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Iron-based and BRD_(4)-downregulated strategy for amplified ferroptosis based on pH-sensitive/NIR-Ⅱ-boosted nano-matchbox

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Acta Pharmaceutica Sinica B 2023年第2期13卷 863-878页

作者： Lujing Geng Tong Lu Huaqing Jing Yue Zhou xiaoyang liang Jiao Li Nan Li Tianjin Key Laboratory of Drug Delivery&High-Efficiency School of Pharmaceutical Science and TechnologyTianjin UniversityTianjin 300072China School of Precision Instruments and Optoelectronics Engineering Tianjin UniversityTianjin 300072China

Ferroptosis(FPT),a novel form of programmed cell death,is characterized by overwhelming iron/reactive oxygen species(ROS)-dependent accumulation of lipid peroxidation(LPO).However,the insufficiency of endogenous iron and ROS level limited the FPT therapeutic efficacy to a large *** overcome this obstacle,the bromodomain-containing protein 4(BRD_(4))-inhibitor(+)-JQ1(JQ1)and iron-supplement ferric ammonium citrate(FAC)-loaded gold nanorods(GNRs)are encapsulated into the zeolitic imidazolate framework-8(ZIF-8)to form matchbox-like GNRs@JF/ZIF-8 for the amplified FPT *** existence of matchbox(ZIF-8)is stable in physiologically neutral conditions but degradable in acidic environment,which could prevent the loaded agents from prematurely ***,GNRs as the drug-carriers induce the photothermal therapy(PTT)effect under the irradiation of near-infraredⅡ(NIR-Ⅱ)light owing to the absorption by localized surface plasmon resonance(LSPR),while the hyperthermia also boosts the JQ1 and FAC releasing in the tumor microenvironment(TME).On one hand,the FAC-induced Fenton/Fenton-like reactions in TME can simultaneously generate iron(Fe^(3+)/Fe^(2+))and ROS to initiate the FPT treatment by LPO *** the other hand,JQ1 as a small molecule inhibitor of BRD_(4)protein can amplify FPT through downregulating the expression of glutathione peroxidase 4(GPX4),thus inhibiting the ROS elimination and leading to the LPO *** in vitro and in vivo studies reveal that this p H-sensitive nano-matchbox achieves obvious suppression of tumor growth with good biosafety and *** a result,our study points out a PTT combined iron-based/BRD_(4)-downregulated strategy for amplified ferrotherapy which also opens the door of future exploitation of ferrotherapy systems.

关键词： BDR_(4)protein Ferroptosis Photothermal therapy pH-Sensitive NIR-Ⅱlight ZIF-8 Fenton reactions Nano-matchbox

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Enhanced macrophage polarization induced by COX-2 inhibitor-loaded Pd octahedral nanozymes for treatment of atherosclerosis

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Chinese Chemical Letters 2023年第1期34卷 262-269页

作者： Min Xu Chuchu Ren Yue Zhou Zbynek Heger xiaoyang liang Vojtech Adam Nan Li School of Pharmaceutical Science and Technology Tianjin UniversityTainjin 300072China Department of Chemistry and Biochemistry Mendel University in BrnoBrno CZ-61300Czech Republic

Inhibition of foam cell formation is considered a promising treatment method for atherosclerosis,the leading cause of cardiovascular diseases ***,currently available therapeutic strategies have shown unsatisfactory clinical ***,herein,we design aloperine(ALO)-loaded and hyaluronic acid(HA)-modified palladium(Pd)octahedral nanozymes(Pd@HA/ALO)that can synergistically scavenge reactive oxygen species(ROS)and downregulate cyclooxygenase-2(COX-2)expression to induce macrophage polarization,thus inhibiting foam cell formation to attenuate *** to the targeted effect of HA on stabilin-2 and CD44,which are overexpressed in atherosclerotic plaques,Pd@HA/ALO can actively accumulate in atherosclerotic ***,the antioxidative effects of Pd octahedral nanozymes are mediated by their intrinsic superoxide dismutase-and catalase-like activities capable of effective scavenging of *** addition,anti-inflammatory effects are mediated by controlled,on-demand near-infrared-triggered ALO release leading to inhibition of COX-2 ***,the combined therapy can promote the polarization of macrophages to the M2 subtype by upregulating Arg-1 and CD206 expression and downregulating expression of TNF-α,IL-1βand IL-6,thereby inhibiting atherosclerosis-related foam cell *** conclusion,the presented in vitro and in vivo data demonstrate that Pd@HA/ALO enhanced macrophage polarization to reduce plaque formation,identifying an attractive treatment strategy for cardiovascular disease.

关键词： Atherosclerosis COX-2 inhibitor Pd octahedral nanozyme Macrophage polarization Anti-inflammation Antioxidation

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Ion-interferential cell cycle arrest for melanoma treatment based on magnetocaloric bimetallic-ion sustained release hydrogel

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Chinese Chemical Letters 2024年第11期35卷 395-401页

作者： Zheyi Li xiaoyang liang Zitong Qiu Zimeng Liu Siyu Wang Yue Zhou Nan Li Tianjin Key Laboratory of Drug Delivery&High-Efficiency School of Pharmaceutical Science and TechnologyTianjin UniversityTianjin 300072China

Melanoma treatment has been revolutionized with the development of targeted therapies and immunotherapies,which shows a positive influence on the ***,the long-term efficaciousness of such therapy is restricted by side effects,limited clinical effects as well as quick resistance to *** this work,we prepared magnetocaloric carrier-free bimetallic hydrogels,named manganese-iron oxide nanocubes@polyethylene glycol-hydrogels(MFO@PEG-Gels),to realize ion-interferential cell cycle arrest for melanoma *** detail,the tumor site was exposed to alternating magnetic field(AMF)after intratumorally injected MFO@PEG-Gels,which generated hyperthermia and promoted the sol-gel phase transition for MFO sustained *** the tumor microenvironment,hydrogen peroxide triggered MFO degradation to induce Mn^(2+)and Fe^(3+)*** one hand,Mn^(2+)blocked G1/S phase through the activation of p27 *** the other hand,Fe^(3+)could arrest the G2/M phase by upregulating the polo-like kinase 4(PLK4)expression as well as inhibiting autolysosome formation to achieve the enhanced cell cycle arrest,thereby promoting the apoptosis of melanoma *** summary,this study proposed ion-interferential cell cycle arrest strategy by a multifunctional and injectable magnetic bimetallic hydrogel for melanoma treatment,which provided a secure and sustainable regimen for enhancing antitumor efficacy.

关键词： Melanoma Magnetocaloric bimetal Sustained release hydrogel Cell cycle arrest Ion-interferential

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Interpenetrating structure for efficient Sb_(2)Se_(3) nanorod array solar cells loaded with CuInSe_(2) QDs sensitizer

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Journal of Energy Chemistry 2022年第5期31卷 521-528页

作者： Cong Liu Zhenxiao Pan Kai Shen Jianzha Zheng xiaoyang liang Hongbing Zhu Fei Guo Zhiqiang Li Ruud E.I.Schropp Yaohua Mai Institute of New Energy Technology College of Information Science and TechnologyJinan UniversityGuangzhou 510632GuangdongChina Key Laboratory for Biobased Materials and Energy of Ministry of Education College of Materials and EnergySouth China Agricultural UniversityGuangzhou 510642GuangdongChina National-Local Joint Engineering Laboratory of New Energy Photoelectric Devices College of Physics Science and TechnologyHebei UniversityBaoding 071002HebeiChina

The strong anisotropic electrical properties of one-dimensional(1 D) nanostructure semiconductors,especially the anisotropic carrier transport, have a negative and significant influence on the performance of solar cells if the nanostructures have random orientation. Considering the advantages of nanorod solar cells in carrier transport, we have achieved growth of vertically aligned Sb_(2)Se_(3) nanorod array with highly(hk1) orientation on Cd S substrate, and constructed superstrate nanorod solar cells for the first time. The Sb_(2)Se_(3) nanorod array solar cells exhibit the more efficient and long-range carrier transport in vertical direction. Furthermore, in order to suppress interface recombination, a CuInSe_(2) quantum dots(QDs) sensitizer has been applied to fill the volume between the nanorods completely, thus forming an interpenetrating nanocomposite structure. The CuInSe_(2) QDs can harvest additional light by absorption of visible light and contribute photocurrent. Meantime, the QDs function as a hole transport material and thus reduce the dependence of lateral transport. Consequently, the interpenetrating nanocomposite CuInSe_(2) / Sb_(2)Se_(3) solar cells display a power conversion efficiency of 7.54% with significant enhancements in the short-circuit current density and open-circuit voltage over pure Sb_(2)Se_(3) nanorod cells. This is the highest efficiency for superstrate solar cells based on Sb_(2)Se_(3) nanorod arrays.

关键词： Superstrate solar cells Sb_(2)Se_(3)nanorod arrays Carrier transport Interpenetrating structure CuInSe_(2)QDs

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Remodeling of the liver fibrosis microenvironment based on nilotinib-loaded multicatalytic nanozymes with boosted antifibrogenic activity

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Acta Pharmaceutica Sinica B 2023年第12期13卷 5030-5047页

作者： Huaqing Jing Yingzi Ren Yue Zhou Min Xu Sona Krizkova Zbynek Heger Qiang Lu Siyu Wang xiaoyang liang Vojtech Adam Nan Li Tianjin Key Laboratory of Drug Delivery&High-Eficiency School of Pharmaceutical Science and TechnologyTianjin UniversityTianjin 300072China Department of Chemistry and Biochemistry Mendel University in BrnoBrno 61300Czech Republic

Liver fibrosis is a reversible pathological process caused by chronic liver damage and a major risk factor for hepatocellular carcinoma(HCC).Hepatic stellate cell(HSC)activation is considered the main target for liver fibrosis ***,the efficiency of this strategy is limited due to the complex microenvironment of liver fibrosis,including excessive extracellular matrix(ECM)deposition and hypoxia-induced imbalanced ECM ***,nilotinib(NIL)-loaded hyaluronic acid(HA)-coated Ag@Pt nanotriangular nanozymes(APNH NTs)were developed to inhibit HSCs activation and remodel the microenvironment of liver *** NTs efficiently eliminated intrahepatic reactive oxygen species(ROS)due to their inherent superoxide dismutase(SOD)and catalase(CAT)activities,thereby downregulating the expression of NADPH oxidase-4(NOX-4)and inhibiting HSCs ***,the oxygen produced by the APNH NTs further alleviated the hypoxic ***,the released NIL promoted collagen depletion by suppressing the expression of tissue inhibitor of metalloproteinase-1(TIMP-1),thus synergistically remodeling the microenvironment of liver ***,an in vivo study in CCl_(4)-induced mice revealed that APNH NTs exhibited significant antifibrogenic effects without obvious long-term *** together,the data from this work suggest that treatment with the synthesized APNH NTs provides an enlightening strategy for remodeling the microenvironment of liver fibrosis with boosted antifibrogenic activity.

关键词： Liver fibrosis Microenvironment remodeling HSCs ECM Collagen Hypoxia Nilotinib Nanozyme

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Generation of oxygen vacancies in NiFe LDH electrocatalysts by ultrasound for enhancing the activity toward oxygen evolution reaction

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Carbon Resources Conversion 2021年第1期4卷 76-83页

作者： Xiumin Li Qianyu Hu Yazhou Xu xiaoyang liang Jiawei Feng Kunyan Zhao Guoqing Guan Yongchao Jiang Xiaogang Hao Keyong Tang School of Materials Science and Engineering Zhengzhou UniversityZhengzhou 450001China Energy Conversion Engineering Laboratory Institute of Regional InnovationHirosaki University2-1-3 MatsubaraAomori 030-0813Japan Department of Chemical Engineering Taiyuan University of TechnologyTaiyuan 030024China

Introduction of vacancies is a promising route to enhance the performance of electrocatalysts by tuning the electronic structure and bonding ***,the influence of ultrasound treatment on the O vacancies formation and interlayer spacing in NiFe layered double hydroxide(LDH)was *** is found that the strong ultrasound treatment results in rich O vacancies on the surface of NiFe LDH,which affect the electrocatalysis ***,the ultrasound treated NiFe LDH electrocatalysts had a reduced thickness with a hexagonal nanosheet morphology and expanded interlayer distance,which could promote the diffusion of reactant and generated *** the obtained defect-rich NiFe LDH electrocatalyst prepared by a 10-min ultrasonic treatment was applied to catalyze oxygen evolution reaction(OER),only 194 mV of overpotential was needed to maintain a current density of 10 mA⋅cm^(-2).

关键词： Oxygen vacancy NiFe LDH Oxygen evolution reaction Ultrasound treatment

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4T1 cell membrane-derived biodegradable nanosystem for comprehensive interruption of cancer cell metabolism

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Chinese Chemical Letters 2023年第9期34卷 210-218页

作者： Yingzi Ren Huaqing Jing Yue Zhou Chuchu Ren Guangxu Xiao Siyu Wang xiaoyang liang Yunsheng Dou Ziqiao Ding Yan Zhu Xinxing Wang Nan Li Tianjin Key Laboratory of Drug Delivery&High-Efficiency School of Pharmaceutical Science and TechnologyTianjin UniversityTianjin 300072China Tianjin Institute of Environmental and Operational Medicine Tianjin 300050China State Key Laboratory of Component-based Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjin 301617China

Glycolysis inhibition can effectively block the energy supply and interrupt tumorigenesis in many types of ***,when glycolysis is inhibited,tumor cells will break down glutamine as the raw material for the replenishment pathway to maintain the tricarboxylic acid cycle ensuring energy supply,therefore inducing ineffective interruption of ***,we designed glutamine transporter antagonist L-γ-glutamyl-p-nitroanilide(GPNA)loaded and 4T1 cancer cell membrane coated iridium oxide nanoparticles(IrO_(2)-GPNA@CCM)to realize a comprehensive inhibition of tumor energy supply which synergistically mediated by glycolysis and glutamine ***_(2)NPs were used to catalyze the O_(2)generation by facilitating the decomposition of endogenous H_(2)O_(2)in tumor cells,which further downregulated the expression of HIF-1αand PI3K/pAKT to interrupt the generation of ***,the loaded GPNA was released under NIR irradiation to bind to alanine-serine-cysteine transporter(ASCT2)for glutamine uptake suppression,therefore realizing the comprehensive dysfunction of cell ***,both in vitro and in vivo results convinced the thorough energy inhibition effect based on Ir O_(2)-GPNA@CCM NPs,which provided an inspiring strategy for future construction of tumor therapeutic regimen.

关键词： Iridium oxide Glycolysis inhibition Glutamine suppression GPNA Tumor cell membrane

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导弹从发射箱热发射过程的数值分析

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航空动力学报 2022年第8期37卷 1643-1653页

作者：梁晓扬苏逸飞乐贵高南京理工大学机械工程学院南京210094

采用三维可压缩雷诺平均Navier-Stokes方程和k-ε湍流模型,研究了导弹出箱过程中,弹体姿态偏转后弹底周围环境及发射箱内的流场特性。首先,以超声速欠膨胀射流撞击平板实验为算例,对数值方法的有效性进行验证。其次,分别对导弹在约束期... 详细信息

采用三维可压缩雷诺平均Navier-Stokes方程和k-ε湍流模型,研究了导弹出箱过程中,弹体姿态偏转后弹底周围环境及发射箱内的流场特性。首先,以超声速欠膨胀射流撞击平板实验为算例,对数值方法的有效性进行验证。其次,分别对导弹在约束期和半约束期箱内流动特性展开研究。研究表明:喷管尾流在发射箱内会形成强烈的引射效应。同时,在弹底会出现明显的回流区域,使导弹出箱时受到额外的阻力。考虑偏转后,发射装置受到的冲击载荷增大2倍以上,发射箱壁面受到的压力增加40%。而且,在半约束期,箱内的流场分布不再对称,会使得导弹受到额外的不平衡力矩。

关键词：射流冲击非同时离轨发射箱引射效应二次流

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Numerical simulation on dynamic behaviors of a towed underwater cable under the pure sway conditions

Numerical simulation on dynamic behaviors of a towed underwa...

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第十八届中国海洋（岸）工程学术讨论会

作者： liang xiaoyang MA Ning LIU Han Gu Xiechong State Key Laboratory of Ocean Engineering Shanghai Jiao Tong University Collaborative Innovation Center for Advanced Ship and Deep-Sea Exploration School of Naval Architecture Ocean and Civil EngineeringShanghai Jiao Tong University

The influence from the sway motion of the small towing ship on the underwater towed system should be considered when the underwater missions and tasks are to be finished safely and *** this paper,a numerical approach is presented which focuses on the hydrodynamic performance and motion of the cable without towed body under the pure sway condition of the towing ***,a three-dimensional dynamics model for the flexible cable is built based on the lump-mass and spring *** the model,the cable is discretized into a finite amount of elements and the effect of the flow is taken into *** equation is solved by the Runge-Kutta *** appropriate time step is selected to calculate the dynamic tension and motion response of the cable under different flow speeds and different sway frequencies of the towing *** results show that,in the sway condition of the towing ship with the flow,the motion responses of the cable are complex,and both flow speeds and sway frequencies affect dynamic performance and attitude *** the flow rate grows,the tension of the cable *** the sway frequency increases,the tension at the top of the cable increases,and the position of the endpoint changes drastically.

关键词： numerical simulation underwater cable pure sway lump-mass-and spring method

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回转体潜器在循环水槽中垂直面大攻角操纵性试验

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上海交通大学学报 2019年第12期53卷 1395-1403页

作者：梁笑阳马宁刘晗顾解忡上海交通大学船舶海洋与建筑工程学院上海200240 上海交通大学海洋工程国家重点实验室上海200240 上海交通大学高新船舶与深海开发协同创新中心上海200240

以半尺寸SUBOFF潜器模型为研究对象,在循环水槽中利用平面运动机构完成包含不确定度分析的模型垂直面静态操纵性试验研究.测试内容包括:潜器在±60°攻角内、流速在1.0~1.2 m/s间的纵向力、垂向力及纵倾力矩.根据试验结果利用分段函数... 详细信息

以半尺寸SUBOFF潜器模型为研究对象,在循环水槽中利用平面运动机构完成包含不确定度分析的模型垂直面静态操纵性试验研究.测试内容包括:潜器在±60°攻角内、流速在1.0~1.2 m/s间的纵向力、垂向力及纵倾力矩.根据试验结果利用分段函数归纳了潜器垂直面操纵运动的数学模型,并应用最小二乘法拟合操纵性方程中的各项水动力系数.试验结果表明:测得无因次水动力的总不确定度较小,试验方法切实可靠;试验垂向力与纵倾力矩的无因次值随攻角值的增加而增大,纵倾力矩的无因次值在攻角超过±25°范围的非线性与非对称性十分明显;分段函数更适用于描述大攻角工况下的潜器垂直面操纵运动.

关键词： SUBOFF潜器模型循环水槽操纵性大攻角水动力数学模型

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