Aberrant,ectopic expression of VEGF and VEGF receptors 1 and 2 in malignant colonic epithelial cells. Implications for these cells growth via an autocrine mechanism

Vascular endothelial growth factor A (referred to as VEGF) is implicated in colon cancer growth. Currently, the main accepted mechanism by which VEGF promotes colon cancer growth is via the stimulation of angiogenesis, which was originally postulated by late Judah Folkman. However, the cellular source of VEGF in colon cancer tissue; and, the expression of VEGF and its receptors VEGF-R1 and VEGF-R2 in colon cancer cells are not fully known and are subjects of controversy.     

Influence of biologically inspired nanometer surface roughness on antigen-antibody interactions for immunoassay-biosensor applications

Current research efforts to improve immunoassay-biosensor functionality have centered on detection through the optimal design of microfluidic chambers, electrical circuitry, optical sensing elements, and so on. To date, little attention has been paid to the immunoassay-biosensor membrane surface on which interactions between antibodies and antigens must occur. For this reason, the objective of the present study was to manipulate the nanometer surface roughness of a model immunoassay-biosensor membrane to determine its role on sensitivity and specificity. It was hypothesized that surface roughness characteristics similar to those used by the body's own immune system with B-lymphocyte cell membranes would promote antigen-antibody interactions and minimize non-specific binding. To test this hypothesis, polystyrene 96-well plate surfaces were modified to possess similar topographies as those of B-lymphocyte cell membranes. This was accomplished by immobilizing Protein A conjugated gold particles and Protein A conjugated polystyrene particles ranging in sizes from 40 to 860 nm to the bottom of polystyrene wells. Atomic force microscopy results provided evidence of well-dispersed immunoassay-biosensor surfaces for all particles tested with high degrees of biologically inspired nanometer roughness. Testing the functionality of these immunosurfaces using antigenic fluorescent microspheres showed that specific antigen capture increased with greater nanometer surface roughness while nonspecific antigen capture did not correlate with surface roughness. In this manner, results from this study suggest that large degrees of biologically inspired nanometer surface roughness not only increases the amount of immobilized antibodies onto the immunosurface membrane, but it also enhances the functionality of those antibodies for optimal antigen capture, criteria critical for improving immunoassay-biosensor sensitivity and specificity.     

纳米珍珠粉/壳聚糖-透明质酸支架修复兔股骨远端骨缺损的实验研究

通过体内实验探讨纳米珍珠粉/壳聚糖-透明质酸(NPP/C-HA)复合支架的促成骨能力。采用双侧兔股骨远端骨缺损模型(直径7 mm,深度10 mm),通过大体标本、影像学检查、分子生物学检查及组织学检查来观察骨缺损的修复效果。发现各组均未出现明显不良组织反应;随观察时间增加实验组骨缺损区范围最小,在第8周和第12周数据的差异存在统计学意义(P<0.05);在第4周、6周、8周时实验组BALP含量与其他组比较P<0.05;实验组缺损区边缘出现更多的新生骨,但在骨质成熟度上未见明显差异。结果表明NPP/C-HA支架具有良好的生物相容性及促成骨作用,为进一步研究NPP/C-HA在骨组织工程中的作用提供了实验和理论基础。     

动脉硬化仿真模拟分析

目的：通过对血管中血液流动对血管的影响及血液内低密度脂蛋白（sLDL）微粒行为的模拟分析,研究动脉粥样硬化产生的血流动力学原因。方法：第一步,使用流体力学软件CFD,建立动脉血管弯曲分叉仿真模型;第二步,分析血液流动特性,跟踪血液中15—25纳米尺度范围类的sLDL粒子在动脉分叉模型中的流体力学行为,研究sLDL在血液流速稳定下在血管中的空间分布及流场特征分布。结果：血管起始段出现压强很高的区域。在动脉血管弯曲内侧处及分岔处的分支外侧血液流动较慢,并且在这些部位出现压强较高的区域。在血管弯曲外侧处及分岔点处,sLDL与血管壁发生碰撞的几率较其它位置较高,粒子在血管上沉积高发区域在这些部位呈斑块状分布。讨论及结论：在血管起始段的高压,可能是导致这一部分血管损伤,并进而引起动脉硬化形成的主要原因;在动脉血管弯曲外侧处及分岔点处出现的高压低速血流分布,一方面增大了血液中包括sLDL粒子在内的致病因子与血管壁的接触时间,另一方面则引起这些部位血清的侧漏加强,出现所谓的’浓度极化’现象,从而导致这些部位出现高浓度的sLDL分布,增大sLDL粒子与血管壁的接触几率;粒子在血管上沉积高发区域往往存在于动脉血管分岔点处,而在血管弯曲外侧处也有较高几率沉淀,呈斑状分布;长期性轻微性振动的剪切压力的作用使多数血管内皮细胞性质改变,促进动脉硬化形成。在动脉血管起始段、弯曲处及分岔点处血液的高压低速分布、sLDL粒子的高沉积率及低剪切应力等是动脉硬化产生及演化的重要因素.     

Nonuniform Ionic and Electronic Transport of Ceramic and Polymer/Ceramic Hybrid Electrolyte by Nanometer‐Scale Operando Imaging for Solid‐State Battery

Replacing the liquid electrolyte in lithium batteries with solid‐state ion conductor is promising for next‐generation energy storage that is safe and has high energy density. Here, nanometer‐resolution ionic and electronic transport imaging of Li₃PS₄ (LPS), a solid‐state electrolyte (SSE), is reported. This nm resolution is achieved by using a logarithm‐scale current amplifier that enhances the current sensitivity to the fA range. Large fluctuations of ion current—one to two orders of magnitude on the LPS and on the LPS region of a polymer/LPS bulk hybrid SSE—that must be mitigated to eliminate Li dendrite formation and growth, are found. This ion current fluctuation is understood in terms of highly anisotropic transport kinetic barriers along the different crystalline axes due to different grain orientations in the polycrystalline and glass ceramic materials. The results on the bulk hybrid SSE show a sharp transition of ionic and electronic transport at the LPS/polymer boundary and decreases in average ionic current with decreasing polyimine particle size and with extensive cycling. The results elucidate the mechanism of polyimine extension into interparticles to prevent Li dendrite growth. This work opens up novel characterization of charge transport, which relates to Li plating and stripping for solid‐state‐batteries.     

辅酶Q10/两亲性木聚糖纳米悬浮剂的制备以及生物利用度

研究一种新型共聚物负载辅酶Q10形成纳米悬浮剂能够增加CoQ10的水溶性,并且提高其口服生物利用度。本研究以槲皮素—木聚糖（QT-Xylan）共聚物偶联为基础进行合成,采用高剪切均质法进一步包载辅酶Q10,形成了一种新型载药纳米悬浮剂。采用单因素实验设计,并以粒径大小作为单因素实验的考察条件,影响其粒径大小的因素包括高压均质压力、高压均质次数、共聚物浓度、共聚物与CoQ10的质量比4个因素,并进行一系列体外实验评价。当均质压力为60 MPa,均质次数为7次,共聚物浓度为1 mg·mL^-1,共聚物与CoQ10的质量比为1∶1,是纳米悬浮剂的最佳制备工艺,此时粒径大小为166.7 nm。在最佳工艺条件下,在体外溶出实验中,包载CoQ10纳米悬浮剂的体外溶出率在人工胃液（SGF）和人工肠液（SIF）中分别是CoQ10原药的1.89和1.48倍。在体内生物利用度实验中,分别对大鼠灌胃CoQ10原药与载药纳米悬浮剂后,检测不同时间点的血药浓度,考察药物在大鼠体内的吸收和代谢情况,负载CoQ10的纳米悬浮剂在大鼠体内的血药浓度明显高于CoQ10原药,生物利用度提高为CoQ10原药的2.64倍。     

Genome sequence of the phage clP1, which infects the beer spoilage bacterium Pediococcus damnosus

Pediococcus damnosus (P. damnosus) bacteriophage (phage) clP1 is a novel virulent phage isolated from a municipal sewage sample collected in Southern Ireland. This phage infects the beer spoilage strain P. damnosus P82 which was isolated from German breweries. Sequencing of the phage has revealed a linear double stranded DNA genome of 38,013 base pairs (bp) with an overall GC content of 47.6%. Fifty seven open reading frames (ORFs) were identified of which 30 showed homology to previously sequenced proteins, and as a consequence 20 of these were assigned predicted functions. The majority of genes displayed homology with genes from the Lactobacillus plantarum phage phiJL-1. All genes were located on the same coding strand and in the same orientation. Morphological characterisation placed phage clP1 as a member of the Siphoviridae family with an isometric head (59 nm diameter) and non-contractile tail (length 175 nm; diameter 10nm. Interestingly, the phage clP1 genome was found to share very limited identity with other phage genome sequences in the database, and was hence considered unique. This was highlighted by the genome organisation which differed slightly to the consensus pattern of genomic organisation usually found in Siphoviridae phages. With the genetic machinery present for a lytic lifecycle and the absence of potential endotoxin factors, this phage may have applications in the biocontrol of beer spoilage bacteria. To our knowledge, this study represents the first reported P. damnosus phage genome sequence.     

Functional genetic variation in aminopeptidase A (ENPEP): lack of clear association with focal and segmental glomerulosclerosis (FSGS)

The aminopeptidase A (APA) ectopeptidase is an integral membrane-bound zinc metalloprotease that cleaves aspartic and glutamic acidic residues from the N-terminus of a number of protein substrates that includes angiotensin II. Angiotensin II, the most vasoactive component of the renin-angiotensin-aldosterone (RAAS) pathway, can contribute to renal disease by causing an increase in arterial blood pressure leading to glomerular injury and fibrosis. APA is expressed in many organs, including the kidney where it localizes mainly to the podocyte cell membrane and brush borders of the proximal tubule cells. Antibodies directed to the APA peptide can induce an acute massive albuminuria in wild-type BALB/c mice after intravenous injection. We examined whether variants in the APA encoding gene (ENPEP) are more frequent in individuals with the proteinuric disease focal and segmental glomerulosclerosis (FSGS) compared to control individuals. The ENPEP coding sequence was re-sequenced in 188 FSGS patients and 48 controls. Genetic variants were further genotyped in 181 individuals without any known kidney disease. We then examined the effect of the non-synonymous coding variants identified on their cell surface APA activity after transfection in COS-1 cells. Several of these ENPEP variants lead to reproducibly altered APA activity. However, we did not see a clear correlation between the presence of a functional ENPEP variant and FSGS. However, the existence of these variants with marked effect on APA activity suggests that both rare and common variation in ENPEP may contribute to the development of renal and hypertensive disorders and warrants further study.