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The age-specific rates of hip fractures have been declining in most countries in the West but a few studies suggest that the rates might be increasing in areas of Asia that are undergoing urbanization. We previously conducted a population-based study of hip fracture rates in Beijing, China, in 1990 to 1992 that included validation of hip fracture cases. Using a similar approach to validate cases, we estimated the age-specific hip fracture rates in Beijing, China, for 2002 to 2006. Specifically, we obtained hospital discharge data for hip fractures that were reported to the Beijing Bureau of Public Health. To confirm the diagnoses, Beijing residence, and find cases missed by the public records we checked individual cases in the public health records against medical records in a random sample of Beijing hospitals. The rates from public health data were adjusted for these under-and overestimations. We found that between 1990 and 1992 and 2002 and 2006, the adjusted age-specific rates of hip fracture over age 50 years increased 2.76-fold (95% confidence interval [CI], 2.68-2.84) in women and 1.61-fold (95% CI, 1.56-1.66) in men. Over age 70 years, the age-specific rates increased 3.37-fold (95% CI, 3.28-3.47) in women and 2.01-fold (95% CI, 1.95-2.07) in men. From 2002 to 2006, the rates over age 50 years increased 58% in women and 49% in men. We conclude that the rate of hip fracture has been rising very rapidly in Beijing, China. Therefore, the burden of hip fractures may be shifting rapidly from the West to urbanizing areas of the East. ß

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In this paper, we demonstrated a room-temperature acetone gas sensor based on tin dioxide (SnO 2 )-reduced graphene oxide (RGO) hybrid composite film. The SnO 2 -RGO composite film sensor was fabricated on PCB substrate with rectangular-ambulatory-plane interdigital microelectrodes by using a facile hydrothermal method. The presence of small-sized SnO 2 nanoparticles on RGO sheets was 10 characterized by SEM, XRD and BET measurement, demonstrating well-structures without irreversible restacking of sheets and agglomeration. The sensing properties of the SnO 2 -RGO hybrid film sensor were investigated by exposing to various concentration of acetone gas at room temperature. It was found that the presented sensor exhibited not only excellent response to acetone gas, but also fast response-recovery time and good repeatability, exhibiting the unique advantages of SnO 2 -RGO hybrid composite as a 15 building block for sensor fabrication. The gas response of the SnO 2 -RGO hybrid composite was about 2-fold higher than that of the pure RGO film, and the possible sensing mechanism was mainly attributed to the high surface area, three-dimensional porous nanostructure and special interactions between RGO sheets and SnO 2 nanoparticles.

No abstract

Activation of pregnane X receptor (PXR), a nuclear receptor that controls xenobiotic and endobiotic metabolism, is known to induce liver enlargement, but the molecular signals and the cell types responding to PXR-induced hepatomegaly remain unknown. In this study, the effect of PXR activation on liver enlargement and cell change was evaluated in several strains of genetically-modified mice and animal models. Lineage labelling using AAV-Tbg-Cre-treated Rosa26 mice or Sox9-Cre , Rosa26 mice was performed and Pxr-null mice or AAV Yap shRNA-treated mice were used to confirm the role of PXR or YAP. Treatment with selective PXR activators induced liver enlargement and accelerated regeneration in wild-type and PXR-humanized mice but not in Pxr-null mice by increase of cell size, induction of a regenerative hybrid hepatocyte (HybHP) reprogramming, and promotion of hepatocyte and HybHP proliferation. Mechanistically, PXR interacted with yes-associated protein (YAP) and PXR activation induced nuclear translocation of YAP. Blockade of YAP abolished PXR-induced liver enlargement in mice. These findings revealed a novel function of PXR in enlarging liver size and changing liver cell fate via activation of the YAP signalling pathway. These results have implications for understanding the physiological functions of PXR and suggest the potential for manipulation of liver size and liver cell fate. This article is protected by copyright. All rights reserved.

Background:VGF (nonacryonimic) and phosphatidylinositol 3-kinase (PI3K)/AKT (also known as protein kinase B, PKB)/mammalian target of rapamycin (mTOR) signaling play pivotal roles in depression. However, whether phosphatidylinositol 3-kinase/AKT/mTOR signaling-mediated VGF participates in rapid-acting antidepressant-like actions of GLYX-13 is unclear.Methods:Herein, we evaluated the effects of acute treatment of GLYX-13 (0.5, 5, and 10mg/kg, i.p.) in the forced swim test. In addition, we assessed whether the acute treatment with GLYX-13 reverses the depressive-like behaviors induced by chronic unpredictable mild stress. Furthermore, we determined whether the Vgf knockdown in hippocampus of mice blocks the effects of GLYX-13. Moreover, we also demonstrated the effects of intra-hippocampus infusion of LY294002 (10 nmol/side), a specific phosphatidylinositol 3-kinase inhibitor prior to the treatment of GLYX-13 in the forced swim test. Lastly, whether alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and mTOR activation involves in the antidepressant-like effects of GLYX-13 was examined.Results:Our results shown that GLYX-13 dose-dependently reversed the depressive-like behaviors in forced swim test. Additionally, GLYX-13 significantly reversed the downregulation of phosphorylation of AKT, mTOR, and eukaryotic elongation factor 2 as well as VGF induced by chronic unpredictable mild stress in hippocampus. Further, Vgf knockdown in hippocampus of mice significantly blocked the rapid-acting antidepressant-like effects and upregulation on phosphatidylinositol 3-kinase/AKT/mTOR/VGF signaling of GLYX-13. Moreover, intra-hippocampus infusion of LY294002 significantly abolished the antidepressant-like effects and upregulation on phosphatidylinositol 3-kinase/AKT/mTOR/VGF signaling of GLYX-13. Finally, antidepressant-like effects of GLYX-13 required AMPA receptor and mTOR activation, as evidenced by the ability of NBQX and rapamycin to block the effects of GLYX-13, respectively.Conclusions:Our results suggest that phosphatidylinositol 3-kinase/AKT/mTOR signaling-mediated VGF in hippocampus may be involved in the antidepressant-like effects of GLYX-13.

Recent advances in analytical methodologies have made it possible to bring metabolomic profiling into quantitative metabolomics that permits precise measurements of comprehensive small-molecule profiles. Modern liquid chromatography-tandem mass spectrometry (LC-MS/MS) with multiple reaction monitoring (MRM) mode serves as the foundation for accurate simultaneous multi-analyte quantitation across large sample sets to provide high-quality information on target molecular profiles in complex systems. Despite the intrinsic multiplexing potential of the LC-MRM-MS technique, the key bottleneck in current LC-MRM-based assays is generally the limited analyte coverage and throughput capacity. Nowadays, the MRM-based approach has emerged as an attractive strategy for quantitative proteomic analysis and high-throughput biomarker discovery. So far, the full potential of the contemporary LCMRM methodology unleashed for quantitative metabolite profiling and metabolomic measurements of non-peptidic small molecules is rarely discussed. In this review we attempt to provide an overview on the major recent developments in LC-MRM-based strategies for quantitative profiling of multi- and non-target small molecules in biological samples. This article highlights the utility and power of the LC-MRM-based targeted approaches as valuable bioanalytical tools for low-cost, multiplexed quantitation on a large scale, with special emphasis on the promise of combining various strategies for expanding coverage and throughput of the LC-MRM-based assays to cover the gap between a widely targeted profiling and large-scale unknown screening towards comparative or quantitative metabolomics. General issues raised in metabolite profiling, such as basic aspects of bioanalysis, methodological dilemmas and challenges in quantitative metabolomics are addressed, and different strategies to circumvent the existing bottleneck and potential pitfalls of the current LC-MRM-MS techniques are outlined. In addition, the rudiments of LC-MRM-MS and its recent applications in combination with such strategies for biomarker quantitation and verification is also described.