Two new classes of near‐infrared molecular probes were prepared and shown to exhibit “turn on” fluorescence when cleaved by the nitroreductase enzyme, a well‐known biomarker of cell hypoxia. The fluorescent probes are heptamethine cyanine dyes with a central 4‘‐carboxylic ester group on the heptamethine chain that is converted by a self‐immolative fragmentation mechanism to a 4‘‐caboxylate group that greatly enhances the fluorescence brightness. Each compound was prepared by ring opening of a Zincke salt. The chemical structures have either terminal benzoindolinenes or propargyloxy auxochromes, which provide favorable red‐shifted absorption/emission wavelengths and a hyperchromic effect that enhances the photon output when excited by 808 nm light. A fluorescent probe with terminal propargyloxy‐indolenines exhibited less self‐aggregation and was rapidly activated by nitroreductase with large “turn on“ fluorescence; thus, it is the preferred choice for translation towards in vivo applications.
Three-dimensional (3D) printed anatomical models are valuable visual aids that are widely used in clinical and academic settings to teach complex anatomy. Procedures for converting human biomedical image datasets, like X-ray computed tomography (CT), to prinTable 3D files were explored, allowing easy reproduction of highly accurate models; however, these largely remain monochrome. While multi-color 3D printing is available in two accessible modalities (binder-jetting and poly-jet/multi-jet systems), studies embracing the viability of these technologies in the production of anatomical teaching models are relatively sparse, especially for sub-structures within a segmentation of homogeneous tissue density. Here, we outline a strategy to manually highlight anatomical subregions of a given structure and multi-color 3D print the resultant models in a cost-effective manner. Readily available high-resolution 3D reconstructed models are accessible to the public in online libraries. From these databases, four representative files (of a femur, lumbar vertebra, scapula, and innominate bone) were selected and digitally color enhanced with one of two strategies (painting or splitting) guided by Feneis and Dauber’s Pocket Atlas of Human Anatomy. Resulting models were created via 3D printing with binder-jet and/or poly-jet machines with important features, such as muscle origin and insertion points, highlighted using multiple colors. The resulting multi-color, physical models are promising teaching tools that will enhance the anatomical learning experience.
The Front Cover illustrates the action of a cyanine‐based fluorescent probe inside a hypoxic A549 cell. Nitroreductase enzyme, a well‐known biomarker of hypoxia, transforms a carboxylic ester group on the central heptamethine chain through a self‐immolative fragmentation mechanism into a brightly fluorescent carboxylate group, resulting in a “turn on” fluorescent response. The cell elements were provided by Reactome.org under the CC BY 4.0 license. More information can be found in the Research Article by P. Štacko, B. D. Smith et al.
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