The gastrointestinal mucus layer represents the last barrier between ingested food or orally administered pharmaceuticals and the mucosal epithelium. This complex gel structure plays an important role in the process of small intestinal absorption. It provides protection against hazardous particles such as bacteria but allows the passage of nutrients and drug molecules towards the intestinal epithelium. In scientific research, mucus from animal sources is usually used to simulate difficult-to-obtain human small intestinal mucus for investigating the intramucus transport of drug delivery systems or food nanoparticles. However, there is a lack of evidence the human mucus can be reliably substituted by animal counterparts for human-relevant transport models. In this report, a procedure for collecting human mucus has been described. More importantly, the permeability characteristics of human and porcine small intestinal mucus secretions to sub-micron sized particles have been compared under simulated intestinal conditions. Negatively charged, 500 nm latex beads were used in multiple-particle tracking experiments to examine the heterogeneity and penetrability of mucus from different sources. Diffusion of the probe particles in adult human ileal mucus and adult pig jejunal and ileal mucus revealed no significant differences in microstructural organisation or microviscosity between the three mucus types (P > 0.05). In contrast to this interspecies similarity, the intraspecies comparison of particle diffusivity in the mucus obtained from adult pigs vs. 2-week old piglets showed better penetrability of the piglet mucus. The mean Stokes–Einstein viscosity of the piglet jejunal mucus was approx. two times lower than the viscosity of the pig jejunal mucus (P < 0.05). All mucus structures were also visualised by scanning electron microscopy. This work validates the use of porcine small intestinal mucus collected from fully-grown pigs for studying colloidal transport of sub-micron sized particles in mucus under conditions mimicking the adult human small intestinal environment.

Red‐emissive π‐expanded diketopyrrolopyrroles (DPPs) with fluorescence reaching λ=750 nm can be easily synthesized by a three‐step strategy involving the preparation of diketopyrrolopyrrole followed by N‐arylation and subsequent intramolecular palladium‐catalyzed direct arylation. Comprehensive spectroscopic assays combined with first‐principles calculations corroborated that both N‐arylated and fused DPPs reach a locally excited (S1) state after excitation, followed by internal conversion to states with solvent and structural relaxation, before eventually undergoing intersystem crossing. Only the structurally relaxed state is fluorescent, with lifetimes in the range of several nanoseconds and tens of picoseconds in nonpolar and polar solvents, respectively. The lifetimes correlate with the fluorescence quantum yields, which range from 6 % to 88 % in nonpolar solvents and from 0.4 % and 3.2 % in polar solvents. A very inefficient (T1) population is responsible for fluorescence quantum yields as high as 88 % for the fully fused DPP in polar solvents.

A B S T R A C TCorticosteroids are used widely to treat many types of disease. In general, these drugs are considered safe for the liver; however, recent reports have demonstrated that highdose methylprednisolone (MT) may cause severe liver injury. Here, we report a case of a 24-year-old female who was given pulsed MT therapy for multiple sclerosis. MT induced icteric hepatitis and impaired liver synthetic function. Hepatotoxicity developed several weeks after drug exposure, and the causal association with MT was confirmed by unintentional rechallenge test. A brief review of the literature on corticosteroid-induced hepatotoxicity is presented.

A new methodology for the double N-arylation of diketopyrrolopyrroles with aryl triflates has been developed. It is now possible to prepare diketopyrrolopyrroles bearing Nsubstituents derived from naphthalene, anthracene and coumarin in two steps from commercially available phenols. This represents the first time arenes lacking strong electronwithdrawing groups were inserted onto lactamic nitrogen atoms via arylation. The ability to incorporate heretofore unprecedented substituents translates to increased modulation of the resulting photophysical properties such as switching-on/off solvatofluorochromism. TD-DFT calculations have been performed to explore the nature of the relevant excited states. This new synthetic method made it possible to elucidate the influence of such substituents on the absorption and emission properties of tetraaryl substituted diketopyrrolopyrroles.