戊型肝炎病毒衣壳蛋白特异性人源单克隆抗体的筛选与鉴定

目的:建立从外周血快速筛选戊型肝炎病毒(Hepatitis E virus,HEV)衣壳蛋白特异性人源抗体的方法,从疫苗免疫者外周血中筛选出相应抗体并进行鉴定。方法:采用分选型流式细胞仪获得外周血中HEV衣壳蛋白特异性的记忆B细胞,通过单细胞RT-PCR的方法获得抗体序列,并进行重组表达,最后对获得的人源单克隆抗体进行初步性质鉴定。结果:成功筛选到识别HEV衣壳蛋白的6株人源单克隆抗体,6株抗体均具有抗原结合活性,4株抗体具有中和活性。结论:成功获得HEV衣壳蛋白特异性人源单克隆抗体序列,并进行真核表达,对抗体的性质进行初步鉴定,为后期研究疫苗免疫的人体内的抗体演化打下基础。国家自然科学基金(No.81571996);;福建省自然科学基金(No.2016J05201)资

Study of the growth mechanism of microfracture networks in tight sandstones

非常规油气在全球能源中扮演的角色越来越重要。致密砂岩储层作为非常规储层的典型代表，对其实现大规模经济开采一直是能源行业关注的焦点。但致密砂岩通常具有低孔隙度和低渗透率的特点，所以需要在储层中构建人工缝网来增加油气从孔隙向井筒运移的能力。因此研究致密砂岩微裂缝网形成的力学机制至关重要。本文聚焦于以脆性矿物为主的致密砂岩，基于二维离散元法构建了数值模拟模型，模型考虑了多组分矿物特性以及岩石微结构的影响，实现了多种加载方式下的缝网生长模拟。同时，针对当前受困于原位高分辨率观测压裂缝网的难题，搭建了水力压裂在线扫描平台（HFCP），并设计了相应的实验流程和分析方法，探讨了致密砂岩原位水力压裂的一般规律。具体的研究工作如下： 探究了拉应力下岩石缝网生成和扩展机制。采用巴西劈裂的加载方式，研究了岩石模型中心形成微裂缝网的规律。通过实验结果验证了模型的力学性能和缝网生长计算的准确性。并采用局部拉伸模型证明了原生微裂缝具有比微孔更加明显的优先取向效应。随后进一步讨论了原生微裂缝和微孔对模型宏观断裂和应力-应变曲线的影响。计算结果表明孔密度升高会使得岩心发育扭转拉伸裂缝，而裂缝密度升高则没有出现这种现象。在相同的中心拉伸应力下，受优先取向效应影响的原生微裂缝比微孔更容易诱导岩石微裂缝的形成。当裂缝密度超过0.324&nbsp; 或孔密度超过0.041&nbsp; 时，生长微裂缝的数量主要由微缺陷密度控制，此时可以忽略弹簧刚度比的影响。 提出了原位水力压裂实验及结果分析方法。针对在微米CT中观测水力压裂缝网遇到的难点，设计了新的压裂零件、并提出了适配的安装方式和功率调整方案。最终搭建了开展原位水力压裂实验的HFCP，设计了相应的实验流程。利用HFCP开展了致密砂岩水力压裂实验，并在实验过程中实现注入流体压力的全程监测以及缝网图像的后处理。随后基于压裂实验结果讨论了注入速度和围压对流体压力曲线的影响。实验结果表明，在不同围压下，随注入速度的增加，流体的破裂压力和平均裂缝开度都有所升高，但分支裂缝体积分数变化呈现多样化特征。 明确了水力压裂对岩石缝网生成和扩展的影响机制。基于真实岩石的物理性质构建了水力压裂数值模型，模型的加载与室内HFCP压裂实验保持一致。在数值理论解和压裂实验验证的基础上，讨论了缝网生长中的注入速度和围压变化的最优方案。随后在岩石模型中添加原生微裂缝和微孔，比较了两类微缺陷对流体压力曲线、颗粒云图和缝网分布的影响。计算结果表明随着围压升高，破裂压力呈线性增加，而裂缝平均宽度呈指数函数单调减少。当应力系数在0.532-0.572之间时，压裂缝网的分支裂缝面积分数最高。与不同矿物和微裂缝相比，微孔能引起模型内流体压力曲线更强烈的波动以及颗粒位移和应力分布的显著变化。此外，各向应力能改变模型的裂缝生长方向并对缝网分布产生影响。 本文的研究结果有助于压裂施工中进一步控制人工缝网的生长，同时为提高致密砂岩储层油气采收率提供了理论基础。</p

基于Voronoi模型的脆性岩石微观结构数值模拟

基于离散元软件UDEC中的Voronoi模型,构建了致密岩石的标准压缩数值试件;应用FISH语言编译相关程序,监测不同脆性致密岩石的裂纹数量和密度在压缩过程中的变化特征。研究发现,随着岩石脆性指数的增加,岩石的起裂应力逐渐增加,而起裂点裂纹密度逐渐减小,高脆性岩石则是在较高的应力状态和较低的裂纹损伤状态下达到裂纹起裂点。岩石的峰值应力随着脆性指数的增加而增加,峰值点裂纹密度和脆性指数符合一拟合公式,根据该公式可以对峰值应力处岩石的裂纹损伤程度进行估计。可以把脆性指数0.6作为区分页岩脆性的经验值

New method of in situ high-resolution experiments and analysis of fracture networks formed by hydraulic fracturing

Hydraulic fracturing plays a key role in the oil and gas development of unconventional tight reservoirs. Therefore, it is important to study the fracturing mechanism of rocks. Thus far, the exploration of this problem through laboratory experiments has been regarded as the best method. However, the current laboratory ex-periments cannot achieve in situ high-resolution observation and analysis. Accordingly, an online scanning platform composed of hydraulic fracturing and micro-computed tomography (HFCP) was developed in this study. The in situ measurements obtained using the HFCP include three parts: a computed tomography (CT) system with a maximum imaging resolution of 7 mu m, a power system with a continuous changeable fluid pressure, and a post-processing system with rock reconstruction, grayscale calibration, threshold segmentation and efficient extraction of the fracture network. Furthermore, we carried out hydraulic fracturing experiments on tight sandstone samples using the HFCP, and the entire experimental process was conducted in situ. The statistics showed that under different confining pressures, the breakdown pressure and average fracture aperture increased with increasing injection rate, but the branch fracture volume fraction exhibited diverse characteristics. The HFCP provides a new method of studying the mechanism of the hydraulic fracturing of rocks, and it has the potential to reveal the in situ differences in fracture networks in tight reservoirs

Investigation of the mechanism of secondary microcrack growth in rocks with native microdefects

Exploring secondary microcracks (SMC) growth during hydraulic fracturing in rocks with native microdefects is a challenging task in unconventional oil and gas exploitation. The effect of native microdefects on the SMC growth currently remains unclear. In this study, conceptual models by discrete element method (DEM) are established for rocks with the native microdefects assuming to be micropores (MP) and microfractures (MF), respectively. Based on the benchmark simulation, the influence of oriental relationship between microdefects and tensile stress on the cracking process is summarized. Furthermore, we investigate the effects of MP and MF on the growth of SMC during the Brazilian splitting loading. The results show that the cluster trend of SMC in the spindle-shaped zone becomes more significant with increasing microdefect densities. Torsion SMC appear outside the zone in the highly dense MP model, which does not occur in the MF model. The central part of MF model induces more SMC than the MP model under the same horizontal tensile stress. The SMC growth is controlled by both microdefect densities and spring stiffness ratios, but the latter could be ignored for the microdefect density over 0.041 (MP) and 0.324 (MF), respectively. The numerical experiments reveal the mechanism of SMC growth in rocks with native microdefects under the tensile stress

Mortar dynamic coupled model for calculating interface gas exchange between organic and inorganic matters of shale

Shale gas has revolutionized the world energy in recent years. In this work, a mortar dynamic coupled model (MDCM) is successfully built for simulating gas transport from molecular motion in nanopores to highly permeable fractures. Results show that the production duration of MDCM can reach about tenfold that of a single medium model, which affords a microscale explanation for the long tail production. We also propose a two-stage process in the variation of the mass-exchange-rate with the pressure difference of organic matter and inorganic matter: it is nonlinear in Stage I, while shows a linear relationship in Stage II. Combined with theoretical analyses, numerical simulations and dimensional analyses, an effi-cient and practical relation for calculating the interface gas exchange in tail production is obtained. The relation offers a valuable tool for the gas transport properties in fractured shale and is finally validated by a gas expansion experiment. Better performance can be obtained in terms of accuracy and precision than the current model. These results stress the need for a change of paradigm from statistic to dynamic trans scale transport. The new insights into transport in the long-term shale gas production suggest new leads for the industry. (c) 2021 Elsevier Ltd. All rights reserved

壳寡糖抑制apoe基因敲除小鼠动脉粥样硬化的形成

壳寡糖具有抗氧化、抗炎、降血糖、降血脂等丰富的保健活性,但壳寡糖对动脉粥样硬化的改善作用并不明确。为深入探究壳寡糖是否可改善动脉粥样硬化,喂食ApoE~(-/-)转基因小鼠高脂饲料以构建动脉粥样硬化小鼠模型。试验分别设置3组小鼠(n=10):正常小鼠喂食普通饲料的对照组;ApoE~(-/-)转基因小鼠喂食高脂饲料的模型组;ApoE~(-/-)转基因小鼠喂食高脂饲料并给药壳寡糖的给药组。给药组给予该模型小鼠聚合度2~6的壳寡糖隔天灌胃处理,处理剂量为150 mg·kg~(-1),整个动物试验持续12周。结果表明:小鼠的脏器指数分析结果显示,壳寡糖对疾病小鼠的体重无明显影响,但可促进脾脏增重(0.11±0.01)g。分析小鼠的血液细胞组成发现,壳寡糖可有效提高白细胞含量(6.9±1.3)×10~9·L~(-1)以及白细胞中淋巴细胞比例(73.2±15.2)