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Glymphatic System and Subsidiary Pathways Drive Nanoparticles Away from the Brain

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Research 2022年第3期2022卷 13-30页

作者： Rui Liu Wenfeng Jia yushan Wang Chuan Hu wenqi yu yuan Huang Ling Wang Huile Gao Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China

Although drug delivery systems(DDS)are efficient in brain delivery,they face failure in clinical settings due to their potential toxicity to the central nervous *** is known about where the DDS will go after brain delivery,and no specific elimination route that shares a passage with DDS has been ***,identifying harmless DDS for brain delivery and determining their fate there would strongly contribute to their clinical *** this study,we investigated nonreactive gold nanoclusters,which can deliver into the brain,to determine the elimination route of ***,nanoclusters in the brain were systemically tracked and were found to be critically drained by the glymphatic system from the blood vessel basement membrane to periphery circulations(77.8±23.2%and 43.7±23.4%contribution).Furthermore,the nanoclusters could be actively transported across the blood-brain barrier(BBB)by exosomes(30.5±27.3%and 29.2±7.1%contribution).In addition,microglia promoted glymphatic drainage and passage across the *** simultaneous work of the glymphatic system,BBB,and microglia revealed the fate of gold nanoclusters for brain delivery and provided a basis for further braindelivery DDS.

关键词： drain passage elimination

Intelligent lesion blood–brain barrier targeting nano-missiles for Alzheimer's disease treatment by anti-neuroinflammation and neuroprotection

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Acta Pharmaceutica Sinica B 2022年第4期12卷 1987-1999页

作者： Xueqin He Xiaorong Wang Lianyi Yang Zhihang Yang wenqi yu Yazhen Wang Rui Liu Meiwan Chen Huile Gao Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610041China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China

The treatment of Alzheimer's disease(AD)is one of the most difficult challenges in neurodegenerative diseases due to the insufficient blood‒brain barrier(BBB)permeability and unsatisfactory intra-brain distribution of ***,we established an ibuprofen and FK506 encapsulated drug co-delivery system(Ibu&FK@RNPs),which can target the receptor of advanced glycation endproducts(RAGE)and response to the high level of reactive oxygen species(ROS)in *** is highly and specifically expressed on the lesion neurovascular unit of AD,this property helps to improve targeting specificity of the system and reduce unselective distribution in normal ***,these two drugs can be specifically released in astrocytes of AD lesion in response to high levels of *** a result,the cognition of AD mice was significantly improved and the quantity of Aβplaques was *** was also alleviated with structural regeneration and functional recovery of ***,the neuroinflammation dominated by NF-κB pathway was significantly inhibited with decreased NF-κB and IL-1βin the ***,Ibu&FK@RNPs can efficiently and successively target diseased BBB and astrocytes in AD *** it significantly enhances intracephalic accumulation of drugs and efficiently treats AD by anti-neuroinflammation and neuroprotection.

关键词： Receptor for advanced glycation end products ROS-responsive Blood‒brain barrier transcytosis Alzheimer’s disease Drug combination Anti-neuroinflammation Neuroprotection Nano drug delivery system

Dual-responsive nanoparticles with transformable shape and reversible charge for amplified chemo-photodynamic therapy of breast cancer

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Acta Pharmaceutica Sinica B 2022年第8期12卷 3354-3366页

作者： Wenfeng Jia Rui Liu yushan Wang Chuan Hu wenqi yu Yang Zhou Ling Wang Mengjiao Zhang Huile Gao Xiang Gao Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610064China Department of Neurosurgery and Institute of Neurosurgery State Key Laboratory of BiotherapyWest China HospitalWest China Medical SchoolSichuan University and Collaborative Innovation Center for BiotherapyChengdu 610041China

Herein, we designed a dual-response shape transformation and charge reversal strategy with chemo-photodynamic therapy to improve the blood circulation time, tumor penetration and retention,which finally enhanced the anti-tumor effect. In the system, hydrophobic photosensitizer chlorin e6(Ce6), hydrophilic chemotherapeutic drug berberrubine(BBR) and matrix metalloproteinase-2(MMP-2) response peptide(PLGVRKLVFF) were coupled by linkers to form a linear triblock molecule BBR-PLGVRKLVFF-Ce6(BPC), which can self-assemble into nanoparticles. Then, positively charged BPC and polyethylene glycol-histidine(PEG-His) were mixed to form PEG-His@BPC with negative surface charge and long blood circulation time. Due to the acidic tumor microenvironment, the PEG shell was detached from PEG-His@BPC attributing to protonation of the histidine, which achieved charge reversal, size reduction and enhanced tumor penetration. At the same time, enzyme cutting site was exposed, and the spherical nanoparticles could transform into nanofibers following the enzymolysis by MMP-2, while BBR was released to kill tumors by inducing apoptosis. Compared with original nanoparticles, the nanofibers with photosensitizer Ce6 retained within tumor site for a longer time. Collectively,we provided a good example to fully use the intrinsic properties of different drugs and linkers to construct tumor microenvironment-responsive charge reversal and shape transformable nanoparticles with synergistic antitumor effect.

关键词： Shape transformation Charge reversal Chemo-photodynamic therapy Self-delivery MMP-2 response p H response Carrier-free nanoparticles Breast cancer

Self-propelled nanomotor reconstructs tumor microenvironment through synergistic hypoxia alleviation and glycolysis inhibition for promoted anti-metastasis

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Acta Pharmaceutica Sinica B 2021年第9期11卷 2924-2936页

作者： wenqi yu Ruyi Lin Xueqin He Xiaotong Yang Huilin Zhang Chuan Hu Rui Liu yuan Huang Yi Qin Huile Gao Industrial Technology West China School of PharmacySichuan UniversityChengdu 610041China Department of Orthopedics Zhuhai HospitalJinan UniversityZhuhai People’s HospitalGuangdong 519000China

Solid tumors always exhibit local hypoxia,resulting in the high metastasis and inertness to *** of hypoxic tumor microenvironment(TME)is considered a potential therapy compared to directly killing tumor ***,the insufficient oxygen delivery to deep tumor and the confronting Warburg effect"compromise the efficacy of hypoxia ***,we construct a cascade enzyme-powered nanomotor(NM-si),which can simultaneously provide sufficient oxygen in deep tumor and inhibit the aerobic glycolysis to potentiate anti-metastasis in ***(Cat)and glucose oxidase(GOx)are co-adsorbed on our previously reported CAuNCs@HA to form self-propelled nanomotor(NM),with hexokinase-2(HK-2)siRNA further condensed(NM-si).The persistent production of oxygen bubbles from the cascade enzymatic reaction propels NM-si to move forward autonomously and in a controllable direction along H_(2)O_(2) gradient towards deep tumor,with hypoxia successfully alleviated in the *** autonomous movement also facilitates NM-si with lysosome escaping for efficient HK-2 knockdown to inhibit *** vivo results demonstrated a promising anti-metastasis effect of commercially available albumin-bound paclitaxel(PTX@HSA)after pre-treated with NM-si for TME *** cascade enzyme-powered nanomotor provides a potential prospect in reversing the hypoxic TME and metabolic pathway for reinforced anti-metastasis of chemotherapy.

关键词： Nanomotor Microenvironment modulation Hypoxia Aerobic glycolysis Triple negative breast cancer Anti-metastasis Enzyme-powered Chemotherapy

A multi-attention RNN-based relation linking approach for question answering over knowledge base

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Journal of Southeast University(English Edition) 2020年第4期36卷 385-392页

作者： Li Huiying Zhao Man yu wenqi School of Computer Science and Engineering Southeast University Nanjing 211189 China

Aiming at the relation linking task for question answering over knowledge base,especially the multi relation linking task for complex questions,a relation linking approach based on the multi-attention recurrent neural network(RNN)model is proposed,which works for both simple and complex ***,the vector representations of questions are learned by the bidirectional long short-term memory(Bi-LSTM)model at the word and character levels,and named entities in questions are labeled by the conditional random field(CRF)*** entities are generated based on a dictionary,the disambiguation of candidate entities is realized based on predefined rules,and named entities mentioned in questions are linked to entities in knowledge ***,questions are classified into simple or complex questions by the machine learning *** from the identified entities,for simple questions,one-hop relations are collected in the knowledge base as candidate relations;for complex questions,two-hop relations are collected as ***,the multi-attention Bi-LSTM model is used to encode questions and candidate relations,compare their similarity,and return the candidate relation with the highest similarity as the result of relation *** is worth noting that the Bi-LSTM model with one attentions is adopted for simple questions,and the Bi-LSTM model with two attentions is adopted for complex *** experimental results show that,based on the effective entity linking method,the Bi-LSTM model with the attention mechanism improves the relation linking effectiveness of both simple and complex questions,which outperforms the existing relation linking methods based on graph algorithm or linguistics understanding.

关键词： question answering over knowledge base(KBQA) entity linking relation linking multi-attention bidirectional long short-term memory(Bi-LSTM) large-scale complex question answering dataset(LC-QuAD)

天波超视距雷达电离层相位污染时频校正方法综合性能评估

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电子与信息学报 2018年第4期40卷 992-1001页

作者：于文启陈建文李雪空军预警学院武汉430019 中国电波传播研究所青岛266107

电离层相位污染严重制约天波超视距雷达对低可探测慢速舰船目标的检测性能,时频校正法成为目标检测的重要手段,对其进行分类并选取6种典型方法进行了去污染的综合性能评估。首先分析了性能比较的影响因素,然后从去污染的有效性、鲁棒性... 详细信息

电离层相位污染严重制约天波超视距雷达对低可探测慢速舰船目标的检测性能,时频校正法成为目标检测的重要手段,对其进行分类并选取6种典型方法进行了去污染的综合性能评估。首先分析了性能比较的影响因素,然后从去污染的有效性、鲁棒性和运算量等几个方面进行了校正方法的综合比较。为电离层相位污染校正算法库的丰富和实际工程应用提供参考。

关键词：天波超视距雷达电离层相位污染时频校正性能评估

PRESSURE LOSS THROUGH A VERTICAL PIPE IN AIR-SOLID FLOWS

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PRESSURE LOSS THROUGH A VERTICAL PIPE IN AIR-SOLID FLOWS

The First International Conference on Measurement and Control of Granular Materials

作者： WANG wenqi yu PONGXIAN DEPARTMENT OF POWER ENGINEERING SOUTHEAST UNIVERSITY NANJING JIANGSU P.R.CHINA

＜正＞In this paper,an investigation has been conducted into the pressure drop occuring in vertical pipe of 50 mm bore,in which there is upward flow of air-fluidised suspension of small *** experimental facility used is of the vacuum *** velocity varied from 10 m/s to 28 m/s,and solids/air mass flow rate ratio were in the range 0 Ms/Ma *** type of solids were conveyed:talcum powder and glass *** mean diameter of these particles is 17 um and 150 um respec- *** formulae of total pressure drop in the pneumatic transport through a vertical pipe are obtained and the results from these formulae are agree with the experiment data.

关键词：

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基于小波变换的天波雷达舰船目标检测方案

华中科技大学学报（自然科学版） 2019年第8期47卷 23-28页

作者：关泽文陈建文于文启鲍拯空军预警学院一系

针对天波超视距雷达(OTHR)舰船目标自适应检测的难题,提出一种基于修正的峰值信噪比(MPSNR)-离散小波变换(DWT)的方案.首先在预处理过程中拼接接收数据各通道中当前监视区域的距离多普勒谱,然后通过令MPSNR最大化实现海杂波的自适应抑制... 详细信息

针对天波超视距雷达(OTHR)舰船目标自适应检测的难题,提出一种基于修正的峰值信噪比(MPSNR)-离散小波变换(DWT)的方案.首先在预处理过程中拼接接收数据各通道中当前监视区域的距离多普勒谱,然后通过令MPSNR最大化实现海杂波的自适应抑制,最后利用排序统计-恒虚警率检测器进行舰船目标检测.理论上本方案中的MPSNR较已有方案中的峰值信噪比对海杂波被抑制的程度更为敏感,因此本方案较已有方案对海杂波的抑制更为充分,进而可以改善目标检测性能.仿真数据和实测数据的结果表明本方案对舰船目标的信杂噪比提升了2.6 dB.

关键词：天波超视距雷达海杂波抑制舰船目标检测图像处理离散小波变换

基于权矩阵低秩逼近的MIMO-OTHR多模SDC抑制算法

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系统工程与电子技术 2019年第6期41卷 1249-1257页

作者：于文启陈建文关泽文鲍拯空军预警学院预警技术系湖北武汉430019

扩展多普勒杂波是天波超视距雷达(over-the-horizon radar,OTHR)慢速舰船目标检测面临的关键问题。在新一代多输入多输出天波超视距雷达系统下,基于最小方差无失真响应(minimum variance distortionless response,MVDR)权矢量,提出一种... 详细信息

扩展多普勒杂波是天波超视距雷达(over-the-horizon radar,OTHR)慢速舰船目标检测面临的关键问题。在新一代多输入多输出天波超视距雷达系统下,基于最小方差无失真响应(minimum variance distortionless response,MVDR)权矢量,提出一种权矩阵低秩逼近的多模扩展多普勒杂波抑制算法。利用阻塞矩阵进行数据预处理,并利用"发射-接收"二维权矩阵的特征分解对双迭代MVDR算法进行了多级扩展,在减小了计算量和样本需求的基础上,进一步改善俯仰空域滤波的输出信杂噪比,提升OTHR对低可探测慢速舰船目标的检测性能。理论分析和仿真验证了算法的有效性。

关键词：天波超视距雷达扩展多普勒杂波多输入多输出低秩逼近多模传播