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Click-Nucleic-Acid-Containing Codelivery System Inducing Collapse of Cellular Homeostasis for Tumor Therapy through Bidirectional Regulation of Autophagy and Glycolysis

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ACS APPLIED MATERIALS & INTERFACES 2020年第52期12卷 57757-57767页

作者： Guo, Qin chen, Qinjun Zhang, Yujie Zhou, Wenxi Li, xuwen Li, Chao Zhang, Yiwen chen, Hongyi Liu, Peixin Chu, Yongchao Sun, Tao Jiang, chen Fudan Univ State Key Lab Med Neurobiol Key Lab Smart Drug Delivery Minist Educ Shanghai 201203 Peoples R China Fudan Univ MOE Frontiers Ctr Brain Sci Sch Pharm Dept Pharmaceut Shanghai 201203 Peoples R China

As a rapid proliferating tissue, tumor cells have to optimize nutrient utilization to withstand harsh conditions. Several approaches have been explored to inhibit the growth and metastasis of tumor by disrupting the reprogrammed tumor metabolism. However, nutrient limitations within solid tumors may induce the metabolic flexibility of malignant cells to sustain growth and survival using one nutrient to fill metabolite pools normally supplied by the other. To overcome this predicament, a promising click-nucleic-acid-containing platform for codelivery of rapamycin, anti-PFKFB4 siRNA, and targeting ligand aptamer AS1411 was applied. PFKFB4 could act as a promising target for tumor therapy for being a molecular fulcrum that could couple glycolysis to autophagy by promoting aggressive metastatic tumors. The downregulation of PFKFB4 can help inhibit the SRC3/Akt/mTOR pathway, leading autophagy to the direction of promoting apoptosis of tumor cells, which is induced by the collapse of tumor cellular homeostasis, while low dosages of rapamycin could decrease surgery-induced immune dysfunction. Enhanced tumor autophagy, favorable in vivo antitumor efficacy, and effective systematic immune activation are observed after treatment, suggesting that autophagy and glycolysis can serve as an integrated target for tumor treatment.

关键词： tumor metabolism codelivery click nucleic acid immune activation tumor therapy

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Adhesive Coacervates Driven by Hydrogen-Bonding Interaction

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SMALL 2020年第43期16卷 2004132-2004132页

作者： Peng, Qiongyao chen, Jingsi Zeng, Zicheng Wang, Tao Xiang, Li Peng, xuwen Liu, Jifang Zeng, Hongbo Univ Alberta Dept Chem & Mat Engn Edmonton AB T6G 1H9 Canada Guangzhou Med Univ Affiliated Hosp 5 Guangzhou 510700 Guangdong Peoples R China

Coacervation plays a critical role in numerous biological activities such as constructing biological tissues and achieving robust wet adhesion of marine sessile organisms, which conventionally occurs when oppositely charged polyelectrolytes are mixed in aqueous solutions driven by electrostatic attraction. Here, a novel type of adhesive coacervate is reported, driven by hydrogen-bonding interactions, readily formed by mixing silicotungstic acid and nonionic polyethylene glycol in water, providing a new approach for developing coacervates from nonionic systems. The as-prepared coacervate is easily paintable underwater, show strong wet adhesion to diverse substrates, and has been successfully applied as a hemostatic agent to treat organ injuries without displaying hemolytic activity, while with inherent antimicrobial properties thus avoiding inflammations and infections due to microorganism accumulation. This work demonstrates that coacervation can occur in salt-free environments via non-electrostatic interactions, providing a new platform for engineering multifunctional coacervate materials as tissue glues, wound dressings and membrane-free cell systems.

关键词： adhesive coacervates antimicrobial properties coacervation hydrogen bonding wet adhesion

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Fabrication and properties of MEMS compatible energetic arrays based on carbon-based copper azide

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APPLIED SURFACE SCIENCE 2022年 577卷 150643-150643页

作者： Liu, xuwen Hu, Yan chen, Bingwen Wei, Hai Su, Jiaxin Yang, Caimin Hu, Jiaheng Ye, Yinghua Shen, Ruiqi Nanjing Univ Sci & Technol Sch Chem & Chem Engn Nanjing 210094 Peoples R China Minist Ind & Informat Technol Micronano Energet Devices Key Lab Nanjing 210094 Peoples R China

Copper azide is a promising primary explosive with low toxicity and high energy density. However, due to the extreme electrostatic sensitivity, it does not have many practical applications in the miniaturized pyrotechnics. In this work, we constructed an energetic composite, embedding in oriented carbon nanotubes (CNTs) arrays grown on a silicon substrate, which is compatible with the micmfabrication technique of Micro-Electro-Mechanical Systems (MEMS). Since it has excellent electrical conductivity and mechanical strength, oriented CNTs, as nano-containers of Cu(N-3)(2), can availably reduce the electrostatic sensitivity and bring about the directional output of detonation energy. The oriented CNTs arrays were prepared by magnetron sputtering, anodization and chemical vapor deposition successively. Electrochemical deposition was used to deposit copper nanoparticles in the cavities of CNTs, which were converted into copper azide by subsequent in-situ azide reaction. The electrostatic sensitivity test, thermal performance analysis and laser ignition experiment were conducted on the energetic composite, respectively. The results show that the energetic composite kept safe under an electrostatic stimulation of 3.18 mJ, while original copper azide exploded when subjected to stimulation of 0.05 mJ. The energetic composite opens a new route of introducing hazardous primary explosives into micro-initiators and modern pyrotechnics.

关键词： Composite energetic materials Copper azide Oriented CNTs array Template method Electrochemical deposition Electrostatic safety

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Establishment of a personalized fetal growth curve model

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TECHNOLOGY AND HEALTH CARE 2021年第1_suppl期29卷 S311-S317页

作者： Bao, Xinyu Wang, Yan Zhang, Song Yang, Lin Liu, Guoli Yang, Yimin Li, xuwen Hao, Dongmei chen, Aiqing Liu, Xiaohong Shao, Jing Beijing Univ Technol Fac Environm & Life Sci Beijing 100124 Peoples R China Beijing Int Sci & Technol Cooperat Base Intellige Beijing 100124 Peoples R China Peking Univ Peoples Hosp Beijing 100044 Peoples R China Beijing Yes Med Devices Co Ltd Beijing 100152 Peoples R China

BACKGROUND: Fetal weight is one of the important indicators for judging whether fetal growth and development are normal. Fetal weight exceeding the normal range may lead to poor delivery outcomes. OBJECTIVE: We aimed to establish a personalized fetal growth curve in order to effectively monitor fetal growth during pregnancy. Fetal weight can be monitored while fetal growth and development are assessed. METHODS: This study retrospectively analyzed the birth weight and ultrasound database of 3,093 newborns delivered at normal term. The personalized fetal growth curve model was generated based on the birth weight formula established by Gardosi combined with the proportional weight equation. RESULTS: (1) The average birth weight of the single fetus at normal term was 3,457g. (2) According to the regression results of the proportion of fetal weight in full-term pregnancy and gestational week, the proportional weight equation is Weight% = 500.9 + 51.60GA + 1.727GA(2) 0.01718GA(3) (GA is gestational week), R-2 is 98%, P < 0.001. CONCLUSIONS: In this study, the normal birth weight of newborns and normal range of fetal weight can be estimated by using the personalized fetal growth curve model.

关键词： Fetal weight fetal growth curve birth weight proportional weight equation normal range

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基于Milk-Run的生鲜农产品取货物流优化方法研究

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计算机与数字工程 2023年第12期51卷 3020-3027页

作者：李建华陈聪赵旭雯西安科技大学机械工程学院西安710054

生鲜农产品不易储存、易腐性要求科学制定物流模式与路径,以最大程度保障产品鲜活度。针对取货车辆到达生鲜农产品供应商的不准时与物流费用高的问题,提出基于Milk-Run的生鲜农产品物流优化方法。依据生鲜农产品物流的构成,引入Milk-Ru... 详细信息

生鲜农产品不易储存、易腐性要求科学制定物流模式与路径,以最大程度保障产品鲜活度。针对取货车辆到达生鲜农产品供应商的不准时与物流费用高的问题,提出基于Milk-Run的生鲜农产品物流优化方法。依据生鲜农产品物流的构成,引入Milk-Run循环取货模式并给出最优取货期量确定方法。同时,为最大限度对企业成本、驾驶安全、客户需求和产品质量进行平衡与保障,综合考虑装载率、出车数量、疲劳驾驶、客户时间等因素构建多目标VRPTW模型,结合评价函数法与线性加权法对目标进行转换,设计了一种遗传算法求解模型,并引入栅格法测量各节点间实际配送距离。最后,结合实际物流问题,检验Milk-Run循环取货模式的可行性与优越性,通过仿真实验证明了文章提出的方法可以为企业的物流决策提供参考。

关键词： Milk-Run 循环取货 VRPTW问题疲劳驾驶遗传算法栅格法

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Sequentially Triggered Bacterial Outer Membrane Vesicles for Macrophage Metabolism Modulation and Tumor Metastasis Suppression

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ACS NANO 2021年第8期15卷 13826-13838页

作者： Guo, Qin Li, xuwen Zhou, Wenxi Chu, Yongchao chen, Qinjun Zhang, Yiwen Li, Chao chen, Hongyi Liu, Peixin Zhao, Zhenhao Wang, Yu Zhou, Zheng Luo, Yifan Li, Chufeng You, Haoyu Song, Haolin Su, Boyu Zhang, Tongyu Sun, Tao Jiang, chen Fudan Univ Sch Pharm Dept Pharmaceut Key Lab Smart Drug DeliveryMinist EducState Key Shanghai 201203 Peoples R China

Metabolic interactions between different cell types in the tumor microenvironment (TME) often result in reprogramming of the metabolism to be totally different from their normal physiological processes in order to support tumor growth. Many studies have attempted to inhibit tumor growth and activate tumor immunity by regulating the metabolism of tumors and other cells in TME. However, metabolic inhibitors often suffer from the heterogeneity of tumors, since the favorable metabolic regulation of malignant cells and other cells in TME is often inconsistent with each other. Therefore, we reported the design of a pH-sensitive drug delivery system that targets different cells in TME successively. Outer membrane vesicles (OMVs) derived from Gram-negative bacteria were applied to coload paclitaxel (PTX) and regulated in development and DNA damage response 1 (Redd1)-siRNA and regulate tumor metabolism microenvironment and suppress tumor growth. Our siRNA@M-/PTX-CA-OMVs could first release PTX triggered by the tumor pH (pH 6.8). Then the rest of it would be taken in by M2 macrophages to increase their level of glycolysis. Great potential was observed in TAM repolarization, tumor suppression, tumor immune activation, and TME remolding in the triple-negative breast cancer model. The application of the OMV provided an insight for establishing a codelivery platform for chemical drugs and genetic medicines.

关键词： bacterial OMVs pH sensitive TAM polarization immune therapy cancer treatment

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Biochemical and structural characterization of the first-discovered metazoan DNA cytosine-N4 methyltransferase from the bdelloid rotifer Adineta vaga

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JOURNAL OF BIOLOGICAL CHEMISTRY 2023年第8期299卷 105017页

作者： Zhou, Jujun Horton, John R. Kaur, Gundeep chen, Qin Li, xuwen Mendoza, Fabian Wu, Tao Blumenthal, Robert M. Zhang, Xing cheng, Xiaodong Univ Texas MD Anderson Canc Ctr Dept Epigenet & Mol Carcinogenesis Houston TX 77030 USA Baylor Coll Med Dept Mol & Human Genet Houston TX USA Univ Toledo Coll Med & Life Sci Dept Med Microbiol & Immunol Program Bioinformat Toledo OH 43614 USA

Much is known about the generation, removal, and roles of 5-methylcytosine (5mC) in eukaryote DNA, and there is a growing body of evidence regarding N6-methyladenine, but very little is known about N4-methylcytosine (4mC) in the DNA of eukaryotes. The gene for the first metazoan DNA methyltransferase generating 4mC (N4CMT) was reported and characterized recently by others, in tiny freshwater invertebrates called bdelloid rotifers. Bdelloid rotifers are ancient, apparently asexual animals, and lack canonical 5mC DNA methyltransferases. Here, we characterize the kinetic properties and structural features of the catalytic domain of the N4CMT protein from the bdelloid rotifer Adineta vaga. We find that N4CMT generates high-level methylation at preferred sites, (A/C)CG(T/C/A), and low-level methylation at disfavored sites, exemplified by ACGG. Like the mammalian de novo 5mC DNA methyltransferase 3A/3B (DNMT3A/3B), N4CMT methylates CpG dinucleotides on both DNA strands, generating hemimethylated intermediates and eventually fully methylated CpG sites, particularly in the context of favored symmetric sites. In addition, like DNMT3A/3B, N4CMT methylates non-CpG sites, mainly CpA/TpG, though at a lower rate. Both N4CMT and DNMT3A/3B even prefer similar CpGflanking sequences. Structurally, the catalytic domain of N4CMT closely resembles the Caulobacter crescentus cell cycle-regulated DNA methyltransferase. The symmetric methylation of CpG, and similarity to a cell cycle-regulated DNA methyltransferase, together suggest that N4CMT might also carry out DNA synthesis-dependent methylation following DNA replication.

关键词： DNA methylation N4-methylcytosine metazoan cytosine-N4 DNA methyltransferase bdelloid rotifer Adineta vaga

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Fetal growth prediction: Establishing fetal growth prediction curves in the second trimester

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TECHNOLOGY AND HEALTH CARE 2021年第1_suppl期29卷 S345-S350页

作者： Wang, Yan Bao, Xinyu Zhang, Song Yang, Lin Liu, Guoli Yang, Yimin Li, xuwen Hao, Dongmei chen, Aiqing Liu, Xiaohong Shao, Jing Peking Univ Peoples Hosp Beijing 100044 Peoples R China Beijing Univ Technol Fac Environm & Life Sci Beijing 100124 Peoples R China Beijing Int Sci & Technol Cooperat Base Intellige Beijing 100124 Peoples R China Beijing Yes Med Devices Co Ltd Beijing 100152 Peoples R China

BACKGROUND: Monitoring fetal weight during pregnancy has a guiding role in prenatal care. OBJECTIVE: To establish a personalized fetal growth curve for effectively monitoring fetal growth during pregnancy. METHODS: (1) This study retrospectively analyzed the birth weight database of 2,474 singleton newborns delivered normally at term. The personalized fetal growth curve model was formed by combining the estimating birth weight of newborns with the proportional weight formula. (2) Multiple linear stepwise regression method was used to estimate the birth weight of newborns. RESULTS: (1) Delivery gestational age, weight at first visit, maternal height, pre-pregnancy body mass index, fetal sex, parity had significant effects on birth weight. Based on these parameters, the formula for calculating term optimal weight was obtained (R-2 = 22.8%, P < 0.001). (2) The personalized fetal growth curve was obtained according to the epidemiological factors input model of each pregnant woman. CONCLUSIONS: A model of personalized fetal growth curve can be established, and be used to evaluate fetal growth and development through estimated fetal weight monitoring.

关键词： Fetal weight growth charts personal health services

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Economic evaluation of varicella vaccination strategies in Jiangsu province, China: a decision-tree Markov model

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HUMAN VACCINES & IMMUNOTHERAPEUTICS 2021年第11期17卷 4194-4202页

作者： Wang, Qiang Xiu, Shixin Yang, Liuqing Huang, Jinxin Cui, Tingting Shi, Naiyang Wang, xuwen Shen, Yuan chen, Enpin Lu, Bing Jin, Hui Lin, Leesa Southeast Univ Sch Publ Hlth Dept Epidemiol & Hlth Stat 87 Dingjiaqiao Nanjing 210009 Peoples R China Southeast Univ Sch Publ Hlth Key Lab Environm Med Engn Minist Educ Nanjing Peoples R China Wuxi Ctr Dis Control & Prevent Dept Immunizat Planning Wuxi Jiangsu Peoples R China London Sch Hyg & Trop Med Dept Infect Dis Epidemiol London England Hong Kong Sci Pk Lab Data Discovery Hlth D24H Hong Kong Peoples R China

This study evaluated different varicella vaccination strategies in Jiangsu province, China. A decision-tree Markov model was used to evaluate the cost effectiveness of various varicella vaccination strategies for children, including direct and selective vaccination (serotesting pre-vaccination). A cohort of one-year-old children was followed through 60 one-year Markov cycles. The parameter estimation was based on field work, the literature, and statistical yearbooks. We calculated the incremental cost-utility ratio (ICUR) using the saved quality-adjusted life year (QALY). One-way and probability sensitivity analyses were performed to assess uncertainty. Among 100,000 cohort members, one-dose and two-dose direct vaccination averted 8061 and 10,701 varicella cases, respectively, compared with no vaccination. Furthermore, compared with no vaccination, one-dose and two-dose direct vaccination saved one QALY at the ICUR of USD 21,401.33 and USD 35,420.81, respectively, at less than three times the per capita gross domestic product (USD 47,626.86) of Jiangsu. The ICURs of the one-dose and two-dose selective strategies versus no vaccination were USD 42,623.62 and USD 51,406.35 per QALY gained, respectively. The cost effectiveness results were most sensitive to the QALY loss of outpatients and vaccine prices. Thus, in Jiangsu, one-dose and two-dose direct varicella vaccination in children could be cost effective at the willingness to pay threshold of three times provincial GDP per capita from a societal perspective. The findings were sensitive to the vaccine price and health utility of varicella cases.

关键词： Varicella vaccination children cost utility decision tree model China

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Recent Advance in 1-D Organic Semiconductors for Waveguide Applications

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MINI-REVIEWS IN ORGANIC CHEMISTRY 2019年第3期16卷 244-252页

作者： Zhang, Rong Jin, Xiaobei Wen, xuwen chen, Qi Int Ctr Bamboo & Rattan Beijing Peoples R China

One dimensional (1-D) micro-/nanostructures provide a good system to investigate the dependence of various properties on dimensionality and size reduction, especially in optoelectronic field. Organic conjugates including small molecules and polymers exhibit good optoelectronic properties and are apt to assemble into ordered nanostructures with well-defined shapes, tunable sizes and defect-free structures. In this review, we focus on recent progress of 1-D organic semiconductors for waveguide applications. Fabrication methods and materials of 1-D organic semiconductors are introduced. The morphology influence on the properties is also summarized.

关键词： Organic semiconductors conjugated polymers one-dimensional waveguide fabrication method electrospinning

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