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Engineered Bacterial Outer Membrane Vesicles-Based Doxorubicin and CD47-siRNA Co-Delivery Nanoplatform Overcomes Immune Resistance to Potentiate the Immunotherapy of Glioblastoma

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ADVANCED MATERIALS 2025年第15期37卷 e2418053页

作者： You, Haoyu Zhang, Shilin Zhang, Yiwen Chen, Qinjun Wu, Yuxing Zhou, Zheng Zhao, Zhenhao Su, Boyu Li, xuwen guo, Yun Chen, Yun Tang, Weiyi Liu, Bing Fan, Hongrui Geng, Shuo Fang, Mingzhu Li, Fangxin Liu, Guangna Jiang, Chen Sun, Tao Fudan Univ Sch Pharm State Key Lab Med Neurobiol Minhang HospInnovat Ctr New Drug Dev Immune Infla Shanghai 201203 Peoples R China Fudan Univ MOE Frontiers Ctr Brain Sci Sch Pharm Dept Pharmaceut Shanghai 201203 Peoples R China Fujian Med Univ Affiliated Hosp 1 Natl Reg Med Ctr Dept Orthoped Binhai Campus Fuzhou 350212 Peoples R China Quzhou Fudan Inst Quzhou 324003 Peoples R China

Apart from the blood-brain barrier (BBB), the efficacy of immunotherapy for glioblastoma (GBM) is limited by the presence of intrinsic and adaptive immune resistance, implying that co-delivery of various immunotherapeutic agents or simultaneous regulation of different cells is urgently needed. Bacterial outer membrane vesicles (OMVs) offer a unique advantage in the treatment of GBM, owing to their multifunctional properties as carriers and immune adjuvants and their ability to cross the BBB. However, traditional OMVs can lead to toxic side effects and disruption of tight junctions in the BBB. Therefore, to enhance the in vivo safety and targeting capability of OMVs, we introduced engineered OMVs to reduce toxicity and further constructed a modularly assembled nanoplatform by performing simple peptide modifications. This nanoplatform demonstrates satisfactory biosafety and is able to continuously cross the BBB and target GBM with the assistance of Angiopep-2. Subsequently, immunogenic substances on OMVs, along with carried small-interfering RNA (siRNA) and doxorubicin, can promote and enhance the reprogramming and phagocytic abilities of macrophages and microglia, respectively, and increase the immunogenicity of GBM, ultimately overcoming GBM immune resistance to enhance the efficacy of immunotherapy. This OMVs-based nanoplatform provides a new paradigm and insights into the development of immunotherapy for GBM.

关键词： engineering technology glioblastoma immune resistance immunotherapy outer membrane vesicles

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Facile fabrication of cross-linked n-Al/PVDF films with the tunability of reactivity and laser sensitivity

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JOURNAL OF ALLOYS AND COMPOUNDS 2023年 936卷

作者： Li, Jingwei Liu, xuwen Zhang, Zihao Wang, Yikai Zhang, Mingxing guo, Kaige Duanmu, Fanshun Zhu, Chenguang Nanjing Univ Sci & Technol Sch Chem & Chem Engn Nanjing 210094 Peoples R China Sci & Technol Electro Opt Informat Secur Control L Tianjin 300308 Peoples R China Jianghan Univ State Key Lab Precis Blasting Wuhan 430113 Peoples R China

Metastable intermolecular complexes (MICs), which have exceptional energy density and reactivity, have drawn considerable attention in the field of energetic materials. In this work, a facile cryogel method is explored for fabricating n-Al/PVDF energetic films with the controllable tuning of reactivity and laser sensitivity. The microstructure of the films was transformed from dense packing to 3D cross-linking by adjusting the process parameters. With the formation of the porous structure, the energetic film exhibits a higher energy release rate (the flame propagation speed increases from 8.2 cm center dot s-1 to 13.5 cm center dot s-1) and a lower laser ignition delay (from 33.6 ms to 10.1 ms). The mechanisms underlying the altered reactivity are discussed in depth to provide insights into understanding changes in energy properties. This work provides an effective and facile strategy for realizing the tunability of the reactivity and sensitivity of n-Al/PVDF composites, which will aid to broaden their use in micro-transducers.(c) 2022 Elsevier B.V. All rights reserved.

关键词： Nanostructured energetic materials Conformational relationships Reaction tunability Cryogel method Laser sensitivity

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Chemical Constituents of the Marine Traditional Chinese Medicine of Pegasus laternarius Cuvier (Hai-E Yu)

Pharmaceutical Fronts

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Pharmaceutical Fronts 2024年第2期6卷 E149-E154页

作者： Sun, Shuqian Gao, Zhen Wang, Mengxue Chen, Sha guo, Wenjuan Li, xuwen School of Chemistry and Chemical Engineering University of Jinan Shandong Laboratory of Yantai Drug Discovery Bohai Rim Advanced Research Institute for Drug Discovery State Key Laboratory of Chemical Biology Shanghai Institute of Materia Medica Chinese Academy of Sciences

Pegasus laternarius Cuvier (Hai-E Yu) is a marine traditional Chinese medicine that has been used to treat cancers and reduce inflammation. Previous chemical investigations have only revealed the occurrence of high levels of protein, fatty acids, and a large number of steroids, thusmore active compounds in P. laternarius still need to be further discovered. The present study aims to search for new bioactive constituents of P. laternarius with cytotoxic effects and nitric oxide (NO) inhibitory activities. In this work, 16 pure compounds from the ethyl acetate fraction of Pegasus laternarius Cuvier were successively obtained by various chromatographic techniques, and the structure of the isolates was elucidated by spectroscopic analyses. The isolated and identified compounds included one 2H-1,2,3-triazole-4-carboxylate derivative (1), two oxadiazines (2, 3), two amino acids (4, 5), three nucleosides (6-8), three steroids (9-11), and five others (12-16). All the obtained compounds were evaluated for their antitumor activity on A549 and HCT-116 cell lines along with their inhibitory effects on lipopolysaccharide-induced NO production in RAW264.7 cells. The triazole compound 1 was found to exhibit moderate cytotoxicity against two human cell lines (A549 and HCT-116) with IC₅₀ values of 44.5 and 32.9 μmol/L, respectively. The steroid compound 10 inhibited NO production with IC₅₀ values lower than 50 μmol/L. Consequently, this study provides insight into the cytotoxic and NO inhibitory activities of the marine traditional Chinese medicines in Hai-E-Yu. © 2024. The Author(s).

关键词： anti-inflammatory cytotoxicity marine traditional Chinese medicine Pegasus laternarius Cuvier

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Molecular simulation studies on the water/methane two-phase flow in a cylindrical silica nanopore: Formation mechanisms of water lock and implications for gas hydrate exploitation

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FUEL 2023年第Part1期333卷

作者： Zheng, Chao guo, Guang-Jun Qin, xuwen Dong, Yanhui Lu, Cheng Peng, Bo Tang, Wei Bian, Hang Chinese Acad Sci Inst Geol & Geophys Key Lab Petr Resource Res Beijing 100029 Peoples R China Univ Chinese Acad Sci Coll Earth & Planetary Sci Beijing 100049 Peoples R China China Geol Survey Guangzhou Marine Geol Survey Guangzhou 511458 Peoples R China Natl Engn Res Ctr Gas Hydrate Explorat & Dev Guangzhou 511458 Peoples R China Chinese Acad Sci Inst Geol & Geophys Key Lab Shale Gas & Geoengn Beijing 100029 Peoples R China China Geol Survey Ctr Oil & Nat Gas Resource Explorat Beijing 100083 Peoples R China China Univ Geosci Sch Energy Resources Beijing 100083 Peoples R China

The water/gas two-phase flow is a frequently encountered question in the percolation field, and is especially important for the exploitation of natural gas hydrates because their decomposition products are exactly liquid water and natural gas. We studied the water/methane two-phase flow in a hydrophilic cylindrical nanopore by performing molecular simulations, and obtained high-quality nanoflows under different water saturation (Sw) thanks to the newly established nano-manometer method to control pressure difference accurately. With increasing Sw, the methane flow decreases almost linearly until a sudden stop when Sw >= 0.52. The formation of the water lock accounting for this phenomenon is observed clearly, and the larger Sw, the earlier formation of the water lock as well as the longer water lock. Based on careful data analysis, a water lock model and its formation mechanism are newly proposed with two pieces of strong evidence - the continuous reduction of the surface area of the water/gas interface when the water lock forms and the existence of maximum thickness of water film for different Sw. Thus, the competition between the surface tension of the water/gas interface and the adsorption of the water/wall interface controls the development of the water lock. These findings are very helpful for un-derstanding the two-phase percolation and optimizing the gas production and water removal schemes during hydrate exploitation. In addition, the nano-manometer can be widely used in other nanoflow simulations for measuring the local pressure accurately.

关键词： Water methane two-phase flow Cylindrical nanopore Nano -manometer Relative permeability Water lock Natural gas hydrates

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Microenvironment-tailored micelles restrain carcinoma-astrocyte crosstalk for brain metastasis

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JOURNAL OF CONTROLLED RELEASE 2022年 349卷 520-532页

作者： Zhao, Zhenhao Zhang, Yujie Li, Chao Li, xuwen Chu, Yongchao guo, Qin Zhang, Yiwen Xia, Weiyi Liu, Peixin Chen, Hongyi Wang, Yu Li, Chufeng Sun, Tao Jiang, Chen Fudan Univ Sch Pharm Dept Pharmaceut Key Lab Smart Drug Delivery Shanghai 201203 Peoples R China Fudan Univ MOE Frontiers Ctr Brain Sci Shanghai 201203 Peoples R China

Breast-to-brain metastatic cells can interact with the surrounding cells, including astrocytes and microglia, to generate a pro-tumorigenic niche. Breast-to-brain metastasis can be treated using a dual strategy of eliminating metastatic tumor cells and normalizing their localized microenvironment. The effective accumulation of drugs at the action site of metastasis is crucial to realizing the above strategy, especially when dealing with the bloodbrain barrier (BBB)-penetrating and tumor-targeting tactics. Here, we establish an in-situ microenvironmenttailored micelle (T-M/siRNA) to co-deliver therapeutic siRNA and paclitaxel (PTX) into the breast-to-brain metastasis. Anchored with a D-type cyclic peptide, T-M/siRNA can penetrate the BBB and subsequently target the brain metastases. Upon internalization by metastatic tumor cells, T-M/siRNA can release PTX in the highlevel glutathione (GSH), resulting in killing cancer cells. Meanwhile, the micellar structure is dissociated, resulting in lowering the charge density to release the loaded siRNA that can targeted downregulate the expression of protocadherin 7 (PCDH7). Treatment of model mice revealed that T-M/siRNA can inhibit the abnormal activation of astrocytes and immunosuppressive activation of microglia, resulting in significantly enhanced synergistic anti-tumor efficacy. This study indicates that the micelle system can serve as a hopeful strategy to treat breast-to-brain metastasis.

关键词： Breast -to -brain metastasis Micelle Microenvironment Protocadherin 7 Paclitaxel

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Influence of hydrostatic pressure on the corrosion and discharging behavior of Al-Zn-In-Mg-Ti alloy

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JOURNAL OF ALLOYS AND COMPOUNDS 2023年 936卷

作者： Hu, Shengbo Yuan, xuwen Liu, Li Liu, Rui Li, Fengguang Liu, Jianyong guo, Rui Yang, Wei Wang, Fuhui Hubei Univ Automot Technol Sch Mat Sci & Engn Shiyan 442002 Peoples R China Northeastern Univ Shenyang Natl Lab Mat Sci 3-11 Wenhua Rd Shenyang 110819 Peoples R China

The corrosion and discharging behavior of Al-Zn-In-Mg-Ti alloy were studied at a series pressures ranged from 0.1 MPa to 13.0 MPa using weigh loss experiments, electrochemical techniques, and imaging mea-surements et al. Results reveal that the self-corrosion and self-discharging process of Al-Zn-In-Mg-Ti alloy live through the same three stages, which are all accelerated by hydrostatic pressure. The discharging performance of Al-Zn-In-Mg-Ti drops with increasing pressure, which is caused by the acceleration of cathodic process and severer intergranular corrosion. The corresponding cathodic protection design based on Al-Zn-In-Mg-Ti sacrificial anode with the changing pressure has been set up, which follows exponential function.(c) 2022 Elsevier B.V. All rights reserved.

关键词： Sacrificial anode Hydrostatic pressure Intergranular corrosion EIS

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Polyoxygenated anti-inflammatory biscembranoids from the soft coral Sarcophyton tortuosum and their stereochemistry

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Chinese Chemical Letters 2021年第1期32卷 271-276页

作者： Yufen Li Songwei Li Cristina Cuadrado Chenglong Gao Qihao Wu Xiaolu Li Tao Pang Antonio Hernandez Daranas Yuewei guo xuwen Li State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China School of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210023China Instituto de Productos Naturalesy Agrobiologi’a Consejo Superior de Investigaciones Científicas(IPNA-CSIC)La Laguna 38206Spain Jiangsu Key Laboratory of Drug Screening State Key Laboratory of Natural MedicinesJiangsu Key Laboratory of Drug Discovery for Metabolic DiseasesChina Pharmaceutical UniversityNanjing210009 China

Five novel biscembranoids,ximaolides H-L(1-5),along with four known related compounds(6-9) were isolated from the Hainan soft coral Sarcophyton *** structures of the new compounds were determined by extensive spectroscopic analysis,quantum chemical calculations,and/or by comparing their CD spectra with those of the known *** 1 and 2 are the first examples of biscembranoids bearing a 1,35-bridged lactone moiety,4 is the first biscembranoid comprising an uncommon oxetane ring,and 5 represents the first 36-peroxyl *** Ⅰ(2),K(4) and F(9) exhibited interesting anti-inflammatory activity by the inhibition of LPS-induced TNF-α protein release in RAW264.7 macrophages.

关键词： Soft coral Sarcophyton tortuosum Biscembranoid Stereochemistry Anti-inflammatory

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NIR light-driven photocatalytic NAD(P)H oxidation and H2O2 generation in situ for enhanced chemodynamic therapy and immune response

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NANO TODAY 2023年第1期50卷

作者： Zhang, Chao Huang, Jia guo, Xusheng Da, xuwen Dai, Zhifei Hassan, Moustapha Yu, Yingjie Wang, Xuesong Zhou, Qianxiong Chinese Acad Sci Tech Inst Phys & Chem Key Lab Photochem Convers & Optoelect Mat Beijing 100190 Peoples R China Univ Chinese Acad Sci Beijing 100049 Peoples R China China Japan Friendship Hosp Dept Hepatobiliary Surg Beijing 100029 Peoples R China Peking Univ Coll Future Technol Natl Biomed Imaging Ctr Dept Biomed Engn Beijing Peoples R China Karolinska Inst Dept Lab Med LABMED Div Expt Canc Med SE-14186 Stockholm Sweden Karolinska Univ Hosp Huddinge Clin Res Ctr SE-14186 Stockholm Sweden Karolinska Univ Hosp Huddinge Ctr Allogene Stem Cell Transplantat CAST SE-14186 Stockholm Sweden Beijing Univ Chem Technol State Key Lab Organ Inorgan Composites Beijing Lab Biomed Mat Beijing 100029 Peoples R China

Chemodynamic therapy (CDT) is an appealing cancer treatment that converts endogenous H2O2 into highly toxic hydroxyl radicals to kill cancer cells. However, the limited amount of H2O2 in tumor cells constrains the application of CDT. Therefore, the strategy that can increase H2O2 level in situ could broaden its clinical application. Herein, we synthesized a supramolecule [Ru(bpy)2(Nabpy)](PF6)2 (Ru1) which can efficiently photo-catalyze NAD(P)H oxidation with simultaneous generation of H2O2 with a high yield at 76.4 %. The Ru1 and Fe2+ were then loaded on the mesoporous silica-encapsulated rare earth-doped upconversion nanoparticles (UCSRF), the intracellular H2O2 level can be elevated by 2.8 times upon the irradiation of near-infrared (NIR) light irradiation. Then, the intracellular H2O2 was transformed into hydroxyl radicals through Fenton reaction to achieve efficient CDT both in vitro and in vivo. Furthermore, we demonstrated that UCSRF could effectively enhance immunogenic cell death (ICD) effect, resulting in the reprogramming of the immunosuppressive tumor microenvironment to stimulate immune response. This work represents the first proof-of-concept study on photo-catalytically enhancing H2O2 production in situ upon NIR irradiation for spatiotemporal CDT.(c) 2023 Elsevier Ltd. All rights reserved.

关键词： Chemodynamic therapy Photocatalytic NAD(P)H oxidation Immunotherapy Upconversion nanoparticle

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Fabrication of NiZn bimetallic oxides catalysts supported on carbon black waste for catalytic pyrolysis of fatty acid

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APPLIED CATALYSIS A-GENERAL 2023年 668卷

作者： Zhang, Yang Zhang, xuwen guo, Fangsong Tan, Kok Bing Wang, Youting Sun, Kang Rao, Xiaoping Zhang, Xiaodong Zhan, guowu Huaqiao Univ Acad Adv Carbon Convers Technol Coll Chem Engn Fujian Prov Key Lab Biomass Low Carbon Convers 668 Jimei Ave Xiamen 361021 Fujian Peoples R China Jimei Univ Coll Marine Equipment & Mech Engn 185 Yinjiang Rd Xiamen 361021 Fujian Peoples R China Chinese Acad Forestry CAF Inst Chem Ind Forest Prod 16 Suojin F Village Nanjing 210042 Jiangsu Peoples R China

Herein, NiZn bimetallic oxides derived from calcination treatment of metal-organic frameworks (MOFs) were successfully loaded onto the carbon black waste as support obtained from the oil refinery. The resulting hybrids could serve as environmentally friendly and cost-effective catalysts for the deoxygenation of biomass-derived fatty acids under an inert atmosphere. An online pyrolysis-gas chromatography/mass spectrometry (Py-GC/ MS) system was employed to evaluate their deoxygenation performance. The optimized catalysts demonstrated remarkably high stearic acid conversion of 99.6% and selectivity towards C8-C17 olefins of 57.2%. Furthermore, these catalysts with varying metal loadings also exhibited excellent efficiency in deoxygenation reactions of other types of fatty acids, such as myristic acid and palmitic acid, achieving conversion exceeding 85% and selectivities towards olefins of ca. 50%. When converting coconut oil, the supported NiZn bimetallic oxides showed excellent selectivity towards olefins (>60%). Furthermore, in-situ DRIFTS results suggest that fatty alcohols might be the key intermediates in the deoxidation reactions of fatty acid. This study not only demonstrates the great potential for obtaining valuable chemicals from biomass but also provides some insights into the fabrication of catalyst materials by using industrial solid waste.

关键词： Carbonaceous residue Metal oxide Stearic acid Deoxygenation reaction Resource utilization Olefin

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Modeling and analyzing of waterlogging in typical urban area 7

Modeling and analyzing of waterlogging in typical urban area

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7th International Conference on Hydraulic and Civil Engineering and Smart Water Conservancy and Intelligent Disaster Reduction Forum, ICHCE and SWIDR 2021

作者： Cai, Haotian Meng, Fanzhi Yang, Shen guo, Runyan Wang, xuwen Xiang, Long Hohai University College of Hydrology and Water Resources Jiangsu Nanjing China CMA-HHU Joint Laboratory for HydroMeteorological Studies Nanjing210098 China

ISBN: (纸本)9781665408653

With the acceleration of urbanization, urban waterlogging has become a difficult problem, which restricts the sustainable development and urbanization in China. This paper evaluates, analyzes and summarizes the current waterlogging research in China from three aspects: waterlogging control standards, waterlogging control models and methods, and current research difficulties. We take the Jiangbei District, Fuzhou City as an example. A waterlogging model was established to obtain the stage hydrographs and design flood flow, comprehensively evaluating the waterlogging situation and the comprehensive waterlogging prevention capacity. The results show that, accurate waterlogging simulation plays an important role in the construction of urban waterlogging prevention. While addressing the existing controllable difficulties, the research on urban waterlogging in China should actively work on coping strategies for uncontrollable difficulties, and enhance the ability of the regional waterlogging management system to deal with various extreme weather conditions and human activities. © 2021 IEEE.

关键词： Analytical models Systematics Urban areas Process control Distributed databases Water conservation Floods

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