Polyphenols are a group of micronutrients widely existing in plant foods including fruits, vegetables, and teas that can improve nonalcoholic fatty liver disease (NAFLD). In this review, the existing knowledge of dietary polyphenols for the development of NAFLD regulated by intestinal microecology is discussed. Polyphenols can influence the vagal afferent pathway in the central and enteric nervous system to control NAFLD via gut-brain-liver cross-talk. Crenolanib manufacturer The possible mechanisms involve in the alteration of microbial community structure, effects of gut metabolites (short-chain fatty acids (SCFAs), bile acids (BAs), endogenous ethanol (EnEth)), and stimulation of gut-derived hormones (ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and leptin) based on the targets excavated from the gut-brain-liver axis. Consequently, the communication among the intestine, brain, and liver paves the way for new approaches to understand the underlying roles and mechanisms of dietary polyphenols in NAFLD pathology.The availability of high-resolution structures of ion channels opens the doors to reliable computations of electrophysiological properties, such as the dependence of ionic currents and selectivities on applied voltage. We develop two theoretical approaches for calculating these properties from molecular dynamics simulations at a single voltage, or even in the absence of voltage, combined with the electrodiffusion model in which ion motion in the channel is represented as one-dimensional diffusion in the potential of mean force exerted by other components of the system and the applied electric field. No knowledge of diffusivity or ion densities at other voltages is needed. Instead, in one approach, one-sided ion fluxes and density profiles are used to determine the free energy profile. In the other approach, committor probabilities for ions transported at the selected voltage are used for this purpose. Both approaches have been validated in an example of a simple ion channel formed by trichotoxin. The potentials of mean force calculated by way of the proposed approaches and obtained from traditional methods are in excellent agreement. Furthermore, the current-voltage dependence agrees very well with results obtained by way of computationally more demanding methods. We also have readily calculated the reversal potential, a computationally challenging electrophysiological property. The key assumptions of the electrodiffusion model, such as the independence of crossing events or the insensitivity of the potential of mean force to applied voltage, have been found to be satisfied. We also show that the voltage changes linearly in the hydrophobic core of the membrane and is constant elsewhere.The aggregation and formation of heterometallic nanoclusters usually involves a variety of complex self-assembly processes; thus, the exploration of their assembly mechanisms through process tracking is more challenging than that for homometallic nanoclusters. We explored here the effect of solvent on the formation of heterometallic clusters, which gave two heterometallic nanoclusters, [Dy2Co8(μ3-OCH3)2(L)4(HL)2(OAc)2(NO3)2(CH3CN)2]·CH3CN·H2O (1) and [Dy4Co6(L)4(HL)2(OAc)6(OCH2CH2OH)2(HOCH2CH2OH)(H2O)]·9CH3CN (2), with the H3L ligand formed from the in situ condensation reaction of 3-amino-1,2-propanediol with 2-hydroxy-1-naphthaldehyde in the presence of Co(OAc)2·4H2O and Dy(NO)3·6H2O. It is worth noting that the skeleton of cluster 1 has a high stability under high-resolution electrospray ionization mass spectrometry (HRESI-MS) conditions with a gradually increasing energy of the ion source. Cluster 2 underwent a multistep fragmentation even under a zero ion-source voltage for the measurement of HRESI-MS. Further analysis showed that cluster 2 underwent a possible fragmentation mechanism of Dy4Co6L6 → Dy2Co6L5/DyL → DyCo2L3/DyCo2L → DyL/Co2L2. Most notably, the species emerging in the formation process of cluster 1 were tracked using time-dependent HRESI-MS, from which we proposed its possible formation mechanism of H2L → Co2L2 → Co2DyL2/Co3L2 → Co3DyL2 → Co4DyL2 → Co5Dy2L4 → Co8Dy2L6. As far as we know, it is the first time to track the formation process of Dy-Co heterometallic clusters through HRESI-MS with the proposed assembly mechanism. The magnetic properties of the two titled DyIIIxCoII10-x (x = 2, 4) clusters were studied. Both of them exhibit slow magnetic relaxation, and 1 is a single-molecule magnet at zero direct-current field.The development of high-brilliance third- and fourth-generation light sources such as synchrotrons and X-ray free-electron lasers (XFELs), the emergence of laboratory-based X-ray spectrometers, and instrumental and methodological advances in X-ray absorption (XAS) and (non)resonant emission (XES and RXES/RIXS) spectroscopies have had far-reaching effects across the natural sciences. However, new kinds of experiments, and their ever-higher resolution and data acquisition rates, have brought acutely into focus the challenge of accurately, quickly, and cost-effectively analyzing the data; a far-from-trivial task that demands detailed theoretical calculations that are capable of capturing satisfactorily the underlying physics. The past decade has seen significant advances in the theory of core-hole spectroscopies for this purpose, driven by all of the developments above and-crucially-a surge in demand. In this Perspective, we discuss the challenges of calculating core-excited states and spectra, and state-of-the-art developments in electronic structure theory, dynamics, and data-driven/machine-led approaches toward their better description.RV521 is an orally bioavailable inhibitor of respiratory syncytial virus (RSV) fusion that was identified after a lead optimization process based upon hits that originated from a physical property directed hit profiling exercise at Reviral. This exercise encompassed collaborations with a number of contract organizations with collaborative medicinal chemistry and virology during the optimization phase in addition to those utilized as the compound proceeded through preclinical and clinical evaluation. RV521 exhibited a mean IC50 of 1.2 nM against a panel of RSV A and B laboratory strains and clinical isolates with antiviral efficacy in the Balb/C mouse model of RSV infection. Oral bioavailability in preclinical species ranged from 42 to >100% with evidence of highly efficient penetration into lung tissue. In healthy adult human volunteers experimentally infected with RSV, a potent antiviral effect was observed with a significant reduction in viral load and symptoms compared to placebo.