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Gradient tumor microenvironment-promoted penetrating micelles for hypoxia relief and immunosuppression reversion in pancreatic cancer treatment

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ACTA BIOMATERIALIA 2023年第1期167卷 387-400页

作者： Luo, Yifan Li, Chao zhang, Yiwen Liu, Peixin Chen, Hongyi Zhao, Zhenhao Wang, Yu Zhou, Zheng Song, Haolin Su, Boyu Li, Chufeng Li, xuwen zhang, Tongyu You, Haoyu Wu, Yuxing Tian, Zonghua zhang, Shilin Guo, Yun Fan, Hongrui Chen, Qinjun Jiang, Chen Sun, Tao Fudan Univ Minhang Hosp Sch Pharm Dept Pharmaceut Shanghai 201203 Peoples R China Fudan Univ MOE Frontiers Ctr Brain Sci Shanghai 201203 Peoples R China

The tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) is the main block for the penetration of chemotherapy. In the tumor microenvironment, a dense matrix composed of fibrin is formed on the exterior, while the interior is featured by high reduction, hypoxia and low pH. How to match the special microenvironment to on-demand drug release is the key to improve chemotherapeutic efficacy. Herein, a microenvironment-responsive micellar system is developed to deepen tumoral penetration. Briefly, the conjugation of a fibrin-targeting peptide to PEG-poly amino acid has been utilized to achieve accumulation of micelles in the tumor stroma. By modification of micelles with hypoxia-reducible nitroimidazole which becomes protonated under acidic conditions, their surface charge is more positive, facilitating deeper penetration into tumors. Paclitaxel was loaded onto the micelles via a disulfide bond to enable glutathione (GSH)-responsive release. Therefore, the immunosuppressive microenvironment is relived through the alleviation of hypoxia and depletion of GSH. Hopefully, this work could establish paradigms by designing sophisticated drug-delivery systems to tactfully employ and retroact the tamed tumoral microenvironment to improve the therapeutic efficacy based on understanding the multiple hallmarks and learning the mutual regulation.

关键词： Pancreatic cancer Penetration Nitroimidazole Tumor hypoxia Gemcitabine

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Risk prevention of different forms of gestational diabetes mellitus based on energy metabolism prior to diagnosis

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TECHNOLOGY AND HEALTH CARE 2022年第1_suppl期30卷 S285-S292页

作者： Lu, Jiayu Jiang, Hongqing zhang, Song Yang, Yimin Hao, Dongmei Li, xuwen Chen, Aiqing Shao, Jing Liu, Xiaohong Yang, Lin Beijing Univ Technol Fac Environm & Life Sci Beijing Int Base Sci & Technol Cooperat Intelligent Physiol Measurement & Clin Translat Beijing Peoples R China Haidian Maternal & Children Hlth Hosp Beijing Peoples R China Beijing Yes Med Devices Co Ltd Beijing Peoples R China

BACKGROUND: Gestational diabetes mellitus (GDM) is a metabolic disease that seriously endangers the health of mothers and children. It is important to monitor GDM in real-time before diagnosis and to prevent it effectively. OBJECTIVE: GDM was divided into the second trimester diagnosed diabetes mellitus (GDM_24) and the third trimester diagnosed diabetes mellitus (GDM_30). The risk prediction of two types of GDM was performed in normal pregnant women at 11-13 and 16-19 weeks of pregnancy, respectively. METHODS: By stages, the K-W test was used to analyze the differences between basic information and energy metabolism factors, and multiple logistic regression was used to analyze the risk of energy metabolism factors and to correct the confounders with significant differences. RESULTS: For the GDM_24 group, each additional unit of oxygen consumption (VO2), carbon dioxide production, and resting energy expenditure (REE) increased the risk by 2.4%, 3.5%, 0.4%, and 2.1%, 2.6%, and 0.3%, respectively, at 11-13 and 16-19 weeks of pregnancy. For the GDM_30 group, each additional unit of VO2 and REE was associated with an increased risk of 2.3% and 0.3%, respectively, at 16-19 weeks of pregnancy. CONCLUSION: The risk of GDM_30 only appeared in pregnant women during 16-19 weeks of pregnancy, which may indicate that GDM_24 and GDM_30 have different pathogenesis.

关键词： Diabetes mellitus in the second trimester diagnosis of diabetes mellitus in the third trimester energy metabolism

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Enhanced strategies for depressurization in offshore natural gas hydrate exploitation: An in-depth investigation into pathway optimization and production stability mechanisms

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MARINE AND PETROLEUM GEOLOGY 2024年 170卷

作者： Li, Yuxuan zhang, Zhaobin Li, Shouding He, Jianming Li, Xiao Xu, Tao Lu, Cheng Qin, xuwen Chinese Acad Sci Key Lab Shale Gas & Geoengn Inst Geol & Geophys Beijing 100029 Peoples R China Chinese Acad Sci Innovat Acad Earth Sci Beijing 100029 Peoples R China Univ Chinese Acad Sci Coll Earth & Planetary Sci Beijing 100049 Peoples R China China Geol Survey Minist Nat Resources Oil & Gas Resources Survey Beijing 100083 Peoples R China China Geol Survey Minist Nat Resources China Ctr Aerial Geophys & Remote Sensing Nat Reso Beijing 100083 Peoples R China

Natural gas hydrates have garnered widespread attention as a high-quality energy resource. Recent offshore extraction experiences suggest that depressurization is a technically mature and economically viable option. However, challenges such as reservoir temperature reduction, reservoir subsidence, secondary hydrate formation, and insufficient dynamics in later-stage hydrate decomposition still require improvements to the depressurization method. This study, based on field data from Japan's first offshore natural gas hydrate extraction, utilizes a self-developed numerical simulator to model and validate reservoirs at the field scale. Long-term production rate stability, total production, secondary hydrate formation, reservoir subsidence, evolution of permeability, and temperature-pressure paths were analyzed and optimized for the three mainstream depressurization modes: steady depressurization, stepwise depressurization, and cyclic depressurization. The results indicate that, under the condition of equal total work done throughout the entire depressurization process, steady depressurization with an effectively lower depressurization rate is the optimal choice. Cyclic depressurization, due to the formation of secondary hydrates reducing the permeability of certain reservoir zones, adversely affects gas production efficiency during the long-term stable production phase. This study enhances insights into the coupled evolution of multiple physical fields during the depressurization of offshore natural gas hydrates, providing valuable guidance for future on-site extraction plan designs.

关键词： Natural gas hydrates Depressurization modes Numerical simulation Multiple physical fields On-site extraction plan

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The exploration of N6-deoxyadenosine methylation in mammalian genomes

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Protein & Cell 2021年第10期12卷 756-768页

作者： xuwen Li Zijian zhang Xinlong Luo Jacob Schrier Andrew D.Yang Tao P.Wu Department of Molecular and Human Genetics Baylor College of MedicineHoustonTX 77030USA Medical Scientist Training Program Baylor College of MedicineHoustonTX 77030USA Huffington Center on Aging Baylor College of MedicineHoustonTX 77030USA Dan L Duncan Comprehensive Cancer Center Baylor College of MedicineHoustonTX 77030USA

N^(6)-methyladenine(N^(6)-mA,m^(6)dA,or 6mA),a prevalent DNA modification in prokaryotes,has recently been identified in higher eukaryotes,including *** 6mA has been well-studied in prokaryotes,the function and regulatory mechanism of 6mA in eukaryotes are still poorly *** studies indicate that 6mA can serve as an epigenetic mark and play critical roles in various biological processes,from transposable-element suppression to environmental stress ***,we review the significant advances in methodology for 6mA detection and major progress in understanding the regulation and function of this non-canonical DNA methylation in eukaryotes,predominantly mammals.

关键词： DNA N^(6)-methyladenine(6mA) mammalian DNA modification norvcanonical mammalian DNA methylation

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Enhanced gas production from low-permeability hydrate reservoirs based on embedded discrete fracture models: Influence of branch parameters

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ENERGY 2023年第1期282卷

作者： Guo, Yang Li, Shuxia Qin, xuwen Lu, Cheng Wu, Didi Liu, Lu zhang, Ningtao China Univ Petr East China Key Lab Unconvent Oil & Gas Dev Minist Educ Qingdao 266580 Peoples R China China Univ Petr East China Sch Petr Engn Qingdao 266580 Peoples R China Minist Nat Resources China Geol Survey Beijing 100037 Peoples R China Minist Nat Resources China Geol Survey Oil & Gas Resources Survey Beijing 100083 Peoples R China East China Bur Sinopec Explorat & Dev Res Inst Nanjing 210019 Peoples R China

The low permeability of marine hydrate reservoirs makes it difficult for trail results to meet the demand for exploitation. Hydraulic fracturing and multi-branch wells are the primary methods for enhancing productivity. This study proposed a new production enhancement method of multi-branch wells combined with multi-stage fracturing (MWMF) based on the embedded discrete fracture model (EDFM). By simulation of the Shenhu area, the multi-physical field evolution of the MWMF production process was first revealed, followed by the systematic analysis of the MWMF production enhancement effect with branch parameters. Results indicated that the cumulative gas production of MWMF increased by 327% compared with only horizontal wells. The production of four-branch wells exhibited a 7% reduction compared to horizontal wells using the MWMF method, suggesting increased branch numbers inhibit production. Increasing branch length was positively correlated with enhanced production. Notably, the influence of branch length on gas production became more pronounced as the number of branches increased. The interface of the three-phase layer (TPL) and hydrate-bearing layer (HBL) was the most suitable location for branch well placement. This novel study provides valuable insights into new applications of the MWMF method in developing low-permeability hydrate reservoirs.

关键词： Natural gas hydrate Multi-branch well Multi-stage fracture Embedded discrete fracture model Enhanced gas production

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Efficient removal and recovery of phosphorus from industrial wastewater in the form of vivianite

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ENVIRONMENTAL RESEARCH 2023年第1期228卷 115848页

作者： zhang, Yangzhong Qin, Jiafu Chen, Zhenguo Chen, Yongxing Zheng, xuwen Guo, Lu Wang, Xiaojun South China Univ Technol Sch Environm & Energy Guangzhou 510006 Peoples R China South China Normal Univ Sch Environm Guangzhou 510006 Peoples R China Hua An Biotech Co Ltd Foshan 528300 Peoples R China

With the shortage of phosphorus resources, the concept of phosphorus recovery from wastewater is generally proposed. Recently, phosphorus recovery from wastewater in the form of vivianite has been widely reported, which could be used as a slow-release fertilizer as well as the production of lithium iron phosphate for Li-ion batteries. In this study, chemical precipitation thermodynamic modeling was applied to evaluate the effect of solution factors on vivianite crystallization with actual phosphorus containing industrial wastewater. The modeling results showed that the solution pH influences the concentration of diverse ions, and the initial Fe2+ concentration affects the formation area of vivianite. The saturation index (SI) of vivianite increased with the initial Fe2+ concentration and Fe:P molar ratio. pH 7.0, initial Fe2+ concentration 500 mg/L and Fe:P molar ratio 1.50 were the optimal conditions for phosphorus recovery. Mineral Liberation Analyzer (MLA) accurately determined the purity of vivianite was 24.13%, indicating the feasibility of recovering vivianite from industrial wastewater. In addition, the cost analysis showed that the cost of recovering phosphorus by the vivianite process was 0.925 USD/kg P, which can produce high-value vivianite products and realize "turn waste into treasure".

关键词： Phosphorus recovery Vivianite Crystallization zone Resource recycling

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An Improved Design of Atomic-Beam Fluorescence Collector

An Improved Design of Atomic-Beam Fluorescence Collector

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European Frequency and Time Forum (EFTF)

作者： xuwen Hu Fuyu Sun Chao Li Jie Liu Xiaofeng Li Shougang zhang National Time Service Center Chinese Academy of Sciences Xi'an China Key Laboratory of Time Reference and Applications Chinese Academy of Sciences Xi'an China

ISBN: (数字)9798350354270

ISBN: (纸本)9798350354287

Efficient fluorescence detection is crucial in the field of precision spectral analysis. This paper presents an improved design of an atomic-beam fluorescence collector that utilizes the convergence characteristics of ellipsoidal surfaces and the reflection characteristics of spherical surfaces. It calculates the parameter relationship for achieving full-angle fluorescence collection. The study fine-tunes the structural parameters and simulates the fluorescence collection efficiency and losses under different conditions when emitting from a non-ideal point light source. The improved fluorescence collector captures photons with nearly 4n solid angle coverage, allowing photons to be reflected at most twice before reaching the photo detector, thereby increasing collection efficiency. This improved collector can be used in various fields for detecting weak fluorescence signals.

关键词： Time-frequency analysis Europe Detectors Fluorescence Solids Reflection Structural engineering Spectral analysis Photonics Light sources

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Preparation of a novel dual structure graded cemented carbides induced by bidirectional diffusion

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MATERIALS LETTERS 2022年 312卷 131689-131689页

作者： Wang, Qiwei He, xuwen Li, Na zhang, Weibin Du, Yong Shandong Univ Key Lab Liquid Solid Struct Evolut & Proc Mat Minist Educ Jinan 250061 Peoples R China Shandong Univ Suzhou Inst Suzhou 215123 Jiangsu Peoples R China China Acad Engn Phys Inst Mat Mianyang 621908 Sichuan Peoples R China Cent South Univ State Key Lab Powder Met Changsha 410083 Hunan Peoples R China

Based on the thermodynamic calculations, a novel dual graded WC-Co-Ti(C, N)-ZrC-HfC cemented carbides was designed and prepared by introducing the combination of spinodal decomposition and denitrification process. The dual graded structures of the cemented carbides have a smooth fcc-rich surface and toughness fcc-free interlayer, which can improve the coating adhesion and inhibit the cracks propagation. Microstructure characterizations and composition distributions elucidated the principle of multi-factors diffusion migration and the formation mechanism of dual structure graded layers.

关键词： Cemented carbides Thermodynamics Sintering Multilayer structure

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DEGENERATING HYPERBOLIC SURFACES AND SPECTRAL GAPS FOR LARGE GENUS

arXiv

引用

arXiv 2022年

作者： Wu, Yunhui zhang, Haohao Zhu, xuwen Tsinghua University Haidian District Beijing100084 China Northeastern University BostonMA02115 United States

In this article we study the differences of two consecutive eigenvalues λi-λi-1 up to i = 2g-2 for the Laplacian on hyperbolic surfaces of genus g, and show that the supremum of such spectral gaps over the moduli space has infimum limit at least 41 as genus goes to infinity. A min-max principle for eigenvalues on degenerating hyperbolic surfaces is also established. © 2022, CC BY.

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Synthesis and characterization of photo-responsive azobenzene side-chain liquid crystalline polystyrenes with a mesogenic phase of wide temperature range

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DYES AND PIGMENTS 2023年 210卷

作者： zhang, Ruixue Ma, Hongwei Li, xuwen Yang, Jiaxin Lai, Meng zhang, Xueli Wang, Yu Li, Yang Han, Li Dalian Univ Technol Sch Chem Engn Dept Polymer Sci & Engn State Key Lab Fine ChemLiaoning Key Lab Polymer S Dalian 116024 Peoples R China

Polystyrenes (PSs) that provide photochemical stability are commonly used as the chromophore macromolecular carriers. Herein, PS-based alternating copolymers, i.e., alt-P(D-SiH/Ip), alt-P(D-2SiH/Ip) and alt-P(D-SiH/St), are synthesized through anionically copolymerized Si-H functionalized 1,1-diphenylethylene (DPE-SiH/2SiH) with isoprene (Ip)/styrene (St). Anionically polymerized (4-vinylphenyl)-dimethyl-silane is used as the uniform hydrosilylated PS, i.e., Uni.-P(St-SiH). A series of photo-responsive azobenzene side-chain liquid crystalline PSs combine the above PS-based main chains and the mesogenic moiety composed of azobenzene (Azo) and cholesterol (Chol) groups, i.e., Azo-Chol (M), via the hydrosilylation. The polarized optical microscopic (POM) morphologies and thermal properties of Azo-Chol (M) and Azo-Chol-PSs are studied. As desired, they produce the cholesteric phase of wide temperature range due to the PSs and Chol-groups. Moreover, the photo-responsive behavior irradiated under UV-light of different wavelengths are quantitatively evaluated by time-dependent UV-Vis spectroscopy. Azo-Chol-PSs undergo rapid and reversible trans-cis isomerization under the alternating irradiation of UV and visible light. The trans-to -cis isomerization efficiency under 365 nm UV-light is over that under 290-320 nm UV-light, while over 80% of cis-to-trans efficiency can be realized under 400-500 nm Vis-light irradiation This work would provide guidelines for the effective design of photo-responsive anisotropic materials.

关键词： Polystyrenes Living anionic copolymerization Side-chain liquid crystalline polymers Photo-responsive Cholesteric phase

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