Pontoppidansandoval5442

Positive correlation between systemic levels of PTH and whole-body metabolic preference for lipids as well as BAT volume was found across the two populations. Moreover, NST-cooling protocol-induced changes in metabolic preference for lipids correlated positively with changes in PTH. Finally, variability in circulating PTH correlated positively with UCP1/UCP1, PPARGC1A and DIO2 in BAT from neck surgery patients. Our data suggest that regulation of PTH and thyroid hormones during cold exposure in humans varies by cold acclimatization level and/or cold stimulus intensity. Possible role of PTH in NST is indicated by its positive relationships with whole-body metabolic preference for lipids, BAT volume and UCP1 content. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.BACKGROUND Oxidative stress is known to be associated with the development of diabetes. Cinnamaldehyde (CA) is a spice compound in cinnamon that enhances the antioxidant defense against reactive oxygen species (ROS) by activating nuclear factor erythroid-related factor 2 (Nrf2), which has been shown to have a cardioprotection effect. However, the relationship between CA and Nrf2 in diabetic vascular complications remains unclear. METHODS Leptin receptor-deficient (db/db) mice were fed normal chow or diet containing 0.02% CA for 12 weeks. The vascular tone, blood pressure, superoxide level, nitric oxide (NO) production, renal morphology, and function were measured in each group. RESULTS CA remarkably inhibited ROS generation, preserved NO production, increased phosphorylated endothelial nitric oxide synthase (p-eNOS), attenuated the upregulation of nitrotyrosine, P22 and P47 in aortas of db/db mice, and apparently ameliorated the elevation of type IV collagen, TGF-β1, P22, and P47 in kidney of db/db mice. Feeding with CA improved endothelium-dependent relaxation of aortas and mesenteric arteries, and alleviated the remodeling of mesenteric arteries in db/db mice. Additionally, dietary CA ameliorated glomerular fibrosis and renal dysfunction in diabetic mice. Nrf2 and its targeted genes heme oxygenase-1 (HO-1) and quinone oxidoreductase-1 (NQO-1) were slightly increased in db/db mice and further upregulated by CA. However, these protective effects of CA were reversed in Nrf2 downregulation mice. CONCLUSIONS A prolonged diet of CA protects against diabetic vascular dysfunction by inhibiting oxidative stress through activating of Nrf2 signaling pathway in db/db mice. selleck © American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email journals.permissions@oup.com.BACKGROUND The development of trio binning as an approach for assembling diploid genomes has enabled the creation of fully haplotype-resolved reference genomes. Unlike other methods of assembly for diploid genomes, this approach is enhanced, rather than hindered, by the heterozygosity of the individual sequenced. To maximize heterozygosity and simultaneously assemble reference genomes for 2 species, we applied trio binning to an interspecies F1 hybrid of yak (Bos grunniens) and cattle (Bos taurus), 2 species that diverged nearly 5 million years ago. The genomes of both of these species are composed of acrocentric autosomes. RESULTS We produced the most continuous haplotype-resolved assemblies for a diploid animal yet reported. Both the maternal (yak) and paternal (cattle) assemblies have the largest 2 chromosomes in single haplotigs, and more than one-third of the autosomes similarly lack gaps. The maximum length haplotig produced was 153 Mb without any scaffolding or gap-filling steps and represents the longest haplotig reported for any species. The assemblies are also more complete and accurate than those reported for most other vertebrates, with 97% of mammalian universal single-copy orthologs present. CONCLUSIONS The high heterozygosity inherent to interspecies crosses maximizes the effectiveness of the trio binning method. The interspecies trio binning approach we describe is likely to provide the highest-quality assemblies for any pair of species that can interbreed to produce hybrid offspring that develop to sufficient cell numbers for DNA extraction. © The Author(s) 2020. Published by Oxford University Press.In this issue of the Journal, Upson et al. assess urinary cadmium as a potential environmental influence of ovarian reserve, as measured using serum follicle stimulating hormone (FSH), in data from 1,681 women and compare three methods for modeling urinary proxy exposures - standardization, covariate adjustment (CA) and covariate adjusted standardization (CAS). Observing positive associations in all three approaches, but higher magnitude of estimates using CA compared to standardization and CAS - proposed to be the result of collider-stratification bias - the authors conclude that cadmium may affect ovarian aging, and recommend careful consideration of modeling approach. Comparisons of methodology in practice using real data is not straightforward, and additional complication arises from using a proxy outcome - serum FSH to represent diminished ovarian reserve. The aims of this commentary are to describe the theoretical basis for approaches for modeling urinary proxy exposures; consider potential explanations for why the approaches may yield different results in practice and describe why measurement error may play a larger role than collider-stratification bias; discuss challenges related to studies of ovarian reserve; and, emphasize the importance of addressing both theoretical concerns and real-world challenges in methodologic research and epidemiologic studies of ovarian reserve. © The Author(s) 2020. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.The injectable composite hydrogel based on collagen and hyaluronic acid provided a bionic three-dimensional microenvironment and mimetic natural extracellular matrix (ECM) for the growth of cells in vivo and has been widely researched and developed for cartilage tissue engineering. Here, a novel injectable bionic hydrogel with hybrid covalent/noncovalent network derived from covalent conjugation of HA-SH and noncovalent supramolecular self-assembly of BPAA-AFF-OH short peptide was fabricated to overcome the collagen immunogenicity of animal origin and effectively maintain its biological function. Moreover, through optimizing the network structure and polymer composition, the bionic HS5FFAB5 hydrogel presented a reliable mechanical strength which depended on the highly integrated fiber structure between HA-SH and FFAB-AFF-OH molecules. The results in vitro and in vivo proved that HA-SH could provide a fundamental frame structure, while the supramolecular hydrogels could reinforce this structure via hydrogen bonds and hydrophilic/hydrophobic interactions, and endow bionic hydrogels with more abundant cell adhesion sites. The bionic composite hydrogel could improve the cell adhesion and proliferation when compared to HA-SH hydrogel, and enhanced chondrogenic related gene expression and matrix secretion by three-dimensional co-cultured in vitro and subcutaneous implantation in vivo, which further promoted phenotypic maintenance of hyaline cartilage. This bionic hydrogel with a hybrid covalent/noncovalent network is supposed to have potential application prospects in cartilage regeneration.A novel and practical protocol for the synthesis of fully substituted pyrazoles from pyridinium 1,4-zwitterionic thiolates and hydrazonoyl chlorides in excellent yields under mild conditions is described. The transformation proceeds via an unusual [[3 + 3] - 1] pathway, which involves a formal [3 + 3] cascade cyclization followed by a spontaneous ring-contraction/sulfur extrusion reaction from 4H-1,3,4-thiadiazine intermediates.The clinical outcomes of polymethylmethacrylate (PMMA) bone cement used to fill gaps or marrow cavities of bones and bone defects are limited due to poor handling properties, mismatched mechanical properties with natural bone and lack of osteogenesis for bone healing. In this study, a series of PMMA bone cements containing active nano-MgO particles (nano-MgO/PMMA) were prepared. The handling and mechanical properties were systemically evaluated according to an International Standardization Organization standard (ISO 58332002). The biocompatibility and osteogenic activity of nano-MgO/PMMA were also analysed in vitro. The osteogenic effects of nano-MgO/PMMA were assessed in a rat calvarial critical bone defect model. The addition of less than 15 wt% nano-MgO to PMMA improved the handling properties of PMMA. Compared with PMMA, the compression modulus and strength of 20MP (20 wt% nano-MgO to PMMA) decreased to 0.725 ± 0.023 GPa and 25.38 ± 2.82 MPa, respectively. In vitro studies with MC3T3-E1 showed that nano-MgO/PMMA had better biocompatibility than the PMMA group after 7 days of culture. The nano-MgO/PMMA groups showed more calcium nodules and higher osteogenic gene expression levels than PMMA after 12 days of osteogenic induction of the rat BMSCs. The in vivo studies analysed by micro-CT and histomorphology results proved that nano-MgO/PMMA could significantly enhance new bone formation. The mean new bone mineral density in the nano-MgO/PMMA group was 50% greater than that in the PMMA group. In addition, biomechanical tests showed that nano-MgO/PMMA was superior to PMMA in bone-bonding strength after 12 weeks implantation. Therefore, the nano-MgO/PMMA bone cement has good potential in joint fixation and bone defect filling applications.Patchy colloids and associating fluids have attracted continued interest due to the interesting phase behavior and self-assembly in solution. The ability to fabricate patchy colloids with multiple attractive surface patches of different number, size, shape, and relative location makes patchy colloids a good candidate as building blocks to form complex advanced materials. However, a theory that clearly relates the self-assembled structures that form based on the anisotropic interactions has been missing. Although Wertheim's theory in the form of the SAFT model is widely used to predict self-assembly and phase behavior in solution, SAFT does not include multibody correlations necessary to model any shape of association site or sites that can form multiple bonds. We have recently developed a new theory for associating colloids that naturally incorporates multibody correlations based on a cluster distribution approach due to Bansal, Asthagiri, Marshall, and Chapman (BAMC). In this paper, we extended the cluster distribution theory to predict the thermodynamic properties and phase behavior of binary systems consisting of anisotropic particles with any geometry of bonding site. In particular, we consider self-assembly of Janus particles, Saturn particles, and ternary particles mixed with solvent colloids that have two directional patchy sites. Good agreement between theoretical predictions and molecular simulation is shown for self-assembly, thermodynamic properties in this system. Re-entrant phase behavior has been investigated and low density gels is predicted.