纳米药物非临床药代动力学的研究策略及关注要点

随着纳米技术的迅速发展，纳米药物的研发已成为目前药物创新的发展方向之一。纳米药物具有基于纳米结构的尺度效应，其药代动力学特征与普通药物相比存在明显差异，其药代动力学研究与普通药物相比也有其特殊性。本文着重探讨纳米药物的非临床药代动力学的研究策略及关注要点，包括受试物、体内/外试验、生物样本分析、数据评价分析等，期望为研发者提供参考。     

A dotted nanowire arrayed by 5 nm sized palladium and nickel composite nanopaticles showing significant electrocatalytic activity towards ethanol oxidation reaction (EOR)

To the best of our knowledge, this is the first time to report the preparation of a dotted nanowire arrayed by 5 nm sized palladium and nickel composite nanoparticles (denoted as Pd_xNi_y NPs) via a hydrothermal method using NU and PdO·H₂O as the starting materials. The samples prepared at the mass ratio of NU to PdO·H₂O 1:1, 1:2 and 2:1 were, respectively, nominated as catalyst c₁, c₂ and c₃. The chemical compositions of all synthesized catalysts were mainly studied by using X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), revealing that metallic Ni was one main component of all prepared catalysts. Surprisingly, the main diffraction peaks appearing in the XRD patterns of all prepared catalysts were assigned to the metallic Ni rather than the metallic Pd. Very interestingly, as indicated by the TEM images, a large number of dotted nanowires arrayed by numerous equidistant 5 nm sized nanoparticles were distinctly exhibited in catalyst c₁. More importantly, when being used as electrocatalysts for EOR, all prepared catalysts exhibited an evident electrocatalytic activity towards EOR. In the cyclic voltammetry (CV) test, the peak current density of the forward peak of EOR on catalyst c₁ measured at 50 mV s^?1 was as high as 56.1 mA cm^?2, being almost 9 times higher than that of EOR on catalyst c₃ (6.3 mA cm^?2). Particularly, the polarized current density of EOR on catalyst c₁ at 3600 s, as indicated by the chronoamperometry (CA) experiment, was still maintained to be around 1.47 mA cm^?2, a value higher than the latest reported data of 1.3 mA cm^?2 (measured on the pure Pd/C electrode). Presenting a novel method to prepare dotted nanowires arranged by 5 nm sized nanoparticles and showing the significant eletrocatalytic activities of the newly prepared dotted nanowires towards EOR were the major contributions of this preliminary work.     

Structure-sensitive semantic matching for aggregate question answering over knowledge base

Aggregate question answering essentially returns answers for given questions by obtaining query graphs with unique dependencies between values and corresponding objects. Word order dependency, as the key to uniquely identify dependency of the query graph, reflects the dependencies between the words in the question. However, due to the semantic gap caused by the expression difference between questions encoded with word vectors and query graphs represented with logical formal elements, it is not trivial to match the correct query graph for the question. Most existing approaches design more expressive query graphs for complex questions and rank them just by directly calculating their similarities, ignoring the semantic gap between them. In this paper, we propose a novel Structure-sensitive Semantic Matching(SSM) approach that learns aligned representations of dependencies in questions and query graphs to eliminate their gap. First, we propose a cross-structure matching module to bridge the gap between two modalities(i.e., textual question and query graph). Then, we propose an entropy-based gated AQG filter to remove the structural noise caused by the uncertainty of dependencies. Finally, we present a two-channel query graph representation that fuses the semantics of abstract structure and grounding content of the query graph explicitly. Experimental results show that SSM could learn aligned representations of questions and query graphs to eliminate the gaps between their dependencies, and improves up to 12% (F1 score) on aggregation questions of two benchmark datasets.     

Performance of BaZrO3/Y2O3 dual-phase refractory applied to TiAl alloy melting

Vacuum induction melting is a potential process for the preparation of TiAl alloys with good homogeneity and low cost. But the crucial problem is a selection of high stability refractory. In this study, a BaZrO₃/Y₂O₃ dual-phase refractory was prepared and its performance for melting TiAl alloys was studied and compared with that of a Y₂O₃ refractory. The results showed the dual-phase refractory consisted of BaZr_1-xY_xO_3-δ and Y₂O₃(ZrO₂), exhibited a thinner interaction layer (30 μm) than the Y₂O₃ refractory (90 μm) after melting the TiAl alloy. Although the TiAl alloys melted in the dual-phase and Y₂O₃ refractory exhibited similar oxygen contamination (<0.1 wt%), the alloy melted in the dual-phase refractory had smaller Y₂O₃ inclusion content and size than that in the Y₂O₃ refractory, indicating that the dual-phase refractory exhibited a better melting performance than the Y₂O₃ refractory. This study provides insights into the process of designing highly stable refractory for melting TiAl alloys.     

High-temperature oxidation behavior of monolithic Zr3[Al(Si)]4C6 and its composite incorporating 30vol% ZrB2-SiC: Providing a basis for broadening the service temperature

To provide a basis for the high-temperature oxidation of ultra-high temperature ceramics (UHTCs), the oxidation behavior of Zr₃[Al(Si)]₄C₆ and a novel Zr₃[Al(Si)]₄C₆-ZrB₂-SiC composite at 1500 °C were investigated for the first time. From the calculation results, the oxidation kinetics of the two specimens follow the oxidation dynamic parabolic law. Zr₃[Al(Si)]₄C₆ exhibited a thinner oxide scale and lower oxidation rate than those of the composite under the same conditions. The oxide scale of Zr₃[Al(Si)]₄C₆ exhibited a two-layer structure, while that of the composite exhibited a three-layer structure. Owing to the volatilization of B₂O₃ and the active oxidation of SiC, a porous oxide layer formed in the oxide scale of the composite, resulting in the degradation of its oxidation performance. Furthermore, the cracks and defects in the oxide scale of the composite indicate that the reliability of the oxide scale was poor. The results support the service temperature of the obtained ceramics.     

Nickel‒cobalt bimetallic catalysts prepared from hydrotalcite-like compounds for dry reforming of methane

Ni–Co/Mg(Al)O alloy catalysts with different Co/Ni molar ratios have been prepared from Ni- and Co-substituted Mg–Al hydrotalcite-like compounds (HTlcs) as precursors and tested for dry reforming of methane. The XRD characterization shows that Ni–Co–Mg–Al HTlcs are decomposed by calcination into Mg(Ni,Co,Al)O solid solution, and by reduction finely dispersed alloy particles are formed. H₂-TPR indicates a strong interaction between nickel/cobalt oxides and magnesia, and the presence of cobalt in Mg(Ni,Co,Al)O enhances the metal-support interaction. STEM-EDX analysis reveals that nickel and cobalt cations are homogeneously distributed in the HTlcs precursor and in the derived solid solution, and by reduction the resulting Ni–Co alloy particles are composition-uniform. The Ni–Co/Mg(Al)O alloy catalysts exhibit relatively high activity and stability at severe conditions, i.e., a medium temperature of 600 °C and a high space velocity of 120000 mL g^?1 h^?1. In comparison to monometallic Ni catalyst, Ni–Co alloying effectively inhibits methane decomposition and coke deposition, leading to a marked enhancement of catalytic stability. From CO₂-TPD and TPSR, it is suggested that alloying Ni with Co favors the CO₂ adsorption/activation and promotes the elimination of carbon species, thus improving the coke resistance. Furthermore, a high and stable activity with low coking is demonstrated at 750 °C. The hydrotalcite-derived Ni–Co/Mg(Al)O catalysts show better catalytic performance than many of the reported Ni–Co catalysts, which can be attributed to the formation of Ni–Co alloy with uniform composition, proper size, and strong metal-support interaction as well as the presence of basic Mg(Al)O as support.     

Essential (Mg,Fe, Zn and Cu) and Non-Essential (Cd and Pb) Elements in Predatory Insects (Vespa crabro and Vespa velutina): A Molecular Perspective

The recent introduction of the Asian yellow-legged hornet, Vespa velutina, into Europe has raised concern regarding the threat to honeybees and the competition with the European hornet, Vespa crabro. The aim of this study was to investigated essential (Mg, Fe, Zn, Cu) and non-essential (Cd and Pb) elements in these two species. Element concentrations were determined in the whole body and separately in the head, thorax and abdomen using atomic absorption spectrometry (AAS). The changes in essential element concentration and speciation during metamorphosis were also studied using size exclusion chromatography followed by AAS and proteomic analysis. In both species, the essential elements were more concentrated in the abdomen due to the presence of fat bodies. Magnesium, Fe and Zn concentrations were significantly higher in V. crabro than in V. velutina and could have been related to the higher aerobic energy demand of the former species required to sustain foraging flight. Low concentrations of Cd and Pb were indicative of low environmental exposure. The concentration and speciation of essential elements, particularly Fe, varied among the developmental stages, indicating a modification of ligand preferences during metamorphosis. Overall, the results in the present study provide a better understanding of the hornet metal metabolism and a foundation for additional studies.