检索结果-南通市图书馆

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

引用

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

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Spatially targeting of tumor-associated macrophages and cancer cells for suppression of spontaneously metastatic tumor

引用

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 metastasis.However,cancer cells and M2-TAMs have different spatial distribution patterns,which requires distinct drug delivery strategies.Herein,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 cells.Thereafter,we found iRGD-HD induced cancer cells undergoing immunogenic cell death to enhance tumor infiltration of CD8^(+)T cells.Meanwhile,AAN-Lip-Rego efficiently repolarized TAMs from M2 into M1 to alleviate tumor immunosuppression,thus reviving CD8^(+)T cells.Moreover,the repolarization of TAMs led to dramatic downregulation of prometastatic factors expressed on cancer cells.As 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

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

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

引用

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 cells.However,tumor cells impede the efficiency of mitochondrial targeted drugs by protecting mitochondria through an intrinsic and adaptive antioxidant mechanism.We 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 cells.Dual-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 cells.The 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 molecules.As a result,TL-ATRA NPs significantly suppressed the growth of primary tumors and the formation of lung metastasis nodes.Collectively,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

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

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

引用

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

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

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

引用

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

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

RP-3航油火焰三维温度场和碳烟浓度场测量

引用

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

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

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

引用

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)equation.For 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 speed.Furthermore,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 equation.As 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 equation.To further enhance the network’s generalization ability and noise robustness,the author incorporates two regularization strategies into the PPINNs.An 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

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

An Environment‑Tolerant Ion‑Conducting Double‑Network Composite Hydrogel for High‑Performance Flexible Electronic Devices

引用

Nano-Micro Letters 2024年第5期16卷 352-369页

作者： Wenchao Zhao Haifeng zhou Wenkang Li Manlin Chen Min zhou Long Zhao State Key Laboratory of Advanced Electromagnetic Technology School of Electrical and Electronic EngineeringHuazhong University of Science and TechnologyWuhan 430074People’s Republic of China School of Chemistry and Chemical Engineering Huazhong University of Science and TechnologyWuhan 430074People’s Republic of China

High-performance ion-conducting hydrogels(ICHs)are vital for developing flexible electronic devices.However,the robustness and ion-conducting behavior of ICHs deteriorate at extreme tempera-tures,hampering their use in soft electronics.To resolve these issues,a method involving freeze–thawing and ionizing radiation technology is reported herein for synthesizing a novel double-network(DN)ICH based on a poly(ionic liquid)/MXene/poly(vinyl alcohol)(PMP DN ICH)system.The well-designed ICH exhibits outstanding ionic conductivity(63.89 mS cm^(-1) at 25℃),excellent temperature resistance(-60–80℃),prolonged stability(30 d at ambient temperature),high oxidation resist-ance,remarkable antibacterial activity,decent mechanical performance,and adhesion.Additionally,the ICH performs effectively in a flexible wireless strain sensor,thermal sensor,all-solid-state supercapacitor,and single-electrode triboelectric nanogenerator,thereby highlighting its viability in constructing soft electronic devices.The highly integrated gel structure endows these flexible electronic devices with stable,reliable signal output performance.In particular,the all-solid-state supercapacitor containing the PMP DN ICH electrolyte exhibits a high areal specific capacitance of 253.38 mF cm^(-2)(current density,1 mA cm^(-2))and excellent environmental adaptability.This study paves the way for the design and fabrication of high-performance mul-tifunctional/flexible ICHs for wearable sensing,energy-storage,and energy-harvesting applications.

关键词： Ionic liquids Double-network hydrogels Temperature tolerance Multifunctionality Flexible electronic devices

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

Effects of nitrogen and phosphorus additions on soil nematode community of soybean farmland

引用

Soil Ecology Letters 2024年第2期6卷 45-55页

作者： Huiying Zhang Mengyang Tian Meiguang Jiang Jingyuan Yang Qi Xu Ying Zhang minglu Ji Yuteng Yao Cancan Zhao Yuan Miao International Joint Research Laboratory for Global Change Ecology School of Life SciencesHenan UniversityKaifeng475004China Henan Dabieshan National Field Observation and Research Station of Forest Ecosystem Xinyang Academy of Ecological ResearchXinyang464000China

The nitrogen(N)and phosphorus(P)addition promotes the abundance of soybean soil nematodes.The addition of nitrogen can alleviate the suppression of phosphorus on nematodes.Phosphorus addition affects nematode abundanc... 详细信息

关键词： soil nematodes nitrogen addition phosphorus addition soil food web soybean

来源：

维普期刊数据库评论

在线全文

维普期刊数据库

学校读者我要写书评

暂无评论

Perturbation of autophagy pathways in murine alveolar macrophage by 2D TMDCs is chalcogen-dependent

引用

Journal of Environmental Sciences 2024年第1期135卷 97-107页

作者： Xiaofei zhou Weitao Jin Rui Zhang Xuan Mao Jianbo Jia Hongyu zhou College of Science&Technology Hebei Agricultural UniversityHuanghua 061100China Institute of Environmental Research at Greater Bay Area Key Laboratory for Water Quality and Conservation of the Pearl River DeltaMinistry of EducationGuangzhou UniversityGuangzhou 510006China

Increasing risks of incidental and occupational exposures to two-dimensional transition metal dichalcogenides(2D TMDCs)due to their broad application in various areas raised their public health concerns.While the composition-dependent cytotoxicity of 2D TMDCs has been well-recognized,how the outer chalcogenide atoms and inner transition metal atoms differentially contribute to their perturbation on cell homeostasis at non-lethal doses remains to be identified.In the present work,we compared the autophagy induction and related mechanisms in response to WS_(2),NbS_(2),WSe_(2)and Nb Se_(2)nanosheets exposures in MH-S murine alveolar macrophages.All these 2D TMDCs had comparable physicochemical properties,overall cytotoxicity and capability in triggering autophagy in MH-S cells,but showed outer chalcogen-dependent subcellular localization and activation of autophagy pathways.Specifically,WS_(2)and NbS_(2)nanosheets adhered on the cell surface and internalized in the lysosomes,and triggered m TOR-dependent activation of autophagy.Meanwhile,WSe_(2)and Nb Se_(2)nanosheets had extensive distribution in cytoplasm of MH-S cells and induced autophagy in an m TOR-independent manner.Furthermore,the 2D TMDCs-induced perturbation on autophagy aggravated the cytotoxicity of respirable benzo[a]pyrene.These findings provide a deeper insight into the potential health risk of environmental 2D TMDCs from the perspective of homeostasis perturbation.

关键词： Chalcogen group Autophagy pathway Cell function Endosomal escape Inhalation toxicity

来源：

维普期刊数据库

同方期刊数据库评论

在线全文

学校读者我要写书评

暂无评论

欢迎您,

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案：

请选择收藏分类：

通借通还

欢迎您,

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

在线全文

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：