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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 drugs.Therefore,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 AD.RAGE 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 brain.Meanwhile,these two drugs can be specifically released in astrocytes of AD lesion in response to high levels of ROS.As a result,the cognition of AD mice was significantly improved and the quantity of Aβplaques was decreased.Neurotoxicity was also alleviated with structural regeneration and functional recovery of neurons.Besides,the neuroinflammation dominated by NF-κB pathway was significantly inhibited with decreased NF-κB and IL-1βin the brain.Overall,Ibu&FK@RNPs can efficiently and successively target diseased BBB and astrocytes in AD lesion.Thus 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

Co-firing of coal and biomass in oxy-fuel fluidized bed for CO2 capture: A review of recent advances

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Chinese Journal of Chemical Engineering 2019年第10期27卷 2261-2272页

作者： Qinwen Liu Yan Shi wenqi Zhong Aibing yu Key Laboratory of Energy Thermal Conversion and Control of the Ministry of Education School of Energy and EnvironmentSoutheast UniversityNanjing 210096China Center for Simulation and Modelling of Particulate Systems Southeast University-Monash University Joint Research InstituteSuzhou 215000China 3 ARC Research Hub for Computational Particle TechnologyDepartment of Chemical EngineeringMonash UniversityClaytonVIC 3800Australia

The co-firing of coal and biomass in oxy-fuel fluidized beds is one of the most promising technologies for capturing CO2.This technology has attracted wide attention from academia and industry in recent years as a negative emission method to capture CO2 produced by carbon contained in biomass.In the past decades,many studies have been carried out regarding experiments and numerical simulations under oxy-fuel combustion conditions.This paper firstly briefly discusses the techno-economic viability of the biomass and coal co-firing with oxycombustion and then presents a review of recent advancements involving experimental research and computational fluid dynamics(CFD)simulations in this field.Experimental studies on mechanism research,such as thermogravimetric analysis and tube furnace experiments,and fluidized bed experiments based on oxy-fuel fluidized beds with different sizes as well as the main findings,are summarized as a part of this review.It has been recognized that CFD is a useful approach for understanding the behaviors of the co-firing of coal and biomass in oxyfuel fluidized beds.We summarize a recent survey of published CFD research on oxy-fuel fluidized bed combustion,which categorized into Eulerian and Lagrangian methods.Finally,we discuss the challenges and interests for future research.

关键词： Oxy-fuel combustion Co-firing of coal and biomass Oxy-fuel fluidized bed CFD simulation

Metal-organic frameworks based single-atom catalysts for advanced fuel cells and rechargeable batteries

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Journal of Energy Chemistry 2023年第5期80卷 501-534,I0012页

作者： Yifei Wu Peng Hu Fengping Xiao Xiaoting yu wenqi Yang Minqi Liang Ziwei Liang Aixin Zhu College of Chemistry and Chemical Engineering Yunnan Normal UniversityKunming 650500YunnanChind School of Energy and Environment Science Yunnan Normal UniversityKunming 650500.YunnanChina Key Laboratory of Advanced Energy Materials Chemistry(Ministry of Education) Nankai UniversityTianjin 300071China School of Environment and Chemical Engineering Zhaoqing UniversityZhaoqing 526061GuangdongChina

The next-generation energy storage systems such as fuel cells,metal-air batteries,and alkali metal(Li,Na)-chalcogen(S,Se)batteries have received increasing attention owing to their high energy density and low cost.However,one of the main obstacles of these systems is the poor reaction kinetics in the involved chemical reactions.Therefore,it is essential to incorporate suitable and efficient catalysts into the cell.These years,single-atom catalysts(SACs)are emerging as a frontier in catalysis due to their maximum atom efficiency and unique reaction selectivity.For SACs fabrication,metal-organic frameworks(MOFs)have been confirmed as promising templates or precursors due to their high metal loadings,structural adjustability,porosity,and tailorable catalytic site.In this review,we summarize effective strategies for fabricating SACs by MOFs with corresponding advanced characterization techniques and illustrate the key role of MOFs-based SACs in these batteries by explaining their reaction mechanisms and challenges.Finally,current applications,prospects,and opportunities for MOFs-based SACs in energy storage systems are discussed.

关键词： Metal-organic frameworks Single-atom catalysts Rechargeable batteries Electrocatalysts Coordination configuration

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 system.Little is known about where the DDS will go after brain delivery,and no specific elimination route that shares a passage with DDS has been verified.Hence,identifying harmless DDS for brain delivery and determining their fate there would strongly contribute to their clinical translation.In this study,we investigated nonreactive gold nanoclusters,which can deliver into the brain,to determine the elimination route of DDS.Subsequently,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 BBB.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

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 chemotherapy.Reconstruction of hypoxic tumor microenvironment(TME)is considered a potential therapy compared to directly killing tumor cells.However,the insufficient oxygen delivery to deep tumor and the confronting Warburg effect"compromise the efficacy of hypoxia alleviation.Herein,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 chemotherapy.Catalase(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 meantime.The autonomous movement also facilitates NM-si with lysosome escaping for efficient HK-2 knockdown to inhibit glycolysis.In vivo results demonstrated a promising anti-metastasis effect of commercially available albumin-bound paclitaxel(PTX@HSA)after pre-treated with NM-si for TME reconstruction.This 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 Data-Driven Oil Production Prediction Method Based on the Gradient Boosting Decision Tree Regression

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Computer Modeling in Engineering & Sciences 2023年第3期134卷 1773-1790页

作者： Hongfei Ma wenqi Zhao yurong Zhao yu He School of Energy Resources China University of Geosciences(Beijing)Beijing100083China Research Institute of Petroleum Exploration and Development China National Petroleum CorporationBeijing100083China

Accurate prediction ofmonthly oil and gas production is essential for oil enterprises tomake reasonable production plans,avoid blind investment and realize sustainable development.Traditional oil well production trend prediction methods are based on years of oil field production experience and expertise,and the application conditions are very demanding.With the rapid development of artificial intelligence technology,big data analysis methods are gradually applied in various sub-fields of the oil and gas reservoir development.Based on the data-driven artificial intelligence algorithmGradient BoostingDecision Tree(GBDT),this paper predicts the initial single-layer production by considering geological data,fluid PVT data and well data.The results show that the GBDT algorithm prediction model has great accuracy,significantly improving efficiency and strong universal applicability.The GBDTmethod trained in this paper can predict production,which is helpful for well site optimization,perforation layer optimization and engineering parameter optimization and has guiding significance for oilfield development.

关键词： Gradient boosting decision tree production prediction data analysis

SAM Era:Can It Segment Any Industrial Surface Defects?

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Computers, Materials & Continua 2024年第3期78卷 3953-3969页

作者： Kechen Song wenqi Cui Han yu Xingjie Li yunhui Yan National Key Laboratory of Advanced Casting Technologies Shenyang110022China School of Mechanical Engineering&Automation Northeastern UniversityShenyang110819China

Segment Anything Model(SAM)is a cutting-edge model that has shown impressive performance in general object segmentation.The birth of the segment anything is a groundbreaking step towards creating a universal intelligent model.Due to its superior performance in general object segmentation,it quickly gained attention and interest.This makes SAM particularly attractive in industrial surface defect segmentation,especially for complex industrial scenes with limited training data.However,its segmentation ability for specific industrial scenes remains unknown.Therefore,in this work,we select three representative and complex industrial surface defect detection scenarios,namely strip steel surface defects,tile surface defects,and rail surface defects,to evaluate the segmentation performance of SAM.Our results show that although SAM has great potential in general object segmentation,it cannot achieve satisfactory performance in complex industrial scenes.Our test results are available at:https://***/VDT-2048/SAM-IS.

关键词： Segment anything SAM surface defect detection salient object detection

Experimental-computational study of fibrous particle transport and deposition in a bifurcating lung model

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Particuology 2016年第5期14卷 102-113页

作者： Xiaole Chen wenqi Zhong Josin Tom Clement Kleinstreuer yu Feng Xiaopu He Key Laboratory of Energy Thermal Conversion and Control of the Ministry of Education School of Energy and Environment Southeast University Nanjing210096 China Department of Mechanical and Aerospace Engineering North Carolina State University Raleigh NC 27695 USA Department of Biomedical Engineering North Carolina State University Raleigh NC27695 USA School of Chemical Engineering Oklahoma State University Stillwater OK 74078 USA First Affiliated Hospital of Nanjing Medical University Nanjing 210029 China

Experiments carried out using a lung model with a single horizontal bifurcation under different steady inhalation conditions explored the orientation of depositing carbon fibers, and particle deposition frac- tions. The orientations of deposited fibers were obtained from micrographs. Specifically, the effects of the sedimentation parameter （γ）, fiber length, and flow rate on orientations were analyzed. Our results indicate that gravitational effect on deposition cannot be neglected for 0.0228 〈 γ 〈 0.247. The absolute orientation angle of depositing fibers decreased linearly with increasing y for values 0.0228 〈 γ 〈 0.15. Correspondence between Stokes numbers and y suggests these characteristics can be used to estimate fiber deposition in the lower airways. Computer simulations with sphere-equivalent diameter models for the fibers explored deposition efficiency vs. Stokes number. Using the volume-equivalent diameter model, our experimental data for the horizontal bifurcation were replicated. Results for particle deposition using a lung model with a vertical bifurcation indicate that body position also affects deposition.

关键词： Lung aerosol dynamics Image-processing method Fiber deposition data Computer simulations Deposited fiber orientations