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Identification of Dynamic Active Sites Among Cu Species Derived from MOFs@CuPc for Electrocatalytic Nitrate Reduction Reaction to Ammonia 被引量:1
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作者 Xue‑Yang Ji Ke Sun +5 位作者 Zhi‑Kun Liu Xinghui Liu Weikang Dong Xintao Zuo Ruiwen Shao Jun Tao 《Nano-Micro Letters》 SCIE EI CAS CSCD 2023年第8期20-34,共15页
Direct electrochemical nitrate reduction reaction(NITRR)is a promising strategy to alleviate the unbalanced nitrogen cycle while achieving the electrosynthesis of ammonia.However,the restructuration of the high-activi... Direct electrochemical nitrate reduction reaction(NITRR)is a promising strategy to alleviate the unbalanced nitrogen cycle while achieving the electrosynthesis of ammonia.However,the restructuration of the high-activity Cu-based electrocatalysts in the NITRR process has hindered the identification of dynamical active sites and in-depth investigation of the catalytic mechanism.Herein,Cu species(single-atom,clusters,and nanoparticles)with tunable loading supported on N-doped TiO_(2)/C are successfully manufactured with MOFs@CuPc precursors via the pre-anchor and post-pyrolysis strategy.Restructuration behavior among Cu species is co-dependent on the Cu loading and reaction potential,as evidenced by the advanced operando X-ray absorption spectroscopy,and there exists an incompletely reversible transformation of the restructured structure to the initial state.Notably,restructured CuN_(4)&Cu_(4) deliver the high NH_(3) yield of 88.2 mmol h^(−1)g_(cata)^(−1) and FE(~94.3%)at−0.75 V,resulting from the optimal adsorption of NO_(3)^(−) as well as the rapid conversion of^(*)NH_(2)OH to^(*)NH_(2) intermediates originated from the modulation of charge distribution and d-band center for Cu site.This work not only uncovers CuN_(4)&Cu_(4) have the promising NITRR but also identifies the dynamic Cu species active sites that play a critical role in the efficient electrocatalytic reduction in nitrate to ammonia. 展开更多
关键词 Metal-organic frameworks Copper phthalocyanine Electrocatalytic nitrate reduction reaction
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Advances of mRNA vaccines for COVID-19:A new prophylactic revolution begins 被引量:3
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作者 Yuhua Weng Yuanyu Huang 《Asian Journal of Pharmaceutical Sciences》 SCIE CAS 2021年第3期263-264,共2页
The world is in the midst of 2019 coronavirus infection disease(COVID-19)pandemic.As of 30 January 2021,more than 100 million cases and 2.1 million deaths were confirmed according to the data from the World Health Org... The world is in the midst of 2019 coronavirus infection disease(COVID-19)pandemic.As of 30 January 2021,more than 100 million cases and 2.1 million deaths were confirmed according to the data from the World Health Organization(WHO),resulting in a widespread social and economic turmoil.Therefore,researches worldwide are racing to deploy safe and effective COVID-19 vaccines. 展开更多
关键词 vaccines INFECTION CASES
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In vivo analysis of intestinal permeability following hemorrhagic shock 被引量:1
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作者 Tom Alsaigh Marisol Chang +2 位作者 Michael Richter Rafi Mazor Erik B Kistler 《World Journal of Critical Care Medicine》 2015年第4期287-295,共9页
AIM: To determine the time course of intestinal permeability changes to proteolytically-derived bowel peptides in experimental hemorrhagic shock. METHODS: We injected fluorescently-conjugated casein protein into the s... AIM: To determine the time course of intestinal permeability changes to proteolytically-derived bowel peptides in experimental hemorrhagic shock. METHODS: We injected fluorescently-conjugated casein protein into the small bowel of anesthetized Wistar rats prior to induction of experimental hemorrhagic shock. These molecules, which fluoresce when proteolytically cleaved, were used as markers for the ability of proteolytically cleaved intestinal products to access the central circulation. Blood was serially sampled to quantify the relative change in concentration of proteolytically-cleaved particles in the systemic circulation. To provide spatial resolution of their location, particles in the mesenteric microvasculature were imaged using in vivo intravital fluorescent microscopy. The experiments were then repeated using an alternate measurement technique, fluorescein isothiocyanate(FITC)-labeled dextrans 20, to semi-quantitatively verify the ability of bowel-derived low-molecular weight molecules(< 20 k D) to access the central circulation.RESULTS: Results demonstrate a significant increase in systemic permeability to gut-derived peptides within 20 min after induction of hemorrhage(1.11 ± 0.19 vs 0.86 ± 0.07, P < 0.05) compared to control animals. Reperfusion resulted in a second, sustained increase in systemic permeability to gut-derived peptides in hemorrhaged animals compared to controls(1.2 ± 0.18 vs 0.97 ± 0.1, P < 0.05). Intravital microscopy of the mesentery also showed marked accumulation of fluorescent particles in the microcirculation of hemorrhaged animals compared to controls. These results were replicated using FITC dextrans 20 [10.85 ± 6.52 vs 3.38 ± 1.11 fluorescent intensity units(× 105, P < 0.05, hemorrhagic shock vs controls)], confirming that small bowel ischemia in response to experimental hemorrhagic shock results in marked and early increases in gut membrane permeability. CONCLUSION: Increased small bowel permeability in hemorrhagic shock may allow for systemic absorption of otherwise retained proteolytically-generated peptides, with consequent hemodynamic instability and remote organ failure. 展开更多
关键词 Small BOWEL ISCHEMIA HEMORRHAGIC shock PEPTIDES MICROCIRCULATION PROTEOLYSIS
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Molecular and Cellular Immuno-Engineering
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作者 Peter Yingxiao Wang 《医用生物力学》 EI CAS CSCD 北大核心 2019年第A01期5-5,共1页
Genetically-encoded biosensors based on fluorescence proteins(FPs)and fluorescence resonance energy transfer(FRET)have enabled the specific targeting and visualization of signaling events in live cells with high spati... Genetically-encoded biosensors based on fluorescence proteins(FPs)and fluorescence resonance energy transfer(FRET)have enabled the specific targeting and visualization of signaling events in live cells with high spatiotemporal resolutions.Single-molecule FRET biosensors have been successfully developed to monitor the activity of a variety of signaling molecules,including tyrosine/serine/threonine kinases.We have a developed a general high-throughput screening(HTS)method based on directed evolution to develop sensitive and specific FRET biosensors.We have first applied a yeast library and screened for a mutated binding domain for phosphorylated peptide sequence.When this mutated binding domain and the peptide sequence are connected by a linker and then concatenated in between a pair of FRET FPs,a drastic increase in sensitivity can be achieved.It has also been increasingly clear that controlling protein functions using lights and chemical compounds to trigger allosteric conformational changes can be applied to manipulate protein functions and control cellular behaviors.In this work,we first engineered a novel class of machinery molecules which can provide a surveillance of the intracellular space,visualizing the spatiotemporal patterns of molecular events and automatically triggering corresponding molecular actions to guide cellular functions.We have adopted a modular assembly approach to develop these machinery molecules.We engineered such a molecule for the sensing of intracellular tyrosine phosphorylation based on fluorescence resonance energy transfer(FRET)and the consequent activation of a tyrosine phosphatase(PTP)Shp2,which plays a critical and positive role in various pathophysiological processes[1-3].We have further integrated this machinery molecule to the'don’t eat me'CD47 receptor SIRPa on macrophages such that the engagement of SIRPa and its activation of naturally negative signals will be rewired to turn on the positive Shp2 action to facilitate phagocytosis of red blood cells and target tumor cells,initiated by the specific antigen-targeting antibodies and their interaction with Fcg receptors.Because of the modular design of our engineered molecule,our approach can be extended to perform a broad range of cell-based imaging and immunotherapies,and hence highlight the translational power in bridging the fundamental molecular engineering to clinical medicine.We have also integrated with lights and ultrasound to manipulate the molecular activation of genes and enzymes,which allowed us to control the cellular functions of immunocells with high precision in space and time. 展开更多
关键词 MOLECULAR and CELLULAR Immuno-Engineering
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Warmest Congratulations to the Journal of Medical Biomechanics on Its 30^(th) Anniversary
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作者 Shu Chien 《医用生物力学》 EI CAS CSCD 北大核心 2016年第4期F0002-F0002,共1页
It is my great pleasure and privilege to write this message of congratulation to commemorate the auspicious occasion of the 30^(th) anniversary of the Journal of Medical Biomechanics(JMB),which was first published in ... It is my great pleasure and privilege to write this message of congratulation to commemorate the auspicious occasion of the 30^(th) anniversary of the Journal of Medical Biomechanics(JMB),which was first published in 1986 as the Journal of Biomechanics.The JMB,which is sponsored by Shanghai Jiao Tong University and supervised by the Ministry of Education of People’s Republic of China,has made outstanding accomplishments over the thirty-year period since its inception.It is 展开更多
关键词 作者介绍 编辑工作 主编 《医学生物力学》
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Mixing Dynamics and Synthesis Performance of Staggered Herringbone Micromixer for Limit Size Lipid Nanoparticles
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作者 Shuai Zhang Yunlong Fan +4 位作者 Chenmu Xue Yuanzhan Yang Xiaoqiong Li Xiaodong Chen Yulin Deng 《Journal of Beijing Institute of Technology》 EI CAS 2022年第3期293-301,共9页
Staggered herringbone micromixer has shown good efficiency of mixing and performance of synthesizing nanoparticles.To bring a detailed understanding of the mixing dynamics and syn-thesis performance of this kind of mi... Staggered herringbone micromixer has shown good efficiency of mixing and performance of synthesizing nanoparticles.To bring a detailed understanding of the mixing dynamics and syn-thesis performance of this kind of micromixer,this paper carries out a high-fidelity numerical simu-lation and a parametrial experimental study on a well-established design.A passive tracer is induced in the numerical simulation to analyze mixing dynamics induced by the staggered herring-bone structures.Three effects are identified to reveal the underlying mechanisms,including folding,stretching,and splitting.To the authors’knowledge,the splitting effect is identified for the first time by the isosurface of the passive tracer,to show the high efficiency of the staggered herring-bone design.The micromixer is then used to synthesize lipid nanoparticles by mixing a mixture of lipid and poly(lactic-co-glycolic acid)(PLGA)solutions with deionized water.Under a wide mass ratio of lipid and PLGA solutions,nanoparticles with good monodispersity are synthesized to reflect the good compatibility of the micromixer and the mixture.In addition,an optimized mass ratio is identified from the parametrical experiment. 展开更多
关键词 mixing dynamics staggered herringbone micromixer FOLDING STRETCHING splitting
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力传导中亚细胞水平的分子FRET成像(英文) 被引量:2
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作者 王英晓 《医用生物力学》 EI CAS CSCD 北大核心 2016年第4期308-318,共11页
体内细胞受到含有化学和力学因素的生理和病理生理的刺激,故研究这些因素在细胞和器官水平如何调节功能就尤为重要。有关细胞和器官对化学因素的反应已开展诸多研究,而力学因素的影响却鲜有报道。近年来,荧光蛋白和显微镜技术的发展已... 体内细胞受到含有化学和力学因素的生理和病理生理的刺激,故研究这些因素在细胞和器官水平如何调节功能就尤为重要。有关细胞和器官对化学因素的反应已开展诸多研究,而力学因素的影响却鲜有报道。近年来,荧光蛋白和显微镜技术的发展已成为阐明力传导过程的有用工具,先进的信号活细胞成像技术促进了力学生物学中分子机制的时空因素研究。本文综述荧光蛋白的基本知识以及其在生物学研究中的应用,特别讨论了以荧光共振能量迁移(fluorescence proteins and microscopy,FRET)技术为基础的生物传感器的发展和特征。基因编码的FRET生物传感器能够实现分子时空活动的成像和定量,使得活细胞中生物化学信号在力学刺激下的反应和传导可视化。同时,本文重点阐述分子水平力学刺激下的活细胞信号传导。 展开更多
关键词 荧光共振能量迁移 荧光蛋白 力学刺激 信号传导 生物传感器 力学生物学
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Multifunctional stimuli responsive polymer-gated iron and gold-embedded silica nano golf balls:Nanoshuttles for targeted on-demand theranostics 被引量:1
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作者 Liping Wang Grace Jang +11 位作者 Deependra Kumar Ban Vrinda Sant Jay Seth Sami Kazmi Nirav Patel Qingqing Yang Joon Lee Woraphong Janetanakit Shanshan Wang Brian P Head Gennadi Glinsky Ratneshwar Lai 《Bone Research》 SCIE CAS CSCD 2017年第4期343-356,共14页
Multi-functional nanoshuttles for remotely targeted and on-demand delivery of therapeutic molecules and imaging to defined tissues and organs hold great potentials in personalized medicine, including precise early dia... Multi-functional nanoshuttles for remotely targeted and on-demand delivery of therapeutic molecules and imaging to defined tissues and organs hold great potentials in personalized medicine, including precise early diagnosis,efficient prevention and therapy without toxicity. Yet, in spite of 25 years of research, there are still no such shuttles available. To this end, we have designed magnetic and gold nanoparticles(NP)-embedded silica nanoshuttles(MGNSs) with nanopores on their surface. Fluorescently labeled Doxorubicin(DOX), a cancer drug, was loaded in the MGNSs as a payload. DOX loaded MGNSs were encapsulated in heat and pH sensitive polymer P(NIPAM-coMAA) to enable controlled release of the payload. Magnetically-guided transport of MGNSs was examined in:(a) a glass capillary tube to simulate their delivery via blood vessels; and(b) porous hydrogels to simulate their transport in composite human tissues, including bone, cartilage, tendon, muscles and blood–brain barrier(BBB). The viscoelastic properties of hydrogels were examined by atomic force microscopy(AFM). Cellular uptake of DOXloaded MGNSs and the subsequent pH and temperature-mediated release were demonstrated in differentiated human neurons derived from induced pluripotent stem cells(iPSCs) as well as epithelial HeL a cells. The presence of embedded iron and gold NPs in silica shells and polymer-coating are supported by SEM and TEM. Fluorescence spectroscopy and microscopy documented DOX loading in the MGNSs. Time-dependent transport of MGNSs guided by an external magnetic field was observed in both glass capillary tubes and in the porous hydrogel. AFM results affirmed that the stiffness of the hydrogels model the rigidity range from soft tissues to bone. pH and temperature-dependent drug release analysis showed stimuli responsive and gradual drug release. Cells' viability MTT assays showed that MGNSs are non-toxic. The cell death from on-demand DOX release was observed in both neurons and epithelial cells even though the drug release efficiency was higher in neurons. Therefore, development of smart nanoshuttles have significant translational potential for controlled delivery of theranostics' payloads and precisely guided transport in specified tissues and organs(for example, bone, cartilage, tendon, bone marrow, heart,lung, liver, kidney, and brain) for highly efficient personalized medicine applications. 展开更多
关键词 MAA Nanoshuttles for targeted on-demand theranostics Multifunctional stimuli responsive polymer-gated iron and gold-embedded silica nano golf balls DOX Figure NIPAM
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冯元桢先生百岁大寿贺喜
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作者 钱煦 《医用生物力学》 EI CAS CSCD 北大核心 2018年第S1期5-6,共2页
我最初认识冯先生是经由读他的奠基文章和经典书籍以及听他的卓越演讲,也曾经在开会时简短见过。第一次和冯先生真正见面是1965年在美国新泽西州大西洋城参加微循环学会会议的时候。我和内人匡政及两个女儿在一家饭馆吃饭,冯先生在另一... 我最初认识冯先生是经由读他的奠基文章和经典书籍以及听他的卓越演讲,也曾经在开会时简短见过。第一次和冯先生真正见面是1965年在美国新泽西州大西洋城参加微循环学会会议的时候。我和内人匡政及两个女儿在一家饭馆吃饭,冯先生在另一桌和微循环学会理事们开会用餐。他过来和我们打招呼,结果就坐下来和我们一起吃,谈得很高兴(图1),他没有回去参加理事会,使我非常感动,永远铭记在心。这件事明确地显示冯先生对年轻后辈的关怀提携。 展开更多
关键词 冯先生 讲座教授 生物工程学 生物医学工程 生物力学
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Comparative study on Photobiomodulation between 630 nm and 810 nm LED in diabetic wound healing both in vitro and in vivo
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作者 Hongyou Zhao Tengda Ji +8 位作者 Tianzhen Sun Haolin Liu Yidi Liu Defu Chen Ying Wang Yizhou Tan Jing Zeng Haixia Qiu Ying Gu 《Journal of Innovative Optical Health Sciences》 SCIE EI CAS 2022年第2期58-67,共10页
Photobiomodulation(PBM)promoting wound healing has been demonstrated by many studies.Currently,630 nm and 810 nm light-emitting diodes(LEDs),as light sources,are frequently used in the treatment of diabetic foot ulcer... Photobiomodulation(PBM)promoting wound healing has been demonstrated by many studies.Currently,630 nm and 810 nm light-emitting diodes(LEDs),as light sources,are frequently used in the treatment of diabetic foot ulcers(DFUs)in clinics.However,the dose-effect relationship of LED-mediated PBM is not fully understood.Furthermore,among the 630 nm and 810 nm LEDs,which one gets a better effect on accelerating the wound healing of diabetic ulcers is not clear.The aim of this study is to evaluate and compare the effects of 630 nm and 810 nm LED-mediated PBM in wound healing both in vitro and in vivo.Our results showed that both 630 nm and 810 nm LED irradiation significantly promoted the proliferation of mouse fibroblast cells(L929)at different light irradiances(1,5,and 10 mW/cm^(2)).The cell proliferation rate increased with the extension of irradiation time(100,200,and 500 s),but it decreased when the irradiation time was over 500 s.Both 630 nm and 810nm LED irradiation(5 mW/cm^(2))significantly improved the migration capability of L929 cells.No difference between 630 nm and 810 nm LED-mediated PBM in promoting cell proliferation and migration was detected.In vivo results presented that both 630 nm and 810 nm LED irradiation promoted the wound healing and the expression of the vascular endothelial growth factor(VEGF)and transforming growth factor(TGF)in the wounded skin of type 2 diabetic mice.Overall,these results suggested that LED-mediated PBM promotes wound healing of diabetic mice through promoting fibroblast cell proliferation,migration,and the expression of growth factors in the wounded skin.LEDs(630 nm and 810 nm)have a similar outcome in promoting wound healing of type 2 diabetic mice. 展开更多
关键词 Photobiomodulation(PBM) light-emitting diode(LED) wound healing diabetic ulcers
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The radioresistant and survival mechanisms of Deinococcus radiodurans
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作者 Feng Liu Nuomin Li Yongqian Zhang 《Radiation Medicine and Protection》 CSCD 2023年第2期70-79,共10页
Deinococcus radiodurans (D. radiodurans) is distinguished by the most radioresistant organism ever known, and can tolerate extreme environments such as ionizing radiation, ultraviolet radiation, oxidation, and desicca... Deinococcus radiodurans (D. radiodurans) is distinguished by the most radioresistant organism ever known, and can tolerate extreme environments such as ionizing radiation, ultraviolet radiation, oxidation, and desiccation. D. radiodurans is an important model for studying DNA damage/repair and redox regulation upon high dose ionizing radiation. How D. radiodurans response and repair ROS-induced oxidative damage remains a subject of ongoing investigation. This review provides an overview of the radioresistance characteristics of D. radiodurans. Among them, the DNA damage repair pathway and high-efficiency antioxidant defense system are summarized in detail. Furthermore, a novel model that protects the cell against the ionizing radiation is proposed. This review also discusses the potential application , future challenges and directions in advancing towards D. radiodurans studies. 展开更多
关键词 Deinococcus radiodurans Radioresistant mechanism Oxidative stress DNA repair Antioxidant defense system
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HPDA/Zn as a CREB Inhibitor for Ultrasound imaging and Stabilization of Atherosclerosis Plaque+
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作者 Linzi Chen Zhenqi Jiang +7 位作者 Lifei Yang Ye Fang Shuwei Lu Ozioma U.Akakuru Shuaishuai Huang Juan Li Suya Ma Aiguo Wu 《Chinese Journal of Chemistry》 SCIE CAS CSCD 2023年第2期199-206,共8页
Thrombosis,secondary to rupture of unstable plaque,is a fatal risk factor for myocardial infarction and ischemic stroke.At present,more novel methods are needed for the diagnosis and treatment of vulnerable plaque.Her... Thrombosis,secondary to rupture of unstable plaque,is a fatal risk factor for myocardial infarction and ischemic stroke.At present,more novel methods are needed for the diagnosis and treatment of vulnerable plaque.Here,we report a hollow polydopamine/Zn(HPDA/Zn)ultrasound contrast agent.Through western-blot,Elisa,and other experiments,we found that in addition to having a good contrast-enhancement capability in ultrasound imaging in vitro and in vivo,HPDA/Zn also has the effect of reducing the expres-sion of CREB.CREB protein and its downstream-regulated proteins and factors are closely related to the stability of plaque.HPDA/Zn has the effect of reducing the expression of CREB protein,which leads to the decrease of expression of MMP-9,the regulatory pro-tein downstream of the CREB protein.In addition,it also reduces the secretion of inflammatory factors hs-CRP and IL-17A.Thus,HPDA/Zn can stabilize plaque by inhibiting CREB and reducing plaque vulnerable markers and inflammatory factors.In a word,HPDA/Zn is a kind of ultrasound contrast agent,which can stabilize plaques by inhibiting CREB protein. 展开更多
关键词 ATHEROSCLEROSIS ZINC POLYMERIZATION CREB Nanoparticles Ultrasound imaging
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Therapeutic siRNA:state of the art 被引量:6
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作者 Bo Hu Liping Zhong +4 位作者 Yuhua Weng Ling Peng Yuanyu Huang Yongxiang Zhao Xing-Jie Liang 《Signal Transduction and Targeted Therapy》 SCIE CSCD 2020年第1期1532-1556,共25页
RNA interference(RNAi)is an ancient biological mechanism used to defend against external invasion.It theoretically can silence any disease-related genes in a sequence-specific manner,making small interfering RNA(siRNA... RNA interference(RNAi)is an ancient biological mechanism used to defend against external invasion.It theoretically can silence any disease-related genes in a sequence-specific manner,making small interfering RNA(siRNA)a promising therapeutic modality.After a two-decade journey from its discovery,two approvals of siRNA therapeutics,ONPATTRO®(patisiran)and GIVLAARI™(givosiran),have been achieved by Alnylam Pharmaceuticals.Reviewing the long-term pharmaceutical history of human beings,siRNA therapy currently has set up an extraordinary milestone,as it has already changed and will continue to change the treatment and management of human diseases.It can be administered quarterly,even twice-yearly,to achieve therapeutic effects,which is not the case for small molecules and antibodies.The drug development process was extremely hard,aiming to surmount complex obstacles,such as how to efficiently and safely deliver siRNAs to desired tissues and cells and how to enhance the performance of siRNAs with respect to their activity,stability,specificity and potential off-target effects.In this review,the evolution of siRNA chemical modifications and their biomedical performance are comprehensively reviewed.All clinically explored and commercialized siRNA delivery platforms,including the GalNAc(N-acetylgalactosamine)–siRNA conjugate,and their fundamental design principles are thoroughly discussed.The latest progress in siRNA therapeutic development is also summarized.This review provides a comprehensive view and roadmap for general readers working in the field. 展开更多
关键词 APPROVAL summarized thoroughly
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Ionizable lipid-assisted efficient hepatic delivery of gene editing elements for oncotherapy 被引量:2
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作者 Chunhui Li Tongren Yang +9 位作者 Yuhua Weng Mengjie Zhang Deyao Zhao Shuai Guo Bo Hu Wanxuan Shao Xiaoxia Wang Abid Hussain Xing-Jie Liang Yuanyu Huang 《Bioactive Materials》 SCIE 2022年第3期590-601,共12页
CRISPR/Cas9-based gene editing has emerged as a powerful biotechnological tool,that relies on Cas9 protein and single guided RNA(sgRNA)to edit target DNA.However,the lack of safe and efficient delivery carrier is one ... CRISPR/Cas9-based gene editing has emerged as a powerful biotechnological tool,that relies on Cas9 protein and single guided RNA(sgRNA)to edit target DNA.However,the lack of safe and efficient delivery carrier is one of the crucial factors restricting its clinical transformation.Here,we report an ionizable lipid nanoparticle(iLP181,pKa=6.43)based on iLY1809 lipid enabling robust gene editing in vitro and in vivo.The iLP181 effectively encapsulate psgPLK1,the best-performing plasmid expressing for both Cas9 protein and sgRNA targeting Polo-like kinase 1(PLK1).The iLP181/psgPLK1 nanoformulation showed uniformity in size,regular nanostructure and nearly neutral zeta potential at pH 7.4.The nanoformulation effectively triggered editing of PLK1 gene with more than 30%efficiency in HepG2-Luc cells.iLP181/psgPLK1 significantly accumulated in the tumor for more than 5 days after a single intravenous injection.In addition,it also achieved excellent tumor growth suppression compared to other nucleic acid modalities such as siRNA,without inducing adverse effects to the main organs including the liver and kidneys.This study not only provides a clinically-applicable lipid nanocarrier for delivering CRISPR/Cas system(even other bioactive molecules),but also constitutes a potential cancer treatment regimen base on DNA editing of oncogenes. 展开更多
关键词 CRISPR/Cas Gene editing Lipid nanoparticle PLK1 Cancer therapy
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Ionizable liposomal siRNA therapeutics enables potent and persistent treatment of Hepatitis B 被引量:1
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作者 Yuanyu Huang Shuquan Zheng +6 位作者 Zhaoxu Guo Xavier de Mollerat du Jeu Xing-Jie Liang Zhiwei Yang Hong-Yan Zhang Shan Gao Zicai Liang 《Signal Transduction and Targeted Therapy》 SCIE CSCD 2022年第3期802-815,共14页
Small interfering RNA(siRNA)constitutes a promising therapeutic modality supporting the potential functional cure of hepatitis B.A novel ionizable lipidoid nanoparticle(RBP131)and a state-of-the-art lyophilization tec... Small interfering RNA(siRNA)constitutes a promising therapeutic modality supporting the potential functional cure of hepatitis B.A novel ionizable lipidoid nanoparticle(RBP131)and a state-of-the-art lyophilization technology were developed in this study,enabling to deliver siRNA targeting apolipoprotein B(APOB)into the hepatocytes with an ED_(50)of 0.05 mg/kg after intravenous injection.In addition,according to the requirements of Investigational New Drug(IND)application,a potent siRNA targeting hepatitis B virus(HBV)was selected and encapsulated with RBP131 to fabricate a therapeutic formulation termed RB-HBV008. 展开更多
关键词 injection APOB INTRAVENOUS
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Breaking pore size limit of metal–organic frameworks:Bio-etched ZIF-8 for lactase immobilization and delivery in vivo
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作者 Xiaoyue Qi Qizhe Chen +1 位作者 Ziyong Chang Yulin Deng 《Nano Research》 SCIE EI CSCD 2022年第6期5646-5652,共7页
Expanding pore size range of metal–organic frameworks(MOFs)promotes their versatility and feasibility for various biomedical applications.However,natural pore size greatly restricts large guest molecule accommodation... Expanding pore size range of metal–organic frameworks(MOFs)promotes their versatility and feasibility for various biomedical applications.However,natural pore size greatly restricts large guest molecule accommodation.Customizing and tailoring pore apertures ranging from micropores to mesopores controllably is desired but still critically challenging.Herein,we developed a facile method with super mildness based on pH-sensitive zeolitic imidazolate framework(ZIF)-8 to increase porosity,providing pore size with maximum 20 nm,which is 8 times larger than average.Glucose oxidase(GOx)was introduced in ZIF-8 for bioetching,benefitted from the resultant acidic microe-nvironment during biocatalytic process.Different synthesis methods were assessed for obtaining different morphologies and size distributions.Reaction time,GOx encapsulation efficiency,and Zn2+concentration was optimized to precisely control the mesopore size distribution of MOFs.It was found that bio-etching strategy was capable of producing stable mesopores which were large enough for loading lactase with good enzymatic activity retained,verified both in vitro and in vivo.This strategy breaks natural pore size limitation of MOFs and thereby facilitates biomolecule delivery,catalysis,and other biomedical applications with enhanced stability and performance. 展开更多
关键词 metal-organic frameworks enzyme immobilization drug delivery oral biocompatibility
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Malignant field expression signatures in biopsy samples at diagnosis predict the likelihood of lethal disease in patients with localized prostate cancer
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作者 Gennadi V.Glinsky 《Journal of Cancer Metastasis and Treatment》 CAS 2017年第1期177-189,共13页
Aim:Overtreatment of early-stage low-risk prostate cancer patients represents a significant problem in disease management and has significant socio-economic implications.Changes in prostate cancer screening and treatm... Aim:Overtreatment of early-stage low-risk prostate cancer patients represents a significant problem in disease management and has significant socio-economic implications.Changes in prostate cancer screening and treatment practices in the United States have been associated with the recent decline in overall incidence and concomitant significant increase of the annual incidence of metastatic prostate cancer has been documented.Therefore,development of genetic and molecular markers of clinically significant disease in patients diagnosed with low grade localized prostate cancer would have a major impact in disease management.Methods:Identification of gene expression signatures(GES)associated with lethal prostate cancer has been performed using microarray analyses of biopsy specimens obtained at the time of diagnosis from 281 patients with Gleason 6(G6)and G7 tumors in a Swedish watchful waiting cohort with up to 30 years follow-up.The performance of GES has been validated in independent cohort of 568 prostate cancer patients of the Cancer Genome Anatomy Project Prostate Cancer database.Results:GES c omprising 98 genes identified 89%and 100%of all death events 4 years after diagnosis in G7 and G6 patients,respectively.At 6 years follow-up,83%and 100%of all deaths events were captured in G7 and G6 patients,respectively.Remarkably,the 98-gene signature appears to perform successfully in patients stratification with as little as 2%of cancer cells in a specimen,strongly indicating that it captures a malignant field effect in human prostates harboring cancer cells of different degrees of aggressiveness.In G6 and G7 tumors from prostate cancer patients of age 65 or younger,GES identified 86%of all death events during the entire follow-up period.In G6 and G7 tumors from prostate cancer patients of age 70 or younger,GES identified 90%of all death events 6 years after diagnosis.Conclusion:Classification performance of the reported in this study 98-genes GES of lethal prostate cancer appeared suitable to meet design and feasibility requirements of a prospective 4 to 6 years clinical trial,which is essential for regulatory approval of diagnostic and prognostic tests in clinical setting.Prospectively validated GES of lethal PC in biopsy specimens of G6 and G7 tumors will help physicians to identify,at the time of diagnosis,patients who should be considered for exclusion from active surveillance programs and who would most likely benefit from immediate curative interventions. 展开更多
关键词 Gene expression signatures lethal prostate cancer localized prostate cancer active surveillance curative interventions clinical management of earlystage prostate cancer malignant field effect
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Identification of SARS-CoV-2-against aptamer with high neutralization activity by blocking the RBD domain of spike protein 1
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作者 Ge Yang Ziyue Li +7 位作者 Irfan Mohammed Liping Zhao Wei Wei Haihua Xiao Weisheng Guo Yongxiang Zhao Feng Qu Yuanyu Huang 《Signal Transduction and Targeted Therapy》 SCIE CSCD 2021年第7期1985-1988,共4页
Dear Editor,The ongoing outbreak of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)poses a great threat to the public health of people and the normal economic an... Dear Editor,The ongoing outbreak of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)poses a great threat to the public health of people and the normal economic and social development around the world.As of January 8,2021,more than 88 million people were infected with SARS-CoV-2,resulting in more than 1.9 million death. 展开更多
关键词 DEATH acute RESPIRATORY
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Deep Membrane Proteome Profiling of Rat Hippocampus in Simulated Complex Space Environment by SWATH
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作者 Yun Wang Peibin Qin +3 位作者 Jie Hong Nuomin Li Yongqian Zhang Yulin Deng 《Space(Science & Technology)》 2021年第1期208-219,共12页
Despite the development and great progress in the field of space biology,the astronauts are still facing many challenges in space.The space environment in which astronauts stay includes microgravity,noise,circadian rh... Despite the development and great progress in the field of space biology,the astronauts are still facing many challenges in space.The space environment in which astronauts stay includes microgravity,noise,circadian rhythms disorder,and confinement,which has deep effect both on the physiology and psychology of astronauts.It was reported that long-term flight could cause the astronauts’anxiety and depression.However,the underlying mechanism is not yet fully understood.Therefore,in the present study,the rat tail suspension model with noise,circadian rhythms,and confinement was employed to simulate complex space environment.We found that the rats exhibited the depressive-like behavior by the sucrose preference,forced swimming,and open-field tests.The membrane proteome of the rat hippocampus was investigated by“SWATH quantitation”technology both in control and simulated complex space environment(SCSE)groups.Out of 4520 quantified proteins,244 differentially expressed membrane proteins were obtained between the SCSE and control rats,which were functionally enriched in a series of biological processes,such as translation,protein phosphorylation,brain development,endocytosis,nervous system development,axonogenesis,and vesicle-mediated transport.We found a reduction level of neurexin-2,the light,medium,heavy polypeptide of neurofilament,rab 18,synaptogyrin 1,and syntaxin-1A and an increase level of neuroligin-1,munc18,snapin,synaptotagmin XII,complexin-1,etc.,which may play a key part in the development of depression.Furthermore,GSK-3βprotein was upregulated in mass spectrometry,which was further validated by western blotting.The results of the study do the favor in designing the effective countermeasures for the astronauts in the future long-term spaceflight. 展开更多
关键词 SPITE DEEP COMPLEX
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Inhibitory effect of lanosterol on cataractous lens of cynomolgus monkeys using a subconjunctival drug release system Keke
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作者 Zhang Wenwen He +6 位作者 Yu Du Yugui Zhou Xiaokang Wu Jie Zhu Xiangjia Zhu Kang Zhang Yi Lu 《Precision Clinical Medicine》 2022年第3期166-175,共10页
Background:To evaluate the effect of lanosterol on cataractous lens of cynomolgus monkeys using a subconjunctival drug release system.Methods:Nine elder cynomolgus monkeys were used,consisting of three monkeys without... Background:To evaluate the effect of lanosterol on cataractous lens of cynomolgus monkeys using a subconjunctival drug release system.Methods:Nine elder cynomolgus monkeys were used,consisting of three monkeys without cataract as controls,three monkeys with naturally occurring cortical cataract,and three monkeys with nuclear cataract as intervention groups.Nanoparticulated thermogel with lanosterol and fluorescein was administered by subconjunctival injection in the monkeys with cataract.Fluorescence changes of injected thermogel and cataract progression were observed.Lanosterol concentration in aqueous humor,solubility changes in lens proteins,and oxidative stress levels were analyzed in the lenses of the control and intervention groups.Results:Injected thermogel showed decreased fluorescence during follow up.Lanosterol concentration in aqueous humor increased in the first 2 weeks and then gradually decreased,which was in accordance with the changes in cortical lens clarity.However,lenses with nuclear opacification showed little change.In the cortical region of lenses with cortical cataract,solubility ofα-crystallin was significantly increased after administration of lanosterol,as well as the reduction of oxidative stress.Conclusions:We demonstrated the effect of lanosterol on cataract progression based on in vivo models of primates.Lanosterol showed a short-term and reliable reversal effect on reducing cataract severity in cortical cataract in the early stages,possibly due to the increase in the solubility of lens proteins and changes in the oxidative stress status.Lanosterol administration using subconjunctival drug release system could be a promising nonsurgical approach for future clinical studies of cataract prevention and treatment. 展开更多
关键词 LANOSTEROL drug release CATARACT LENS MONKEYS
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