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。     

Synthesis and performance evaluation of a new drag reducer based on acrylamide/12-allyloxydodecyl acid sodium

Hydraulic fracturing with slickwater is a field-proven stimulation technology used in tight reservoirs. Because of the high pumping rate associated with slickwater fracturing, drag reduction (DR) is critical in minimizing pressure drop and the success of oilfield operations. In this paper, a new type of drag reducer (SPR) was synthesized with acrylamide and 12-allyloxydodecyl acid sodium, and its drag reduction performance was evaluated. The results showed that the new drag reducer features low molecular weight, fast-dissolving rate and low interfacial tension. The algorithm of estimating the drag reduction rate of non-Newtonian fluid SPR was proposed and validated. Empirical or semianalytical models for estimating the friction ratio (σ) or friction factor (λ or f) were used to simulate the turbulence behavior of the SPR drag reducer under different Reynolds numbers (Re). The modified Virk's correlation could accurately model the turbulent behavior of the SPR drag reducer. A unified calculation formula was established in this study for different pipe diameters.     

煤矸石粉/聚酯纤维沥青混合料盐冻损伤研究EI北大核心CSCD

针对煤矸石粉替代率50%、聚酯纤维掺量0.4%的沥青混合料,开展盐冻耦合作用(NaCl溶液质量分数为0%、7.0%、13.0%、26.5%,冻融循环次数为0、2、4、6、8)下的半圆弯曲(SCB)试验,分析了盐冻耦合作用对SCB试件内部损伤劣化过程的影响.结果表明:NaCl溶液质量分数为13.0%、冻融循环为8次时,盐冻耦合作用对沥青混合料的侵蚀破坏作用最强,试件内部损伤最严重;在煤矸石粉与矿粉质量比为1∶1、聚酯纤维掺量为0.4%的条件下,沥青混合料能够形成高黏性、致密、厚实的沥青膜以及由纤维形成的三维网状结构,从而显著降低盐冻侵蚀对沥青混合料的损伤.通过Poly2D模型对SCB试件的极限拉应力损伤量进行拟合,拟合系数为0.944.     

基于禁忌搜索的晶体位置谱分割与校准方法

为满足不同规格晶体探测器对分割校准晶体条响应事件位置数据的需求，开发了一种以禁忌搜索算法为核心，结合UDP数据帧、二维高斯模型及光导折射率的位置信息分割校准方法。实验结果表明，本方法在溢出率为5%时，峰谷比可达1218，空间分辨率达17 mm，晶体条响应位置识别准确度高达99%，滤除了引发伪峰的噪声，避免了过分割问题。在面对多种规格晶体阵列的位置谱时，本方法能依照阵列规格将晶体条区域的响应自动校准编号并输出晶体位置查找表，实现响应事件的精确校准。     

Effect of PyC interface phase on the cyclic ablation resistance and flexural properties of two-dimensional Cf/HfC composites

Composites based on hafnium carbide and reinforced with continuous naked carbon fiber with and without PyC interface were prepared at low temperature by precursor infiltration and pyrolysis and chemical vapor deposition method. The microstructure, mechanical property, cyclic ablation and fiber bundle push-in tests of the composites were investigated. The results show that after three times ablation cycles, the bending strength of samples without PyC interface decreased by 63.6 %; the bending strength of samples with PyC interface only decreased by 37.8 %. The force displacement curve of the samples with PyC interface presented a well pseudoplastic deformation state. The mechanical behavior difference of two kinds of composites was due to crucial function of PyC interface phase including protection of fiber and weakening of fiber/matrix interface.     

The effect of alkali metal oxide on the properties of borosilicate fireproof glass: Structure,thermal properties,viscosity, chemical stability

The purpose of the current work was to research the effect of alkali metal oxide on the structure, thermal properties, viscosity and chemical stability in the glass system (R₂O–CaO–B₂O₃–SiO₂) systematically. Because the glass would emulsify when Li₂O was added to the glass batch, this article did not discuss Li₂O. The results showed that when the amount of Na₂O was less than 4 mol.%, there was a higher interconnectivity of borate and silicate sub-networks in glass, as more mixed Si–O–B bonds were present in glass. The glass samples exhibited excellent thermal properties and chemical stabilities. As the amount of Na₂O exceeded 4 mol.%, the interconnectivity of borate and silicate sub-networks was weakened. The thermal properties and chemical stabilities of the glass samples were reduced. The connectivity of the silicate sub-network was weakened slightly as the Na/K ratio varied, and the coefficient of thermal expansion (CTE) of the glass samples gradually increased, and the resistance to thermal shock (RTS) value gradually decreased. Moreover, the viscosity of the glass samples decreased with the ratio of Na/Si and Na/K increased.     

Nanovaccine-Mediated Cell Selective Delivery of Neoantigens Potentiating Adoptive Dendritic Cell Transfer for Personalized Immunization

Neoantigen vaccines and adoptive dendritic cell (DC) transfer are major clinical approaches to initiate personalized immunity in cancer patients. However, the immunization efficacy is largely limited by the in vivo trajectory including neoantigens’ access to resident DCs and DCs’ access to lymph nodes (LNs). Herein, an innovative strategy is proposed to improve personalized immunization through neoantigen-loaded nanovaccines synergized with adoptive DC transfer. It is found that it enables selective delivery of neoantigens to resident DCs and macrophages by coating cancer cell membranes onto neoantigen-loaded nanoparticles. In addition, the nanovaccines promote the secretion of chemokine C-C motif ligand 2 (CCL2), CCL3, and C-X-C motif ligand 10 from macrophages, thus potentiating the access of transferred DCs to LNs. This immunization strategy enables coordinated delivery of identified neoantigens and autologous tumor lysate-derived undefined antigens, leading to initiation of antitumor T cell immunity in a personalized manner. It significantly inhibits tumor growth in prophylactic and established mouse tumor models. The findings provide a new vision for potentiating adoptive cell transfer by nanovaccines, which may open the door to a transformative possibility for improving personalized immunization.