Establishment and validation of an SIL-IS LC–MS/MS method for the determination of ibuprofen in human plasma and its pharmacokinetic study

In this work, we developed and validated a highly sensitive, rapid and stable LC–MS/MS method for the determination of ibuprofen in human plasma with ibuprofen-d3 as a stable isotopically labeled internal standard (SIL-IS). Human plasma samples were prepared by one-step protein precipitation. The chromatographic separation was achieved on a Poroshell 120 EC-C₁₈ (2.1 × 50 mm, 2.7 μm). Aqueous solution (containing 0.05% acetic acid and 5 mm NH₄Ac) and methanol were selected as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in negative ion mode. Multiple reaction monitoring mode was used for quantification using target fragment ions m/z 205.0 → 161.1 for ibuprofen and m/z 208.0 → 164.0 for SIL-IS, respectively. This method exhibited a linear range of 0.05–36 μg/ml for ibuprofen with correlation coefficient >0.99. Mean recoveries of ibuprofen in human plasma ranged from 78.4 to 80.9%. The RSD of intra- and inter-day precision were both < 5%. The accuracy was between 88.2 and 103.67%. The matrix effect was negligible in human plasma, including lipidemia and hemolytic plasma. A simple, efficient and accurate LC–MS/MS method was successfully established and applied to a pharmacokinetic study in healthy Chinese volunteers after a single oral administration of ibuprofen granules.     

Conformational Selection Mechanism Provides Structural Insights into the Optimization of APC-Asef Inhibitors

Metastasis is the major cause of death in colorectal cancer and it has been proven that inhibiting an interaction between adenomatous polyposis coli (APC) and Rho guanine nucleotide exchange factor 4 (Asef) efficaciously restrain metastasis. However, current inhibitors cannot achieve a satisfying effect in vivo and need to be optimized. In the present study, we applied molecular dynamics (MD) simulations and extensive analyses to apo and holo APC systems in order to reveal the inhibitor mechanism in detail and provide insights into optimization. MD simulations suggested that apo APC takes on a broad array of conformations and inhibitors stabilize conformation selectively. Representative structures in trajectories show specific APC-ligand interactions, explaining the different binding process. The stability and dynamic properties of systems elucidate the inherent factors of the conformation selection mechanism. Binding free energy analysis quantitatively confirms key interface residues and guide optimization. This study elucidates the conformation selection mechanism in APC-Asef inhibition and provides insights into peptide-based drug design.     

MOF Encapsulated AuPt Bimetallic Nanoparticles for Improved Plasmonic-induced Photothermal Catalysis of CO2 Hydrogenation

Exploring new catalytic strategies for achieving efficient CO₂ hydrogenation under mild conditions is of great significance for environmental remediation. Herein, a composite photocatalyst Zr-based MOF encapsulated plasmonic AuPt alloy nanoparticles (AuPt@UiO-66-NH₂) was successfully constructed for the efficient photothermal catalysis of CO₂ hydrogenation. Under light irradiation at 150 °C, AuPt@UiO-66-NH₂ achieved a CO production rate of 1451 μmol g_metal⁻¹ h⁻¹ with 91 % selectivity, which far exceeded those obtained by Au@Pt@UiO-66-NH₂ with Pt shell on Au (599 μmol g_metal⁻¹ h⁻¹) and Au@UiO-66-NH₂ (218 μmol g_metal⁻¹ h⁻¹). The outstanding performances of AuPt@UiO-66-NH₂ were attributed to the synergetic effect originating from the plasmonic metal Au, doped active metal Pt, and encapsulation structure of UiO-66-NH₂ shell. This work provides a new way for photothermal catalysis of CO₂ and a reference for the design of high-performance plasmonic catalysts.     

Contradictory effect of gold nanoparticle-decorated molybdenum sulfide nanocomposites on amyloid-β-40 aggregation

The effect of gold nanoparticle-decorated molybdenum sulfide (AuNP-MoS₂) nanocomposites on amyloid-β-40 (Aβ₄₀) aggregation was investigated. The interesting discovery was that the effect of AuNP-MoS₂ nanocomposites on Aβ₄₀ aggregation was contradictory. Low concentration of AuNP-MoS₂ nanocomposites could enhance the nucleus formation of Aβ₄₀ peptides and accelerate Aβ₄₀ fibrils aggregation. However, although high concentration of AuNP-MoS₂ nanocomposites could enhance the nucleus formation of Aβ₄₀ peptides, it eventually inhibited Aβ₄₀ aggregation process. It might be attributed to the interaction between AuNP-MoS₂ nanocomposites and Aβ₄₀ peptides. For low concentration of AuNP-MoS₂ nanocomposites, it was acted as nuclei, resulting in the acceleration of the nucleation process. However, the structural flexibility of Aβ₄₀ peptides was limited as the concentration of AuNP-MoS₂ nanocomposites was increased, resulting in the inhibition of Aβ₄₀ aggregation. These findings suggested that AuNP-MoS₂ nanocomposites might have a great potential to design new multifunctional material for future treatment of amyloid-related diseases.     

大吨位基桩抗压载荷试验中的锚桩预应力保护技术

竖轴向承载力是桩基础设计的重要参数,现场静载试验是目前确定桩基承载力的主要手段之一。本文依托黄陵—延安段高速公路洛河特大桥试桩工程,通过对原有工程桩施加预应力,形成了以工程桩为锚桩的锚拔体系。加载过程中试桩应力、锚桩应力及桩顶位移测试,结果表明,结合预应力技术,以工程桩作为锚桩构成桩基础静载试验的锚拔体系是可行的,同时提出了施加预应力大小的原则、方法以及确保后期曾作为锚桩的工程桩有足够承载能力应采取的必要措施。     

理想导体中具有两个松弛时间的电磁热弹性波

研究处于均布磁场中的理想导体的二维电磁热弹性耦合问题，引入势函数使控制方程转化为3个偏微分方程．运用Laplace变换和Fourier变换得到该问题在变换域内的精确表达式，再通过级数展开和Laplace逆变换法求得在时间较短时的逆变换，得到时间-空间域内问题的解．运用此方法研究了表面受到热冲击的半无限空间问题．给出了电磁热弹性波、膨胀波和横向波传播的速度，并通过数值计算，给出了各个场量的分布图．所得结论与已有的结论一致．     

A novel cationic emulsifier used for preparing slow-cracking and rapid-setting asphalt: Synthesis,surface activity,and emulsification ability

A novel cationic emulsifier including nonionic fatty alcohol polyoxyethylene ether was synthesized in two steps from epichlorohydrin, octadecyl dimethyl amine, and fatty alcohol polyoxyethylene ether, and the intermediate product could also be used as an emulsifier. Their structures were characterized by FTIR, and the surface activities were investigated by surface tension, electrical conductivity, and HLB. The obtained results indicated that the critical micelle concentration (CMC) of the final product was low, 0.442 mmol/L, and the surface tension at the CMC was 41.02 mN/m. The hydrophile-lipophile balance (HLB) value was 12, which meet the requirements of asphalt emulsifiers. A series of experiments of the emulsified asphalt prepared by the emulsifiers were performed. The results showed that the emulsified asphalt could be stably stored for more than 5 days when the emulsifier was 2 wt% and the pH value was between 3 and 4. The result of demulsification experiments showed that the emulsifier is a slow-cracking and rapid-setting asphalt emulsifier.     

Transient analysis on surface heated piezoelectric semiconductor plate lying on rigid substrate

Based on the thermo-electro-elastic coupling theory, the mathematical model for a surface heated piezoelectric semiconductor (PS) plate is developed in the time domain. Applying the direct and inverse Laplace transformations to the established model, the mechanical and electrical responses are investigated. The comparison between the analytical solution and the finite element method (FEM) is conducted, which illustrates the validity of the derivation. The calculated results show that the maximum values of the mechanical and electrical fields appear at the heating surface. Importantly, the perturbation carriers tend to concentrate in the zone near the heating surface under the given boundary conditions. It can also be observed that the heating induced elastic wave leads to jumps for the electric potential and perturbation carrier density at the wavefront. When the thermal relaxation time is introduced, all the field quantities become smaller because of the thermal lagging effect. Meanwhile, it can be found that the thermal relaxation time can describe the smooth variation at the jump position. Besides, for a plate with P-N junction, the effect of the interface position on the electrical response is studied. The effects of the initial carrier density on the electrical properties are discussed in detail. The conclusions in this article can be the guidance for the design of PS devices serving in thermal environment.     

芳纶纤维/SMPU-SiO2复合材料的界面性能研究

选用形状记忆聚氨酯(SMPU)和正硅酸乙酯(TEOS)为前驱体,固体酸对甲基苯磺酸(PTSA)为催化剂,利用空气中的水分为水解水源,通过溶胶-凝胶法原位制备了形状记忆聚氨酯与二氧化硅( SMPU-SiO2)杂化材料,并将杂化材料应用于芳纶纤维增强的柔性复合材料中,以期改善芳纶纤维与基体的界面性能.同时,针对芳纶纤维表面...