BAY41-4109对乙肝病毒衣壳组装的影响

乙肝病毒衣壳蛋白成功组装成衣壳二十面体的过程是病毒前基因组RNA逆转录形成成熟DNA的必要步骤。衣壳结构的轻微改变或破坏能对病毒子代传播产生巨大影响。应用透射电子显微镜研究发现小分子抗病毒化合物（heteroaryldihvdropyrimidine,HAP）BAY41．4109在与衣壳蛋白二聚体摩尔浓度比达到1：2时,能干扰乙肝病毒衣壳蛋白组装成衣壳二十面体。在BAY41—4109的作用下,衣壳蛋白发生错误组装,形成不规则球体、平面片状结构和管状结构。应用图像处理技术对管状结构进行分析,发现它是衣壳蛋白重新装配形成的具有螺旋对称性的规则组装体,衣壳蛋白按六角晶格方式排列,其最小组成单位是衣壳蛋白的二聚体。     

A Protein-Adsorbent Hydrogel with Tunable Stiffness for Tissue Culture Demonstrates Matrix-Dependent Stiffness Responses

Although tissue culture plastic has been widely employed for cell culture, the rigidity of plastic is not physiologic. Softer hydrogels used to culture cells have not been widely adopted in part because coupling chemistries are required to covalently capture extracellular matrix (ECM) proteins and support cell adhesion. To create an in vitro system with tunable stiffnesses that readily adsorbs ECM proteins for cell culture, a novel hydrophobic hydrogel system is presented via chemically converting hydroxyl residues on the dextran backbone to methacrylate groups, thereby transforming non-protein adhesive, hydrophilic dextran to highly protein adsorbent substrates. Increasing methacrylate functionality increases the hydrophobicity in the resulting hydrogels and enhances ECM protein adsorption without additional chemical reactions. These hydrophobic hydrogels permit facile and tunable modulation of substrate stiffness independent of hydrophobicity or ECM coatings. Using this approach, it is shown that substrate stiffness and ECM adsorption work together to affect cell morphology and proliferation, but the strengths of these effects vary in different cell types. Furthermore, it is revealed that stiffness-mediated differentiation of dermal fibroblasts into myofibroblasts is modulated by the substrate ECM. The material system demonstrates remarkable simplicity and flexibility to tune ECM coatings and substrate stiffness and study their effects on cell function.     

Inkjet Printing of Self‐Assembled 2D Titanium Carbide and Protein Electrodes for Stimuli‐Responsive Electromagnetic Shielding

2D titanium carbides (MXene) possess significant characteristics including high conductivity and electromagnetic interference shielding efficiency (EMI SE) that are important for applications in printed and flexible electronics. However, MXene‐based ink formulations are yet to be demonstrated for proper inkjet printing of MXene patterns. Here, tandem repeat synthetic proteins based on squid ring teeth (SRT) are employed as templates of molecular self‐assembly to engineer MXene inks that can be printed as stimuli‐responsive electrodes on various substrates including cellulose paper, glass, and flexible polyethylene terephthalate (PET). MXene electrodes printed on PET substrates are able to display electrical conductivity values as high as 1080 ± 175 S cm^?1, which significantly exceeds electrical conductivity values of state‐of‐the‐art inkjet‐printed electrodes composed of other 2D materials including graphene (250 S cm^?1) and reduced graphene oxide (340 S cm^?1). Furthermore, this high electrical conductivity is sustained under excessive bending deformation. These flexible electrodes also exhibit effective EMI SE values reaching 50 dB at films with thicknesses of 1.35 µm, which mainly originate from their high electrical conductivity and layered structure.     

银屑病患者皮损中角蛋白10、14、17及丝聚蛋白表达与分布

目的：研究银屑病患者皮损中角蛋白10、14、17及丝聚蛋白的分布、表达与皮肤屏障功能受损的相关性。方法以20例银屑病患者皮损及10例正常人皮肤为研究对象,运用免疫组化及westerm blot测定两组角蛋白10、14、17及丝聚蛋白的分布与表达。结果：与正常人皮肤相比,银屑病患者的皮损组织中角蛋白10表达和丝聚蛋白表达下调;角蛋白14及17表达上调,但表达程度及部位不同,其差异均具有统计学意义。结论银屑病患者的皮肤屏障功能有受损,可能是银屑病持续发病机制之一。     

Managing the Public Sphere: Journalistic Construction of the Great Globalization Debate

There is little consensus on what constitutes open, deliberative media discourse. We offer a simple, measurable, and comparative model based on 3 aspects of source and issue construction in news accounts: access, recognition, and responsiveness. The model is applied to coverage of 2001–2003 World Economic Forum (WEF) meetings and protests against the organization's role in global economic policies. Both demonstrators and WEF participants were granted news access, but WEF actors were recognized more formally and given greater input in news content, including ownership claims to many activist issue positions. Journalistic deference to the WEF communication agenda limited mutual responsiveness. The journalistic process systematically managed the debate about globalization on terms that favored elites over citizen-activists.     

Size Switchable Nanoclusters Fueled by Extracellular ATP for Promoting Deep Penetration and MRI‐Guided Tumor Photothermal Therapy

Protein‐based theranostic agents (PBTAs) exhibit superior performance in the diagnosis and therapy of cancers. However, the in vivo applications of PBTA are largely limited by undesired accumulation, penetration, or selectivity. Here, an ATP‐supersensitive protein cluster is fabricated for promoting PBTA delivery and enhancing magnetic resonance imaging (MRI)‐guided tumor photothermal therapy. Gd³⁺‐ and CuS‐coloaded small bovine serum albumin nanoparticles (GdCuB) are synthesized as the model protein with a size of 9 nm and are encapsulated into charge switchable polycations (DEP) to form DEP/GdCuB nanoclusters of 120 nm. In blood circulation, DEP/GdCuB significantly extends the half‐lifetime and thereby enhances the tumor accumulation of GdCuB. When the clusters reach the tumor site, the extracellular adenosine triphosphate (ATP) can effectively trigger the release of GdCuB, resulting in tumoral deep penetration as well as the activation of T₁‐weighted MRI (r₁ value switched from 2.8 × 10^?3 to 11.8 × 10^?3 m ^?1 s^?1). Furthermore, this delivery strategy also improves the tumoral photothermal therapy efficacy with the MRI‐guided therapy. The study of ATP‐activated nanoclusters develops a novel strategy for tumor deep penetration and on/off imaging of PBTA by size switchable technology, and reveals the potential for MRI‐guided therapy of cancers.     

对NpHR光敏感蛋白具有刺激作用的光电极研制

光电极是研究光遗传学不可或缺的工具之一。波长为460nm的蓝光可以对ChR2神经蛋白产生刺激,而波长为580nm的黄光可以刺激NpHR神经蛋白,对生物体的反应产生抑制。目前,蓝光波段的光电极具有很高的功率密度,可以满足光遗传学的研究,而黄光波段半导体发光器件的发光效率较低,因此对黄光波段的光电极研究较少。在蓝宝石衬底蓝光光电极研制的基础上,通过激发黄色荧光粉和量子点两种形式获得黄光,并通过沉积SiO2/TiO2分布式布拉格反射镜（DBR）有效滤除了蓝光波段的激发光,最后通过沉积Ag金属反射镜增强黄光信号,制备出荧光粉基和量子点基黄光光电极。与荧光粉基黄光光电极相比,量子点基黄光光电极具有更高的功率密度、更窄的光谱半宽和更薄的厚度。在1～10mA的注入电流下,量子点基黄光光电极的功率密度为4.46～15.37mW/mm2,满足刺激NpHR神经蛋白的要求。     

乙酰胆碱酯酶分子的原子力显微成像

本文研究了用原子力显微技术对乙酰胆碱酯酶进行成像的方法。在新鲜裂解的云一表面镀一层金膜,金膜与疏基丙酸（ＭＰＡ）的疏基形成Ｓ－Ａｕ键。使ＭＰＡ的游离羧基再通过碳二亚胺反应与ＡＣｈＥ的碱性氨基酸的氨基形成肽键连接,ＡＣｈＥ因而被固定于支持物表面,这样固定的ＡＣｈＥ可获得清晰成像而不脱落。     

壬基酚对大鼠F1子代脑基因表达的影响

目的:研究壬基酚通过妊娠期暴露是否会影响F1子代的脑发育。方法:对SD孕鼠染毒NP,从妊娠第7天开始持续到产后第二天,分别提取NP组和对照组F1代2d龄大鼠的脑组织mRNA,表达谱基因芯片检测脑基因的表达。用Q-PCR法验证F1雄性子代大脑泛素特异性蛋白酶8、ATP结合盒转运子和内磺肽蛋白这三个下调基因的表达,然后用Western blotting法检测F1子代大脑泛素特异性蛋白酶8的蛋白表达。结果:ATP结合盒转运子(ATP-binding cassette,ABCA)、内璜肽蛋白(Endosulfine alph,Ensa)、泛素特异性蛋白酶8(Ubiquitin Specific Protease 8,USP8/UBPy)基因和蛋白表达下调。结论:NP可影响神经细胞的正常结构和信号转导功能,并提示可以干扰机体内分泌系统、脂质和能量代谢及一系列正常生理功能。     

High Precision,Electrochemical Detection of Reversible Binding of Recombinant Proteins on Wide Bandgap GaN Electrodes Functionalized with Biomembrane Models

We report a novel hybrid charge sensor realized by the deposition of phospholipid monolayers on highly doped n‐GaN electrodes. To detect the binding of recombinant proteins with histidine‐tags, lipid vesicles containing chelator lipids were deposited on GaN electrodes pre‐coated with octadecyltrimethoxysilane monolayers. Owing to its optical transparency, GaN allows the confirmation of the fluidity of supported membranes by fluorescence recovery after photo‐bleaching (FRAP). The electrolyte‐(organic) insulator‐semiconductor (EIS) setup enables one to transduce variations in the surface charge density ΔQ into a change in the interface capacitance ΔC _p and, thus, the flat‐band potential ΔU _FB. The obtained results demonstrate that the membrane‐based charge sensor can reach a high sensitivity to detect reversible changes in the surface charge density on the membranes by the formation of chelator complexes, docking of eGFP with histidine tags, and cancellation by EDTA. The achievable resolution of ΔQ ≥ 0.1 μC/cm² is better than that obtained for membrane‐functionalized p‐GaAs, 0.9 μC/cm², and for ITO coated with a polymer supported lipid monolayer, 2.2 μC/cm². Moreover, we examined the potential application of optically active InGaN/GaN quantum dot structures, for the detection of changes in the surface potential from the photoluminescence signals measured at room temperature.