Glioma cell membrane camouflaged cinobufotalin delivery system for combinatorial orthotopic glioblastoma therapy

Glioblastoma(GBM)belongs to the deadliest primary malignancies with high mortality rate and poor prognosis.Over the past decades,less progress has been made to treat GBM,owing largely to the lack of effective chemotherapeutics and poor drug accumulation in the glioma tissue.In order to address this issue,we present an efficient biomimetic nanocomposite(Cu_(2−x)Se-CB@MEM,CCM),consisting of Cu_(2−x)Se nanoparticle core modified by cinobufotalin(CB),a toad venom extract,which is camouflaged with glioma cell Ln229 membrane.It is demonstrated that CB can decrease the protein activity of inosine monophosphate dehydrogenase 1(IMPDH1),a key target correlated with prognosis,through intermolecular hydrogen bonding with amino acid residues ARG-105 and ASP-77.The glioma cell membrane-camouflage endows the CCM with blood-brain barrier penetration and homology tumor-targeted ability.The optimized cinobufotalin based chemotherapy combining with the near-infrared-II(NIR-II)irradiation shows outstanding inhibition effect to glioma cells,by blocking cell cycle and inducing apoptosis.In vivo mice bearing orthotopic Ln229 GBM treated with CCM+NIR-II(CCM+L)have significantly suppressed tumor growth and extended survival,without side effect.The glioma cell membrane camouflaged nanocomposite of Cu_(2−x)Se and cinobufotalin with its significant anti-glioma property and well biosafety will provide novel alternatives for clinical treatment of GBM.

Numerical simulation of gas-solid flow with two fluid model in a spouted-fluid bed

The flow characteristics in a spouted-fluid bed differ from those in spouted or fluidized beds because of the injection of the spouting gas and the introduction of a fluidizing gas. The flow behavior of gas-solid phases was predicted using the Eulerian-Eulerian two-fluid model （TFM） approach with kinetic theory for granular flow to obtain the flow patterns in spouted-fluid beds. The gas flux and gas incident angle have a significant influence on the porosity and particle concentration in gas-solid spouted-fluid beds. The fluidizing gas flux affects the flow behavior of particles in the fountain. In the spouted-fluid bed, the solids volume fraction is low in the spout and high in the annulus. However, the solids volume fraction is reduced near the wall.

Inter-satellite link augmented BeiDou-3 orbit determination for precise point positioning

Precise Point Positioning(PPP) requires precise products, including high-accuracy satellite orbit and clock parameters. It is impossible to obtain an orbit solution that is sufficiently accurate for PPP services with a regional tracking network;therefore, satellite orbits are usually estimated by a global tracking network with a large number of ground stations. However, it is expensive to build globally distributed stations. Fortunately, BeiDou-3 satellites carry an InterSatellite Link(ISL) payload, which can track the whole arc of the BeiDou-3 satellites and enhance the orbit determination accuracy with regional ground stations. In this contribution, a novel orbit determination strategy for BeiDou-3 PPP is proposed, in which the BeiDou-3 satellite orbits are enhanced by the ISL. First, the generation of precise satellite products is demonstrated in detail.In addition, the products are assessed by Satellite Laser Ranging(SLR) residuals and overlap comparisons. Moreover, the products are used for receivers in China's Mainland to carry out the static and kinematic modes to research the PPP performance of Bei Dou-3’s 3IGSO/24MEO constellation.The SLR validations of the satellite orbits demonstrate an accuracy better than 0.1 m in the radial component, and the orbit overlap comparisons show accuracies of 0.016 m in the radial component,0.088 m in the along-track component and 0.087 m in the cross-track component. The Standard Deviation(STD) in the differences in overlapping arcs for the estimated satellite clocks is approximately 0.10 ns. The static PPP results demonstrate that the error in both the horizontal and vertical components is smaller than 10 cm after 30 minutes of convergence. After 24 hours of convergence,the errors are 0.70 cm, 0.63 cm and 1.99 cm for the north, east and up components, respectively.The kinematic PPP experiment illustrates that the Root Mean Square(RMS) position errors in the north, east and up components are approximately 3.23 cm, 5.27 cm and 8.64 cm, respectively,after convergence. The obtainable positioning and convergence performances are comparable to those using products generated by global tracking networks.