University of Chemistry and Technology

Rhomboid proteases, a class of intramembrane proteases characterized by a Ser-His catalytic dyad, have recently emerged as promising therapeutic targets. While inhibitors for soluble serine proteases have been extensively studied, the spectrum of potent rhomboid protease inhibitor chemotypes is limited to active-site targeted nucleophiles. To address this limitation, we conducted a high-throughput screen of over 68,000 compounds targeting the E. coli rhomboid protease GlpG, using a fluorescent liposome-based assay. A selection of 326 inhibitory compounds was evaluated in a subsequent IC50 screen against two variants of GlpG (core domain and full length), a soluble serine protease (chymotrypsin), as well as the human mitochondrial rhomboid PARL. Of these, the selective inhibitory effects of 2 compounds and their analogues on GlpG were confirmed through further biochemical and biophysical characterisation, molecular docking, and solid-state NMR spectroscopy. This study paves the way for developing small-molecule tool compounds and drug-like molecules targeting rhomboid proteases.

Reverse transcriptase (RT) of retroviruses orchestrates viral replication, yet its structural diversity remains poorly understood. Well‐studied RTs, such as those from HIV‐1, murine leukemia virus, and avian myeloblastosis virus, were characterized decades ago, but less prominent retroviruses have escaped detailed analysis. Despite being discovered alongside HIV‐1, the RT of Mason‐Pfizer monkey virus (M‐PMV) has resisted recombinant expression, leaving its properties unresolved. Here, we report the first detailed analysis of M‐PMV RT, a betaretroviral enzyme previously thought challenging to obtain recombinantly. Using baculovirus‐based expression in insect cells, we produced soluble full‐length RT that, upon proteolytic maturation by the M‐PMV protease, yielded a heterodimer composed of p65 and p51 subunits. Mass spectrometry, N‐terminal sequencing, and analytical ultracentrifugation demonstrated that full‐length RT forms a homodimer, which converts into a stable and more enzymatically active heterodimer following proteolytic removal of the C‐terminal RNase H domain from one subunit. Functional assays revealed that heterodimer formation enhances polymerase activity while preserving RNase H function, directly linking proteolytic maturation to enzymatic activation. Notably, this heterodimeric architecture is uncommon among betaretroviruses and resembles the well‐characterized lentiviral HIV‐1 RT. These results broaden the evolutionary perspective on RT heterodimerisation by revealing that this architecture extends into betaretroviruses.

van der Waals magnets are attracting a great deal of attention for their potential integration into spintronic and magnonic technologies. CrSBr is an A-type antiferromagnet that shows a coupling between its electronic band structure and magnetic properties. This property is appealing for applications, and it also offers the possibility to investigate magnetic ground states and gigahertz magnons using visible optics techniques. Using Raman scattering and (magneto)-optical experiments, we describe the magnetic and optical properties of alloys of CrSBr1-xClx with x ⩽ 0.46. Similar to CrSBr, these alloys are direct band gap semiconductors with a coupling of their electronic and magnetic properties. Exciton energies evolve weakly with composition, and we describe the large changes in the saturation magnetic fields and their implications for the magnetic properties. We show that both the interlayer magnetic exchange and electronic interactions are modified by halogen mixing, offering the possibility to tune magnon energies with alloy composition.

ABSTRACT Methanol (MeOH) and acetonitrile (MeCN) are highly polar organic compounds occurring in HPLC waste eluates. Neither of them is evidently more hydrophilic, which renders their pervaporative separation unusual. To identify suitable membrane materials, the pervaporation of MeOH‐MeCN mixtures having composition near the azeotrope (68.3 mol % MeOH at 35.0°C) was studied. For this purpose, homogeneous membranes from well‐established polymers were investigated, namely cellulose triacetate (CTA), polysulfone (PSU), poly(1‐trimethylsilyl‐1‐propyne) (PTMSP), Matrimid (MIM), poly(dimethyl siloxane) rubber (PDMS), polylactic acid (PLA), and chloroprene rubber (CR). Materials with discernible MeCN selectivity, namely CR, MIM, and PDMS, were further examined at 35.0°C, 45.0°C, and 52.9°C with feeds of varying composition. Plasticization and swelling effects were analyzed using Broadband Dielectric Spectroscopy (BDS) and liquid sorption measurements. Permeability decreased with increasing content of the less sorbing MeOH (except for MIM); BDS measurements indicated plasticization by both components; MeCN sorbed more and appears more organophilic.

Photodynamic therapy (PDT) emerges as an innovative strategy combining light and drug treatment. The most prevalent use of this therapy is for the elimination of cancerous and pre-cancerous cells. However, in recent years PDT has been shown to be a suitable approach to combat the rising threat of antimicrobial resistance through the photoinactivation of pathogenic bacteria. Photosensitizers predicated on octahedral hexa-molybdenum cluster (Mo6) complexes activated by blue light were formulated into semi-solid topical pharmaceutics containing three distinct types of Mo6 clusters as potential novel actives for cosmetics purposes. For the first time, semi-solid cosmetic formulations were developed utilizing natural deep eutectic solvents as carriers of these active compounds and tested for their stability, viscosity, skin penetration, and singlet oxygen formation. After that, negligible toxicity for human cells was confirmed using in vitro testing on HaCaT cell lines. Finally, photoinactivation of the most prevalent skin bacterial pathogens Staphylococcus aureus and Cutibacterium acnes was demonstrated under mild conditions that preserve viability of natural symbiotic skin microflora.

Defect-induced magnetism in two-dimensional (2D) materials holds enormous potential for next-generation spintronic and quantum devices, yet its realization in multilayer systems remains elusive. In this work, we investigate the emergence and modulation of magnetism in multilayer PtSe₂ via a combined theoretical–experimental approach, integrating hybrid density functional theory (DFT) calculations with aberration-corrected scanning transmission electron microscopy (AC-STEM). In multilayer PtSe₂ with the presence of Pt vacancies, magnetism is typically quenched due to interlayer interactions, but it can be restored by complex defect structures comprising, in addition to a Pt vacancy, a PtSe antisite. These configurations induce magnetic moments of up to 3.16 μB and give rise to a two-dimensional half-metallic state in bilayer PtSe₂, which is highly desirable for spin-polarized transport. Furthermore, the electronic and magnetic properties can be tuned by nearby Se vacancies, which drive transitions between different types of magnetic states depending on the number of vacancies. When embedded in the middle layer of trilayer PtSe₂, this combination of defects extends the magnetic moments beyond the defect-carrying layer. Overall, these findings demonstrate that defect engineering enables robust magnetic phase control and spin-filtering behavior without external doping or strain, establishing PtSe₂ as a tunable 2D magnetic material platform for scalable, room-temperature spintronic and valleytronic applications.

Macrophages are critical components of the innate immune system that adapt their function based on local microenvironmental cues. In adipose tissue, macrophage polarization is intimately linked to metabolic regulation and inflammation. In this pilot study, we performed lipidomic profiling to characterize the phospholipid composition of pro-inflammatory (PI-ATM) and non-inflammatory (NI-ATM) macrophages isolated from visceral adipose tissue of living kidney donors. Tissue samples were processed, and macrophages were isolated and sorted using CD14 and CD16 markers. Lipids were extracted by methyl tert-butyl ether, and differences in the lipidome were analyzed using the optimized UHPLC-MS method. PI-ATM exhibited a higher abundance of lipids across various lipid classes than NI-ATM. Phosphatidylethanolamines and ether lipids derived from phosphatidylethanolamines and phosphatidylcholines were most frequently found among the significantly altered lipids. The majority of significantly altered lipid species contained an octadecenoic aliphatic chain. These findings suggest that alterations in membrane lipid composition - particularly ether lipids and phosphatidylethanolamines - may play a pivotal role in macrophage polarization and adipose tissue inflammation. Our study provides novel insights into the lipidomic regulation of macrophage function in human adipose tissue and identifies potential targets for therapeutic intervention in metabolic disorders.

Transition metal dichalcogenides (TMD) combine semiconducting properties with stability and are therefore widely studied for future microelectronic devices. However, applications require integration with a suitable dielectric at a planar, defect-free interface. For Hf- and Zr-based TMDs, the good dielectric properties of hafnia and zirconia imply that direct oxidation is a promising strategy, provided that a high-quality interface and suitable oxide morphology can be formed. Here, we investigate HfS2 and ZrS2 oxidation, aiming to understand pathways toward planar oxide layer formation and the mechanisms that determine the characteristics of the semiconductor/dielectric interface. We use conventional and environmental transmission electron microscopy to reveal changes in morphology and composition of the TMDs under different gaseous environments. We show that oxidation at ambient conditions causes compositional heterogeneities, with local replacement of S by O in both materials. Thermal oxidation causes desulfurization and formation of a smooth but defective oxide layer. In contrast, plasma oxidation appears the best-suited to forming a controlled TMD/dielectric interface with a smooth oxide layer and without major defects. These results provide insight into the opportunities available from HfS2 and ZrS2 through oxidation and suggest a materials processing strategy for electronic device fabrication.