-
Bowen posted an update 7 months, 1 week ago
In eukaryotes, the C204 polyunsaturated fatty acid arachidonic acid (AA) plays important roles as a phospholipid component, signaling molecule and precursor of the endocannabinoid-prostanoid axis. Accordingly, the absence of AA causes detrimental effects. Here, compensatory mechanisms involved in AA deficiency in Caenorhabditis elegans were investigated. We show that the ω-3 C204 polyunsaturated fatty acid juniperonic acid (JuA) is generated in the C. elegansfat-3(wa22) mutant, which lacks Δ6 desaturase activity and cannot generate AA and ω-3 AA. JuA partially rescued the loss of function of AA in growth and development. Additionally, we observed that supplementation of AA and ω-3 AA modulates lifespan of fat-3(wa22) mutants. We described a feasible biosynthetic pathway that leads to the generation of JuA from α-linoleic acid (ALA) via elongases ELO-1/2 and Δ5 desaturase which is rate-limiting. Employing liquid chromatography mass spectrometry (LC-MS/MS), we identified endocannabinoid-like ethanolamine and glycerol derivatives of JuA and ω-3 AA. Like classical endocannabinoids, these lipids exhibited binding interactions with NPR-32, a G protein coupled receptor (GPCR) shown to act as endocannabinoid receptor in C. elegans. Our study suggests that the eicosatetraenoic acids AA, ω-3 AA and JuA share similar biological functions. This biosynthetic plasticity of eicosatetraenoic acids observed in C. elegans uncovers a possible biological role of JuA and associated ω-3 endocannabinoids in Δ6 desaturase deficiencies, highlighting the importance of ALA.National surveys of U.S. adults have observed significant increases in health-related internet use (HRIU), but there are documented disparities. The study aims to identify social and demographic patterns of health-related internet use among U.S. adults. Using data from the Health Information National Trends Survey (HINTS) 4 cycle 3 and HINTS 5 cycle 1, we examined HRIU across healthcare, health information seeking, and participation on social media. Primary predictors were gender, race/ethnicity, age, education, income, and nativity with adjustments for smoking and survey year. We used multivariable logistic regression with survey weights to identify independent predictors of HRIU. Of the 4817 respondents, 43% had used the internet to find a doctor; 80% had looked online for health information. Only 20% had used social media for a health issue; 7% participated in an online health support group. In multivariable models, older and low SES participants were significantly less likely to use the internet to look for a provider, use the internet to look for health information for themselves or someone else, and less likely to use social media for health issues. Use of the internet for health-related purposes is vast but varies significantly by demographics and intended use.This work was designed to investigate antithrombotic drug utilization and its link with the socioeconomic characteristics of specific population groups in Hungary by a comparative analysis of data for prescriptions by general practitioners and the redeemed prescriptions for antithrombotic drugs. Risk analysis capabilities were applied to estimate the relationships between socioeconomic status, which was characterized by quintiles of a multidimensional composite indicator (deprivation index), and mortality due to thromboembolic diseases as well as antithrombotic medications for the year 2016 at the district level in Hungary. According to our findings, although deprivation is a significant determinant of mortality due to thromboembolic diseases, clusters can be identified that represent exemptions to this rule an eastern part of Hungary, consisting of two highly deprived counties, had significantly lower mortality than the country average; by contrast, the least-deprived northwestern part of the country, consisting of five counties, had significantly higher mortality than the country average. The fact that low socioeconomic status in general and poor adherence to antithrombotic drugs irrespective of socioeconomic status were associated with increased mortality indicates the importance of more efficient control of preventive medication and access to healthcare in all districts of the country to reduce mortality due to thromboembolic diseases.B-cell maturation antigen (BCMA), a member of the tumor necrosis factor receptor superfamily, is universally expressed by normal and neoplastic plasma cells and plays a critical role in the proliferation, survival and tumor progression in multiple myeloma (MM). B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) have been recognized as proliferation ligands for BCMA in the bone marrow microenvironment. Soluble BCMA levels in the serum correlates with disease phase and tumor burden and is a predictor of progression-free survival (PFS) and overall survival (OS). Recently, the introduction of new monoclonal antibodies against CD38 (Daratumumab and Isatuximab) and SLAM7 (Elotuzumab) has changed the therapeutic approach to MM, improving the response rate and the time to progression, both in newly diagnosed and refractory/relapsed patients. Among the surface antigens on MM cells, BCMA is a suitable target for the design of new antibody-based strategies. learn more Experimental approaches targeting BCMA are currently being investigated and include antibody-drug conjugates (ADCs), bispecific antibodies (bsAbs) and genetically engineered T-cells with chimeric antigen receptors (CAR). In this review we summarize the more recent findings about BCMA biologic rationale as a therapeutic target and report the updated results of preclinical and clinical studies focused on ADCs and bsAbs targeting BCMA.Effects of processing parameters on preheated (heat-assisted) clinching process to join aluminum alloy 5052-H32 (AA5052) and thermoplastic carbon-fiber-reinforced-plastic (TP-CFRP) sheets for cross-tension (CT) specimens were first studied. Preheating was critical since brittle TP-CFRP could be softened to avoid fracturing or cracking during clinching process. Four processing parameters, including punching force, die depth, heating mode, and heating temperature, were considered. Quasi-static tests and microscope observations were taken to evaluate AA5052/TP-CFRP clinch joints in CT specimens and determine appropriate processing parameters for fatigue tests. Finally, fatigue data and failure mode of clinch joints in CT specimens were obtained and discussed.