Mechanisms of Osteoporosis Associated With Common Allelic Variants of the COL1A1 Gene

INTRODUCTION: Osteoporosis is a common disease with a strong genetic component and the collagen type I alpha I gene (COL1A1) is an important candidate for susceptibility. Three single nucleotide polymorphisms (SNP) have been identified in the 5' flank of the COLIA1 gene (-1997G/T; -1663IndelT and +1245G/T) which have been associated with osteoporosis in various populations. The mechanisms by which these SNP predispose to osteoporosis are unclear however.METHODS: I analyzed the effects of the individual SNPs and associated haplotypes on bone mineral density (BMD) and risk of osteoporotic fracture in women in association studies. I also studied associations between the SNPs, haplotypes and bone strength ex-vivo by biomechanical testing of bone cores obtained from femoral heads of patients undergoing surgery for hip fracture. The effects of the SNPs and haplotypes on gene expression were studied using promoter-reporter assays and gel shift assays were performed to investigate whether the SNPs were situated at transcription factor binding sites and whether the polymorphic variants affected DNA protein binding. In order to investigate the possible effects of the polymorphisms in vivo, gene targeting constructs were prepared containing two common haplotypes and these were transfected into ES cells.RESULTS: The individual polymorphisms were all associated with BMD, but the haplotypes defined by all three SNPs showed a stronger association with BMD, biomechanical strength of bone and hip fracture. Two haplotypes increased in frequency with age suggesting an effect on survival. However these haplotypes were particularly enriched in hip fracture patients. Biomechanical testing showed that all three SNPs were strongly associated with reduced bone strength, independently of BMD. Gel shift assays showed that the region surrounding the -1663insdelT polymorphism recognized the nuclear binding proteins Spl, Nmp4 and Osterix and the -1663delT allele had greater binding affinities for Nmp4 and Osterix than -1663insT allele. The region surrounding the -1997 G/T polymorphism also recognized DNA binding proteins but the polymorphism did not affect DNA protein binding significantly. Reporter assays showed significant differences between the ability of different haplotypes to drive gene expression and constructs containing haplotype2 (G-delT-T) had the highest transcriptional activity (pO.OOl). Transgenic constructs containing different 5' COL1A1 haplotypes were completed and transformed into mouse embryonic stem cells by electroporation in an attempt to generate a disease model of osteoporosis associated with common variants in the COLIA1 geneCONCLUSION: The studies suggest that haplotypes, rather than individual polymorphisms in the 5' flank of COL1A1 predispose to osteoporosis, by affecting DNA protein interactions and gene expression

Effects of Remote Ischemic Preconditioning in Patients Undergoing Off-Pump Coronary Artery Bypass Graft Surgery

PurposeThis study aimed to evaluate effects of remote ischemic preconditioning (RIPC) on myocardial injury in patients undergoing off-pump coronary artery bypass graft surgery (OPCABG).MethodsSixty-five patients scheduled for the OPCABG were randomly assigned to control (n = 32) or RIPC group (n = 33). All patients received general anesthesia. Before the surgical incision, RIPC was induced on an upper limb with repeated 5-min ischemia and 5-min reperfusion for four times. Blood samples were collected from right internal jugular vein. Plasma levels of IL-6, IL-8, IL-10, TNF-α, cTnT, HFABP, IMA, and MDA were detected at pre-operatively and 0, 6, 18, 24, 48, 72, and 120 h after the surgery. Left internal mammary artery (LIMA) and great saphenous vein (GSV) was cut into 2–3 mm for Western blot analysis of Hif-1α.ResultsIn the present study, RIPC treatment significantly reduced plasma levels of cardiac troponin T (p < 0.05), heart-type fatty acid binding protein (p < 0.05), ischemia modified albumin (p < 0.05), malondialdehyde (p < 0.05), as well as plasma levels of pro-inflammatory cytokines including IL-6, IL-8, and TNF-α (P < 0.05, respectively). RIPC treatment significantly increased hypoxia-inducible factor-1α (p < 0.05) expression as well. Mechanical ventilation time for postoperative patients was shortened in RIPC group than those in control group (17.4 ± 3.8 h vs. 19.7 ± 2.9 h, respectively, p < 0.05).ConclusionRIPC by upper limb ischemia shortens mechanical ventilation time in patients undergoing OPCABG. RIPC treatment reduces postoperative myocardial enzyme expression and pro-inflammatory cytokine production. RIPC is a protective therapeutic approach in the coronary artery bypass graft surgery

Characterization of multi-wavelength polarized light transmission in the real sea spray environment

Sea spray particles are a type of non-uniform, non-spherical, non-isotropic, and complex medium, and the study of the transmission characteristics of polarized light in a real sea spray environment can provide reference values in many fields, such as polarization imaging, marine target detection, and LiDAR, which can make up for the vacancy of polarized light transmission in a complex sea spray environment. In this paper, a real sea fog test is carried out in the Qingdao Sea area of China in the horizontal/oblique direction, and a platform for generating and detecting polarized light with multiple tilt angles is constructed by using the active test method, which realizes the test scheme for the characteristics of energy change and polarization state change in the linearly polarized light and circularly polarized light at different visibility levels in sea fog environments. The results show that it is more difficult to deflect the circularly polarized light than linearly polarized light at the same sea spray visibility level. With the increase in the tilt angle, a decrease in the polarization is observed. The polarization of the near-infrared light is always larger than that of the visible light, which indicates that the circularly polarized light has better polarization preservation than the linearly polarized light and the polarization preservation of the near-infrared light is better than that of the visible light

Oxidative dehydrogenation of ethane to ethylene over LiCl/SO42--ZrO2 catalyst

Sulfated zirconia (SO42--ZrO2) samples were prepared by a modified two-step method (refluxing ZrO(OH)(2) precursor in basic solution followed by drying and (NH4)(2)SO4 impregnation) and then impregnated with a LiCl solution to give the SO42--ZrO2-supported LICI catalysts with Li mass content of 0.5% similar to 15%. The catalysts were characterized by X-ray diffraction, scanning electron microscopy, N-2 adsorption, temperature-programmed desorption-mass spectrometry, and X-ray photoelectron spectroscopy. The results show that with increasing LiCl loading, the specific surface area and acidity of the catalysts as well as the volume fraction of tetragonal zirconia in the catalysts decrease, while the catalytic performance of the catalysts for oxidative dehydrogenation of ethane (ODHE) to ethylene increases. Over the LiCl/SO42--ZrO2 catalyst with a Li content of 15% ethylene yield of 77.8% with an ethane conversion of 90.6% is achieved at 650 degrees C, and the yield higher than 71% is maintained over a period of 24 h. The textural structure of ZrO? has little effect on the catalytic behavior of the LiCl/SO42--ZrO2 catalysts. The specific surface area of SO42--ZrO2 samples prepared by the fled two-step method is much bigger than that of the SO42--ZrO2 samples made by the method reported in literature, and therefore more LiCl call be loaded on unit mass of support. This is favorable to improve the catalyst stability and slow down catalyst deactivation during the ODHE reaction due to the loss of LiCl

Evaluation of carbonyl sulfide biosphere exchange in the Simple Biosphere Model (SiB4)

The uptake of carbonyl sulfide (COS) by terrestrial plants is linked to photosynthetic uptake of CO2 as these gases partly share the same uptake pathway. Applying COS as a photosynthesis tracer in models requires an accurate representation of biosphere COS fluxes, but these models have not been extensively evaluated against field observations of COS fluxes. In this paper, the COS flux as simulated by the Simple Biosphere Model, version 4 (SiB4), is updated with the latest mechanistic insights and evaluated with site obser- vations from different biomes: one evergreen needleleaf forest, two deciduous broadleaf forests, three grasslands, and two crop fields spread over Europe and North America. We improved SiB4 in several ways to improve its representation of COS. To account for the effect of atmospheric COS mole fractions on COS biosphere uptake, we replaced the fixed atmospheric COS mole fraction boundary condition originally used in SiB4 with spatially and temporally varying COS mole fraction fields. Seasonal amplitudes of COS mole fractions are similar to 50-200 ppt at the investigated sites with a minimum mole fraction in the late growing season. Incorporating seasonal variability into the model reduces COS uptake rates in the late growing season, allowing better agreement with observations. We also replaced the empirical soil COS uptake model in SiB4 with a mechanistic model that represents both uptake and production of COS in soils, which improves the match with observations over agricultural fields and fertilized grassland soils. The improved version of SiB4 was capable of simulating the diurnal and seasonal variation in COS fluxes in the boreal, temperate, and Mediterranean region. Nonetheless, the daytime vegetation COS flux is underestimated on average by 8 +/- 27 %, albeit with large variability across sites. On a global scale, our model modifications decreased the modeled COS terrestrial biosphere sink from 922 Gg S yr(-1) in the original SiB4 to 753 Gg S yr(-1) in the updated version. The largest decrease in fluxes was driven by lower atmospheric COS mole fractions over regions with high productivity, which highlights the importance of accounting for variations in atmospheric COS mole fractions. The change to a different soil model, on the other hand, had a relatively small effect on the global biosphere COS sink. The secondary role of the modeled soil component in the global COS budget supports the use of COS as a global photosynthesis tracer. A more accurate representation of COS uptake in SiB4 should allow for improved application of atmospheric COS as a tracer of local- to global-scale terrestrial photosynthesis.Peer reviewe

The Epidemiological Characteristics of Stroke in Hunan Province, China

Previous studies have shown that Hunan Province has a high incidence of stroke and a high proportion of intracerebral hemorrhage (ICH). Considering the changes over the past three decades, little is known about the current epidemiological characteristics of stroke in Hunan Province. In 2013, a cross-sectional study was conducted at seven national disease surveillance points (DSPs) in Hunan Province. A multistage cluster sampling method was used to select a representative sample. A total of 21,156 participants aged 20 years and older were examined. Among the 21,156 participants, the number of prevalent strokes, incident strokes and deaths was 307, 87, and 36, respectively. The 2010 China census-standardized prevalence, incidence and mortality were 1191.0 per 100,000 people [95% confidence interval (CI) 1044.8–1337.2], 333.6 per 100,000 person-years (95% CI 255.7–411.5) and 129.7 per 100,000 person-years (95% CI 81.1–178.3), respectively. Ischemic stroke (IS), ICH, subarachnoid hemorrhage (SAH), and stroke of undetermined type (UND) constituted 50.6, 41.4, 5.7, and 2.3% of all incident stroke cases, respectively. Tianxin, Liuyang, Wuling, and Hongjiang have high proportions of ICH (61.5, 58.3, 60, and 50%, respectively). Hypertension is the most common risk factor for prevalent stroke (71.34%), followed by smoking (30.62%) and alcohol use (25.73%). In conclusion, Hunan Province has an extremely heavy stroke burden. The high proportion of ICH is not limited to the Changsha community; it represents an important issue for all of Hunan Province

The large area detector onboard the eXTP mission

The Large Area Detector (LAD) is the high-throughput, spectral-timing instrument onboard the eXTP mission, a flagship mission of the Chinese Academy of Sciences and the China National Space Administration, with a large European participation coordinated by Italy and Spain. The eXTP mission is currently performing its phase B study, with a target launch at the end-2027. The eXTP scientific payload includes four instruments (SFA, PFA, LAD and WFM) offering unprecedented simultaneous wide-band X-ray timing and polarimetry sensitivity. The LAD instrument is based on the design originally proposed for the LOFT mission. It envisages a deployed 3.2 m2 effective area in the 2-30 keV energy range, achieved through the technology of the large-area Silicon Drift Detectors - offering a spectral resolution of up to 200 eV FWHM at 6 keV - and of capillary plate collimators - limiting the field of view to about 1 degree. In this paper we will provide an overview of the LAD instrument design, its current status of development and anticipated performance