Mechanism Study on Nanoparticle Negative Surface Charge Modification by Ascorbyl Palmitate and Its Improvement of Tumor Targeting Ability

Surface charge polarity and density influence the immune clearance and cellular uptake of intravenously administered lipid nanoparticles (LNPs), thus determining the efficiency of their delivery to the target. Here, we modified the surface charge with ascorbyl palmitate (AsP) used as a negatively charged lipid. AsP-PC-LNPs were prepared by dispersion and ultrasonication of AsP and phosphatidylcholine (PC) composite films at various ratios. AsP inserted into the PC film with its polar head outward. The pK_a for AsP was 4.34, and its ion form conferred the LNPs with negative surface charge. Zeta potentials were correlated with the amount and distribution of AsP on the LNPs surface. DSC, Raman and FTIR spectra, and molecular dynamics simulations disclosed that AsP distributed homogeneously in PC at 1–8% (w/w), and there were strong hydrogen bonds between the polar heads of AsP and PC (PO²⁻), which favored LNPs’ stability. But at AsP:PC > 8% (w/w), the excessive AsP changed the interaction modes between AsP and PC. The AsP–PC composite films became inhomogeneous, and their phase transition behaviors and Raman and FTIR spectra were altered. Our results clarified the mechanism of surface charge modification by AsP and provided a rational use of AsP as a charged lipid to modify LNP surface properties in targeted drug delivery systems. Furthermore, AsP–PC composites were used as phospholipid-based biological membranes to prepare paclitaxel-loaded LNPs, which had stable surface negative charge, better tumor targeting and tumor inhibitory effects.     

In Vitro and In Vivo Antibacterial Activity,Toxicity and Resistance Analysis of Pleuromutilin Derivative Z33 against Methicillin-Resistant Staphylococcus aureus

The novel pleuromutilin derivative, which showed excellent in vitro antibacterial activity against MRSA, 22-(2-(2-(4-((4-(4-nitrophenyl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)acetamido)phenyl)thioacety-l-yl-22-deoxypleuromutilin (Z33), was synthesized and characterized in our previous work. In this study, the preliminary pharmacodynamics and safety of Z33 were further evaluated. In in vitro antibacterial activity assays, Z33 was found to be a potent bactericidal antibiotic against MRSA that induced dose-dependent growth inhibition and long-term post-antibiotic effect (PAE). The drug-resistance test demonstrated that Z33 possessed a narrow mutant selection window and lower propensities to select resistance than that of tiamulin. Cytochrome P450 (CYP450) inhibition assay determined that the inhibitory effect of Z33 was similar to that of tiamulin against the activity of CYP3A4, and was lower than that of tiamulin on the activity of CYP2E1. Toxicity determination showed that both Z33 and tiamulin displayed low cytotoxicity of RAW264.7 cells. Furthermore, Z33 was found to be a high-security compound with a 50% lethal dose (LD₅₀) above 5000 mg/kg in the acute oral toxicity test in mice. In an in vivo antibacterial activity test, Z33 displayed better therapeutic effectiveness than tiamulin in the neutropenic mouse thigh infection model. In summary, Z33 was worthy of further development as a highly effective and safe antibiotic agent against MRSA infection.     

离焦激光直写的线宽稳定方法

为了提高激光直写加工衍射光学元件时的线条质量,提出一种离焦激光直写的线宽稳定方法.该方法通过同时调节激光功率和离焦量,使光刻胶的曝光阈值处于线宽对曝光量的变化率较小位置,从而可以弱化线宽对实际曝光量或光刻胶阈值等变化的敏感度,提高利用离焦方法进行衍射光学元件制作时的线宽稳定性.推导了稳定线宽后的光功率控制模型和线宽模型,模型中的变量仅为离焦量,降低了光功率控制的复杂性.利用632.8 nm的He-Ne激光和NA-0.1的物镜在CCD上对采用该方法后的离焦线宽模型进行验证,实验结果与理论模型吻合较好.该方法对于线宽稳定度较高的衍射光学元件制作具有重要价值.     

高性能激光全息防伪标识特性参数测量系统

提出了一种高性能激光全息防伪标识参数的检测方法,利用同一束光在分束器分成的反射光和透射光光强度比例恒定的性质,实时探测衍射方向光强和标识入射光强值,通过一维线性扫描实现激光全息防伪标识衍射效率和信噪比的自动测量。实验数据表明：入射光强测量值相对误差不超过0．29％;衍射效率及信噪比的测量值最大相对误差分别不超过0．81％和2．0％,比第一代检测仪采用的方法测量精度提高近一倍。该方法降低了对光源稳定度的要求,大大降低了激光器的成本,有利于测量仪器的推广。     

Promote the conductivity of solid polymer electrolyte at room temperature by constructing a dual range ionic conduction path

Poly(ethylene oxide)(PEO) is a classic matrix model for solid polymer electrolyte which can not only dissociate lithium-ions(Li+),but also can conduct Li+through segmental motion in long-range.However,the crystal aggregation state of PEO restricts the conduction of Li⁺ especially at room temperature.In this work,an amorphous polymer electrolyte with ethylene oxide(EO) and propylene oxide(PO) block structure(B-PEG@DMC) synthesized by the transesterification is firstly obtained,showing ...     

一例含阴离子水簇的钴配合物的合成、结构及理论研究

金属配合物中的水簇研究为研究宏观意义上的水以及与蛋白质分子有关的水分子提供了有效途径。本文合成了一个含有阴离子水簇的带状超分子配合物[Co(2,2-bipy)₂(N₃)₂](N₃)_0.5Cl_0.5·2H₂O(1,2, 2-bipy=2, 2-联吡啶)。单晶结构解析表明,配合物属于三斜晶系,P-1空间群,晶胞参数为:a=0.822 54(7) nm,b=1.175 58(9) nm,c=1.237 06(10) nm,α=91.379 0(10)°,β=92.151 0(10)°,γ=108.119 0(10)°,V=1.135 27(16) nm³,由一个单核[Co(2,2-bipy)₂(N₃)₂]⁺配合物阳离子、两个非配位水分子、0.5个游离的叠氮离子和0.5个氯离子组成,叠氮离子和氯离子位置无序,占有率各为50%。两个客体水分子通过强烈的分子间氢键作用形成了环状水四聚体,且与无序的N^-₃和Cl^-通过氢键作用形成了一个[(H₂O)₄(N₃)Cl]^2- 阴离子水簇。此外,本文基于密度泛函理论(DFT)对配合物[Co(2,2-bipy)₂(N₃)₂]⁺阳离子进行了量子化学计算,分析了其单点能和原子电荷,并计算了中心金属离子的氧化态,计算结果与实验相吻合。     

氨对硅基铁纳米薄膜高温重凝核的影响

采用弧过滤离子沉积系统（arc filtered deposition,AFD）在纯硅表面制备铁纳米薄膜。研究了750℃下铁纳米薄膜在氢气氛围以及氨气氛围中重凝核的规律。研究表明,在氢气氛围中,铁纳米薄膜重凝核以后形成的铁纳米颗粒随薄膜的厚度增加以及保温时间的延长而增大;但在氨气氛围中,铁纳米薄膜重凝核后形成的纳米颗粒的尺寸随保温时间的变化更为复杂：在氨气作用的初始阶段,铁颗粒的尺寸随氨气作用时间的延长而逐渐变大,但一段时间以后,铁颗粒的尺寸又随氨气作用时间的延长而变小,直到铁颗粒平均直径达到一个最小值（大约在氨气介入后的12min）,随后铁颗粒的尺寸又逐渐变大,并最终达到一稳定值。     

Dielectric Properties Investigation of Metal–Insulator–Metal (MIM) Capacitors

This study presents the construction and dielectric properties investigation of atomic-layer-deposition Al₂O₃/TiO₂/HfO₂ dielectric-film-based metal–insulator–metal (MIM) capacitors. The influence of the dielectric layer material and thickness on the performance of MIM capacitors are also systematically investigated. The morphology and surface roughness of dielectric films for different materials and thicknesses are analyzed via atomic force microscopy (AFM). Among them, the 25 nm Al₂O₃-based dielectric capacitor exhibits superior comprehensive electrical performance, including a high capacitance density of 7.89 fF·µm⁻², desirable breakdown voltage and leakage current of about 12 V and 1.4 × 10⁻¹⁰ A·cm⁻², and quadratic voltage coefficient of 303.6 ppm·V⁻². Simultaneously, the fabricated capacitor indicates desirable stability in terms of frequency and bias voltage (at 1 MHz), with the corresponding slight capacitance density variation of about 0.52 fF·µm⁻² and 0.25 fF·µm⁻². Furthermore, the mechanism of the variation in capacitance density and leakage current might be attributed to the Poole–Frenkel emission and charge-trapping effect of the high-k materials. All these results indicate potential applications in integrated passive devices.     

Nonlinear Modeling Study of Aerodynamic Characteristics of an X38-like Vehicle at Strong Viscous Interaction Regions

Strong viscous interaction and multiple flow regimes exist when vehicles fly at high altitude and high Mach number conditions. The Navier–Stokes(NS) solver is no longer applicable in the above situation. Instead, the direct simulation Monte Carlo (DSMC) method or Boltzmann model equation solvers are usually needed. However, they are computationally more expensive than the NS solver. Therefore, it is of great engineering value to establish the aerodynamic prediction model of vehicles at high altitude and high Mach number conditions. In this paper, the hypersonic aerodynamic characteristics of an X38-like vehicle in typical conditions from 70 km to 110 km are simulated using the unified gas kinetic scheme (UGKS), which is applicable for all flow regimes. The contributions of pressure and viscous stress on the force coefficients are analyzed. The viscous interaction parameters, Mach number, and angle of attack are used as independent variables, and the difference between the force coefficients calculated by UGKS and the Euler solver is used as a dependent variable to establish a nonlinear viscous interaction model between them in the range of 70–110 km. The evaluation of the model is completed using the correlation coefficient and the relative orthogonal distance. The conventional viscous interaction effect and rarefied effect are both taken into account in the model. The model can be used to quickly obtain the hypersonic aerodynamic characteristics of X38-like vehicle in a wide range, which is meaningful for engineering design.