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Nano Research 2022年第4期15卷 3446-3457页

作者： minglu zhou Dandan Xie zhou zhou Lian Li Yuan Huang 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

The interaction between cancer cells and M2 tumor-associated macrophages(M2-TAMs)facilitates tumor growth and ***,cancer cells and M2-TAMs have different spatial distribution patterns,which requires distinct drug delivery ***,based on different tumor-penetrating ability of nanocarriers,we developed a combinatory strategy that consists of a TAMs-targeting liposome(alanine-alanine-asparagine(AAN)-Lip-regorafenib(Rego))and a cancer cells-targeting copolymer(internalizing RGD modified with N-(2-hydroxypropyl)methacrylamide-doxorubicin(iRGD-HD)).Our study confirmed AAN-Lip-Rego accumulated at perivascular sites where M2-TAM is located,while iRGD-HD penetrated into deep site of tumor to enter cancer ***,we found iRGD-HD induced cancer cells undergoing immunogenic cell death to enhance tumor infiltration of CD8^(+)T ***,AAN-Lip-Rego efficiently repolarized TAMs from M2 into M1 to alleviate tumor immunosuppression,thus reviving CD8^(+)T ***,the repolarization of TAMs led to dramatic downregulation of prometastatic factors expressed on cancer *** a result,such combinatory approach elicited robust antitumor immune responses and generated considerable anti-tumor and anti-metastasis efficacy to markedly inhibit primary tumor and spontaneous lung metastasis.

关键词： spatial distribution tumor-associated macrophage immunogenic cell death anti-tumor immunity cancer metastasis

Immunogenic hydrogel toolkit disturbing residual tumor “seeds” and pre-metastatic “soil” for inhibition of postoperative tumor recurrence and metastasis

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Acta Pharmaceutica Sinica B 2022年第8期12卷 3383-3397页

作者： minglu zhou Qingting Zuo Yuan Huang Lian Li 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

Tumor recurrence and metastasis is the leading cause of mortality for postoperative breast cancer patients. However, chemotherapy intervention after surgery is often unsatisfactory, because residual microtumors are difficult to target and require frequent administration. Here, an all-in-one and oncefor-all drug depot based on in situ-formed hydrogel was applied to fit the irregular surgical trauma, and enable direct contact with residual tumors and sustained drug release. Our immunological analysis after resection of orthotopic breast tumor revealed that postsurgical activation of CXCR4-CXCL12 signal exacerbated the immunosuppression and correlated with adaptive upregulation of PD-L1 in recurrent tumors. Thus, a multifunctional hydrogel toolkit was developed integrating strategies of CXCR4 inhibition,immunogenicity activation and PD-L1 blockade. Our results showed that the hydrogel toolkit not only exerted local effect on inhibiting residual tumor cell “seeds” but also resulted in abscopal effect on disturbing pre-metastatic “soil”. Furthermore, vaccine-like effect and durable antitumor memory were generated, which resisted a secondary tumor rechallenge in 100% cured mice. Strikingly, one single dose of such modality was able to eradicate recurrent tumors, completely prevent pulmonary metastasis and minimize off-target toxicity, thus providing an effective option for postoperative intervention.

关键词： Hydrogel Postoperative treatment Tumor recurrence Pre-metastatic niche CXCR4 inhibition Immunotherapy Local therapy Immunogenic cell death

Co-delivery of mitochondrial targeted lonidamine and PIN1 inhibitor ATRA by nanoparticulate systems for synergistic metastasis suppression

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Nano Research 2022年第4期15卷 3376-3386页

作者： Cheng Chen Qiuyi Li Liyun Xing minglu zhou Chaohui Luo Shujie Li Lian Li Yuan Huang 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

Mitochondria are highly involved in the metastasis of cancer ***,tumor cells impede the efficiency of mitochondrial targeted drugs by protecting mitochondria through an intrinsic and adaptive antioxidant *** aim to disturb the redox homeostasis by prolyl-isomerase PIN1 inhibitor all-trans retinoic acid(ATRA)to improve the therapeutic efficacy of mitochondrial targeted lonidamine(TL).The combination of ATRA and TL with a ratio of 2:1 was found to have the best synergistic effect in inhibiting the proliferation and metastasis of metastatic 4T1 breast cancer ***-drug loaded nanoparticles(TL-ATRA NPs)were further developed by self-assembly and were observed to disturb the redox homeostasis drastically and triggered a robust mitochondrial disruption on metastatic 4T1 breast cancer *** molecular mechanism was related to the downregulation of nuclear factor E2-related factor 2(NRF2),a critical transcription factor that regulated antioxidant responses,and its downstream *** a result,TL-ATRA NPs significantly suppressed the growth of primary tumors and the formation of lung metastasis ***,our findings showed that sensitizing mitochondria to anti-cancer drugs by disturbing redox homeostasis achieved a satisfactory therapeutic effect to inhibit tumor growth and metastasis.

关键词： tumor metastasis mitochondrial dysfunction PIN1 inhibition redox homeostasis disruption combinatorial therapy

Overcoming chemotherapy resistance via simultaneous drug-efflux circumvention and mitochondrial targeting

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Acta Pharmaceutica Sinica B 2019年第3期9卷 615-625页

作者： minglu zhou Lijia Li Lian Li Xi Lin Fengling Wang Qiuyi Li Yuan Huang Key Laboratory of Drug Targeting and Drug Delivery System(Ministry of Education) West China School of PharmacySichuan UniversityChengdu610041China Department of Pharmaceutics and Pharmaceutical Chemistry/Center for Controlled Chemical Delivery University of UtahSalt LakeCityUT84112USA

Multidrug resistance(MDR) has been considered as a huge challenge to the effective chemotherapy. Therefore, it is necessary to develop new strategies to effectively overcome MDR. Here,based on the previous research of N-(2-hydroxypropyl)methacrylamide(HPMA) polymer–drug conjugates, we designed an effective system that combined drug-efflux circumvention and mitochondria targeting of anticancer drug doxorubicin(Dox). Briefly, Dox was modified with mitochondrial membrane penetrating peptide(MPP) and then attached to(HPMA) copolymers(P-M-Dox). Our study showed that macromolecular HPMA copolymers successfully bypassed drug efflux pumps and escorted Dox into resistant MCF-7/ADR cells via endocytic pathway. Subsequently, the mitochondria accumulation of drugs was significantly enhanced with 11.6-fold increase by MPP modification. The excellent mitochondria targeting then resulted in significant enhancement of reactive oxygen species(ROS) as well as reduction of adenosine triphosphate(ATP)production, which could further inhibit drug efflux and resistant cancer cell growth. By reversing Dox resistance, P-M-Dox achieved much better suppression in the growth of 3D MCF-7/ADR tumor spheroids compared with free Dox. Hence, our study provides a promising approach to treat drug-resistant cancer through simultaneous drug efflux circumvention and direct mitochondria delivery.

关键词： Drug resistance P-gp pumps Mitochondrial targeting HPMA copolymer Drug delivery Doxorubicin

RP-3航油火焰三维温度场和碳烟浓度场测量

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北京航空航天大学学报 2024年第4期50卷 1273-1281页

作者：左冰娴周宾戴明露东南大学能源与环境学院南京210096

RP-3航空煤油是航空发动机的常用燃料之一,火焰温度及碳烟浓度分布作为反映燃烧状态最直接的参数,是燃料优化配比的重要数据支撑。针对三维测量中,重建路径计算的准确性受相机位姿影响的问题,提出了一种将三维辐射成像法与相机立体标定... 详细信息

RP-3航空煤油是航空发动机的常用燃料之一,火焰温度及碳烟浓度分布作为反映燃烧状态最直接的参数,是燃料优化配比的重要数据支撑。针对三维测量中,重建路径计算的准确性受相机位姿影响的问题,提出了一种将三维辐射成像法与相机立体标定技术相结合的测量方法。数值模拟结果表明,所提方法可以在提供较高的空间分辨率的同时保证测量结果的可靠性。利用标定后的六相机测量系统,对RP-3、空气预混火焰进行了实验测量,获得了其三维温度及碳烟浓度分布。测量的空间分辨率为1 mm×1 mm×1 mm,重建与热电偶测量温差的标准不确定度为0.58 K,证明了测量方法的精确性。

关键词： RP-3航空煤油 CCD相机相机立体标定温度碳烟浓度

Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury

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Asian Journal of Pharmaceutical Sciences 2024年第2期19卷 89-101页

作者： Yunhan Zhang Zhulin Zou Shuang Liu Fangfang Chen minglu Li Haoyang Zou Haiyan Liu Jianxun Ding Key Laboratory of Pathobiology Ministry of Education Department of AnatomyCollege of Basic Medical SciencesJilin UniversityChangchun 130061China Key Laboratory of Polymer Ecomaterials Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China Department of Gastrointestinal Colorectaland Anal SurgeryChina-Japan Union Hospital of Jilin UniversityChangchun 130033China

Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.

关键词： Poly(amino acid)nanogel Controlled drug delivery Inhibition of ferroptosis Neuroprotection Cerebral ischenia injury therapy

Parallel Physics-Informed Neural Networks Method with Regularization Strategies for the Forward-Inverse Problems of the Variable Coefficient Modified KdV Equation

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Journal of Systems Science & Complexity 2024年第2期37卷 511-544页

作者： zhou Huijuan School of Science Shanghai Maritime UniversityShanghai 201306China

This paper mainly introduces the parallel physics-informed neural networks(PPINNs)method with regularization strategies to solve the data-driven forward-inverse problems of the variable coefficient modified Korteweg-de Vries(VC-MKdV)*** the forward problem of the VC-MKdV equation,the authors use the traditional PINN method to obtain satisfactory data-driven soliton solutions and provide a detailed analysis of the impact of network width and depth on solving accuracy and ***,the author finds that the traditional PINN method outperforms the one with locally adaptive activation functions in solving the data-driven forward problems of the VC-MKdV *** for the data-driven inverse problem of the VC-MKdV equation,the author introduces a parallel neural networks to separately train the solution function and coefficient function,successfully addressing the function discovery problem of the VC-MKdV *** further enhance the network’s generalization ability and noise robustness,the author incorporates two regularization strategies into the *** amount of numerical experimental data in this paper demonstrates that the PPINNs method can effectively address the function discovery problem of the VC-MKdV equation,and the inclusion of appropriate regularization strategies in the PPINNs can improves its performance.

关键词： Data-driven forward-inverse problems parallel physics-informed neural networks regularization strategies variable coefficient modified KdV equation

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Deep-reinforcement-learning-based UAV autonomous navigation and collision avoidance in unknown environments

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Chinese Journal of Aeronautics 2024年第3期37卷 237-257页

作者： Fei WANG Xiaoping ZHU zhou zhou Yang TANG School of Astronautics Northwestern Polytechnical UniversityXi’an 710072China School of Aeronautics Northwestern Polytechnical UniversityXi’an 710072China

In some military application scenarios,Unmanned Aerial Vehicles(UAVs)need to perform missions with the assistance of on-board cameras when radar is not available and communication is interrupted,which brings challenges for UAV autonomous navigation and collision *** this paper,an improved deep-reinforcement-learning algorithm,Deep Q-Network with a Faster R-CNN model and a Data Deposit Mechanism(FRDDM-DQN),is proposed.A Faster R-CNN model(FR)is introduced and optimized to obtain the ability to extract obstacle information from images,and a new replay memory Data Deposit Mechanism(DDM)is designed to train an agent with a better *** training,a two-part training approach is used to reduce the time spent on training as well as retraining when the scenario *** order to verify the performance of the proposed method,a series of experiments,including training experiments,test experiments,and typical episodes experiments,is conducted in a 3D simulation *** results show that the agent trained by the proposed FRDDM-DQN has the ability to navigate autonomously and avoid collisions,and performs better compared to the FRDQN,FR-DDQN,FR-Dueling DQN,YOLO-based YDDM-DQN,and original FR outputbased FR-ODQN.

关键词： Faster R-CNN model Replay memory Data Deposit Mechanism(DDM) Two-part training approach Image-based Autonomous Navigation and Collision Avoidance(ANCA) Unmanned Aerial Vehicle(UAV)

Oxidation of emerging organic contaminants by in-situ H_(2)O_(2) fenton system

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Green Energy & Environment 2024年第3期9卷 417-434页

作者： Yuqin Ni Chuxiang zhou Mingyang Xing Yi zhou State Environmental Protection Key Lab of Environmental Risk Assessment and Control on Chemical Processes School of Resources&Environmental EngineeringEast China University of Science and TechnologyShanghai200237China Key Laboratory for Advanced Materials and Institute of Fine Chemicals National Engineering Laboratory for Industrial Wastewater TreatmentSchool of Chemistry and Molecular EngineeringEast China University of Science and Technology130 Meilong RoadShanghai200237China Department of Applied Natural Sciences Technische Hochschule LubeckMonkhofer Weg 23923562 LubeckGermany

The existence and risk of emerging organic contaminants(EOCs)have been under consideration and paid much effort to degrade these *** system is one of the most widely used technologies to solve this *** original Fenton system relies on the hydroxyl radicals produced by Fe(Ⅱ)/H_(2)O_(2) to oxidize the organic ***,the application of the Fenton system is limited by its low iron cycling efficiency and the high risks of hydrogen peroxide transportation and *** introduction of external energy(including light and electricity etc.)can effectively promote the Fe(Ⅲ)/Fe(Ⅱ)cycle and the reduction of oxygen to produce hydrogen peroxide in *** review introduces three in-situ Fenton systems,which are electro-Fenton,Photo-Fenton,and chemical *** mechanism,influencing factors,and catalysts of these three in-situ Fenton systems in degrading EOCs are discussed *** review strengthens the understanding of Fenton and in-situ Fenton systems in degradation,offering further insight into the real application of the in-situ Fenton system in the removal of EOCs.

关键词： In-situ H_(2)O_(2)production Fenton Emerging organic contaminants Photocatalysis Electrocatalysis

SPARSE RECOVERY BASED ON THE GENERALIZED ERROR FUNCTION

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Journal of Computational Mathematics 2024年第3期42卷 679-704页

作者： Zhiyong zhou Department of Statistics and Data Science and Institute of Digital FinanceHangzhou City UniversityHangzhou 310015China

In this paper,we offer a new sparse recovery strategy based on the generalized error *** introduced penalty function involves both the shape and the scale parameters,making it extremely *** both constrained and unconstrained models,the theoretical analysis results in terms of the null space property,the spherical section property and the restricted invertibility factor are *** practical algorithms via both the iteratively reweighted■_(1)and the difference of convex functions algorithms are *** experiments are carried out to demonstrate the benefits of the suggested approach in a variety of *** practical application in magnetic resonance imaging(MRI)reconstruction is also investigated.

关键词： Sparse recovery Generalized error function Nonconvex regularization Itera-tive reweighted Li Difference of convex functions algorithms