OBJECTIVES The objective of the study was to establish the repeatability of baseline diagnostic images of the dorsum of the hands acquired using a high resolution Laser Doppler imager in patients with Raynaud's phenomenon secondary to Systemic Sclerosis (SSc). METHODS The dorsal side of the hands of 22 patients (8 male 14 female) , age range 29-73, median 62, with SSc and secondary Raynaud's phenomenon were imaged over two consecutive days at approximately the same time using a Moor Instruments High Resolution Laser Doppler imaging unit. The images were analysed by taking regions of interest at discrete locations in the images to calculate dimensionless values of flux(PU). Repeatability of the diagnostic investigation was assessed by using methods described by Bland and Altman and by also plotting the results from visit 1 against visit 2 and calculating the line of best fit. RESULTS AND CONCLUSIONS Based on the criteria that 95% of all measurement differences should be within a factor of 1.96 of the standard deviations of the mean values, then high resolution Laser Doppler Imaging technique is probably repeatable when acquiring and analysing baseline images of patients with Raynaud's phenomenon secondary to SSc. However a larger study with more patients is required to prove this conclusively - as only data from 19 patients was analysed [3 patients were not included due to technical issues] - and was therefore susceptible to marked clinical variations in patients presenting on different days for the investigations. This article is protected by copyright. All rights reserved.Cysteine-rich with epidermal growth factor (EGF)-like domains 2 (CRELD2) is an endoplasmic reticulum (ER)-resident chaperone highly activated under ER-stress in conditions such as chondrodysplasias; however, its role in healthy skeletal development is unknown. We show for the first time that cartilage-specific deletion of Creld2 results in disrupted endochondral ossification and short limbed dwarfism, whilst deletion of Creld2 in bone results in osteopenia, with a low bone density and altered trabecular architecture. Our study provides the first evidence that CRELD2 promotes the differentiation and maturation of skeletal cells by modulating non-canonical WNT4 signalling regulated by p38 MAPK. Furthermore, we show that CRELD2 is a novel chaperone for the receptor Low density lipoprotein receptor-related protein 1 (LRP1), promoting its transport to the cell surface, and that LRP1 directly regulates WNT4 expression in chondrocytes through TGF-β1 signalling. Therefore, our data provide a novel link between an ER-resident chaperone and the essential WNT signalling pathways active during skeletal differentiation that could be applicable in other WNT-responsive tissues. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.BACKGROUND Remnant cholesterol in triglyceride-rich lipoproteins is associated observationally and genetic, causally with increased risk of atherosclerotic cardiovascular disease in healthy individuals. OBJECTIVES We tested the hypothesis that an unmet medical need exists in individuals with high nonfasting remnant cholesterol and prior atherosclerotic cardiovascular disease. METHODS From among 109,574 individuals in a prospective cohort study of the Danish general population we included 2973 individuals aged 20-80 with baseline diagnoses of myocardial infarction/ischemic stroke ascertained from national Danish health registries. RESULTS The recurrent major cardiovascular event(MACE) incidence rates per 1000 person-years were 39(95% confidence interval 30-50) for individuals with remnant cholesterol levels ≥1.5mmol/L(≥58mg/dL), 31(26-37) for 1-1.49mmol/L(39-57mg/dL), 27(24-31) for 0.5-0.99mmol/L(19-38mg/dL), and 23(19-27) for individuals with remnant cholesterol less then 0.5mmol/L( less then 19mg/dL). Compantion. Our data indicate an unmet medical need for secondary prevention in individuals with high nonfasting remnant cholesterol levels. This article is protected by copyright. All rights reserved.Previous studies have shown that four and a half LIM domain protein (FHL2) plays an essential role in the regulation of follicular development in mammals. Although the FHL2 genes of human and mouse have been well characterized, the expression and location of FHL2 in ovary and the biological functions of FHL2 on granulosa cells (GCs) of ovine are still not clear. https://www.selleckchem.com/products/nmda-n-methyl-d-aspartic-acid.html In this study, full-length complementary DNA (cDNA) of FHL2 from ovine follicular GCs was amplified by real-time PCR (RT-PCR). The expression and location of FHL2 in ovary and GCs of ovine were studied by immunohistochemistry and immunofluorescence, and the biological effects of FHL2 on the cell proliferation, cell apoptosis, cell cycles, and expression level of related genes of ovine GCs were also explored by overexpression or knockdown of FHL2. The results indicated that FHL2 was expressed in ovine follicular GCs and the sequence of the FHL2 cDNA was consistent with that predicted in GenBank, which did not cause an amino acid change. According to the results, FHL2 was expressed in ovine ovary and mainly located in the cytoplasm and nucleus of GCs. In addition, overexpression of FHL2 significantly reduced the cell viability, promoted the cell apoptosis and decreased the percentage of G0/G1 and S phase cells. RT-PCR showed that overexpression of FHL2 significantly increased the mRNA expression level of Bax and decreased the expression of Bcl-2 and the Bcl-2/Bax mRNA ratio compared to the control group. Besides, the knockdown of FHL2 gene in ovine GCs significantly improved the cell viability, suppressed the cell apoptosis, decreased the mRNA expression level of Caspase3 gene and increased the Bcl-2/Bax mRNA ratio, and increased the percentage of S and G2/M phase cells. Our results suggest that FHL2 may play an important role in the biological functions of GCs in ovine. This article is protected by copyright. All rights reserved.Converting CO 2 to high value chemicals has been regarded as an important solution for a sustainable low-carbon economy. Here, we theoretically designed an innovative strategy for the absorption and activation of CO 2 by the electride N3Li which is 1,3,5(2,6)-tripyridinacyclohexaphane (N3) intercalated by lithium. Density functional theory (DFT) computations show that the interaction of CO 2 to N3Li leads to the catalytic complex N3Li(η 2 -O 2 C) which can initiate the radical-controlled reduction of another CO 2 to form organic acids through radical reactions in gas phase. The CO 2 reduction consists of four steps, including (1) the formation of N3Li(η 2 -O 2 C) through the combination of N3Li with CO 2 ; (2) the hydrogen abstraction from RH (R=H, CH 3 and C 2 H 5 ) by N3Li(η 2 -O 2 C) to form the radical R • and N3Li(η 2 -O 2 C)H; (3) the combination of CO 2 with the radical R • to form RCOO • ; and (4) intermolecular hydrogen transfer from the intermediate N3Li(η 2 -O 2 C)H to RCOO • . In the whole reaction process, the CO 2 moiety in the complex N3Li(η 2 -O 2 C) maintains certain radical character at the carbon atom of CO 2 and plays a self-catalyzing role.