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Engineered protein nanodrug as an emerging therapeutic tool

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Nano Research 2022年第6期15卷 5161-5172页

作者： yuanxin li Jing Sun Jingjing li Kai liu Hongjie Zhang State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China University of Science and Technology of China Hefei 230026China Institute of Organic Chemistry University of UlmAlbert-Einstein-Allee 11Ulm 89081Germany Department of Chemistry Tsinghua UniversityBeijing 100084China

Functional proteins are the most versatile macromolecules.They can be obtained by extraction from natural sources or by genetic engineering technologies.The outstanding selectivity,specificity,binding activity,and biocompatibility endow engineered proteins with outstanding performance for disease therapy.Nevertheless,their stability is dramatically impaired in blood circulation,hindering clinical translations.Thus,many strategies have been developed to improve the stability,efficacy,bioavailability,and productivity of therapeutic proteins for clinical applications.In this review,we summarize the recent progress in the fabrication and application of therapeutic proteins.We first introduce various strategies for improving therapeutic efficacy via bioengineering and nanoassembly.Furthermore,we highlight their diverse applications as growth factors,nanovaccines,antibody-based drugs,bioimaging molecules,and cytokine receptor antagonists.Finally,a summary and perspective for the future development of therapeutic proteins are presented.

关键词： therapeutic proteins nanodrug genetic engineering structural modification therapeutic efficacy

The evolution of prehistoric arrowheads in northern China and its influential factors

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Science China Earth Sciences 2023年第9期66卷 2109-2124页

作者： Juanting YAO Huan XIA Ting li Dongpeng liN yuanxin li Xuke SHEN Jian WANG Dongju ZHANG Key Laboratory of Western China’s Environmental Systems(Ministry of Education) College of Earth and Environmental SciencesLanzhou UniversityLanzhou 730000China

Prehistoric projectile weapons are crucial for understanding the hunting behavior,survival strategies,and subsistence patterns of prehistoric humans.Arrowheads were the primary prehistoric projectile weapon,and here we review the spatiotemporal distribution and changes in the morphology,quantity,and materials composition of arrowheads in the northern regions of China from the Middle and Upper Paleolithic periods to the Bronze Age,together with the factors that influenced these changes.The results reveal that primitive stone arrowheads appeared sporadically in the Middle Paleolithic period.Additionally,the“broad spectrum revolution”and microblade technology during the Upper Paleolithic promoted the regional-scale diffusion of broad and thick stone arrowheads in northern China.During the Neolithic period,relatively narrow and thin stone and bone arrowheads spread rapidly across the entire Yellow River Basin and most of northeastern China.The dominance of these two types of arrowheads alternated,during the period of 7000–5000 yr BP,the number of arrowheads peaked,possibly closely related to changes in the role of hunting(fishing and hunting)and gathering in the subsistence economy,human population size,and the emergence and development of a grinding technology.During the Bronze Age,a significant number of bronze arrowheads appeared,and the total number of arrowheads increased again,and their distribution expanded to northwestern China.The emergence of a bronze smelting technology and inter-group conflicts may have been the primary factors influencing this trend.Our results demonstrate that arrowheads were always an essential component of prehistoric tool kits.Due to technological developments in subsistence strategies,the morphology,function,and popularity of arrowheads underwent substantial changes during different periods.Therefore,a comprehensive study of prehistoric arrowheads can help better understand the subsistence patterns and processes of economic and societal development of prehistoric humans.

关键词： Northern China Prehistoric arrowheads Spatio-temporal distribution Morphology changes Subsistence patterns

Engineered protein and Jakinib nanoplatform with extraordinary rheumatoid arthritis treatment

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Nano Research 2023年第8期16卷 11197-11205页

作者： yuanxin li Bo li Gang Wang Juanjuan Su Yilin Qiao Chao Ma Fan Wang Jian Zhu Jingjing li Hongjie Zhang Kai liu Huji Xu State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China University of Science and Technology of China Hefei 230026China Engineering Research Center of Advanced Rare Earth Materials (Ministry of Education)Department of ChemistryTsinghua UniversityBeijing 100084China School of Clinical Medicine Tsinghua UniversityBeijing 100084China College of Materials Science and Opto-Electronic Technology University of Chinese Academy of SciencesBeijing 100049China First Medical Centre Chinese PLA General HospitalBeijing 100853China

Rheumatoid arthritis(RA)is a relatively common inflammatory disease that affects the synovial tissue,eventually results in joints destruction and even long-term disability.Although Janus kinase inhibitors(Jakinibs)show a rapid efficacy and are becoming the most successful agents in RA therapy,high dosing at frequent interval and severe toxicities cannot be avoided.Here,we developed a new type of fully compatible nanocarriers based on recombinant chimeric proteins with outstanding controlled release of upadacitinib.In addition,the fluorescent protein component of the nanocarriers enabled noninvasive fluorescence imaging of RA lesions,thus allowing real-time detection of RA therapy.Using rat models,the nanotherapeutic is shown to be superior to free upadacitinib,as indicated by extended circulation time and sustained bioefficacy.Strikingly,this nanosystem possesses an ultralong half-life of 45 h and a bioavailability of 4-times higher than pristine upadacitinib,thus extending the dosing interval from one day to 2 weeks.Side effects such as over-immunosuppression and leukocyte levels reduction were significantly mitigated.This smart strategy boosts efficacy,safety and visuality of Jakinibs in RA therapy,and potently enables customized designs of nanoplatforms for other therapeutics.

关键词： engineered protein nanocarrier controlled release bioefficacy rheumatoid arthritis

Modes of occurrence and pre-concentration of rare earth elements in No.17 coal in liupanshui coalfield,China

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Journal of Rare Earths 2022年第8期40卷 1323-1332页

作者： Bo Yang Chen Cheng yuanxin li Wei Cheng Jingkun Zang Xiangping Lai Xiaorui Wang College of Mining Guizhou UniversityGuiyang 550025China National&Local Joint Laboratory of Engineering for Effective Utilization of Regional Mineral Resources from Karst Areas Guiyang 550025China Guizhou Key Laboratory of Comprehensive Utilization of Non-metallic Mineral Resources Guiyang 550025China Guizhou Panjiang Clean Coal Co. Ltd.Liupanshui 553000China

Rare earth elements(lanthanide and yttrium,abbreviated as REY) provide important support for national security,energy production,environmental protection and economic growth.In recent years,many studies have shown that the content of REY in some coal or coal by-products is close to or even higher than that in traditional REY ore,which makes coal a potential source of REY.This study took the No.17 coal of Panzhou mining area in liupanshui coal field as the research object,and the content and occurrence modes of REY in raw coal and 7 density fraction samples were studied.The results show that the content of REY in the raw coal reaches 220.67 μg/g,which is significantly higher than the average REY content in the world coal and Chinese coal as reported in the literature.Gravity separation has a certain pre-enrichment effect on REY and the fraction sample> 1.8 g/cm~3 has the highest REY of 426.27 μg/g(equal to rare earth oxide 0.1%).Study on correlation between REY and ash yields reveals that the organic affinity of the light rare earth is higher than that of the medium rare earth and the heavy rare earth.As shown by X-ray diffraction(XRD) and X-ray flouresence spectroscopy(XRF),the major minerals in coal are kaolinite,quartz and calcite,and the content of REY in coal is significantly related to Al,Si and kaolinite,which implies that REY occur mainly in kaolinite.Laser ablation inductively coupled plasma mass spectroscopy(LA-ICP-MS) was adopted to determine chemical composition of micro-zone in kaolinite in coal and the results show that there is no obvious correlation between REY and the contents of Al and Si.This indicates that the REY occur probably in the form of adsorption.The research results provide a scientific reference for the potential extraction of the associated REY in the coal.

关键词： Coal Rare earth elements Occurrence mode Kaolinite Pre-concentration

粮食安全视域下耕地生态补偿的法治化进路研究

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河南师范大学学报（哲学社会科学版） 2024年第1期51卷 53-60页

作者：李蕊王园鑫中国政法大学民商经济法学院北京100088

耕地生态补偿的法治化契合了粮食安全和生态文明法治保障体系建设的内在要求。我国尚未制定耕地生态补偿专门性法律法规,《耕地保护法(草案)》对于耕地保护补偿制度的设计还存在诸多疏漏,未对耕地生态补偿制度予以明晰表达。为推动耕地... 详细信息

耕地生态补偿的法治化契合了粮食安全和生态文明法治保障体系建设的内在要求。我国尚未制定耕地生态补偿专门性法律法规,《耕地保护法(草案)》对于耕地保护补偿制度的设计还存在诸多疏漏,未对耕地生态补偿制度予以明晰表达。为推动耕地保护,进而保障粮食安全及可持续发展,需要着眼于耕地生态补偿制度建构的权利基础,证成耕地生态补偿制度构造的正当性,厘定耕地生态补偿制度的属性特质,进而着眼于补偿请求权主体、补偿标准、补偿方式、补偿监督等多维度,对耕地生态补偿予以法治构造。

关键词：粮食安全耕地保护耕地生态补偿

基于转录组学探究高糖饮食诱导秀丽线虫衰老的分子机制

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食品科学 2024年第11期45卷 24-30页

作者：李蓉徐艳缪园欣陶明芳荆楚理工学院农业生物技术研究所湖北荆门448000 湖北省农业科学院农业质量标准与检测技术研究所农产品营养品质与安全湖北省重点实验室湖北武汉430064

为了揭示高糖饮食对衰老影响的分子机制,利用转录组学技术探究高糖饮食对秀丽线虫体基因表达谱的影响。结果表明,高糖饮食造成线虫体内4183个基因表达发生显著变化。此外,基因本体论富集分析表明,高糖处理后线虫差异表达基因在衰老、未... 详细信息

为了揭示高糖饮食对衰老影响的分子机制,利用转录组学技术探究高糖饮食对秀丽线虫体基因表达谱的影响。结果表明,高糖饮食造成线虫体内4183个基因表达发生显著变化。此外,基因本体论富集分析表明,高糖处理后线虫差异表达基因在衰老、未折叠蛋白反应、压力应激响应、自噬、转移酶活力、催化酶活力、热休克蛋白连接等方面显著富集。京都基因与基因组百科全书富集分析表明,差异表达基因在线虫寿命调节途径、自噬调节、丙酮酸代谢、FOXO信号通路、糖酵解/糖异生、谷胱甘肽代谢、转化生长因子-β信号通路也显著富集。通过对相关差异基因表达进行验证,发现高糖会上调胰岛素信号通路相关基因和糖脂代谢相关基因的表达,下调热应激抗性和抗氧化调控相关基因的表达。本研究结果可为深入阐释高糖饮食对寿命及代谢影响的分子机制提供理论依据。

关键词：高糖饮食秀丽隐杆线虫转录组学衰老

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农民专业合作社农地金融的法治保障研究

安徽师范大学学报（社会科学版） 2024年第1期52卷 90-96页

作者：李蕊王园鑫中国政法大学民商经济法学院北京100088

农民专业合作社农地金融实践的顺利展开,激发了农村土地资本运作功能,是助推农村经济发展、实现乡村振兴的题中应有之义。目前农民专业合作社农地金融的成效不如预期,究其本质原因在于既有立法对于实践探索自发形成的法秩序缺乏有效回... 详细信息

农民专业合作社农地金融实践的顺利展开,激发了农村土地资本运作功能,是助推农村经济发展、实现乡村振兴的题中应有之义。目前农民专业合作社农地金融的成效不如预期,究其本质原因在于既有立法对于实践探索自发形成的法秩序缺乏有效回应。确保农地金融法律关系主体的金融利益,并促进其所承载的社会公共利益之实现,亟待发挥法律对保障农民专业合作社农地金融实践顺利开展所具有的长效作用。实现农民专业合作社农地金融的法治化,必然要基于农地融资权的社会化向度,以完备农地金融的利益平衡机制为核心任务,以构建农民专业合作社的内部治理结构、完善风险防控和激励保障机制为关键进路。

关键词：农民专业合作社农地金融土地经营权融资

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基于T形管的自复叠制冷系统性能分析

工程热物理学报 2024年第3期45卷 652-660页

作者：苏丹丹许媛欣许伟聪赵力天津大学机械工程学院天津300350

T形管中非共沸工质的组分分布对组分可调热力循环性能有重要影响。但目前的研究均是基于理想分离假设分析T形管对热力循环的影响。为研究T形管实际分离性能对热力循环性能的影响,设计了一种基于T形管的新型自复叠制冷系统。对制冷工况下... 详细信息

T形管中非共沸工质的组分分布对组分可调热力循环性能有重要影响。但目前的研究均是基于理想分离假设分析T形管对热力循环的影响。为研究T形管实际分离性能对热力循环性能的影响,设计了一种基于T形管的新型自复叠制冷系统。对制冷工况下T形管中R134a/R600a的组分分布进行数值模拟,基于数值模拟结果对新型自复叠制冷系统性能进行计算分析。结果表明:T形管出口的流量分配比越高,其分离效率越大。当干度大于0.8或R134a质量分数大于0.7时,T形管两个出口的分离效率相对较小。与无分离的制冷系统相比,基于T形管的自复叠制冷系统的COP可提升0.83%至18.69%,单位容积制冷量可提高3.09%至36.2%,过冷器热负荷可降低11.6%至31.3%。

关键词：自复叠制冷系统非共沸工质 T形管组分分离热力学分析

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基于全频谱共享的三维轨迹和功率优化方法

电子与信息学报 2024年第3期46卷 835-847页

作者：裴二荣陈新虎陈琪美孙远欣黎伟重庆邮电大学通信与信息工程学院重庆400065 武汉大学电子信息学院武汉430072 重庆金美通信有限公司重庆400035

当前蜂窝系统频谱资源极度短缺,免授权频谱因而被建议在蜂窝系统中使用。无人机(UAV)的飞行轨迹和功率控制对频谱利用效率有重大影响。然而,基于频谱共享的3维轨迹和功率优化方法却鲜少研究。为此,该文首先提出一种全频谱共享方法,即无... 详细信息

当前蜂窝系统频谱资源极度短缺,免授权频谱因而被建议在蜂窝系统中使用。无人机(UAV)的飞行轨迹和功率控制对频谱利用效率有重大影响。然而,基于频谱共享的3维轨迹和功率优化方法却鲜少研究。为此,该文首先提出一种全频谱共享方法,即无人机通过控制上行蜂窝用户和设备到设备(D2D)用户的发射功率,在不影响WiFi设备正常传输的前提下使用免授权频谱;同时无人机也能够在不影响其他下行蜂窝用户的前提下使用授权频谱。然后基于提出的全频谱共享方法,该文构建了无人机电池能量约束下的3维飞行轨迹和发射功率的联合优化问题。为了求解提出的复杂多变量耦合的非凸优化问题,该文采用块坐标下降和连续凸逼近方法将原问题转化为3维轨迹优化和功率控制两个凸优化子问题并迭代求解。大量仿真结果证明提出的基于3维轨迹和功率优化的全频谱共享方法能够显著提高频谱利用效率。

关键词：全频谱共享无人机通信设备到设备 3维轨迹功率控制