Aim High-throughput phenotypic screens have emerged as a promising avenue for small-molecule drug discovery. The challenge faced in high-throughput phenotypic screens is target deconvolution once a small molecule hit is identified. Chemogenomics libraries have emerged as an important tool for meeting this challenge. Here, we investigate their target-specificity by deriving a 'polypharmacology index' for broad chemogenomics screening libraries. Methods All known targets of all the compounds in each library were plotted as a histogram and fitted to a Boltzmann distribution, whose linearized slope is indicative of the overall polypharmacology of the library. Results & conclusion Comparison of libraries clearly distinguished the most target-specific library, which might be assumed to be more useful for target deconvolution in a phenotypic screen. © 2020 Timothy Cardozo.High circulating levels of trans-palmitoleic acid (TPA) are associated with a lower risk of type 2 diabetes in humans. Thus, the origin of circulating TPA matters. Direct intakes of TPA are ensured by dairy products, and perhaps by partially hydrogenated oils (PHOs). Indirect intakes of TPA rely on dietary trans-vaccenic acid (TVA), which occurs in ruminant-derived foods and PHOs. As it is usually assumed that PHOs are not used any longer, we analyzed here a wide range of foods currently available at retail in France. We report that TPA and TVA (1) do occur in ruminant milk and meat, dairy products and in foreign PHOs, (2) do occur in dairy fat-containing foods and (3) do not occur in dairy fat-free foods. Together, our findings demonstrate that ruminant fats are the only contributors to circulating levels of TPA in humans. © 2020 The Authors.Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disease worldwide, and a major cause of liver cirrhosis and hepatocellular carcinoma. NAFLD is intimately linked with other metabolic disorders characterized by insulin resistance. Metabolic diseases are driven by chronic inflammatory processes, in which macrophages perform essential roles. The polarization status of macrophages is itself influenced by metabolic stimuli such as fatty acids, which in turn affect the progression of metabolic dysfunction at multiple disease stages and in various tissues. For instance, adipose tissue macrophages respond to obesity, adipocyte stress and dietary factors by a specific metabolic and inflammatory programme that stimulates disease progression locally and in the liver. Kupffer cells and monocyte-derived macrophages represent ontologically distinct hepatic macrophage populations that perform a range of metabolic functions. These macrophages integrate signals from the gut-liver axis (related to dysbiosis, reduced intestinal barrier integrity, endotoxemia), from overnutrition, from systemic low-grade inflammation and from the local environment of a steatotic liver. This makes them central players in the progression of NAFLD to steatohepatitis (non-alcoholic steatohepatitis or NASH) and fibrosis. Moreover, the particular involvement of Kupffer cells in lipid metabolism, as well as the inflammatory activation of hepatic macrophages, may pathogenically link NAFLD/NASH and cardiovascular disease. In this review, we highlight the polarization, classification and function of macrophage subsets and their interaction with metabolic cues in the pathophysiology of obesity and NAFLD.  https://www.selleckchem.com/products/pargyline-hydrochloride.html  Evidence from animal and clinical studies suggests that macrophage targeting may improve the course of NAFLD and related metabolic disorders. © 2019 The Author(s).The assembly of proteins into amyloid fibrils has become linked not only with the progression of myriad human diseases, but also important biological functions. Understanding and controlling the formation, structure, and stability of amyloid fibrils is therefore a major scientific goal. Here we utilize electron microscopy-based approaches combined with quantitative statistical analysis to show how recently developed kind of amyloid modulators-multivalent polymer-peptide conjugates (mPPCs)-can be applied to control the structure and stability of amyloid fibrils. In doing so, we demonstrate that mPPCs are able to convert 40-residue amyloid beta fibrils into ordered nanostructures through a combination of fragmentation and bundling. Fragmentation is shown to be consistent with a model where the rate constant of fibril breakage is independent of the fibril length, suggesting a local and specific interaction between fibrils and mPPCs. Subsequent bundling, which was previously not observed, leads to the formation of sheet-like nanostructures which are surprisingly much more uniform than the starting fibrils. These nanostructures have dimensions independent of the molecular weight of the mPPC and retain the molecular-level ordering of the starting amyloid fibrils. Collectively, we reveal quantitative and nanoscopic understanding of how mPPCs can be applied to control amyloid structure and stability, and demonstrate approaches to elucidate nanoscale amyloid phase behavior in the presence of functional macromolecules and other modulators.Osteoporosis is associated with systemic bone loss, leading to a significant deterioration of bone microarchitecture and an increased fracture risk. Although recent studies have shown that the distribution of bone mineral becomes more heterogeneous because of estrogen deficiency in animal models of osteoporosis, it is not known whether osteoporosis alters mineral distribution in human bone. Type 2 diabetes mellitus (T2DM) can also increase bone fracture risk and is associated with impaired bone cell function, compromised collagen structure, and reduced mechanical properties. However, it is not known whether alterations in mineral distribution arise in diabetic (DB) patients' bone. In this study, we quantify mineral content distribution and tissue microarchitecture (by μCT) and mechanical properties (by compression testing) of cancellous bone from femoral heads of osteoporotic (OP; n = 10), DB (n = 7), and osteoarthritic (OA; n = 7) patients. We report that though OP cancellous bone has significantly deteriorated compressive mechanical properties and significantly compromised microarchitecture compared with OA controls, there is also a significant increase in the mean mineral content.