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Smart hypoxia-responsive transformable and charge-reversible nanoparticles for the deep penetration and tumor microenvironment modulation of pancreatic cancer

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BIOMATERIALS 2022年第0期287卷 000-000页

作者： Chen, Hongyi Guo, Qin Chu, Yongchao Li, Chao Zhang, Yiwen Liu, Peixin Zhao, Zhenhao Wang, Yu Luo, Yifan Zhou, Zheng Zhang, Tongyu Song, Haolin Li, xuwen Li, Chufeng Su, Boyu You, Haoyu Sun, Tao jiang, Chen Fudan Univ Key Lab Smart Drug Delivery State Key Lab Med Neurobiol Dept PharmaceutSch PharmInst Brain SciMinist Ed Shanghai 201203 Peoples R China Fudan Univ Inst Brain Sci MOE Frontiers Ctr Brain Sci Sch PharmDept Pharmaceut Shanghai 201203 Peoples R China

The compact extracellular matrix (ECM) of pancreatic ductal adenocarcinoma (PDAC) is the major physical barrier that hinders the delivery of anti-tumor drugs, leading to strong inherent chemotherapy resistance as well as establishing an immunosuppressive tumor microenvironment (TME). However, forcibly destroying the stroma barrier would break the balance of delicate signal transduction and dependence between tumor cells and matrix components. Uncontrollable growth and metastasis would occur, making PDAC more difficult to control. Hence, we design and construct an aptamer-decorated hypoxia-responsive nanoparticle s(DGL)(n)@Apt co-loading gemcitabine monophosphate and STAT3 inhibitor HJC0152. This nanoparticle can reverse its surficial charge in the TME, and reduce the size triggered by hypoxia. The released ultra-small DGL particles loading gemcitabine monophosphate exhibit excellent deep-tumor penetration, chemotherapy drugs endocytosis promotion, and autophagy induction ability. Meanwhile, HJC0152 inhibits overactivated STAT3 in both tumor cells and tumor stroma, softens the stroma barrier, and reeducates the TME into an immune-activated state. This smart code -livery strategy provides an inspiring opportunity in PDAC treatment.

关键词： Hypoxia-responsive Sizereduction Chargereversal Deeppenetration TMEmodulation

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Targeting adaptor protein SLP76 of RAGE as a therapeutic approach for lethal sepsis

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NATURE COMMUNICATIONS 2021年第1期12卷 308页

作者： Yan, Zhengzheng Luo, Haihua Xie, Bingyao Tian, Tian Li, Shan Chen, Zhixia Liu, Jinghua Zhao, xuwen Zhang, Liyong Deng, Yongqiang Billiar, Timothy R. jiang, Yong Southern Med Univ State Key Lab Organ Failure Res Guangdong Prov Key Lab Prote Sch Basic Med SciDept Pathophysiol Guangzhou 510515 Peoples R China Univ Pittsburgh Sch Med Dept Surg Pittsburgh PA 15213 USA Southern Med Univ Nanfang Hosp Dept Anesthesiol Guangzhou 510515 Peoples R China

Accumulating evidence shows that RAGE has an important function in the pathogenesis of sepsis. However, the mechanisms by which RAGE transduces signals to downstream kinase cascades during septic shock are not clear. Here, we identify SLP76 as a binding partner for the cytosolic tail of RAGE both in vitro and in vivo and demonstrate that SLP76 binds RAGE through its sterile alpha motif (SAM) to mediate downstream signaling. Genetic deficiency of RAGE or SLP76 reduces AGE-induced phosphorylation of p38 MAPK, ERK1/2 and IKK alpha/beta, as well as cytokine release. Delivery of the SAM domain into macrophages via the TAT cell-penetrating peptide blocks proinflammatory cytokine production. Furthermore, administration of TAT-SAM attenuates inflammatory cytokine release and tissue damage in mice subjected to cecal ligation and puncture (CLP) and protects these mice from the lethality of sepsis. These findings reveal an important function for SLP76 in RAGE-mediated pro-inflammatory signaling and shed light on the development of SLP76-targeted therapeutics for sepsis.

关键词： Bacterial infection Cell signalling Monocytes and macrophages

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石榴皮多酚通过调控miR-4316表达抑制肺癌细胞增殖、迁移及侵袭实验研究

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新中医 2023年第19期55卷 1-7页

作者：施胜钰王旭文赵良伟杜燕青江明刘重斌浙江中医药大学附属湖州中医院普外科浙江湖州313000 浙江中医药大学附属湖州中医院泌尿外科浙江湖州313000 浙江中医药大学附属湖州中医院麻醉科浙江湖州313000 湖州师范学院浙江湖州313000

目的:探讨石榴皮多酚在肺癌中的抗肿瘤作用及可能机制。方法:RT-qPCR检测肺癌组织中miR-4316表达水平。将肺癌细胞A549分为石榴皮多酚-低组、石榴皮多酚-中组、石榴皮多酚-高组、对照组、miR-NC组、miR-4316组、石榴皮多酚+anti-miR-NC... 详细信息

目的:探讨石榴皮多酚在肺癌中的抗肿瘤作用及可能机制。方法:RT-qPCR检测肺癌组织中miR-4316表达水平。将肺癌细胞A549分为石榴皮多酚-低组、石榴皮多酚-中组、石榴皮多酚-高组、对照组、miR-NC组、miR-4316组、石榴皮多酚+anti-miR-NC组、石榴皮多酚+anti-miR-4316组。细胞迁移、增殖及侵袭分别采用划痕愈合实验、平板克隆实验和CCK-8法、Transwell实验检测。结果:肺癌组织中miR-4316表达水平显著降低(P<0.05)。石榴皮多酚(低、中、高)组A549细胞抑制率、miR-4316水平较对照组高,克隆形成数、划痕愈合率、侵袭数较对照组低(P<0.05)。与miR-NC组比较,miR-4316组较miR-NC组A549细胞抑制率更高(P<0.05),克隆形成数、划痕愈合率及侵袭数miR-4316组较miR-NC组低(P<0.05)。石榴皮多酚+anti-miR-4316组较石榴皮多酚+anti-miR-NC组A549细胞抑制率更低(P<0.05),克隆形成数、划痕愈合率及侵袭数石榴皮多酚+anti-miR-4316组较石榴皮多酚+anti-miR-NC组高(P<0.05)。结论:石榴皮多酚通过上调miR-4316表达来抑制肺癌细胞增殖、迁移及侵袭。

关键词：肺癌石榴皮多酚 miR-4316 增殖迁移侵袭

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地质雷达在矿山地裂缝探测中的应用

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当代化工研究 2023年第13期 75-77页

作者：蒋峰闫成祥牛兴国李亮余静薇马旭文郑有伟内蒙古科技大学内蒙古014010 内蒙古有色地质矿业(集团)综合普查有限责任公司内蒙古010010 内蒙古第二水文地质工程地质勘查有限责任公司内蒙古017000

矿山在开采过程中,受到采动影响和地应力的改变,往往在地表引起不同规模的地裂缝。开采方通常对于这些地裂缝的具体展布和贯通性不是很明确,给矿方下部煤层的安全开采造成极大困扰。本文对以往地质、水文资料的分析基础上,采用地质雷达... 详细信息

矿山在开采过程中,受到采动影响和地应力的改变,往往在地表引起不同规模的地裂缝。开采方通常对于这些地裂缝的具体展布和贯通性不是很明确,给矿方下部煤层的安全开采造成极大困扰。本文对以往地质、水文资料的分析基础上,采用地质雷达对内蒙古某煤矿的探测,初步分析地裂缝的成因,了解工区内浅部裂缝空间展布特征及规律;为后续钻探等工程手段提供地球物理依据。

关键词：地裂缝地质雷达煤矿

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Synthesis and biological evaluation of 1,3,4-thiadiazole derivatives as type III secretion system inhibitors against Xanthomonas oryzae

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PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY 2019年 160卷 87-94页

作者： Tao, Hui Tian, Hao jiang, Shan Xiang, xuwen Lin, Yinuo Ahmed, Wasim Tang, Riyuan Cui, Zi-Ning South China Agr Univ Guangdong Prov Key Lab Microbial Signals & Dis Co Integrat Microbiol Res Ctr State Key Lab Conservat & Utilizat Subtrop Agrobi Guangzhou 510642 Guangdong Peoples R China South China Agr Univ Coll Mat & Energy Dept Appl Chem Guangzhou 510642 Guangdong Peoples R China

Xanthomonas oryzae pv. oryzae (Xoo) infection directly leads to a severe disease known as leaf blight, which is a major cause of yield loss of rice. Use of traditional bactericides has resulted in severe resistance in pathogenic bacteria. A new approach screening compounds that target the virulence factors rather than killing bacterial pathogens is imperative. In gram-negative bacteria, the type III secretion system (T3SS) is a conserved and significant virulence factor considered as a target for drug development. Therefore, we designed and synthesized a new series of 5-phenyl-2-furan carboxylic acid derivatives stitched with 2-mercapto-1,3,4-thiadiazole. Bioassays revealed that the title candidates attenuated the hypersensitive response through suppressing the promoter activity of a harpin gene hpa1 without affecting bacterial growth. Quantitative real time polymerase chain reaction (qRT-PCR) analysis demonstrated reduced the expression of several genes associated with T3SS, when title compounds were applied. Additionally, hrp gene cluster members, including hrpG and hrpX, had reduced mRNA levels. In vivo greenhouse tests showed that candidate compounds could alleviate the effects of Xoo infection in rice (Oryza sativa) and possess better protective activity against rice bacterial leaf blight than bismerthiazol and thiodiazole copper. All tested compounds were safe to rice. This work suggests there are new safe options for Xoo control in rice from these 1,3,4-thiadiazole derivatives.

关键词： 2-mercapto-1,3,4-thiadiazole Inhibitors Type III secretion system (T3SS) Anti-virulence factors Xanthomonas oryzae pv. oryzae (Xoo)

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Analysis and Optimization of the Power Generation Right Transfer Mechanism

Analysis and Optimization of the Power Generation Right Tran...

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IEEE PES Asia-Pacific Power and Energy Engineering Conference (APPEEC)

作者： Jie Fan Yu jiang Yang Wang Yu Ding xuwen Liu Yunting Yao State Grid Jiangsu Electric Power Co. Ltd. Nanjing China School of Electrical Engineering Southeast University Nanjing China

ISBN: (数字)9781728157481

ISBN: (纸本)9781728157498

With the further development of China's electricity reform, the consumption of renewable energy in a market-oriented way has become an important goal. The transfer of power generation rights has become the most important form used by Chinese provinces. This paper firstly analyzes the corresponding policy adopted in jiangsu province and the framework of power generation right transfer trading, and then models and simulates the power generation right transfer trading market by using system dynamics through Vensim software. Finally, the key factors influencing the development of renewable energy in the transfer market of power generation rights are analyzed and optimized. According to this, some Suggestions are put forward to improve the market construction policy.

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Paecilomyces variotii extracts (ZNC) enhance plant immunity and promote plant growth

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PLANT AND SOIL 2019年第1-2期441卷 383-397页

作者： Lu, Chongchong Liu, Haifeng jiang, Depeng Wang, Lulu jiang, Yanke Tang, Shuya Hou, xuwen Han, Xinyi Liu, Zhiguang Zhang, Min Chu, Zhaohui Ding, Xinhua Shandong Agr Univ State Key Lab Crop Biol Shandong Prov Key Lab Biol Vegetable Dis & Insect Tai An 271018 Shandong Peoples R China Shandong Pengbo Biotechnol Co LTD Tai An 271018 Shandong Peoples R China Shandong Agr Univ Natl Engn Lab Efficient Utilizat Soil & Fertilize Coll Recourses & Environm Tai An 271018 Shandong Peoples R China

Background and aims The crude extract of the endophyte Paecilomyces variotii known as ZhiNengCong (ZNC) has function of promoting plant growth and enhancing disease resistance and is widely used in China. Our study aims to evaluate the molecular mechanisms of plant growth promotion and disease protection. Methods We generated transcriptome profiles from ZNC-treated seedlings using RNA sequencing. The function of salicylic acid (SA) in ZNC-mediated immunity was examined using SA biosynthesis and signaling pathway mutants. The concentrations of nitrogen (N) and phosphorus (P) in seedlings under ZNC treatment were measured. The effect of ZNC on the level of the hormone auxin in roots was tested using transgenic plants containing DR5::GFP. Results ZNC exhibited ultrahigh activity in promoting plant growth and enhancing disease resistance, even at concentrations as low as 1-10 ng/ml. ZNC induced ROS accumulation, callose deposition, and expression of PR genes. SA biosynthesis and signaling pathways were required for the ZNC-mediated defense response. Moreover, in improving plant growth, ZNC increased the level of auxin in root tips and regulated the absorption of N and P. Conclusion According to these results, ZNC is a highly effective plant elicitor that promotes plant growth by inducing auxin accumulation at the root tip at low concentrations and enhances plant disease resistance by activating the SA signaling pathway at high concentrations.

关键词： Plant elicitors Plant growth promotion Plant endophyte Disease resistance Auxin Salicylic acid

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长江上游大水位落差浮式码头趸船船岸皮带机改造方案

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港口装卸 2021年第2期 53-55页

作者：李云峰舒绪文刘江重庆钢铁股份有限公司武汉港博港机技术有限公司武汉市430063

在大水位落差浮式码头作业中,船岸皮带机的衔接和过渡对码头装卸效率、日常维护以及环保要求影响较大。针对船岸皮带机在使用过程中存在的问题,提出两种解决方案,并通过方案比选,选择了一种合适的改造方案。实践证明了该方案的合理性,... 详细信息

在大水位落差浮式码头作业中,船岸皮带机的衔接和过渡对码头装卸效率、日常维护以及环保要求影响较大。针对船岸皮带机在使用过程中存在的问题,提出两种解决方案,并通过方案比选,选择了一种合适的改造方案。实践证明了该方案的合理性,可为类似改造项目提供借鉴。

关键词：船岸皮带机日常维护环保

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1984—2015年太湖地区大气能见度变化遥感监测与评价

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中国环境监测 2017年第5期33卷 176-179页

作者：姜晟李旭文牛志春王甜甜茅晶晶江苏省环境监测中心江苏南京210036

研究收集整理了1984—2015年太湖区域342幅Landsat系列卫星遥感影像,利用ENVI软件FLAASH模块计算获取了区域大气能见度均值,通过太湖周边苏州、无锡、常州3市地面自动站能见度监测值加以验证,并在此基础上对1984—2015年该地区大气能见... 详细信息

研究收集整理了1984—2015年太湖区域342幅Landsat系列卫星遥感影像,利用ENVI软件FLAASH模块计算获取了区域大气能见度均值,通过太湖周边苏州、无锡、常州3市地面自动站能见度监测值加以验证,并在此基础上对1984—2015年该地区大气能见度遥感监测结果进行了分析与评价。研究结果表明:太湖地区在20世纪80年代能见度水平相对较好,20世纪90年代后逐渐下滑,总体呈下降趋势。2015年遥感反演能见度均值为14.80 km,与1984年的21.46 km相比下降了31.05%,下降速率约为0.21 km/a。

关键词：大气能见度遥感太湖

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Medication safety analysis of elderly inpatients based on improved functional resonance analysis method (FRAM): a mixed methods study

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Scientific reports 2025年第1期15卷 19496页

作者： Jing Yang xuwen Yin Yue Xu Zejuan Gu Tingru Li Yanhong Yan Qiaoling jiang Ting Lu Yangyang Fu Yan Yu Zhongyan Hou The First Affiliated Hospital with Nanjing Medical University Nanjing China. School of Nursing Nanjing University of Chinese Medicine Nanjing China. School of Computer Science and Technology Nanjing University of Posts and Telecommunications Nanjing China. The First Affiliated Hospital with Nanjing Medical University Nanjing China. jassicagu@***. School of Nursing Nanjing University of Chinese Medicine Nanjing China. jassicagu@***.

The study aimed to quantitatively assess functional risks in the medication administration process of elderly inpatients and develop management measures from a holistic system safety perspective. The functional resonance analysis method and decision-making trial and evaluation laboratory (DEMATEL) method were introduced to graphically model the medication administration process in elderly inpatients and identify safety issues affecting the complex interactions of functions. Semi-structured interviews based on the Fit between Individual, task, technology, and environment framework were used to explore medication safety management measures. A total of 18 functional modules were included in the medication process model for elderly inpatients. The DEMATEL results showed that medical order entry accounted for the highest proportion of the medication process, followed by label printing. Patient identification and drug verification, as downstream links, showed high impacts and influence. Among the safety management measures, task-technology fit and technology-individual fit were the most common. In the future, more research on medication management in elderly patients with different levels of care, settings and contexts, such as home and community, is needed. Attention should be paid to the integration and effect of implementing management measures to comprehensively safeguard patient medication safety.

关键词： DEMATEL Elderly patients FITTE FRAM Medication safety

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