Explore the vast range of titles available.

Three-dimensional cell culture systems underpin cell-based technologies ranging from tissue scaffolds for regenerative medicine to tumor models and organoids for drug screening. However, to realise the full potential of these technologies requires analytical methods able to capture the diverse information needed to characterize constituent cells, scaffold components and the extracellular milieu. Here we describe a multimodal imaging workflow which combines fluorescence, vibrational and second harmonic generation microscopy with secondary ion mass spectrometry imaging and transmission electron microscopy to analyse the morphological, chemical and ultrastructural properties of cell-seeded scaffolds. Using cell nuclei as landmarks we register fluorescence with label-free optical microscopy images and high mass resolution with high spatial resolution secondary ion mass spectrometry images, with an accuracy comparable to the intrinsic spatial resolution of the techniques. We apply these methods to investigate relationships between cell distribution, cytoskeletal morphology, scaffold fiber organisation and biomolecular composition in type I collagen scaffolds seeded with human dermal fibroblasts.

The effective treatment of diseases of the nail remains an important unmet medical need, primarily because of poor drug delivery. To address this challenge, the diffusion, in real time, of topically applied chemicals into the human nail has been visualized and characterized using stimulated Raman scattering (SRS) microscopy. Deuterated water (D ₂O), propylene glycol (PG-d ₈), and dimethyl sulphoxide (DMSO-d ₆) were separately applied to the dorsal surface of human nail samples. SRS microscopy was used to image D ₂O, PG-d ₈/DMSO-d ₆, and the nail through the O-D, -CD ₂, and -CH ₂ bond stretching Raman signals, respectively. Signal intensities obtained were measured as functions of time and of depth into the nail. It was observed that the diffusion of D ₂O was more than an order of magnitude faster than that of PG-d ₈ and DMSO-d ₆. Normalization of the Raman signals, to correct in part for scattering and absorption, permitted semiquantitative analysis of the permeation profiles and strongly suggested that solvent diffusion diverged from classical behavior and that derived diffusivities may be concentration dependent. It appeared that the uptake of solvent progressively undermined the integrity of the nail. This previously unreported application of SRS has permitted, therefore, direct visualization and semiquantitation of solvent penetration into the human nail. The kinetics of uptake of the three chemicals studied demonstrated that each altered its own diffusion in the nail in an apparently concentration-dependent fashion. The scale of the unexpected behavior observed may prove beneficial in the design and optimization of drug formulations to treat recalcitrant nail disease. Significance Diseases of the nail are particularly hard to treat because drug penetration to the target (which lies below the tightly woven keratin network) is extremely limited. To shed greater light on the problem, the diffusion of three pharmaceutically relevant solvents across the human nail has been imaged and characterized by stimulated Raman scattering microscopy. Remarkably, the kinetics of water transport were more than 10-fold faster than those of dimethyl sulphoxide and propylene glycol. Furthermore, the uptake of all three solvents, the diffusion of which appeared to be concentration dependent, progressively undermined the integrity of the nail. These new insights may facilitate the improved formulation of drug products effective in the treatment of diseases such as fungal infections and nail psoriasis.

Digital pathology is revolutionising the analysis of histological features and is becoming more and more widespread in both the clinic and research. Molecular pathology extends the tissue morphology information provided by conventional histopathology by providing spatially resolved molecular information to complement the structural information provided by histopathology. The multidimensional nature of the molecular data poses significant challenge for data processing, mining, and analysis. One of the key challenges faced by new and existing pathology practitioners is how to choose the most suitable molecular pathology technique for a given diagnosis. By providing a comparison of different methods, this narrative review aims to introduce the field of molecular pathology, providing a high-level overview of many different methods. Since each pixel of an image contains a wealth of molecular information, data processing in molecular pathology is more complex. The key data processing steps and variables, and their effect on the data, are also discussed.

A new concept for enzyme-catalyzed redox transformations features pairs of electron donor and acceptor enzymes attached to conducting particles. Electrons furnished by oxidation at one enzyme are used at the other. Graphite microparticles modified with hydrogenase and nitrate reductase or fumarate reductase catalyze reductions of nitrate or fumarate ( 1 ) by H 2 .