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Innate and adaptive immune responses toward nanomedicines

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Acta Pharmaceutica Sinica B 2021年第4期11卷 852-870页

作者： Iara maíra de Oliveira Viana Sabrina Roussel Joan Defrêne Eliana martins Lima Frédéric Barabé Nicolas Bertrand Laboratory of Pharmaceutical Technology(FarmaTec) Federal University of GoiásGoiás 74605-220Brazil Faculty of Pharmacy UniversitéLaval and CHU de Québec-UniversitéLaval Research CenterQuébec G1V 4G2Canada Department of Medicine Faculty of MedicineUniversitéLaval and CHU de Québec-UniversitéLaval Research CenterQuébec G1V 4G2Canada

Since the commercialization of the frst liposomes used for drug delivery,Doxil/Caelyx® and Myocet®,tremendous progress has been made in understanding interactions between nanomedicines and biological *** work at the interface of engineering and medicine has allowed nanomedicines to deliver therapeutic small molecules and nucleic acids more *** nanomedicines are used in oncology for immunotherapy or to deliver combinations of cytotoxics,the clinical successes of gene silencing approaches like patisiran lipid complexes(Onpattro®)have paved the way for a variety of therapies beyond *** parallel,the global severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)pandemic has highlighted the potential of mR NA vaccines to develop immunization strategies at unprecedented *** rationally design therapeutic and vaccines,chemists,materials scientists,and drug delivery experts need to better understand how nanotechnologies interact with the immune *** review presents a comprehensive overview of the innate and adaptative immune systems and emphasizes the intricate mechanisms through which nanomedicines interact with these biological functions.

关键词： Cancer immunotherapy mRNA vaccine Complement activation macrophage In vivo clearance Anti-PEG antibody Nanoparticle mRNA-1273 BNT162b2 Immunology

乡村聚落与耕地共生理论模型及案例区情景模拟

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地理学报 2024年第5期79卷 1265-1285页

作者：马利邦张文博王祥陈贤斐白静西北师范大学地理与环境科学学院兰州730070 甘肃省绿洲资源环境与可持续发展重点实验室兰州730070 西北师范大学西北城乡发展与协同治理研究院兰州730070

乡村聚落与耕地作为描述乡村发展的重要子系统,两者互利共生对于乡村可持续发展至关重要。在甘肃省环境异质性背景下,以1384个乡(镇)为研究单元,引入共生理论构建乡村聚落与耕地共生框架,构建乡村聚落、耕地、共生环境评价指标体系,借助... 详细信息

乡村聚落与耕地作为描述乡村发展的重要子系统,两者互利共生对于乡村可持续发展至关重要。在甘肃省环境异质性背景下,以1384个乡(镇)为研究单元,引入共生理论构建乡村聚落与耕地共生框架,构建乡村聚落、耕地、共生环境评价指标体系,借助Lotka-Volterra模型识别其共生模式。新一轮国土空间规划背景下,借助SD-FLUS耦合模型对比分析2035年惯性发展情景(BD)和规划发展情景(PD)下共生模式演变趋势。研究发现:(1) 2000—2020年甘肃省乡村聚落、耕地发展水平呈先增后减趋势,共生环境容量呈持续下降趋势;五大农业区划3个指标差异显著,河西灌溉农业区(IA)具有明显发展优势。(2) 2000—2020年甘肃省乡村聚落与耕地共生模式整体呈互利共生向互害共生转变,互利共生占比由59.80%下降至38.97%;区域间主导模式差异显著,高寒牧区(AP)、陇南山地农业区(ma)、IA以互利共生为主,陇中旱作农业区(DA)、陇东雨养农业区(ra)分别以聚落偏害、耕地偏利为主;2000—2020年各区域主导模式均趋于多元化且呈现出由互利共生向互害共生转移的发展共性。(3)不同情景下共生模式差异显著,BD情景下五大区域延续历史粗放发展模式,互利共生模式占比均持续减少,而PD情景下因共生单元、环境容量水平的提升,共生模式向互利共生进化。

关键词：乡村聚落耕地共生模式多维情景模拟甘肃省

济阳坳陷富有机质页岩记录的中始新世气候适宜期古气候

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第四纪研究 2024年第5期44卷 1273-1281页

作者：郭颖马义权刘惠民陆永潮张晨马超成都理工大学自然资源部深时地理环境重建与应用重点实验室四川成都610059 成都理工大学油气藏地质及开发工程全国重点实验室四川成都610059 成都理工大学沉积地质研究院四川成都610059 成都理工大学管理科学学院四川成都610059 中国石油化工股份有限公司胜利油田分公司山东东营257001 中国地质大学(武汉)资源学院湖北武汉430074 成都理工大学计算机与网络安全学院四川成都610059

中始新世气候适宜期(MECO)是发生在约40.5~40.1 ma的一次全球增温事件。目前该事件在海相环境中的响应特征已相对明晰,而对其发生前、发生期间、发生之后的陆相环境响应及差异的认识仍需进一步研究。济阳坳陷北部的沾化凹陷中始新统沙... 详细信息

中始新世气候适宜期(MECO)是发生在约40.5~40.1 ma的一次全球增温事件。目前该事件在海相环境中的响应特征已相对明晰,而对其发生前、发生期间、发生之后的陆相环境响应及差异的认识仍需进一步研究。济阳坳陷北部的沾化凹陷中始新统沙三下亚段(Es3L)为一套富有机质页岩层系,沉积连续,不仅是该区页岩油勘探的重点层位,也为开展MECO事件的陆相环境响应研究提供了详实的沉积记录。本研究利用沾化凹陷Luo69井跨越Es3L且长度约194 m的高分辨率伽马(GR)数据,开展旋回地层学分析,结合相关系数法(COCO)和演化相关系数法(eCOCO),以Es3L的底界年龄41.21 ma为锚点,建立天文年代标尺。在此基础上,综合Fe含量、Ti/K比值、V/Al比值、TOC含量以及济阳坳陷南部东营凹陷的FY1井的磁性地层,确定MECO事件在研究区的响应时间,查明MECO事件发生前、发生期间、发生后济阳坳陷的气候和水文变化及其对有机质富集的影响。结果表明,Luo69井GR数据中的20.7~27.7 m波长代表405 ka长偏心率,通过调谐,获得GR数据的延续时间为3.34 ma,Es3L的延续时间为2.48 ma,与已报道的FY1井结果一致。结合年龄锚点,建立了41.77 ma至38.43 ma的天文年代标尺,并推定MECO事件在济阳坳陷的响应时间约为40.51~40.06 ma,对应于Luo69井的约3045~3017 m区间。在MECO事件发生之前,气候潮湿-干旱波动较大,引起湖盆流域水动力和湖水氧化还原状态出现较大变化;MECO期间,气候更加潮湿,使得流域水动力增强,导致湖水富氧,但该时期TOC含量整体较高,可能与较高的初级生产力有关;在MECO事件发生后,气候变化幅度较小,相对稳定,相比事件发生前更加潮湿,TOC较事件发生前略有升高,主要受控于升高的初级生产力。

关键词：增温事件统计调谐时间序列分析古气候有机质富集页岩油

Red Yeast Rice Increases Excretion of Bile Acids in Hamsters

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Biomedical and Environmental Sciences 2009年第4期22卷 269-277页

作者： ka-YING ma ZE-SHENG ZHANG SHU-XIN ZHAO QI CHANG YIN-MEI WONG SAI YING VENUS YEUNG Yu HUANG AND ZHEN-YU CHEN Food and Nutritional Sciences Program Department of Biochemistry The Chinese University of Hong Kong Shatin New Territories Hong Kong China Faeulty of Food Engineering & Biotechnology Tianjin University of Science and Technology Tianjin 300457 China Institute of Medicinal Plant Development Chinese Academy of Medical Science & Peking Union Medical College Beijing 100193 China Department of Physiology The Chinese University of Hong Kong Shatin New Territories Hong Kong China

Objective To investigate the hypocholesterolemic activity of red yeast rice （RYR） and its underlying mechanism. Methods Three groups of hamsters were fed either the control diet or one of the two experimental diets containing by weight 0.1% RYR （0.1RYR） or 0.3% RYR （0.3RYR）. Blood （0.5 mL） was collected from the retro-orbital sinus into a heparinized capillary tube at the end of week 0, 3, and 6. Plasma lipoproteins were measured using enzymatic kits, while fecal neutral and acidic sterols were quantified using a gas-liquid chromatography. Results Plasma total cholesterol was reduced by 12% in 0.1RYR group and by 18% in 0.3RYR group compared with the control value. Similarly, plasma triacylglycerol was decreased by 11% in 0.1RYR group and by 24% in 0.3RYR group. Western blotting analysis demonstrated that RYR had no effect on sterol regulatory element binding protein 2, fiver X receptor, 3-hydroxy-3-methylglutary-CoA reductase, LDL receptor, and cholesterol-7α-hydroxylase. HPLC analysis confirmed that RYR contained 0.88% monacolin K. It was recently found that RYR supplementation increased excretion of fecal acidic sterols by 34 folds compared with the conlrol value. Conclusion Hypocholesterolemic activity of RYR is mediated at least partially by enhancement of acidic sterol excretion.

关键词： Bile acid Cholesterol Monacolin Red yeast rice Triacylglcerols

富油煤地下原位热解井下加热器研究现状及展望

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煤田地质与勘探 2024年第7期52卷 35-45页

作者：王振东段中会杨甫马丽自然资源部煤炭资源勘查与综合利用重点实验室陕西西安710021 陕西省煤田地质集团有限公司陕西西安710021

[意义]我国富油煤地质资源丰富,是保障能源安全的潜在煤基油气资源。富油煤地下原位热解“取氢留碳”是煤炭资源清洁低碳利用的发展趋势,而井下加热器是实现富油煤地下原位高效热解的关键设备之一。【进展】在系统收集相关资料、数据和... 详细信息

[意义]我国富油煤地质资源丰富,是保障能源安全的潜在煤基油气资源。富油煤地下原位热解“取氢留碳”是煤炭资源清洁低碳利用的发展趋势,而井下加热器是实现富油煤地下原位高效热解的关键设备之一。【进展】在系统收集相关资料、数据和调研的基础上,简述了地下原位对流加热方法的现状,重点阐述了地下原位对流加热用加热器的研发现状,最后对井下电加热器的应用效果及后续的攻关方向分别进行了简述和展望。地表加热器的发展较为成熟,仅适用于埋深较浅和所需加热温度较低的地层(<350℃)。井下燃烧加热器还需有效解决极端工况下燃烧反应稳定性和二次点火可靠性的问题;井下电加热器通过将强化传热结构与电加热棒结合,不仅可缩小其尺寸,还可降低电加热棒的壁面温度,有效解决其加热效率低及寿命短的问题。此外,密封结构可有效提高井下电加热器在复杂工况下的适应性。采用自主研制的闭式双壳体井下电加热器,在陕北侏罗纪煤田榆神矿区大保当井田成功提取全球第一桶富油煤地下原位热解煤焦油。【展望】为提高富油煤层的加热速度和加热效率,井下电加热器的后续研究可从高功率井下电加热器和复合加热两个方面着手。复合加热在介质输送过程中仍会产生一定量的热损失,随着加热井数量及煤层深度的增加,热损失问题会进一步凸显,故应重点攻关高功率井下电加热器,以期为我国富油煤地下原位热解工艺研发与工业化应用提供技术支撑。

关键词：富油煤地下原位热解对流加热井下电加热器强化传热

胰高血糖素样肽-1受体激动剂类药物疗效及在减重代谢外科中的应用

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中华消化外科杂志 2024年第8期23卷 1022-1028页

作者：王存川马庆阳陈文辉暨南大学附属第一医院肥胖与代谢病外科广州510630

目前,超重和肥胖症患病率增长迅速.减重代谢手术是治疗肥胖及相关合并症的有效手段,但仅少数肥胖症患者接受减重代谢手术,大部分患者选择药物减肥.新兴药物胰高糖素样肽-1受体激动剂(GLP-1ra)对超重和肥胖症患者疗效显著,可作为减重代... 详细信息

目前,超重和肥胖症患病率增长迅速.减重代谢手术是治疗肥胖及相关合并症的有效手段,但仅少数肥胖症患者接受减重代谢手术,大部分患者选择药物减肥.新兴药物胰高糖素样肽-1受体激动剂(GLP-1ra)对超重和肥胖症患者疗效显著,可作为减重代谢手术的有益补充,给减重代谢外科带来深远影响.笔者全面回顾GLP-1ra类药物的应用进展,并深入阐述其在减重代谢外科中应用.

关键词：肥胖症减重代谢手术减肥药物胰高糖素样肽-1受体激动剂应用

基于时间聚类推理的立体车库车位分配策略研究

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重庆大学学报 2024年第8期47卷 47-54页

作者：马尚鹏李建国杨波兰州交通大学自动化与电气工程学院兰州730070 兰州交通大学四电BIM工程与智能应用铁路行业重点实验室兰州730070

采用立体车库车辆到达-离去时间数据,通过k-means聚类方法依据不同时段存取车到达频率对车辆进行类别划分,以立方聚类标准为评价指标对划分可信度进行评估。以车辆到达-离去时间划分推理结果及I/O至待存取车位的设备总服务时间与停留时... 详细信息

采用立体车库车辆到达-离去时间数据,通过k-means聚类方法依据不同时段存取车到达频率对车辆进行类别划分,以立方聚类标准为评价指标对划分可信度进行评估。以车辆到达-离去时间划分推理结果及I/O至待存取车位的设备总服务时间与停留时间长短关系,建立立体车库车位分区分配数学模型。定义顾客平均等待时间为立体车库效率评价指标,仿真对比分析就近分配与本文设计聚类推理分区分配的效率指标。仿真结果表明:本文设计的分配策略相较于就近分配策略能有效缩短顾客等待时间,表现为顾客等待时间减少9.5%。研究结果为此类车库车位分配过程提供参考,为提高车库运行效率提供决策支持。

关键词：交通工程立体车库 k-means聚类车位分配顾客等待时间到达-离去时间

TRPC5 is essential in endothelium-dependent contraction of aorta from diet-induced obese mice

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Fundamental Research 2022年第3期2卷 429-436页

作者： Yifei Zhu Sheng Wang Yuan Chu ka Zhang Xin Wen Lei Feng Fan Yu Xin ma Wuxi School of Medicine Jiangnan UniversityWuxi 214000China

The role of the Ca^(2+)-permeable ion channel TRPC5 in regulating vasocontraction in obesity is poorly ***,we investigated whether TRPC5 contributes to vascular dysfunction in obesity by promoting endothelium-dependent contraction via activation of cytosolic phospholipase A2(cPLA_(2))in the aortic endothelial cells of obese ***-induced endothelium-dependent relaxation and contraction in the aorta were measured us-ing wire ***_(2)activity was measured by the fluorogenic PLA_(2)substrate Bis-BODIPY^(TM)FL C_(11)-*** intracellular Ca^(2+)level in response to acetylcholine was measured by Fluo-4 ***-derived contracting factors were assessed by enzyme ***-induced obesity(DIO)attenuated endothelium-dependent vasodilation,enhanced endothelium-dependent contraction(EDC),and increased the expression of TRPC5 in the mouse *** of TRPC5 promoted EDC in the wild-type mouse aorta,whereas pharma-cological inhibition and genetic knockout of TRPC5 decreased EDC in the DIO mouse ***,cPLA_(2)phosphorylation and activity were higher in aortic endothelial cells from DIO mice,and this was attenuated by inhibition and knockout of *** 2(COX-2)expression was increased in DIO mouse endothe-lium and was decreased by a TRPC5 inhibitor and knockout of *** of prostaglandins F_(2α(PGF_(2α)and E 2(PGE 2)was involved in TRPC5-regulated EDC in DIO *** study demonstrated that TRPC5 contributes to endothelial and vascular dysfunction and is involved in EDC through activation of cPLA_(2)and enhanced COX-2-PGF_(2α)/PGE_(2)levels in DIO mice.

关键词： Transient receptor potential channel canonical family member 5(TRPC5) Endothelium-dependent contraction Vascular function Diet-induced obesity

Three-dimensional reconstruction and comparison of vacuolar membranes in response to viral infection

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Journal of Integrative Plant Biology 2021年第2期63卷 353-364页

作者： Xueting Wang Juncai ma Xuejiao Jin Ning Yue Peng Gao Keith ka Ki mai Xian-Bing Wang Dawei Li Byung-Ho kang Yongliang Zhang State Key Laboratory of Agro-Biotechnology and Ministry of Agriculture Key Laboratory of Soil Microbiology College of Biological SciencesChina Agricultural UniversityBeijing 100193China State Key Laboratory of Agro-Biotechnology School of Life SciencesThe Chinese University of Hong KongHong Kong 999077China

The vacuole is a unique plant organelle that plays an important role in maintaining cellular homeostasis under various environmental stress conditions. However, the effects of biotic stress on vacuole structure has not been examined using three-dimensional(3D) visualization. Here, we performed 3D electron tomography to compare the ultrastructural changes in the vacuole during infection with different viruses. The 3D models revealed that vacuoles are remodeled in cells infected with cucumber mosaic virus(CMV) or tobacco necrosis virus A Chinese isolate(TNV-AC), resulting in the formation of spherules at the periphery of the vacuole. These spherules contain neck-like channels that connect their interior with the cytosol. Confocal microscopy of CMV replication proteins 1 a and 2 a and TNV-AC auxiliary replication protein p23 showed that all of these proteins localize to the *** microscopy revealed that the expression of these replication proteins alone is sufficient to induce spherule formation on the tonoplast, suggesting that these proteins play prominent roles in inducing vacuolar membrane remodeling. This is the first report of the 3D structures of viral replication factories built on the tonoplasts. These findings contribute to our understanding of vacuole biogenesis under normal conditions and during assembly of plant(+) RNA virus replication complexes.

关键词： comparison cucumber mosaic virus electron tomography spherules tobacco necrosis virus A vacuole viral replication