外泌体的生物学特征及其作为靶向药物载体在恶性肿 瘤的应用

肿瘤治疗过程中会出现很多严重的不良反应，如何将药物特异性导向癌细胞就成为了肿瘤治疗中亟需解决的问 题。外泌体是由细胞分泌的、纳米级别的、双层脂质的盘状囊泡结构。正常细胞与肿瘤细胞均可分泌外泌体，供体细胞分泌的 外泌体携带着蛋白质、脂质和核糖核酸（包括microRNA和lncRNA），可直接被同组织内其周围的受体细胞所吸收；同时外泌体 几乎存在于唾液、血液、尿液、脑脊髓液等所有体液中，通过体液运输被不同组织内受体细胞所吸收，为受体细胞的生长提供必 要的营养物质。肿瘤细胞中往往可对外释放出高于正常组织的外泌体，在肿瘤发展过程中外泌体对肿瘤的生长、转移和血管 生成起到重要的作用；同时癌细胞所分泌的外泌体中有着可用来区别与其他细胞外泌体不同的特征性分子，可作为肿瘤临床 诊断的分子标志物，也可作为肿瘤分级、精准治疗及预后评估的重要依据。鉴于此，本文收集国外内相关研究资料，对外泌体 的生物学特征进行总结，并综述了其在临床肿瘤诊断、治疗中的作用及应用潜力，并对外泌体进一步的发展方向进行展望，以 期能为外泌体在临床肿瘤精准治疗中的应用提供理论支持。     

Overcoming the spatial barriers of the stimulus secretion cascade in pancreatic β-cells

The ability of the pancreatic β-cells to adapt the rate of insulin release in accordance to changes in circulating glucose levels is essential for glucose homeostasis. Two spatial barriers imposed by the plasma membrane and inner mitochondrial membrane need to be overcome in order to achieve stringent coupling between the different steps in the stimulus-secretion cascade.

The first spatial barrier is overcome by the presence of a glucose transporter (GLUT) in the plasma membrane, whereas a low affinity hexokinase IV (glucokinase, GK) in the cytosol conveys glucose availability into a metabolic flux that triggers and accelerates insulin release. The mitochondrial inner membrane comprises a second spatial barrier that compartmentalizes glucose metabolism into glycolysis (cytosol) and tricarboxylate (TCA) cycle (mitochondrial matrix).

The exchange of metabolites between cytosol and mitochondrial matrix is mediated via a set of mitochondrial carriers, including the aspartate-glutamate carrier (aralar1), α- ketoglutarate carrier (OGC), ATP/ADP carrier (AAC), glutamate carrier (GC1), dicarboxylate carrier (DIC) and citrate/isocitrate carrier (CIC). The scope of this review is to provide an overview of the role these carriers play in stimulus-secretion coupling and discuss the importance of these findings in the context of the exquisite glucose responsive state of the pancreatic β-cell.     

The potential use of unmanned aircraft systems (drones) in mountain search and rescue operations

Objective

This study explores the potential use of drones in searching for and locating victims and of motorized transportation of search and rescue providers in a mountain environment using a simulation model.

Absence of developmental toxicity in a canine model after infusion of a hemoglobin-based oxygen carrier: Implications for risk assessment

Bovine-derived hemoglobin-based oxygen carriers (HBOCs) have been investigated for use in humans (HBOC-201) and approved for veterinary medicine (HBOC-301). We infused pregnant beagles with HBOC-201 to test whether HBOC-induced developmental toxicity previously observed in rats would occur in a species devoid of an inverted visceral yolk sac (invVYS). Phase 1 assessed developmental toxicity of 6 g/kg HBOC-201 on gestational day (GD) 21. Phase 2 investigated single infusions of 6 g/kg HBOC-201 on one of GDs 21, 25, 29 or 33. Phase 3 studied multiple sequential infusions on GDs 21, 23,25,27,29, 31, and 33 at 0.52 g/kg/day (3.6 g/kg total dose). Mild to moderate maternal toxicity occurred in all phases. There was an unequivocal absence of developmental toxicity in all phases. Overall, our hypothesis that HBOC, which interferes with the function of the invVYS, would not affect the offspring in dogs was supported. The implications relative to human risk are discussed.     

A COMPARISON OF "CARRIER SCREENING" OF HEMOPHILIA BY THE RATIO OF FACTOR VIII COAGULANT ACTIVITY OR ANTIGEN TO FACTOR VIII RELATED ANTIGEN

Abstract: The ratio of factor VIII coagulant activity (VIIIC) or antigen (VIIICAg) to that of factor VIII related antigen (VIIIRAg) was measured in 15 normals, 21 obligatory and 23 possible carriers of hemophilia. Factor VIII coagulant was measured on fresh plasma samples whereas antigenic properties were measured on frozen and thawed samples. In obligatory carriers only, the mean level of VIIICAg was significantly lower than VIIIC and there was a tendency for low VIIICAg levels to be associated with raised VIIIRAg levels. Using both ratios, 13 obligatory carriers were outside the normal tolerance ellipse. In possible carriers, neither ratio showed superior discriminating power. In reference laboratories that perform carrier studies on stored or transported specimens, measurement of VIIICAg/VIIIRAg is a suitable test for diagnosis of carriers.     

De novo design of β-helical polypeptides

Many proteins, including several growth factor receptors such as the IGF-1R and EGFR family, contain variants of the β-helix fold. Inspection of the irregular protein β-helices suggested that different families of regular β-helical polypeptides can be designed using a series of hinged vectors and the constraints imposed by the geometry of a peptide backbone. We have conceived β-helices with five and six β-strands per turn and designed, in detail, a series of regular β-helices with rhomboidal or triangular cross-sections. Each β-helix was modeled by threading C^α atoms to follow the vectorial β-helix and then creating the H-bonded polypeptide backbone and appropriate side-chain orientations. The conformational stability of these regular β-helices was assessed using molecular dynamics simulations. Several potential repeat amino acid sequences were identified for different geometries of β-helix. Regular β-helices offer new possibilities for the study of protein folding, the production of nanofibers, catalysts, inhibitors of growth factor receptors and drug carriers.     

Artificial Organs 2014: A Year in Review

In this Editor's Review, articles published in 2014 are organized by category and briefly summarized. We aim to provide a brief reflection of the currently available worldwide knowledge that is intended to advance and better human life while providing insight for continued application of technologies and methods of organ Replacement, Recovery, and Regeneration. As the official journal of the International Federation for Artificial Organs, the International Faculty for Artificial Organs, the International Society for Rotary Blood Pumps, the International Society for Pediatric Mechanical Cardiopulmonary Support, and the Vienna International Workshop on Functional Electrical Stimulation, Artificial Organs continues in the original mission of its founders “to foster communications in the field of artificial organs on an international level.” Artificial Organs continues to publish developments and clinical applications of artificial organ technologies in this broad and expanding field of organ Replacement, Recovery, and Regeneration from all over the world. We take this time also to express our gratitude to our authors for offering their work to this journal. We offer our very special thanks to our reviewers who give so generously of time and expertise to review, critique, and especially provide meaningful suggestions to the author's work whether eventually accepted or rejected. Without these excellent and dedicated reviewers, the quality expected from such a journal could not be possible. We also express our special thanks to our Publisher, John Wiley & Sons, for their expert attention and support in the production and marketing of Artificial Organs. We look forward to reporting further advances in the coming years.     

Residual Strength Prediction of Aluminum Panels with Multiple Site Damage Using Artificial Neural Networks

Multiple site damage (MSD) cracks are small fatigue cracks that may accumulate at the sides of highly loaded holes in aging aircraft structures. The presence of MSD cracks can drastically reduce the residual strength of fuselage panels. In this paper, artificial neural networks (ANN) modeling is used for predicting the residual strength of aluminum panels with MSD cracks. Experimental data that include 147 unique configurations of aluminum panels with MSD cracks are used. The experimental dataset includes three different aluminum alloys (2024-T3, 2524-T3, and 7075-T6), four different test panel configurations (unstiffened, stiffened, stiffened with a broken middle stiffener, and bolted lap-joints), many different panel widths and thicknesses, and the sizes of the lead and MSD cracks. The results presented in this paper demonstrate that a single ANN model can predict the residual strength for all materials and configurations with high accuracy. Specifically, the overall mean absolute error for the ANN model predictions is 3.82%. Furthermore, the ANN model residual strength predictions are compared to those obtained using the most accurate semi-analytical and computational approaches from the literature. The ANN model predictions are found to be at the same accuracy level of these approaches, and they even outperform the other approaches for many configurations.