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Size-dependent macrophage-targeting of mannose-modified rosiglitazone liposomes to alleviate inflammatory bowel disease

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Chinese Chemical Letters 2024年第1期35卷 385-391页

作者： Erjin Wang run han Mingyue Wu Yuan He Yaxin Cheng Jiahong Lu Ying Zheng State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences(ICMS)University of MacaoMacao 999078China Department of Pharmacy Xuzhou Medical UniversityXuzhou 221004China Faculty of Health Sciences University of MacaoMacao 999078China Guangdong-Hong Kong-Macao Joint Lab on Chinese Medicine and Immune Disease Research University of MacaoMacao 999078China

Inflammatory bowel disease (IBD) is a refractory chronic intestinal inflammatory disease caused by a malfunction of immune system. As the key immune cells in the intestine, macrophages play an important role in maintaining intestinal homeostasis and tissue repair of the IBD. Pharmacological modulation of macrophage function exhibits the promising therapeutic effect for IBD. In this study, mannose-modified liposomes (MAN-LPs) are prepared for macrophage targeting to improve therapeutic efficiency. Rosiglitazone (ROSI) as an agonist of peroxisome proliferators-activated receptor γ (PPAR-γ) is used as the model drug to fabricate different sized liposomes. The impacts of mannose modification and particle size for macrophage targeting are investigated in cells, zebrafish, and mouse models and the therapeutic effects of the MAN-LPs are evaluated on dextran sulfate sodium (DSS)-induced IBD mouse. Compared to unmodified liposome, MAN-LPs display higher uptake by RAW 264.7 cells and better co-localization with macrophage in zebrafish model. Furthermore, MAN-LPs could effectively accumulate in the inflammatory intestinal sites in IBD mouse model. Most importantly, the targeting ability of MAN-LPs is obviously enhanced with the increasing of particle size, whereas the largest MAN-LPs particles achieve the best anti-inflammatory effect in cells, and a higher therapeutic efficiency in IBD mouse model. Therefore, mannose-modified liposome is a promising strategy for macrophage-targeting in IBD treatment. Particle size of MAN-LPs will affect macrophage targeting ability, as well as the therapeutic effect in-vivo.

关键词： Macrophage targeting Liposome Mannose Particle size Inflammatory bowel disease

脑靶向寡核苷酸药物策略用于衰老相关脑部疾病治疗

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生物化学与生物物理进展 2024年第2期51卷 253-268页

作者：杨灏颖刘润涵房梦珂刘洋郑蒙河南大学淮河医院转化医学中心开封475004 河南大学生命科学学院河南省脑靶向生物纳米药物重点实验室开封475004

寡核苷酸药物近10年发展迅速,已有多款应用于临床治疗。因其设计便捷、序列灵活、特异性高,有望解决许多靶点难成药的困境,并且其临床转化周期和成本较低,目前已成为新兴生物技术药物研发的前沿领域。脑部疾病包括多种目前无法治愈的疾... 详细信息

寡核苷酸药物近10年发展迅速,已有多款应用于临床治疗。因其设计便捷、序列灵活、特异性高,有望解决许多靶点难成药的困境,并且其临床转化周期和成本较低,目前已成为新兴生物技术药物研发的前沿领域。脑部疾病包括多种目前无法治愈的疾病,如神经退行性疾病、胶质瘤、运动神经元疾病等,其中很多与年龄相关,被认为是衰老相关脑部疾病。因其病因复杂,许多靶点难成以药,同时由于脑部特殊屏障系统“血脑屏障”的存在,导致大部分药物无法实现脑部病灶的有效积累,众多小分子药物遭遇临床转化失败。寡核苷酸类药物的特异性和序列灵活性提供了新的成药可能性,但同样面临脑部递送的挑战。尽管目前已有多款寡核苷酸类药物应用于医疗市场,但脑靶向寡核苷酸药物仍然极为罕见,随着纳米递送和脑靶向基团研究的逐渐成熟,未来5~10年寡核苷酸药物用于脑部疾病治疗将成为可能。本文针对本领域重点话题如寡核苷酸药物临床批准的应用案例、脑靶向寡核苷酸药物的递送瓶颈和当前策略,以及衰老相关脑部疾病的寡核苷酸药物潜在靶点进行了梳理,同时对临床转化中的难点和面临的挑战展开了综述和讨论。

关键词：寡核苷酸药物血脑屏障脑部疾病老龄化疾病

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基于可调负荷的电网运行优化策略研究

自动化与仪器仪表 2024年第1期 108-111页

作者：孔德全韩忠修王颖韩润张星国网宁夏电力有限公司银川供电公司银川750001 国电南瑞南京控制系统有限公司南京211106

为进一步加强智能电网运行调控,提出一种基于可调负荷的运行优化策略。其中,考虑到传统负荷调控未考虑约束条件的问题,构建含供电约束的实时分布式可调负荷控制算法,从而对某一时刻接入电网的可调负荷进行实时控制,让电力总负荷变化曲... 详细信息

为进一步加强智能电网运行调控,提出一种基于可调负荷的运行优化策略。其中,考虑到传统负荷调控未考虑约束条件的问题,构建含供电约束的实时分布式可调负荷控制算法,从而对某一时刻接入电网的可调负荷进行实时控制,让电力总负荷变化曲线地向电网供电功率曲线逼近。验结果表明:本研究构建的算法可使总负荷功率曲线无限逼近计划供电功率曲线;当t=12,负荷调度得到的用电功率与总负荷功率之间的绝对差值维持在[0,3]kW之间,而不包含供电约束的实时分布式可调负荷控制算法的绝对差值波动范围在[1,6]之间。由此得出,引入包含约束条件的负荷调度效果更好。

关键词：智能电网可调负荷电网优化含供电约束绝对差值波动

基于FLUENT的绝缘化喷涂喷嘴雾化特性有限元分析

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电力设备管理 2024年第11期 129-131页

作者：柳云韩润严升王昊王小明国网银川供电公司

架空电路金属裸露点的存在会降低配电线路可靠性,现阶段对裸露点包裹多采用绝缘漆喷涂方式,喷涂过程中喷嘴特性对喷涂质量有着重要影响,文章利用FLUENT软件对气液两相喷嘴特性进行了仿真模拟求解,讨论了不同压力下喷嘴内流域的速度、液... 详细信息

架空电路金属裸露点的存在会降低配电线路可靠性,现阶段对裸露点包裹多采用绝缘漆喷涂方式,喷涂过程中喷嘴特性对喷涂质量有着重要影响,文章利用FLUENT软件对气液两相喷嘴特性进行了仿真模拟求解,讨论了不同压力下喷嘴内流域的速度、液相体积分数喷嘴雾化角度的变化规律,仿真结果表明:气相压力一定时,喷嘴出口平均液体体积分数值、喷嘴雾化角度与液相压力呈负相关。

关键词： FLUENT 气液两相液相体积分数喷嘴雾化角度

Reducing systemic absorption and macrophages clearance of genistein by lipid-coated nanocrystals for pulmonary delivery

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Chinese Chemical Letters 2023年第1期34卷 245-250页

作者： Yuan He Chang Liu run han Yingmin Liang Judith Choi Wo Mak Yinghao Zhu Haifeng Li Ying Zheng State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacaoChina Department of Pharmacy Xuzhou Medical UniversityXuzhou 221004China LKS Faculty of Medicine Department of MedicineThe University of Hong KongHong KongChina Institute of Applied Physics and Materials Engineering University of MacaoMacaoChina

Pulmonary delivery is an effective drug delivery strategy for the treatment of local respiratory ***,the rapid systemic absorption through the lung due to the thin barrier and persistent lung clearances influence the drug retention in the *** this study,we designed a lipid-coated genistein nanocrystals(Lipo-NCs)formulation to achieve enhanced efficiency of local pulmonary *** LipoNCs were fabricated by modifying genistein nanocrystals(NCs)with phospholipid membrane through thin film hydration following the homogenization *** prepared Lipo-NCs exhibited a decreased drug release rate compared with the naked *** results demonstrated that intracellular uptake and transcellular transport of NCs by the Calu-3 epithelial layer were reduced after lipid ***,the macrophages clearance was also impeded by this Lipo-NCs *** vivo lung retention and distribution revealed that more genistein was retained in the lung after intratracheal administration of *** pharmacokinetic study displayed that the AUC((0-t))values of Lipo-NCs were 1.59-fold lesser than those of the NCs group,indicating a reduced systemic *** conclusion,this research indicated that Lipo-NCs could be a suitable formulation for reducing systemic absorption and macrophages clearance,and thus enhancing drug concentration in lung by pulmonary delivery.

关键词： Pulmonary delivery Lipid-coated nanocrystals Cell uptake Transport Systemic absorption Macrophage clearances

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智能调控辅助决策系统在配电网中的应用

电子技术（上海） 2024年第5期53卷 53-55页

作者：韩润付义豪崇信民赵学华季升国网宁夏电力有限公司银川供电公司宁夏750001 国电南瑞南京控制系统有限公司江苏211106

阐述配电网智能调控辅助决策中的数据采集层、数据传输层、数据处理层、决策支持层、控制执行层系统架构和技术架构设计,分析数据清洗、数据预处理、数据聚合的操作过程,探讨台区负荷管理与预测、区域电压优化控制、台区停电管理、台区... 详细信息

阐述配电网智能调控辅助决策中的数据采集层、数据传输层、数据处理层、决策支持层、控制执行层系统架构和技术架构设计,分析数据清洗、数据预处理、数据聚合的操作过程,探讨台区负荷管理与预测、区域电压优化控制、台区停电管理、台区运行预控管理的策略。

关键词：智能调控系统数据聚合负荷管理与预测

Green synthesis of bifunctional phthalocyanine-porphyrin COFs in water for efficient electrocatalytic CO2 reduction coupled with methanol oxidation

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National Science Review 2023年第11期10卷 160-170页

作者： Mi Zhang Jia-Peng Liao run-han Li Sheng-Nan Sun Meng Lu Long-Zhang Dong Pei Huang Shun-Li Li Yue-Peng Cai Ya-Qian Lan South China Normal University School of Chemistry

Electrocatalytic CO2reduction(ECR) coupled with organic oxidation is a promising strategy to produce high value-added chemicals and improve energy efficiency. However, achieving the efficient redox coupling reaction is still challenging due to the lack of suitable electrocatalysts. Herein, we designed two bifunctional polyimides-linked covalent organic frameworks(PI-COFs) through assembling phthalocyanine(Pc) and porphyrin(Por) by non-toxic hydrothermal methods in pure water to realize the above catalytic *** to the high conductivity and well-defined active sites with different chemical environments, Ni Pc-Ni Por COF performs efficient ECR coupled with methanol oxidation reaction(MOR)(Faradaic efficiency of CO(FECO) = 98.12%, partial current densities of CO(j CO) = 6.14 m A cm-2for ECR, FEHCOOH = 93.75%,j HCOOH = 5.81 m A cm-2for MOR at low cell voltage(2.1 V) and remarkable long-term stability).Furthermore, experimental evidences and density functional theory(DFT) calculations demonstrate that the ECR process mainly conducts on Ni Pc unit with the assistance of Ni Por, meanwhile, the MOR prefers Ni Por conjugating with Ni Pc. The two units of Ni Pc-Ni Por COF collaboratively promote the coupled oxidation-reduction reaction. For the first time, this work achieves the rational design of bifunctional COFs for coupled heterogeneous catalysis, which opens a new area for crystalline material catalysts.

关键词： hydrothermal synthesis phthalocyanine-porphyrin COFs bifunctional electrocatalysts electrocatalytic CO2 reduction methanol oxidation reaction

Lignin-reinforced PVDF electrolyte for dendrite-free quasi-solid-state Li metal battery

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Rare Metals 2024年第3期43卷 1006-1016页

作者： Xin-Yang Chen Xue-Jie Gao han-Yan Wu Yu-Long Liu Xiao-Fei Yang run-Cang Sun Center for Lignocellulosic Chemistry and Biomaterials College of Light Industry and Chemical EngineeringDalian Polytechnic UniversityDalian116034China Division of Energy Storage Dalian National Laboratory for Clean EnergyDalian Institute of Chemical PhysicsChinese Academy of SciencesDalian116023China School of Chemistry Northeast Normal UniversityChangchun130024China

Quasi-solid-state lithium metal batteries(QSSLMBs)assembled with polyvinylidene fluoride(PVDF)are a promising class of next-generation rechargeable batteries due to their safety,high energy density,and superior interfacial ***,PVDF has a series of inherent drawbacks such as low ionic conductivity,ease of crystallization,and hydrophobic character that leading to poor cell *** tackle these issues,a lignin-reinforced PVDF electrolyte is proposed in this work to solve these drawbacks of PVDF and enhance the comprehensive performance of *** lithophilic polar groups of lignin can promote uniform deposition of Li on the *** with the improved mechanical properties can efficiently prevent Li dendrites penetration through the *** addition,more active sites provided by lignin can also enhance Li^(+)transport and lead to a faster electrochemical reaction *** from the ingenious design,Li symmetric cells with 5%lignin-PVDF quasi-solid-state electrolyte can operate for 900 h at a high current density/capacity of 5 mA·cm^(-2)/5 mAh·cm^(-2),while shortcircuiting occurs after 56 h for the counterpart(pure PVDF).Moreover,a full cell of Li/5%lignin-PVDF/LFP cell demonstrates a high capacity of 96.2 mAh·g^(-1)after 2000 cycles at 10 *** work is expected to open up promising opportunities to develop other high-energy/power-density QSSLMBs.

关键词： Quasi-solid-state electrolyte Lignin PVDF Dendrite-free Li metal battery

A LexA-based yeast two-hybrid system for studying light- switchable interactions of phytochromes with their interacting partners

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aBIOTECH 2021年第2期2卷 105-116页

作者： Hong Li Xinyan Qin Pengyu Song run han Jigang Li State Key Laboratory of Plant Physiology and Biochemistry College of Biological SciencesChina Agricultural UniversityBeijing 100193China

Phytochromes are a family of photoreceptors in plants that perceive the red(R)and far-red(FR)components of their light *** exist in vivo in two forms,the inactive Pr form and the active Pfr form,that are interconvertible by treatments with R or FR *** is believed that phytochromes transduce light signals by interacting with their signaling partners.A GAL4-based lightswitchable yeast two-hybrid(Y2H)system was developed two decades ago and has been successfully employed in many studies to determine phytochrome interactions with their signaling ***,several pairs of interactions between phytochromes and their interactors,such as the phyACOP1 and phyA-TZP interactions,were demonstrated by other assay systems but were not detected by this GAL4 Y2H ***,we report a modified LexA Y2H system,in which the LexA DNA-binding domain is fused to the C-terminus of a phytochrome *** conformational changes of phytochromes in response to R and FR light are achieved in yeast cells by exogenously supplying phycocyanobilin(PCB)extracted from *** well-defined interaction pairs,including phyA-FHY1 and phyB-PIFs,are well reproducible in this ***,we show that our system is successful in detecting the phyA-COP1 and phyA-TZP ***,our study provides an alternative Y2H system that is highly sensitive and reproducible for detecting light-switchable interactions of phytochromes with their interacting partners.

关键词： Phytochrome Interaction Yeast two-hybrid LexA Light-switchable