Atangana-Baleanu operator Sun-Hao-Zhang-Baleanu operator generalized Caputo type operator

Vibration mechanism analysis and algorithm optimization of contactor contact system

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Journal of Measurement Science and Instrumentation 2021年第4期12卷 396-404页

作者： HUANG Kepeng wang fazhan ZHAO Mingji GUO Baoliang OU Daquan College of Mechanical and Electrical Engineering Xi’an University of Architecture & Technology Xi’ an 710055 China Technology R&D Center ABB Xinhui Low-Voltage Switchgear Co. Ltd. Jiangmen 529089 China

In order to solve the problem of vibration bounce caused by the contact between moving and stationary contacts in the process of switching on,two-degree-of-freedom motion differential equation of the contact system is *** algorithm is used to optimize the pull in process of AC *** whole process of contact bounce was observed and analyzed by high-speed photography *** theory and experimental results were very *** iron core has collided before the contact is separated,which further aggravates the contact *** the iron core bounces collided again,the bounce of the contact was not *** the operation of the contactor,the movement of the moving iron core will cause slight vibration of the *** contact bounce time and the maximum amplitude are *** research results provide a theoretical basis for further control and reduction of contact bounce.

关键词： electrical switch contact bounce two-degree-of-freedom motion differential equation algorithm optimization high-speed photography

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基于非等距偏置的纤维铺放路径规划算法

航空学报 2015年第11期36卷 3715-3723页

作者：阎龙王发展史耀耀西安建筑科技大学机电工程学院西安710055 西北工业大学机电学院西安710072

复合材料由于其高比强度、高比刚度、耐烧蚀、抗侵蚀等一系列优点,广泛地应用于航空、航天、汽车等领域。纤维铺放是实现复合材料成型的主要方法之一,同时也是近年来发展最快、最有效的先进制造技术。为实现构件(特别是复杂结构件)的成... 详细信息

复合材料由于其高比强度、高比刚度、耐烧蚀、抗侵蚀等一系列优点,广泛地应用于航空、航天、汽车等领域。纤维铺放是实现复合材料成型的主要方法之一,同时也是近年来发展最快、最有效的先进制造技术。为实现构件(特别是复杂结构件)的成型制造,必须将材料精确地铺放到芯模表面。针对上述问题,根据微分几何理论提出了一种面向复杂曲面的路径规划算法。在确定压辊位置和方向的前提下,利用平面-曲面求交构造初始路径,并通过非等距偏置以获得覆盖整个芯模的全部路径。该方法所生成的压辊路径,不仅可使纤维完全贴合到芯模表面,还包含了铺放系统所需的丝数信息,理论上实现了构件的精确铺放成型。通过在MATLAB中进行路径仿真,验证了所提纤维铺放路径规划算法的正确性与有效性。

关键词：复合材料纤维铺放微分几何路径规划算法丝束数目