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Design of nanocarriers for efficient cellular uptake and endosomal release of small molecule and nucleicacid drugs: learning from virus

Vaibhav Mundra, Ram I. Mahato

《化学科学与工程前沿（英文）》 2014年 第8卷 第4期   页码 387-404 doi: 10.1007/s11705-014-1457-3

摘要： There are many challenges in developing efficient and target specific delivery systems of small molecule and nucleic acid drugs. Cell membrane presents one of the major barriers for the penetration of hydrophilic macromolecules across the plasma membrane. Nanocarriers have been designed to enhance their cellular uptake via endocytosis but following their cellular uptake, endosomal escape is the rate limiting step which restricts the value associated with the enhanced uptake by nanocarriers. Viruses are an excellent model for efficient cytosolic delivery by nanocarriers. Viruses exploit intracellular cues to release the genome to cytosol. In this review, we first discuss different endocytic uptake pathways and endosomal escape mechanisms. We then summarize the existing tools for studying the intracellular trafficking of nanocarriers. Finally, we highlight the important design elements of recent virus-based nanocarriers for efficient cellular uptake and endosomal escape.

关键词： nanocarrier     cellular uptake     endosomal release     nucleic acid drug    

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Nucleic acid crystallization and X-ray crystallography facilitated by single selenium atom

Wen Zhang,Jack W. Szostak,Zhen Huang

《化学科学与工程前沿（英文）》 2016年 第10卷 第2期   页码 196-202 doi: 10.1007/s11705-016-1565-3

摘要： X-ray crystallography is a powerful strategy for 3-D structure determination of macromolecules, such as nucleic acids and protein-nucleic acid complexes. However, the crystallization and phase determination are the major bottle-neck problems in crystallography. Recently we have successfully developed synthesis and strategy of selenium-derivatized nucleic acids (SeNA) for nucleic acid crystallography. SeNA might not only provide the rational strategies to solve the phase determination problem, but also offer a potential strategy to explore crystallization solutions.

关键词： selenium     DNA     RNA     nucleic acid     crystallization    

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Invading target cells: multifunctional polymer conjugates as therapeutic nucleic acid carriers

Ulrich L?CHELT, Ernst WAGNER

《化学科学与工程前沿（英文）》 2011年 第5卷 第3期   页码 275-286 doi: 10.1007/s11705-011-1203-z

摘要： Polymer-based conjugates are an interesting option and challenge for the design of nano-sized drug-delivery systems, as they require advanced conjugation chemistry and precise engineering. In the case of nucleic acid therapy, non-viral carriers face several biological barriers during the delivery process, namely 1) protection of the cargo from extracellular degradation, 2) avoidance of non-specific interactions with non-targeted tissues, 3) efficient entry into the target cells, 4) intracellular trafficking to the site of action and 5) cargo release. To take on these obstacles, multifunctional conjugates can act as “smart polymers” with microenvironment-sensing dynamics to facilitate the separate delivery steps. Synthesis of defined polymer architectures with precise functionalization enables structure-activity relationships to be investigated and the integration of key functions for efficient delivery. Thus bioresponsive polymer conjugates, which are equipped with molecular devices responding to the certain microenvironments within the delivery pathway (e.g. pH, redox potential, enzymes) can be assembled. This review focuses on the modular engineering and conjugation of multifunctional polymeric structures for the utilization as “tailor-made” nucleic acid carriers.

关键词： conjugate     DNA     gene transfer     polymer     RNA     targeting    

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Validation of polarizable force field parameters for nucleic acids by inter-molecular interactions

Liaoran Cao,Hong Ren,Jing Miao,Wei Guo,Yan Li,Guohui Li

《化学科学与工程前沿（英文）》 2016年 第10卷 第2期   页码 203-212 doi: 10.1007/s11705-016-1572-4

摘要： Modeling structural and thermodynamic properties of nucleic acids has long been a challenge in the development of force fields. Polarizable force fields are a new generation of potential functions to take charge redistribution and induced dipole into account, and have been proved to be reliable to model small molecules, polypeptides and proteins, but their use on nucleic acids is still rather limited. In this article, the interactions between nucleic acids and a small molecule or ion were modeled by AMOEBAbio09, a modern polarizable force field, and conventional non-polarizable AMBER99sb and CHARMM36 force fields. The resulting intermolecular interaction energies were compared with those calculated by ab initio quantum mechanics methods. Although the test is not sufficient to prove the reliability of the polarizable force field, the results at least validate its capability in modeling energetics of static configurations, which is one basic component in force field parameterization.

关键词： nucleic acid     polarizable force field     AMOEBA    

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Nucleic acid-based diagnostics for infectious diseases in public health affairs

null

《医学前沿（英文）》 2012年 第6卷 第2期   页码 173-186 doi: 10.1007/s11684-012-0195-5

摘要：

Infectious diseases, mostly caused by bacteria and viruses but also a result of fungal and parasitic infection, have been one of the most important public health concerns throughout human history. The first step in combating these pathogens is to get a timely and accurate diagnosis at an affordable cost. Many kinds of diagnostics have been developed, such as pathogen culture, biochemical tests and serological tests, to help detect and fight against the causative agents of diseases. However, these diagnostic tests are generally unsatisfactory because they are not particularly sensitive and specific and are unable to deliver speedy results. Nucleic acid-based diagnostics, detecting pathogens through the identification of their genomic sequences, have shown promise to overcome the above limitations and become more widely adopted in clinical tests. Here we review some of the most popular nucleic acid-based diagnostics and focus on their adaptability and applicability to routine clinical usage. We also compare and contrast the characteristics of different types of nucleic acid-based diagnostics.

关键词： nucleic acid-based diagnostics     infectious disease     PCR     NASBA     LAMP     microarray     LOAC     public health affairs    

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核酸疫苗研发态势与发展建议

李爱花,杨雪梅,孙轶楠,苑亚坤,杨俊涛

《中国工程科学》 2021年 第23卷 第4期   页码 153-161 doi: 10.15302/J-SSCAE-2021.04.018

摘要：

应对新型冠状病毒肺炎（COVID-19）疫情防控的迫切需求，核酸疫苗以其快速高效的优点得到了疫苗研发领域的高度重视，特别是信使核糖核酸（mRNA）疫苗的研发进程显著加快，首次获批上市并在人体中使用。本文从核酸疫苗及相关技术概念、研发轨迹与发展趋势等方面总结梳理核酸疫苗的研发态势，辨识核酸疫苗特征，分析 COVID-19 疫情对 mRNA疫苗研究的促进作用，梳理核酸疫苗拓展应用的主要领域，针对可能存在的技术性、安全性问题开展深入讨论。研究建议，从改良目的基因表达、完善递送系统、提高免疫应答、增强 mRNA 稳定性及易存性等方面着手，着力开展核酸疫苗的关键技术开发；严格监管核酸疫苗的安全性和有效性；引导利益相关方对具有安全性风险、可能对肿瘤与传染病防控带来颠覆性影响的 mRNA 疫苗技术开展改进研究，注重技术研发的前瞻布局并促进应用转化。

关键词： 核酸疫苗     脱氧核糖核酸（DNA）疫苗     核糖核酸（RNA）疫苗     信使核糖核酸（mRNA）疫苗     新型冠状病毒肺 炎     肿瘤    

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Flow cytometric assessment of the effects of chlorine, chloramine, and UV on bacteria by using nucleicacid stains and 5-cyano-2,3-ditolyltetrazolium chloride

Xuebiao Nie, Wenjun Liu, Mo Chen, Minmin Liu, Lu Ao

《环境科学与工程前沿（英文）》 2016年 第10卷 第6期 doi: 10.1007/s11783-016-0884-4

摘要： Flow cytometry based on nucleic acid stains and CTC was established and optimized. Membrane of is more resistant to chlorine/chloramine than . The metabolic activity of bacteria persisted after the cytomembranewas damaged. showed more resistance to UV irradiation than by FCM. MP-UV was a stronger inhibitor of metabolic activity than LP-UV. Flow cytometry (FCM) has been widely used in multi-parametric assessment of cells in various research fields, especially in environmental sciences. This study detected the metabolic activity of and by using an FCM method based on 5-cyano-2,3-ditolyltetrazolium chloride (CTC); the accuracy of this method was enhanced by adding SYTO 9 and 10% R2A broth. The disinfection effects of chlorine, chloramine, and UV were subsequently evaluated by FCM methods. Chlorine demonstrated stronger and faster destructive effects on cytomembrane than chloramine, and nucleic acids decomposed afterwards. The metabolic activity of the bacteria persisted after the cytomembranewas damaged as detected using CTC. Low-pressure (LP) UV or medium-pressure (MP) UV treatments exerted no significant effects on membrane permeability. The metabolic activity of the bacteria decreased with increasing UV dosage, and MP-UV was a stronger inhibitor of metabolic activity than LP-UV. Furthermore, the membrane of Gram-positive was more resistant to chlorine/chloramine than that of Gram-negative . In addition, showed higher resistance to UV irradiation than .

关键词： Flow cytometry     Escherichia coli     Staphylococcusaureus     UV     CTC     SYTO 9    

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微生物安全产业发展策略研究

宋仲戬,李曼,胡梁斌,王春明,鲁曦,刘开辉,张丽佳,宇岩,吴清平

《中国工程科学》 2021年 第23卷 第5期   页码 79-85 doi: 10.15302/J-SSCAE-2021.05.010

摘要：

微生物安全是新时期我国社会与经济健康发展的根本保障，是国家粮食安全、公共卫生、社会稳定的重要支撑。本文梳理了我国微生物安全产业发展面临的问题，结合微生物安全产业的政策环境，分析了微生物安全产业的发展需求和现状；在明晰微生物安全产业国内外发展格局的基础上，综合归纳了制约我国致病微生物检测与控制技术创新及应用研发的瓶颈，提出了构建我国微生物安全产业的发展规划。研究建议，强化微生物安全创新研究平台建设；构建微生物安全科学大数据库，以人才建设驱动能力提升；壮大微生物安全龙头企业，以标准规范保障产业发展；强化微生物安全领域的重大系统创新和工程技术研究，探索出我国微生物安全产业的高质量发展路径。

关键词： 微生物安全     微生物检测     微生物诊断     微生物防控     核酸检测    

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微生物资源分子鉴定技术的研究进展

张羽,马爱进,高利芬,彭海,贾英民,孙宝国

《中国工程科学》 2021年 第23卷 第5期   页码 86-93 doi: 10.15302/J-SSCAE-2021.05.011

摘要：

微生物作为全世界分布最广且拥有量最多的生物资源，应用领域广泛，具有突出的经济价值和社会价值。以往虽已有众多微生物研究，但限于技术方法无法深入展开，随着微生物检测技术的不断发展，为微生物研究提供了新途径和新方法。本文总结了国内外微生物资源分子鉴定技术的发展及其应用情况，主要有脱氧核糖核酸（DNA）含量测定、核酸杂交技术、DNA 指纹图谱技术、核酸扩增技术、基因芯片技术和高通量测序技术等；梳理了现有微生物资源分子鉴定技术的优缺点；分析了微生物资源分子鉴定技术存在的问题，如依赖于实验室环境，实验结果的重现性、准确性不足，缺乏相应的微生物数据库。为促进我国微生物资源的保护和利用，研究建议，要继续加强对各鉴定技术的研究，建立具有自主知识产权的微生物资源鉴定平台，完善微生物资源数据库等。

关键词： 微生物资源，分子鉴定，核酸扩增技术，基因芯片技术，高通量测序技术，微生物数据库    

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Sulfonic acid-functionalized mesoporous silica catalyst with different morphology for biodiesel production

《化学科学与工程前沿（英文）》 2022年 第16卷 第8期   页码 1198-1210 doi: 10.1007/s11705-021-2133-z

摘要： Sulfonic acid functionalized mesoporous silica based solid acid catalysts with different morphology were designed and fabricated. The synthesized materials were characterized by various physicochemical and spectroscopic techniques like scanning electron microscope-energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, Brunauer–Emmett–Teller surface area, thermogravimetric analysis and n-butylamine acidity. The shape of catalysts particles plays an important role in its activity. The sulfonic acid functionalized mesoporous silica catalysts of spherical shape and the cube shape were assessed for catalytic activity in biodiesel production. The catalytic biodiesel production reaction over the catalysts were studied by esterification of free fatty acid, oleic acid with methanol. The effect of various reaction parameters such as catalyst concentration, acid/alcohol molar ratio, catalyst amount, reaction temperature and reaction time on catalytic activity were investigated to optimize the conditions for maximum conversion. It was sulfonated cubic shape mesoporous silica which exhibited better activity as compared to the spherical shape silica catalysts. Additionally, the catalyst was regenerated and reused up to three cycles without any significant loss in activity. The present catalysts exhibit superior performance in biodiesel production and it can be used for the several biodiesel feedstock’s that are rich in free fatty acids.

关键词： solid acid catalyst     mesoporous silica     sulfonic acid     biodiesel     esterification     oleic acid    

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Amino acid promoted hydrogen battery system using Mn-pincer complex for reversible CO hydrogenation toformic acid

《能源前沿（英文）》 2022年 第16卷 第5期   页码 697-699 doi: 10.1007/s11708-022-0843-7

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Enzyme@bismuth-ellagic acid: a versatile platform for enzyme immobilization with enhanced acid-base stability

《化学科学与工程前沿（英文）》 2023年 第17卷 第6期   页码 784-794 doi: 10.1007/s11705-022-2278-4

摘要： In situ encapsulation is an effective way to synthesize enzyme@metal–organic framework biocatalysts; however, it is limited by the conditions of metal–organic framework synthesis and its acid-base stability. Herein, a biocatalytic platform with improved acid-base stability was constructed via a one-pot method using bismuth-ellagic acid as the carrier. Bismuth-ellagic acid is a green phenol-based metal–organic framework whose organic precursor is extracted from natural plants. After encapsulation, the stability, especially the acid-base stability, of amyloglucosidases@bismuth-ellagic acid was enhanced, which remained stable over a wide pH range (2–12) and achieved multiple recycling. By selecting a suitable buffer, bismuth-ellagic acid can encapsulate different types of enzymes and enable interactions between the encapsulated enzymes and cofactors, as well as between multiple enzymes. The green precursor, simple and convenient preparation process provided a versatile strategy for enzymes encapsulation.

关键词： bismuth-ellagic acid     in situ encapsulation     enzyme@MOF biocomposites    

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Discovery of novel ursolic acid derivatives as effective antimicrobial agents through a ROS-mediated

《化学科学与工程前沿（英文）》 2023年 第17卷 第12期   页码 2101-2113 doi: 10.1007/s11705-023-2361-5

摘要： In response to the reduction of food production and economic losses caused by plant bacterial diseases, it is necessary to develop new, efficient, and green pesticides. Natural products are rich and sustainable source for the development of new pesticides due to their low toxicity, easy degradation, and eco-friendliness. In this study, we prepared three series of ursolic acid derivatives and assessed their antibacterial ability. Most target compounds exhibited outstanding antibacterial activities. Among them, the relative optimal EC50 values of Xanthomonas oryzae pv. oryzae and Xanthomonas axonopodis pv. citri were 2.23 (A17) and 1.39 (A16) μg·mL–1, respectively. The antimicrobial mechanism showed that compound A17 induced an excessive accumulation and production of reactive oxygen species in bacteria and damaged the cell membrane integrity to kill bacteria. More interestingly, the addition of low concentrations of exogenous hydrogen peroxide enhanced the antibacterial efficacy of compound A17 against Xanthomonas oryzae pv. oryzae. These entertaining results suggested that compound A17 induced an apparent apoptotic behavior in the tested bacteria. Overall, we developed the promising antimicrobial agents that destroyed the redox system of phytopathogenic bacteria, further demonstrating the unprecedented potential of ursolic acid for agricultural applications.

关键词： ursolic acid     antibacterial activities     reactive oxygen species     apoptosis    

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DNA alkylation promoted by an electron-rich quinone methide intermediate

Chengyun Huang,Steven E. Rokita

《化学科学与工程前沿（英文）》 2016年 第10卷 第2期   页码 213-221 doi: 10.1007/s11705-015-1541-3

摘要： Biological application of conjugates derived from oligonucleotides and quinone methides have previously been limited by the slow exchange of their covalent self-adducts and subsequent alkylation of target nucleic acids. To enhance the rates of these processes, a new quinone methide precursor with an electron donating substituent has been prepared. Additionally, this substituent has been placed to the nascent -methylene group of the quinone methide for maximum effect. A conjugate made from this precursor and a 5'-aminohexyloligonucleotide accelerates formation of its reversible self-adduct and alkylation of its complementary DNA as predicted from prior model studies.

关键词： quione methide     DNA alkylation     reversible covalent reaction     bioconjugation     target-directed modification of nucleic acids    

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标题 作者 时间 类型 操作

Design of nanocarriers for efficient cellular uptake and endosomal release of small molecule and nucleicacid drugs: learning from virus

Vaibhav Mundra, Ram I. Mahato

期刊论文

Nucleic acid crystallization and X-ray crystallography facilitated by single selenium atom

Wen Zhang,Jack W. Szostak,Zhen Huang

期刊论文

Invading target cells: multifunctional polymer conjugates as therapeutic nucleic acid carriers

Ulrich L?CHELT, Ernst WAGNER

期刊论文

Validation of polarizable force field parameters for nucleic acids by inter-molecular interactions

Liaoran Cao,Hong Ren,Jing Miao,Wei Guo,Yan Li,Guohui Li

期刊论文

Nucleic acid-based diagnostics for infectious diseases in public health affairs

null

期刊论文

核酸疫苗研发态势与发展建议

李爱花,杨雪梅,孙轶楠,苑亚坤,杨俊涛

期刊论文

Flow cytometric assessment of the effects of chlorine, chloramine, and UV on bacteria by using nucleicacid stains and 5-cyano-2,3-ditolyltetrazolium chloride

Xuebiao Nie, Wenjun Liu, Mo Chen, Minmin Liu, Lu Ao

期刊论文

李爱花：基于数据视角的核酸疫苗研发态势与发展建议（2021年9月3日）

2021年10月15日

会议视频

微生物安全产业发展策略研究

宋仲戬,李曼,胡梁斌,王春明,鲁曦,刘开辉,张丽佳,宇岩,吴清平

期刊论文

微生物资源分子鉴定技术的研究进展

张羽,马爱进,高利芬,彭海,贾英民,孙宝国

期刊论文

Sulfonic acid-functionalized mesoporous silica catalyst with different morphology for biodiesel production

期刊论文

Amino acid promoted hydrogen battery system using Mn-pincer complex for reversible CO hydrogenation toformic acid

期刊论文

Enzyme@bismuth-ellagic acid: a versatile platform for enzyme immobilization with enhanced acid-base stability

期刊论文

Discovery of novel ursolic acid derivatives as effective antimicrobial agents through a ROS-mediated

期刊论文

DNA alkylation promoted by an electron-rich quinone methide intermediate

Chengyun Huang,Steven E. Rokita

期刊论文