Layered double hydroxides （LDHs） are effective molecular carriers in cytological research, gene therapy, and transgenic applications. Herein, we investigated the internalization behavior of the LDH-DNA biocon- jugat...Layered double hydroxides （LDHs） are effective molecular carriers in cytological research, gene therapy, and transgenic applications. Herein, we investigated the internalization behavior of the LDH-DNA biocon- jugates via a microscopic approach and analyzed the internalization pathway by dissipative particle dynamics （DPD） simulations. We experimentally found that LDH can efficiently carry DNA into the nucleus of cell in BY-2 suspension cells. Furthermore, atomic force microscopy and X-ray diffraction anal- ysis demonstrated that the LDH-DNA bioconjugates mainly exist as a DNA-LDH-DNA sandwich complex, while the LDH-DNA-LDH sandwich complex and DNA-LDH complex cannot be excluded. The DPD simu- lations further indicated that only the DNA-LDH-DNA sandwich structure could penetrate the plasma membrane （PM）, while PM is impermeable to the LDH-DNA-LDH sandwich complex and the DNA-LDH complex. This work provides novel perspective for understanding the membrane penetration mechanism of LDH nano-sheets and new insights into the design of novel molecular delivery systems.展开更多
文摘目的:比较大强度间歇训练(High-intensity Interval Training,HIT)和中等强度持续训练(Moderate-intensity Continuous Training,MCT)对斜坡测试(Ramp)、中等强度及高强度持续运动中耗氧量动力学(OUK,Oxygen Uptake Kinetics)等参数的影响。方法:36名青年男性受试者分为高强度间歇训练组(HIT)、中等强度持续训练组(MCT,)和对照组(NOT),MCT和HIT两干预组分别进行6周、每周3次强度不同而训练量相同的运动干预;各组干预前(Pre)、中(Mid)、后(Post)分别进行Ramp力竭测试及中、高强度持续运动的OUK测试。结果:6周干预后,HIT与MCT两干预组VO_2max/kg(最大耗氧量)、VO_2-VAT(通气无氧阈耗氧量)、VO_2/kg-VAT(通气无氧阈耗氧量相对值)、Waat-VAT(通气无氧阈功率)均表现为干预后值高于干预前(P<0.05)、干预中值(P<0.01);3组受试者之间上述参数组间差异显著(P<0.05),但仅表现HIT、MCT组与NOT组之间差异显著,HIT与MCT两组之间差异不显著(P>0.05);A_(slop)(Delta效率)、A_(OUES)(耗氧效率坡度)组间效应不显著(P>0.05)。中等强度下OUK各参数仅有τ(Tau,OUK时间常数)值组间效应显著(F=3.652,P=0.04<0.05),HIT与MCT两干预组分别与NOT之间组间效应显著(HIT vs NOT,P=0.027<0.05;MCT vs NOT,P=0.027<0.05),但HIT、MCT两干预组Mid、Post阶段,组间差异不显著(P>0.05),各组各时间点TD值、A值组间差异不显著(P>0.05)。大强度运动时A1(A,耗氧幅度)值组间效应显著(F=4.439,P=0.011<0.05),除了MCT及HIT分别与NOT组组间差异显著外,HIT与MCT之间差异显著(P<0.05),6周后HIT组A1值显著高于同阶段MCT组(1 893.9±132.1vs 1 632.3±340.0,P<0.05);而对于观测值τ_1,3组受试者之间组间效应显著(F=9.083,P<0.01),MIT及HIT组和NOT组相比,τ_1显著降低,并且MIT和HIT组间差异显著(P<0.05);3周后HIT组τ_1值已经显著高于NOT组(Mid:42.5±3.8 vs 53.7±4.3,P<0.01),而MCT在6周后出现(Post:43.1±4.6 vs 53.4±6.0,P<0.01)。3周后HIT组A2值比NOT组显著减低(P<0.05),6周后Post值显著低于MCT组及NOT组同阶段值(P<0.01),而MCT组在各阶段与NOT组之间差异不显著(P>0.05)。τ_2虽有所升高,但并无显著意义(P>0.05)。结论:大强度间歇训练和中等强度持续训练均可提高VO_2max、VAT等心肺耐力评定参数,但两种训练模式对上述参数改善并无显著区别;两训练模式对中等强度下耗氧动力参数影响无显著区别,但大强度间歇训练在提高大强度运动过程中氧耗应答速率及减少耗氧量慢成分方面有着更明显的优势。
基金supported by the Fundamental Research Funds for the Central Universities (2016JX01, BLX2015-01)the National Natural Science Foundation of China (31671489, 31601149 and 31271433)+2 种基金the Beijing Nova Programme (Z131109000413013)the Special Program for Applied Research on Super Computation of the NSFC-Guangdong Joint Fundthe Chemical Grid Program and Excellent Talent of Beijing University of Chemical Technology
文摘Layered double hydroxides （LDHs） are effective molecular carriers in cytological research, gene therapy, and transgenic applications. Herein, we investigated the internalization behavior of the LDH-DNA biocon- jugates via a microscopic approach and analyzed the internalization pathway by dissipative particle dynamics （DPD） simulations. We experimentally found that LDH can efficiently carry DNA into the nucleus of cell in BY-2 suspension cells. Furthermore, atomic force microscopy and X-ray diffraction anal- ysis demonstrated that the LDH-DNA bioconjugates mainly exist as a DNA-LDH-DNA sandwich complex, while the LDH-DNA-LDH sandwich complex and DNA-LDH complex cannot be excluded. The DPD simu- lations further indicated that only the DNA-LDH-DNA sandwich structure could penetrate the plasma membrane （PM）, while PM is impermeable to the LDH-DNA-LDH sandwich complex and the DNA-LDH complex. This work provides novel perspective for understanding the membrane penetration mechanism of LDH nano-sheets and new insights into the design of novel molecular delivery systems.
