A dense composite of silver and Ce0.8Sm0.2O2−δ (Ag-CSO) was manufactured from ceramic nanoparticles coated by electroless deposition of silver. At 700 °C, a 1-mm-thick membrane of the composite delivered an excellent oxygen permeation rate from air with a value of 0.04 μmol cm–2 s–1, using argon as the sweep gas and 0.17 μmol cm–2 s–1 using hydrogen. The low sintering temperature of the CSO nanoparticles allows the use of Ag rather than Pt or Pd and reduces the amount of metal needed for electronic conductivity to just 5.6 vol %, which is lower than any value reported in the literature. Oxygen diffusivity measurements confirmed that the oxygen migration remained high in the composite, with an increase in surface exchange coefficient of three orders of magnitude over Gd-doped ceria. The ease of membrane fabrication, combined with encouraging oxygen permeation rates, demonstrate the promise of the material for high-purity oxygen separation below 700 °C.

We identify key SAR features which demonstrate that high parasite vs. G9a selectivity can be achieved for the quinazoline inhibitor chemotype.

Increased CK2 levels are prevalent in many cancers. Combined with the critical role CK2 plays in many cell-signaling pathways, this makes it a prime target for down regulation to fight tumour growth. Herein, we report a fragment-based approach to inhibiting the interaction between CK2α and CK2β at the α-β interface of the holoenzyme. A fragment, CAM187, with an IC of 44 μM and a molecular weight of only 257 gmol has been identified as the most promising compound. Importantly, the lead fragment only bound at the interface and was not observed in the ATP binding site of the protein when co-crystallised with CK2α. The fragment-like molecules discovered in this study represent unique scaffolds to CK2 inhibition and leave room for further optimisation.

Diaminoquinazolines represent a privileged scaffold for antimalarial discovery, including use as putative Plasmodium histone lysine methyltransferase inhibitors. Despite this, robust evidence for their molecular targets is lacking. Here we report the design and development of a small-molecule photo-cross-linkable probe to investigate the targets of our diaminoquinazoline series. We demonstrate the effectiveness of our designed probe for photoaffinity labeling of Plasmodium lysates and identify similarities between the target profiles of the probe and the representative diaminoquinazoline BIX-01294. Initial pull-down proteomics experiments identified 104 proteins from different classes, many of which are essential, highlighting the suitability of the developed probe as a valuable tool for target identification in Plasmodium falciparum.

Zebrafish provide a unique opportunity for drug screening in living animals, with the fast developing, transparent embryos allowing for relatively high-throughput, microscopy-based screens. However, the limited availability of rapid, flexible imaging and analysis platforms has limited the use of zebrafish in drug screens. We have developed an easy-to-use, customisable automated screening procedure suitable for high-throughput phenotype-based screens of live zebrafish. We utilised the WiScan® Hermes High Content Imaging System to rapidly acquire brightfield and fluorescent images of embryos, and the WiSoft® Athena Zebrafish Application for analysis, which harnesses an Artificial Intelligence-driven algorithm to automatically detect fish in brightfield images, identify anatomical structures, partition the animal into regions, and exclusively select the desired side-oriented fish. Our initial validation combined structural analysis with fluorescence images to enumerate GFP-tagged haematopoietic stem and progenitor cells in the tails of embryos, which correlated with manual counts. We further validated this system to assess the effects of genetic mutations and x-ray irradiation in high content using a wide range of assays. Further, we performed simultaneous analysis of multiple cell types using dual fluorophores in high throughput. In summary, we demonstrate a broadly applicable and rapidly customisable platform for high-content screening in zebrafish.