We study, by coarse-grained molecular dynamics simulations, equilibrium and flow properties of a liquid in cylindrical nanochannels, coated with polymer brushes. The parameters of the interaction potential model confer a chemical incompatibility between brush monomers and liquid particles. First, we study cylindrical channels whose radii are larger than the brush height and a continuous column of liquid forms at the center of the channel. These results are contrasted to the limiting case in which the radius of the cylinder is comparable to the brush height. In this second case, the grafted polymers interact across the channel and “close” it. We observe a train of droplets as the stable liquid morphology. The droplet size is comparable to the cylinder radius. By applying a constant body force onto the liquid, we induce a Poiseuille-like flow and investigate the morphology and flow rate as a function of driving force. Upon increasing the driving force, we encounter a nonequilibrium transition from a closed channel with slowly moving droplets to a flowing liquid thread at the center. The switching between these two states is reversible.Cu, Zn, and amyloid-β (Aβ) peptides play an important role in the etiology of Alzheimer’s disease (AD). Their interaction indeed modifies the self-assembly propensity of the peptide that is at the origin of the deposition of insoluble peptide aggregates in the amyloid plaque, a hallmark found in AD brains. Another even more important fallout of the Cu binding to Aβ peptide is the formation of reactive oxygen species (ROS) that contributes to the overall oxidative stress detected in the disease and is due to the redox ability of the Cu ions. Many therapeutic approaches are currently developed to aid fighting against AD, one of them targeting the redox-active Cu ions. Along this research line, we report in the present article the use of a phenanthroline-based peptide-like ligand (L), which is able to withdraw Cu from Aβ and redox-silence it in a very stable 4N Cu(II) binding site even in the presence of Zn(II). In addition and in contrast to what is usually observed, the presence of excess of L lessens the searched effect of ROS production prevention, but it is counterbalanced by the co-presence of Zn(II). To explain such unprecedented trends, we proposed a mechanism that involves the redox reaction between Cu(II)L and Cu(I)L2. We thus illustrated (i) how speciation and redox chemistry can weaken the effect of a ligand that would have appeared perfectly suitable if only tested in a 11 ratio and on CuAβ and (ii) how Zn overcomes the undesired lessening of ROS arrest due to excess of ligand. In brief, we have shown how working in biologically relevant conditions is important for the understanding of all of the reactions at play and this must be taken into consideration for the further rational design of ligands aiming to become drug candidates.Products of dark brown sugar (DBS) from different production processes and raw materials may bring different risks and benefits to human health. Therefore, this study was aimed to evaluate the quality of natural and commercial DBS products. Results showed that physicochemical properties, including pH value, turbidity, and browning degree have no significant difference between natural and commercial DBS products. Total flavonoid content of natural DBS was found to be significantly higher than that of commercial DBS (p less then 0.05). Notably, the levels of harmful Maillard reaction products in natural DBS were significantly lower than that in commercial DBS as evidenced by analyses of methylglyoxal and fluorescent advanced glycation end products (p less then 0.05). However, the amount of acrylamide in natural DBS was significantly higher than that in commercial DBS. In conclusion, this study provides useful information for risk-benefit assessment of DBS products, which is helpful for food safety management.Reactions that occur under physiological conditions find diverse uses in the chemical and biological sciences. However, the limitations that biological systems place on chemical reactions restrict the number of such bioorthogonal reactions. A profound understanding of the mechanistic principles and structure-reactivity trends of these transformations is therefore critical to access new and improved versions of bioorthogonal chemistry. The present article reviews the mechanisms and substituent effects of some of the principal metal-free bioorthogonal reactions based on inverse-electron demand Diels-Alder reactions, 1,3-dipolar cycloadditions, and the Staudinger reaction. Mechanisms of modified versions that link these reactions to a dissociative step are further discussed. The presented summary is anticipated to aid the advancement of bioorthogonal chemistry.Acetylcholinesterase (AChE) is an important drug target in neurological disorders like Alzheimer’s disease, Lewy body dementia, and Parkinson’s disease dementia as well as for other conditions like myasthenia gravis and anticholinergic poisoning. In this study, we have used a combination of high-throughput screening, machine learning, and docking to identify new inhibitors of this enzyme. Bayesian machine learning models were generated with literature data from ChEMBL for eel and human AChE inhibitors as well as butyrylcholinesterase inhibitors (BuChE) and compared with other machine learning methods. see more High-throughput screens for the eel AChE inhibitor model identified several molecules including tilorone, an antiviral drug that is well-established outside of the United States, as a newly identified nanomolar AChE inhibitor. We have described how tilorone inhibits both eel and human AChE with IC50’s of 14.4 nM and 64.4 nM, respectively, but does not inhibit the closely related BuChE IC50 > 50 μM. We have docked tilorone into the human AChE crystal structure and shown that this selectivity is likely due to the reliance on a specific interaction with a hydrophobic residue in the peripheral anionic site of AChE that is absent in BuChE. We also conducted a pharmacological safety profile (SafetyScreen44) and kinase selectivity screen (SelectScreen) that showed tilorone (1 μM) only inhibited AChE out of 44 toxicology target proteins evaluated and did not appreciably inhibit any of the 485 kinases tested. This study suggests there may be a potential role for repurposing tilorone or its derivatives in conditions that benefit from AChE inhibition.