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1.
Maturity-onset diabetes of the young (MODY) type 2 is caused by heterozygous inactivating mutations in the gene encoding glucokinase (GCK), a pivotal enzyme for glucose homeostasis. In the pancreas GCK regulates insulin secretion, while in the liver it promotes glucose utilization and storage. We showed that silencing the Drosophila GCK orthologs Hex-A and Hex-C results in a MODY-2-like hyperglycemia. Targeted knock-down revealed that Hex-A is expressed in insulin producing cells (IPCs) whereas Hex-C is specifically expressed in the fat body. We showed that Hex-A is essential for insulin secretion and it is required for Hex-C expression. Reduced levels of either Hex-A or Hex-C resulted in chromosome aberrations (CABs), together with an increased production of advanced glycation end-products (AGEs) and reactive oxygen species (ROS). This result suggests that CABs, in GCK depleted cells, are likely due to hyperglycemia, which produces oxidative stress through AGE metabolism. In agreement with this hypothesis, treating GCK-depleted larvae with the antioxidant vitamin B6 rescued CABs, whereas the treatment with a B6 inhibitor enhanced genomic instability. Although MODY-2 rarely produces complications, our data revealed the possibility that MODY-2 impacts genome integrity.  相似文献   
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This work deals with the additive manufacturing and characterization of hydroxyapatite scaffolds mimicking the trabecular architecture of cancellous bone. A novel approach was proposed relying on stereolithographic technology, which builds foam-like ceramic scaffolds by using three-dimensional (3D) micro-tomographic reconstructions of polymeric sponges as virtual templates for the manufacturing process. The layer-by-layer fabrication process involves the selective polymerization of a photocurable resin in which hydroxyapatite particles are homogeneously dispersed. Irradiation is performed by a dynamic mask that projects blue light onto the slurry. After sintering, highly-porous hydroxyapatite scaffolds (total porosity ~0.80, pore size 100-800 µm) replicating the 3D open-cell architecture of the polymeric template as well as spongy bone were obtained. Intrinsic permeability of scaffolds was determined by measuring laminar airflow alternating pressure wave drops and was found to be within 0.75-1.74 × 10−9 m2, which is comparable to the range of human cancellous bone. Compressive tests were also carried out in order to determine the strength (~1.60 MPa), elastic modulus (~513 MPa) and Weibull modulus (m = 2.2) of the scaffolds. Overall, the fabrication strategy used to print hydroxyapatite scaffolds (tomographic imaging combined with digital mirror device [DMD]-based stereolithography) shows great promise for the development of porous bioceramics with bone-like architecture and mass transport properties.  相似文献   
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Glass–ceramic scaffolds mimicking the structure of cancellous bone were produced via sponge replication technique by using a polyurethane foam as template and glass powder below 30 μm as inorganic phase. Specifically, a SiO2-based glass of complex composition and its corresponding P2O5-based “specular” glass were used as materials for scaffolding. The polymeric sponge was thermally removed and the glass powders were sintered to obtain a replica of the template structure. The scaffolds were investigated and compared from a structural, morphological and mechanical viewpoint by assessing their crystalline phases, volumetric shrinkage, pores content and interconnection, mechanical strength. In addition, the scaffolds were soaked in acellular simulated body fluid to investigate their in vitro behaviour. The produced scaffolds have a great potential for bone reconstructive surgery because their features, such as shape, strength, bioactivity and bioresorption, can be easily tailored according to the end use.  相似文献   
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Bioactive glasses exhibit the unique ability of bone bonding, thus creating a stable interface by stimulating bone cells toward mechanisms of regeneration and self-repair activated by ionic dissolution products. Therefore, 3D glass-derived scaffolds can be considered ideal porous templates to be used in bone tissue engineering strategies and regenerative medicine. This review provides a comprehensive overview of all technological aspects relevant to the fabrication of bioactive glass scaffolds, including the fundamentals of materials processing, a summary of the conventional porogen, and template-based methods and of recent additive manufacturing technologies, which are promising for large-scale production of highly reproducible and reliable implants suitable for a wide range of clinical applications.  相似文献   
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Na2O-CaO-SiO2 glass- and glass-ceramic matrix/Ti particle biocomposites have been prepared by means of two processes: pressureless sintering and hot pressing. Time and temperature sintering conditions were optimised on the basis of the thermal properties of mixed glass and Ti powders, determined by Differential Thermal Analysis, Differential Scanning Calorimetry, Hot Stage Microscopy, Dilatometry. Each sintered sample was characterised by means of X-ray diffraction, Scanning Electron Microscopy, EDS, density measurements, Young's modulus, induced crack propagation by Vickers indentations, three point bending test, K IC measurements. The in vitro bioactivity was investigated on the sintered composites by soaking them in a simulated body fluid (SBF) with the same ion concentration of the human plasma.  相似文献   
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越来越高的汽车发动机温度对在汽车中使用的胶管和胶带用聚合物提出了更严格的要求。本综述了胶管和胶带中使用的聚合物,并针对提高耐热、耐屈挠疲劳和耐臭氧老化性能讨论了每一种聚合物用的硫化体系和防老剂搭配。  相似文献   
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Advanced bearing materials for future military and commercial gas turbines are required to operate at high speeds, high temperature, and higher thrust loads. At elevated operating conditions, the bearing and gear materials must be able to operate with ultrathin oil films without suffering detrimental effects of adhesive wear. The development of materials with rolling-element fatigue and corrosion resistance properties without deterioration in adhesive wear attributes is a significant challenge. To meet those performance requirements, the forerunner, martensitic stainless steel Pyrowear 675 (AMS 5930), has been in development for aerospace bearing and gear applications. This article addresses the adhesive wear performance of three variants of Pyrowear 675 with silicon nitride ball material simulating a hybrid bearing evaluated using a WAM8 machine. Baseline testing was conducted using conventional bearing steel AISI M-50. Adhesive wear testing was conducted at a temperature of 200°C and at different contact slips (15, 30, 50, and 70%) and entraining velocities (1.3 to 10.2 m/s). Posttest specimens were analyzed by scanning electron microscopy (SEM) and auger electron spectroscopy (AES). All the hybrid material pairs demonstrated very good adhesive wear performance compared to the baseline AISI M-50–AISI M-50 pair.  相似文献   
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