A novel nonviral nanoparticle gene vector: Poly-L-lysine- silica nanoparticles

DNA delivery is a core technology for gene structure and function research as well as clinical settings. The ability to safely and efficiently targeted transfer foreign DNA into cells is a fundamental goal in biotechnology. With the development of nanobiotechnology, nanoparticle gene vectors brought about new hope to reach the goal. In our research, silica nanoparticles (SiNP) were synthesized first in a microemulsion system polyoxyethylene nonylphenyl ether (OP-10)/cyclohexane/ammonium hydroxide, at the same time the effects of SiNP size and its distribution were elucidated by orthogonal analysis; then poly-L-lysine (PLL) was linked on the surface of SiNP by nanoparticle surface energy and electrostatically binding; lastly a novel complex nanomate-rial-poly-L-lysine-silica nanoparticles (PLL-SiNP) wasprepared. The analysis of plasmid DNA binding and DNase I enzymatic degradation discovered that PLL-SiNP could bind DNA, and protect it against enzymatic degradation. Cell transfection showed that

Astragaloside Ⅳ suppresses post-ischemic natural killer cell infiltration and activation in the brain:involvement of histone deacetylase inhibition

Natural killer(NK)cells,a type of cytotoxic lymphocytes,can infiltrate into ischemic brain and exacerbate neuronal cell death.Astragaloside Ⅳ(ASIV)is the major bioactive ingredient of Astragalus membranaceus,a Chinese herbal medicine,and possesses potent immunomodulatory and neuroprotective properties.This study investigated the effects of ASIV on post-ischemic brain infiltration and activation of NK cells.ASIV reduced brain infarction and alleviated functional deficits in MCAO rats,and these beneficial effects persisted for at least 7 days.Abundant NK cells infiltrated into the ischemic hemisphere on day 1 after brain ischemia,and this infiltration was suppressed by ASIV.Strikingly,ASIV reversed NK cell deficiency in the spleen and blood after brain ischemia.ASIV inhibited astrocyte-derived CCL2 upregulation and reduced CCR2+NK cell levels in the ischemic brain.Meanwhile,ASIV attenuated NK cell activating receptor NKG2D levels and reduced interferon-γproduction.ASIV restored acetylation of histone H3 and the p65 subunit of nuclear factor-κB in the ischemic brain,suggesting inhibition of histone deacetylase(HDAC).Simultaneously,ASIV prevented p65 nuclear translocation.The effects of ASIV on reducing CCL2 production,restoring acetylated p65 levels and preventing p65 nuclear translocation were mimicked by valproate,an HDAC inhibitor,in astrocytes subjected to oxygen-glucose deprivation.Our findings suggest that ASIV inhibits post-ischemic NK cell brain infiltration and activation and reverses NK cell deficiency in the periphery,which together contribute to the beneficial effects of ASIV against brain ischemia.Furthermore,ASIV’s effects on suppressing NK cell brain infiltration and activation may involve HDAC inhibition.

Tectonics of the offshore Red River Fault recorded in the junction of the Yinggehai and Qiongdongnan Basins

The Red River Fault,which originated from the southeastern margin of the Tibetan Plateau,has a great significance for obtaining a further understanding of the regional tectonics,topography and river catchment evolution,as well as the petroliferous sedimentary basin formation.The junction of the Yinggehai and Qiongdongnan Basins(YQB Junction)is the key to understanding when and how the strike-slip deformation on the South China Sea resulted from the collision between the Indian and Eurasian plates.In this study,we show regional seismic profiles,3D seismic and drilling core data to analyze the tectonostratigraphy in the YQB Junction,aiming to identify its tectonic framework and the associated faults system.A transitional domain from the strike-slip zone to the extensional deformation zone was mapped,which consisted of the No.1 Fault and the Zhongjian Uplift.The strike-slip faulting in the YQB Junction was active during the Oligocene-Early Miocene,with a period of strong faulting in the Early Oligocene.Integrated with the regional tectonic evolution,a coevolution model of strike-slip and extensional deformation in the YQB Junction and the adjacent area was built.In the Eocene,the YQB Junction was controlled by the NW-SE extension and formed a series of distributed rifts bounded by the NE-striking faults and filled up with proximal sediment.In the earliest Oligocene,a NW-trending strike-slip fault began to develop in the YQB Junction and crosscut the NEstriking normal faults.Since the occurrence of the strike-slip faults,the NE-striking faults,to the west of the No.1 Fault and the Zhongjian Uplift,failed to grow.However,to the east of the No.1 Fault and the Zhongjian Uplift,the faulting continued to develop until the latest Late Oligocene.The faulting of the NW-trending faults was observed to be active until the earliest Middle Miocene.Since then,with the exception of some diapiric structures and associated small-scale faulting in the Yinggehai Basin,we did not observe any basement-involved faulting.Our results will improve our understanding of the tectonics in the southeastern margin of the Tibetan Plateau and the South China Sea.