Xellia (Croatia)

The excessive use of antibiotics in recent years has led to an accelerated development of resistance in bacterial pathogens and thus to one of the greatest problems of our time: antibiotic resistance. Therefore, despite the large number of available drugs, the development of new and structurally diverse antibiotics is urgently needed. In this study, various indole and indene derivatives were prepared and characterised and their antibacterial activity against Gram-positive bacteria Bacillus subtilis 3020 and Gram-negative bacteria Pseudomonas aeruginosa 3011 was investigated. Two fungal strains, Candida lipolytica 59 and Aspergillus niger 405, were used for antifungal activity. In general, most of the prepared compounds showed potential antifungal activity and antibacterial activity against Bacillus subtilis 3020, while all compounds were inactive against Pseudomonas aeruginosa 3011. The most promising compounds were pyrrole, pyridine and phenol derivatives, which showed antibacterial and antifungal activity. In addition, molecular docking studies showed that the most promising indole and indene derivatives exhibited significant binding interaction networks and binding affinity with DNA gyrase B (GyrB) and 14α-sterol demethylase (CYP51), consistent with their observed antibacterial and antifungal activities. Finally, in silico ADME predictions indicated acceptable physicochemical properties of the newly designed compounds.

The paper presents the development of a digitally controlled, passively cooled AC-DC power converter for industrial applications requiring high reliability, high efficiency and compact form factor. The converter consists of an interleaved totem-pole PFC stage followed by a full-bridge LLC resonant converter, designed to deliver up to 3 kW of output power at various DC voltage levels, with a focus on the 110 VDC version. To meet the specific functional and timing requirements of the application, the control architecture is based on custom firmware running on two STM32G474RE microcontrollersone for each power stage. The firmware includes advanced features such as a SOGI-based PLL for grid synchronization, charge-current control for the LLC stage and closed-loop current and voltage regulation, all implemented using low-level peripheral configurations to meet strict real-time constraints. A simulation-based development workflow was employed to validate control strategies prior to hardware testing, significantly reducing the risk of hardware damage during early development. Simulation models were created in LTspice and Plecs, with C-script elements used to prototype embedded control logic.

Phylostratigraphy is a widely used computational approach for predicting gene age by analyzing protein sequence similarities across evolutionary lineages. In this study, we used the Homo sapiens proteome as a reference to analyze the effect of false homology in gene age prediction. We implemented a workflow using state-of-the-art algorithms for sequence similarity searches enhanced by dynamic setting of an E-value threshold. This threshold was calculated for every protein individually using results of similarity searches with reversed database, which identified proteins prone to false homology. We demonstrated that dynamically adjusted E-values effectively reduced false positive rates compared to fixed threshold. However, the results indicate that, while certain proteins are more prone to false homology, they constitute a small proportion of the dataset and, in general, current sequence search algorithms are robust against false homology and thus reliable for phylostratigraphy.

Necessary advancements in the area of organic photovoltaic (OPV) devices include the upgrade of power conversion efficiencies (PCE) and stability. One answer to these demands lies in the research into new absorbers. Here, we focus on the development of new small molecule absorbers from the group of squaraines (SQs). These modular absorbers can be applied as donors in organic solar cells and have the ability to utilize a broad range of solar radiation if blended with suitable acceptors. In order to allow for the compatibility and favorable organization of donor and acceptor in the absorber layer, we intend to optimize the structure of the SQ by varying the groups attached to the squaric acid core. For that purpose, we accordingly developed a well-suited synthesis route. The novel alkyl- and benzyl-substituted aryl aminosquaraines were synthesized through an improved and eco-friendly procedure. Special emphasis was placed on optimizing the amination reaction to obtain initial precursors in the synthesis of squaraine, avoiding hitherto common catalytic processes. All SQ precursors and SQ products were completely described. The derived SQs were additionally characterized in thin-film configuration using cyclic voltammetry and UV-VIS spectroscopy and then processed to prepare self-standing bulk heterojunction (BHJ) thin films in conjunction with fullerene-based electron acceptors, which were characterized via profilometry. The comparison between SQ and BHJ solutions and thin films, using atomic force microscopy and UV-VIS spectroscopy, revealed differences in susceptibility for the organization and orientation of the constituting domains.

Terbuthylazine belongs to the chloro-s-triazine group of herbicides and acts primarily as a photosynthesis inhibitor. The mechanisms of action related to its exposure, relevant both in animals and humans, are still insufficiently investigated. This comprehensive study focused on the outcomes of terbuthylazine exposure at cell level in vitro, and a mice model in vivo. Experiments in vitro were conducted on whole human peripheral blood, isolated lymphocytes, and HepG2 cells exposed for 4h to terbuthylazine at 8.00, 0.80, and 0.58ng/mL, which is comparable with current reference values set by the European Commission in 2011. Terbuthylazine cytotoxicity was evaluated using dual fluorescent staining with ethidium bromide and acridine orange on lymphocytes, and CCK-8 colorimetric assay on HepG2 cells. The levels of DNA damage were measured using alkaline and hOGG1-modified comet assays. The potency of terbuthlyazine regarding induction of oxidative stress in vitro was studied using a battery of standard oxidative stress biomarkers. The in vivo experiment was conducted on Swiss albino mice exposed to terbuthlyazine in the form of an active substance and its formulated commercial product Radazin TZ-50 at a daily dose of 0.0035mg/kgbw for 14days. Following exposure, the DNA damage levels in leukocytes, bone marrow, liver, and kidney cells of the treated mice were measured using an alkaline comet assay. In vitro results suggested low terbuthylazine cytotoxicity in non-target cells. The highest tested concentration (8.00ng/mL) reduced lymphocyte viability by 15%, mostly due to apoptosis, while cytotoxic effects in HepG2 cells at the same concentration were negligible. Acute in vitro exposure of human lymphocytes and HepG2 cells to terbuthylazine resulted in low-level DNA instability, as detected by the alkaline comet assay. Further characterization of the mechanisms behind the DNA damage obtained using the hOGG1-modified comet assay indicated that oxidative DNA damage did not prevail in the overall damage. This was further confirmed by the measured levels of oxidative stress markers, which were mostly comparable to control. Results obtained in mice indicate that both the active substance and formulated commercial product of terbuthylazine produced DNA instability in all of the studied cell types. We found that DNA in liver and kidney cells was more prone to direct toxic effects of the parent compound and its metabolites than DNA in leukocytes and bone marrow cells. The overall findings suggest the formation of reactive terbuthylazine metabolites capable of inducing DNA cross-links, which hinder DNA migration. These effects were most pronounced in liver cells in vivo and HepG2 cells in vitro. To provide a more accurate explanation of the observed effects, additional research is needed. Nevertheless, the present study provides evidence that terbuthylazine at concentrations comparable with current reference values possesses toxicological risk because it caused low-level DNA instability, both at cellular and animal organism level, which should be further established in forthcoming studies.