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Cationic and amphipathic cell-penetrating peptides (CPPs): Their structures and

Jennica L. Zaro,Wei-Chiang Shen

《化学科学与工程前沿（英文）》 2015年 第9卷 第4期   页码 407-427 doi: 10.1007/s11705-015-1538-y

摘要： Over the past few decades, cell penetrating peptides (CPPs) have become an important class of drug carriers for small molecules, proteins, genes and nanoparticle systems. CPPs represent a very diverse set of short peptide sequences (10?30 amino acids), generally classified as cationic or amphipathic, with various mechanisms in cellular internalization. In this review, a more comprehensive assessment of the chemical structural characteristics, including net cationic charge, hydrophobicity and helicity was assembled for a large set of commonly used CPPs, and compared to results from numerous drug delivery studies. This detailed information can aid in the design and selection of effective CPPs for use as transport carriers in the delivery of different types of drug for therapeutic applications.

关键词： cell penetrating peptides     amphipathic peptides     drug delivery    

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Significance and strategies in developing delivery systems for bio-macromolecular drugs

Huining HE, Qiuling LIANG, Meong Cheol SHIN, Kyuri LEE, Junbo GONG, Junxiao YE, Quan LIU, Jingkang WANG, Victor YANG

《化学科学与工程前沿（英文）》 2013年 第7卷 第4期   页码 496-507 doi: 10.1007/s11705-013-1362-1

摘要： Successful development of a new drug is prohibitively expensive, and is estimated to cost approximately $100–500 million US dollars for a single clinical drug. Yet, a newly developed drug can only enjoy its patent protection for 18 years, meaning that after this protected time period, any company can manufacture this product and thus the profit generated by this drug entity would reduce dramatically. Most critically, once a drug is being synthesized, its physical, chemical, and biological attributes such as bioavailability and in vivo pharmacokinetics are all completely fixed and cannot be changed. In principal and practice, only the application of an appropriately designed drug delivery system (DDS) is able to overcome such limitations, and yet the cost of developing a novel drug delivery system is less than 10% of that of developing a new drug. Because of these reasons, the new trend in pharmaceutical development has already begun to shift from the single direction of developing new drugs in the past to a combined mode of developing both new drugs and innovative drug delivery systems in this century. Hence, for developing countries with relatively limited financial resources, a smart strategic move would be to focus on the development of new DDS, which has a significantly higher benefit/risk ratio when comparing to the development of a new drug. Because of the unmatched reaction efficiency and a repetitive action mode, the therapeutic activity of a single bio-macromolecular drug (e.g., protein toxins, gene products, etc.) is equivalent to about 10 –10 of that from a conventional small molecule anti-cancer agent (e.g., doxorubicin). Hence, bio-macromolecular drugs have been recognized around the world as the future “drug-of-choice”. Yet, among the>10000 drugs that are currently available, only ~150 of them belong to these bio-macromolecular drugs (an exceedingly low 1.2%), reflecting the difficulties of utilizing these agents in clinical practice. In general, the bottleneck limitations of these bio-macromolecular drugs are two-fold: (1) the absence of a preferential action of the drug on tumor cells as opposed to normal tissues, and (2) the lack of ability to cross the tumor cell membrane. In this review, we provide strategies of how to solve these problems simultaneously and collectively via the development of innovative drug delivery systems. Since worldwide progress on bio-macromolecular therapeutics still remains in the infant stage and thus open for an equal-ground competition, we wish that this review would echo the desire to industrialized countries such as China to set up its strategic plan on developing delivery systems for these bio-macromolecular drugs, thereby realizing their clinical potential.

关键词： delivery systems     bio-macromolecular drugs     cell penetrating peptides    

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Overcoming oral insulin delivery barriers: application of cell penetrating peptide and silica-based nanoporous

Huining HE, Junxiao YE, Jianyong SHENG, Jianxin WANG, Yongzhuo HUANG, Guanyi CHEN, Jingkang WANG, Victor C YANG

《化学科学与工程前沿（英文）》 2013年 第7卷 第1期   页码 9-19 doi: 10.1007/s11705-013-1306-9

摘要： Oral insulin delivery has received the most attention in insulin formulations due to its high patient compliance and, more importantly, to its potential to mimic the physiologic insulin secretion seen in non-diabetic individuals. However, oral insulin delivery has two major limitations: the enzymatic barrier that leads to rapid insulin degradation, and the mucosal barrier that limits insulin’s bioavailability. Several approaches have been actively pursued to circumvent the enzyme barrier, with some of them receiving promising results. Yet, thus far there has been no major success in overcoming the mucosal barrier, which is the main cause in undercutting insulin’s oral bioavailability. In this review of our group’s research, an innovative silica-based, mucoadhesive oral insulin formulation with encapsulated-insulin/cell penetrating peptide (CPP) to overcome both enzyme and mucosal barriers is discussed, and the preliminary and convincing results to confirm the plausibility of this oral insulin delivery system are reviewed. In vitro studies demonstrated that the CPP-insulin conjugates could facilitate cellular uptake of insulin while keeping insulin’s biologic functions intact. It was also confirmed that low molecular weight protamine (LMWP) behaves like a CPP peptide, with a cell translocation potency equivalent to that of the widely studied TAT. The mucoadhesive properties of the produced silica-chitosan composites could be controlled by varying both the pH and composition; the composite consisting of chitosan (25 wt-%) and silica (75 wt-%) exhibited the greatest mucoadhesion at gastric pH. Furthermore, drug release from the composite network could also be regulated by altering the chitosan content. Overall, the universal applicability of those technologies could lead to development of a generic platform for oral delivery of many other bioactive compounds, especially for peptide or protein drugs which inevitably encounter the poor bioavailability issues.

关键词： insulin     cell penetrating peptide     mucoadhesive composites     oral delivery    

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侵地武器及其气炮实验

林俊德

《中国工程科学》 2003年 第5卷 第11期   页码 25-33

摘要：

简述了侵地武器的发展历史和现状，侵彻战斗部技术在精确制导武器中已被广泛应用，小爆炸威力侵地核武器的开发已经主要不是工程技术方面的问题；介绍了气炮实验技术及其在侵地武器研究中的应用，气炮模拟实验结果表明，岩土侵彻存在良好的力学相似关系，混凝土侵彻同花岗岩侵彻存在许多质的差异；介绍了一种通过侵深实验数据分析计算侵彻弹体加速度、速度和位移变化过程的方法。

关键词： 武器试验     岩土侵彻     气炮     撞击     实验技术    

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Multifunctional peptide conjugated amphiphilic cationic copolymer for enhancing ECs targeting, penetrating

Xinghong Duo, Lingchuang Bai, Jun Wang, Jintang Guo, Xiangkui Ren, Shihai Xia, Wencheng Zhang, Abraham Domb, Yakai Feng

《化学科学与工程前沿（英文）》 2020年 第14卷 第5期   页码 889-901 doi: 10.1007/s11705-020-1919-8

摘要： Gene therapy has drawn great attention in the treatments of many diseases, especially for cardiovascular diseases. However, the development of gene carriers with low cytotoxicity and multitargeting function is still a challenge. Herein, the multitargeting REDV-G-TAT-G-NLS peptide was conjugated to amphiphilic cationic copolymer poly( -caprolactone-co-3(S)-methyl-morpholine-2,5-dione)- -polyethyleneimine (PCLMD- -PEI) via a heterobifunctional orthopyridyl disulfide-poly(ethylene glycol)- -hydroxysuccinimide (OPSS-PEG-NHS) linker to prepare PCLMD- -PEI-PEG-REDV-G-TAT-G-NLS copolymers with the aim to develop the gene carriers with low cytotoxicity and high transfection efficiency. The multitargeting micelles were prepared from PCLMD- -PEI-PEG-REDV-G-TAT-G-NLS copolymers by self-assembly method and used to load pEGFP-ZNF580 plasmids (pDNA) to form gene complexes for enhancing the proliferation and migration of endothelial cells (ECs). The loading pDNA capacity was proved by agarose gel electrophoresis assay. These multitargeting gene complexes exhibited low cytotoxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The high internalization efficiency of these gene complexes was confirmed by flow cytometry. The results of transfection demonstrated that these multitargeting gene complexes possessed relatively high transfection efficiency. The rapid migration of ECs transfected by these gene complexes was verified by wound healing assay. Owing to ECs-targeting ability, cell-penetrating ability and nuclear targeting capacity of REDV-G-TAT-G-NLS peptide, the multitargeting polycationic gene carrier with low cytotoxicity and high transfection efficiency has great potential in gene therapy.

关键词： gene carriers     multitargeting function     ECs     transfection efficiency    

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Enzyme-instructed self-assembly of peptides containing phosphoserine to form supramolecular hydrogels

Jie Zhou, Xuewen Du, Jiaqing Wang, Natsuko Yamagata, Bing Xu

《化学科学与工程前沿（英文）》 2017年 第11卷 第4期   页码 509-515 doi: 10.1007/s11705-017-1613-7

摘要： Enzyme-instructed self-assembly (EISA) offers a facile approach to explore the supramolecular assemblies of small molecules in cellular milieu for a variety of biomedical applications. One of the commonly used enzymes is phosphatase, but the study of the substrates of phosphatases mainly focuses on the phosphotyrosine containing peptides. In this work, we examine the EISA of phosphoserine containing small peptides for the first time by designing and synthesizing a series of precursors containing only phosphoserine or both phosphoserine and phosphotyrosine. Conjugating a phosphoserine to the -terminal of a well-established self-assembling peptide backbone, (naphthalene-2-ly)-acetyl-diphenylalanine (NapFF), affords a novel hydrogelation precursor for EISA. The incorporation of phosphotyrosine, another substrate of phosphatase, into the resulting precursor, provides one more enzymatic trigger on a single molecule, and meanwhile increases the precursors’ propensity to aggregate after being fully dephosphorylated. Exchanging the positions of phosphorylated serine and tyrosine in the peptide backbone provides insights on how the specific molecular structures influence self-assembling behaviors of small peptides and the subsequent cellular responses. Moreover, the utilization of D-amino acids largely enhances the biostability of the peptides, thus providing a unique soft material for potential biomedical applications.

关键词： enzyme-instructed self-assembly     phosphoserine     phosphatase     supramolecular hydrogel    

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钻地武器的毁伤效应及深地下防护工程关键科学问题

范鹏贤,钱七虎,王明洋

《中国工程科学》 2013年 第15卷 第5期   页码 47-58

摘要：

防护工程是国防威慑力量的重要组成部分，具有重要的战略地位。美俄等军事大国大力发展的深钻地（核）武器已经对我国重要防护工程的生存造成了严重的威胁。本文总结了外军现役钻地（核）武器的性能指标与发展前景，对钻地武器的毁伤效应进行了评估和分析，综述了侵彻效应、爆炸成坑效应、爆炸地冲击效应等方面的研究成果。针对新时期的主要威胁，简述了提高防护工程防护能力的主要措施和技术途径，提出了主被动结合的综合防护体系、深部非线性岩体力学、摆型波与超低摩擦现象、多弹聚集打击效应等目前亟需开展研究的关键科学问题。

关键词： 钻地武器     毁伤效应     深地下     防护工程    

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to: Multifunctional peptide conjugated amphiphilic cationic copolymer for enhancing ECs targeting, penetrating

Xinghong Duo, Lingchuang Bai, Jun Wang, Jintang Guo, Xiangkui Ren, Shihai Xia, Wencheng Zhang, Abraham Domb, Yakai Feng

《化学科学与工程前沿（英文）》 2021年 第15卷 第1期   页码 220-220 doi: 10.1007/s11705-020-1995-9

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复杂环境下起伏地形探地雷达逆时偏移成像 Article

John H. Bradford,Janna Privette,David Wilkins,Richard Ford

《工程（英文）》 2018年 第4卷 第5期   页码 661-666 doi: 10.1016/j.eng.2018.09.004

摘要：

探地雷达偏移成像中，基于高程静校正的基准面偏移方法对起伏地表下的复杂地层成像效果较差。为了优化成像效果，本文提出了一种基于麦克斯韦方程组二阶解耦形式的逆时偏移成像（reversetime migration，RTM）算法，该算法特点在于只需计算电场，且可直接从采集面而非基准面进行波场延拓，进而实现地形逆时偏移。数值模拟比较了高程静校正偏移方法和RTM 方法在地表起伏及速度横向变化情况下的成像效果，结果证明RTM 方法成像效果更好。为了进一步验证算法效果，利用美国犹他州珊瑚粉沙丘崎岖地形下的实测数据对两种方法进行了对比分析。研究表明，逆时偏移成像方法能够极大地提高复杂环境下探地雷达深度成像精度。

关键词： 探地雷达     逆时偏移     沙丘     振幅分析    

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大装填比弹侵彻钢筋混凝土实验研究

赵生伟,古仁红,初哲,李明

《中国工程科学》 2009年 第11卷 第8期   页码 44-47

摘要：

设计了一种薄壁弹体，采用YOUNG方程预估该弹体侵彻混凝土靶板的侵彻深度，采用SAMPLL程序预估轴向过载。运用LS-DYNA软件分析弹体的侵彻过程，对材料力学性能进行实验研究。通过在Ø130 mm气炮上的一系列弹体侵彻钢筋混凝土靶实验，考核了弹体的结构强度和侵彻深度。结果表明：弹体在低速侵彻钢筋混凝土靶板时结构不会发生破坏，300 m/s速度下具备侵彻贯穿600 mm钢筋混凝土层的能力。

关键词： 薄壁弹体     钢筋混凝土     侵彻深度    

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Microfluidics for cell-cell interactions: A review

Rui Li,Xuefei Lv,Xingjian Zhang,Omer Saeed,Yulin Deng

《化学科学与工程前沿（英文）》 2016年 第10卷 第1期   页码 90-98 doi: 10.1007/s11705-015-1550-2

摘要： Microfluidic chip has been applied in various biological fields owing to its low-consumption of reagents, high throughput, fluidic controllability and integrity. The well-designed microscale intermediary is also ideal for the study of cell biology. Particularly, microfluidic chip is helpful for better understanding cell-cell interactions. A general survey of recent publications would help to generalize the designs of the co-culture chips with different features. With ingenious and combinational utilization, the chips facilitate the implementation of some special co-culture models that are highly concerned in a different spatial and temporal way.

关键词： microfluidic chip     co-culture     cell-cell interactions     review    

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Distinct mononuclear diploid cardiac subpopulation with minimal cell–cell communications persists in

《医学前沿（英文）》   页码 939-956 doi: 10.1007/s11684-023-0987-9

摘要： A small proportion of mononuclear diploid cardiomyocytes (MNDCMs), with regeneration potential, could persist in adult mammalian heart. However, the heterogeneity of MNDCMs and changes during development remains to be illuminated. To this end, 12 645 cardiac cells were generated from embryonic day 17.5 and postnatal days 2 and 8 mice by single-cell RNA sequencing. Three cardiac developmental paths were identified: two switching to cardiomyocytes (CM) maturation with close CM–fibroblast (FB) communications and one maintaining MNDCM status with least CM–FB communications. Proliferative MNDCMs having interactions with macrophages and non-proliferative MNDCMs (non-pMNDCMs) with minimal cell–cell communications were identified in the third path. The non-pMNDCMs possessed distinct properties: the lowest mitochondrial metabolisms, the highest glycolysis, and high expression of Myl4 and Tnni1. Single-nucleus RNA sequencing and immunohistochemical staining further proved that the Myl4+Tnni1+ MNDCMs persisted in embryonic and adult hearts. These MNDCMs were mapped to the heart by integrating the spatial and single-cell transcriptomic data. In conclusion, a novel non-pMNDCM subpopulation with minimal cell–cell communications was unveiled, highlighting the importance of microenvironment contribution to CM fate during maturation. These findings could improve the understanding of MNDCM heterogeneity and cardiac development, thus providing new clues for approaches to effective cardiac regeneration.

关键词： mononuclear diploid cardiomyocytes     cell–cell communication     cardiac fibroblast     single-cell RNA sequencing     cardiac regeneration    

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Deubiquitinases as pivotal regulators of T cell functions

null

《医学前沿（英文）》 2018年 第12卷 第4期   页码 451-462 doi: 10.1007/s11684-018-0651-y

摘要：

T cells efficiently respond to foreign antigens to mediate immune responses against infections but are tolerant to self-tissues. Defect in T cell activation is associated with severe immune deficiencies, whereas aberrant T cell activation contributes to the pathogenesis of diverse autoimmune and inflammatory diseases. An emerging mechanism that regulates T cell activation and tolerance is ubiquitination, a reversible process of protein modification that is counter-regulated by ubiquitinating enzymes and deubiquitinases (DUBs). DUBs are isopeptidases that cleave polyubiquitin chains and remove ubiquitin from target proteins, thereby controlling the magnitude and duration of ubiquitin signaling. It is now well recognized that DUBs are crucial regulators of T cell responses and serve as potential therapeutic targets for manipulating immune responses in the treatment of immunological disorders and cancer. This review will discuss the recent progresses regarding the functions of DUBs in T cells.

关键词： deubiquitinase     ubiquitination     T cell activation     T cell differentiation     T cell tolerance    

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Cell surface protein engineering for high-performance whole-cell catalysts

Hajime Nakatani,Katsutoshi Hori

《化学科学与工程前沿（英文）》 2017年 第11卷 第1期   页码 46-57 doi: 10.1007/s11705-017-1609-3

摘要： Cell surface protein engineering facilitated by accumulation of information on genome and protein structure involves heterologous production and modification of cell surface proteins using genetic engineering, and is important for the development of high-performance whole-cell catalysts. In this field, cell surface display is a major technology by exposing target proteins, such as enzymes, on the cell surface using a carrier protein. The target proteins are fused to the carrier proteins that transport and tether them to the cell surface, as well as to a secretion signal. This paper reviews cell surface display systems for prokaryotic and eukaryotic cells from the perspective of carrier proteins, which determine the number of displayed molecules, and the localization, size, and direction ( or terminal anchoring) of the passengers. We also discuss advanced methods for displaying multiple enzymes and a new method for the immobilization of whole-cell catalysts using adhesive surface proteins.

关键词： cell surface engineering     surface display     whole-cell catalysts     bioprocess    

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Stem cell niches and endogenous electric fields in tissue repair

null

《医学前沿（英文）》 2011年 第5卷 第1期   页码 40-44 doi: 10.1007/s11684-011-0108-z

摘要：

Adult stem cells are responsible for homeostasis and repair of many tissues. Endogenous adult stem cells reside in certain regions of organs, known as the stem cell niche, which is recognized to have an important role in regulating tissue maintenance and repair. In wound healing and tissue repair, stem cells are mobilized and recruited to the site of wound, and participate in the repair process. Many regulatory factors are involved in the stem cell-based repair process, including stem cell niches and endogenous wound electric fields, which are present at wound tissues and proved to be important in guiding wound healing. Here we briefly review the role of stem cell niches and endogenous electric fields in tissue repair, and hypothesize that endogenous electric fields become part of stem cell niche in the wound site.

关键词： stem cell     stem cell niche     electric field     tissue repair    

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标题 作者 时间 类型 操作

Cationic and amphipathic cell-penetrating peptides (CPPs): Their structures and

Jennica L. Zaro,Wei-Chiang Shen

期刊论文

Significance and strategies in developing delivery systems for bio-macromolecular drugs

Huining HE, Qiuling LIANG, Meong Cheol SHIN, Kyuri LEE, Junbo GONG, Junxiao YE, Quan LIU, Jingkang WANG, Victor YANG

期刊论文

Overcoming oral insulin delivery barriers: application of cell penetrating peptide and silica-based nanoporous

Huining HE, Junxiao YE, Jianyong SHENG, Jianxin WANG, Yongzhuo HUANG, Guanyi CHEN, Jingkang WANG, Victor C YANG

期刊论文

侵地武器及其气炮实验

林俊德

期刊论文

Multifunctional peptide conjugated amphiphilic cationic copolymer for enhancing ECs targeting, penetrating

Xinghong Duo, Lingchuang Bai, Jun Wang, Jintang Guo, Xiangkui Ren, Shihai Xia, Wencheng Zhang, Abraham Domb, Yakai Feng

期刊论文

Enzyme-instructed self-assembly of peptides containing phosphoserine to form supramolecular hydrogels

Jie Zhou, Xuewen Du, Jiaqing Wang, Natsuko Yamagata, Bing Xu

期刊论文

钻地武器的毁伤效应及深地下防护工程关键科学问题

范鹏贤,钱七虎,王明洋

期刊论文

to: Multifunctional peptide conjugated amphiphilic cationic copolymer for enhancing ECs targeting, penetrating

Xinghong Duo, Lingchuang Bai, Jun Wang, Jintang Guo, Xiangkui Ren, Shihai Xia, Wencheng Zhang, Abraham Domb, Yakai Feng

期刊论文

复杂环境下起伏地形探地雷达逆时偏移成像

John H. Bradford,Janna Privette,David Wilkins,Richard Ford

期刊论文

大装填比弹侵彻钢筋混凝土实验研究

赵生伟,古仁红,初哲,李明

期刊论文

Microfluidics for cell-cell interactions: A review

Rui Li,Xuefei Lv,Xingjian Zhang,Omer Saeed,Yulin Deng

期刊论文

Distinct mononuclear diploid cardiac subpopulation with minimal cell–cell communications persists in

期刊论文

Deubiquitinases as pivotal regulators of T cell functions

null

期刊论文

Cell surface protein engineering for high-performance whole-cell catalysts

Hajime Nakatani,Katsutoshi Hori

期刊论文

Stem cell niches and endogenous electric fields in tissue repair

null

期刊论文