Skeletal muscle lipid accumulation is associated with several chronic metabolic disorders, including obesity, insulin resistance (IR) and type 2 diabetes. The aim of this study is to evaluate whether static imaging time-of-flight-secondary-ion mass spectrometry (TOF-SIMS) equipped with a Bismuth-cluster ion source can be used for studying skeletal muscle lipid accumulation associated with obesity. Mouse gastrocnemius muscle tissues in 10-week-old obese ob/ob (n = 8) and lean wild-type C57/BL6 (n = 6) mice were analyzed by TOF-SIMS. Our results showed that signal intensities of fatty acids (FAs) and diacylglycerols (DAGs) were significantly increased in skeletal muscle of the obese ob/ob mice as compared to the lean wild-type mice. These differences were revealed through a global analytical approach, principal component analysis (PCA) of TOF-SIMS spectra, and ion-specific TOF-SIMS images. Region-of-interest (ROI) analysis showed that FA signal intensities within the muscle cell were significantly increased in ob/ob mice. Moreover, analysis of the ratio between different FA peaks revealed changes in monounsaturated FAs (MUFAs) and polyunsaturated FAs (PUFAs), which is in agreement with previous reports on obesity. These changes in FA composition were also reflected in the ratio of different DAGs or phosphatidylcholines (PCs) that contain different FA residues. Imaging TOF-SIMS together with PCA of TOF-SIMS spectra is a promising tool for studying skeletal muscle lipid accumulation associated with obesity. 相似文献
Trachurus japonicus is an economically important fish in the northwestern Pacific Ocean. However, its resources have declined seriously and there is an urgent need for a wide-range of investigations of the existing genetic resources. This requires a large number of diverse molecular markers with high discriminating power. In this study, we identified 43,264 perfect SSRs in T. japonicus genome using SLAF-seq technology. Of these, we randomly selected 106 SSRs (tri-nucleotide to hexa-nucleotide) to test for polymorphism. Eventually, we successfully developed a total of 33 loci including 8 tri-nucleotide and 25 long repeat motifs (tetra-nucleotide to hexa-nucleotide). The number of alleles (Na) of these loci ranged from 4 to 24 (mean 12.6). The observed heterozygosity (Ho) and expected heterozygosity (He) varied from 0.258 to 0.969 (mean 0.723) and from 0.452 to 0.962 (mean 0.827), respectively. All loci except TJ6-7 were highly informative (PIC > 0.5). These results showed that the shortlisted 33 loci exhibited moderate to relatively high genetic diversity, of which 18 were regarded as highly polymorphic and well-resolved. In summary, these diverse and potential microsatellites detected in our study provide substantial genetic basis for the screening of polymorphic SSR markers of T. japonicus and also provide a powerful tool to perform further studies on the genetic resource assessment and conservation of T. japonicus. 相似文献
Based on previous studies, 66 2-phenyl-4H-chromone derivatives containing amide and 1,3,4-oxadiazole moieties were prepared as potential telomerase inhibitors. The results showed most of the title compounds exhibited significantly inhibitory activity on telomerase. Among them, some compounds demonstrated the most potent telomerase inhibitory activity (IC50 < 1 µM), which was significantly superior to the staurosporine (IC50 = 6.41 µM). In addition, clear structure–activity relationships were summarised, indicating that the substitution of the methoxy group and the position, type and number of the substituents on the phenyl ring had significant effects on telomerase activity. Among them, compound A33 showed considerable inhibition against telomerase. Flow cytometric analysis showed that compound A33 could arrest MGC-803 cell cycle at G2/M phase and induce apoptosis in a concentration-dependent way. Meanwhile, Western blotting revealed that this compound could reduce the expression of dyskerin, which is a fragment of telomerase. 相似文献
False lumen thrombosis (FLT) in type B aortic dissection has been associated with the progression of dissection and treatment outcome. Existing computational models mostly assume rigid wall behavior which ignores the effect of flap motion on flow and thrombus formation within the FL. In this study, we have combined a fully coupled fluid–structure interaction (FSI) approach with a shear-driven thrombosis model described by a series of convection–diffusion reaction equations. The integrated FSI-thrombosis model has been applied to an idealized dissection geometry to investigate the interaction between vessel wall motion and growing thrombus. Our simulation results show that wall compliance and flap motion can influence the progression of FLT. The main difference between the rigid and FSI models is the continuous development of vortices near the tears caused by drastic flap motion up to 4.45 mm. Flap-induced high shear stress and shear rates around tears help to transport activated platelets further to the neighboring region, thus speeding up thrombus formation during the accelerated phase in the FSI models. Reducing flap mobility by increasing the Young’s modulus of the flap slows down the thrombus growth. Compared to the rigid model, the predicted thrombus volume is 25% larger using the FSI-thrombosis model with a relatively mobile flap. Furthermore, our FSI-thrombosis model can capture the gradual effect of thrombus growth on the flow field, leading to flow obstruction in the FL, increased blood viscosity and reduced flap motion. This model is a step closer toward simulating realistic thrombus growth in aortic dissection, by taking into account the effect of intimal flap and vessel wall motion.