Hexokinase 2 Inhibition and Biological Effects of BNBZ and Its Derivatives: The Influence of the Number and Arrangement of Hydroxyl Groups

Hexokinase 2 (HK2), an enzyme of the sugar kinase family, plays a dual role in glucose metabolism and mediating cancer cell apoptosis, making it an attractive target for cancer therapy. While positive HK2 expression usually promotes cancer cells survival, silencing or inhibiting this enzyme has been found to improve the effectiveness of anti-cancer drugs and even result in cancer cell death. Previously, benitrobenrazide (BNBZ) was characterized as a potent HK2 inhibitor with good anti-cancer activity in mice, but the effect of its trihydroxy moiety (pyrogallol-like) on inhibitory activity and some cellular functions has not been fully understood. Therefore, the main goal of this study was to obtain the parent BNBZ (2a) and its three dihydroxy derivatives 2b–2d and to conduct additional physicochemical and biological investigations. The research hypothesis assumed that the HK2 inhibitory activity of the tested compounds depends on the number and location of hydroxyl groups in their chemical structure. Among many studies, the binding affinity to HK2 was determined and two human liver cancer cell lines, HepG2 and HUH7, were used and exposed to chemicals at various times: 24 h, 48 h and 72 h. The study showed that the modifications to the structures of the new BNBZ derivatives led to significant changes in their activities. It was also found that these compounds tend to aggregate and exhibit toxic effects. They were found to contribute to: (a) DNA damage, (b) increased ROS production, and (c) disruption of cell cycle progression. It was observed that, HepG2, occurred much more sensitive to the tested chemicals than the HUH7 cells; However, regardless of the used cell line it seems that the increase in the expression of HK2 in cancer cells compared to normal cells which have HK2 at a very low level, is a serious obstacle in anti-cancer therapy and efforts to find the effective inhibitors of this enzyme should be intensified.     

Investigating the Potential Use of Chemical Biopsy Devices to Characterize Brain Tumor Lipidomes

The development of a fast and accurate intraoperative method that enables the differentiation and stratification of cancerous lesions is still a challenging problem in laboratory medicine. Therefore, it is important to find and optimize a simple and effective analytical method of enabling the selection of distinctive metabolites. This study aims to assess the usefulness of solid-phase microextraction (SPME) probes as a sampling method for the lipidomic analysis of brain tumors. To this end, SPME was applied to sample brain tumors immediately after excision, followed by lipidomic analysis via liquid chromatography-high resolution mass spectrometry (LC-HRMS). The results showed that long fibers were a good option for extracting analytes from an entire lesion to obtain an average lipidomic profile. Moreover, significant differences between tumors of different histological origin were observed. In-depth investigation of the glioma samples revealed that malignancy grade and isocitrate dehydrogenase (IDH) mutation status impact the lipidomic composition of the tumor, whereas 1p/19q co-deletion did not appear to alter the lipid profile. This first on-site lipidomic analysis of intact tumors proved that chemical biopsy with SPME is a promising tool for the simple and fast extraction of lipid markers in neurooncology.     

On the Effect of pH,Temperature, and Surfactant Structure on Bovine Serum Albumin–Cationic/Anionic/Nonionic Surfactants Interactions in Cacodylate Buffer–Fluorescence Quenching Studies Supported by UV Spectrophotometry and CD Spectroscopy

Due to the fact that surfactant molecules are known to alter the structure (and consequently the function) of a protein, protein–surfactant interactions are very important in the biological, pharmaceutical, and cosmetic industries. Although there are numerous studies on the interactions of albumins with surfactants, the investigations are often performed at fixed environmental conditions and limited to separate surface-active agents and consequently do not present an appropriate comparison between their different types and structures. In the present paper, the interactions between selected cationic, anionic, and nonionic surfactants, namely hexadecylpyridinium chloride (CPC), hexadecyltrimethylammonium bromide (CTAB), sodium dodecyl sulfate (SDS), polyethylene glycol sorbitan monolaurate, monopalmitate, and monooleate (TWEEN 20, TWEEN 40, and TWEEN 80, respectively) with bovine serum albumin (BSA) were studied qualitatively and quantitatively in an aqueous solution (10 mM cacodylate buffer; pH 5.0 and 7.0) by steady-state fluorescence spectroscopy supported by UV spectrophotometry and CD spectroscopy. Since in the case of all studied systems, the fluorescence intensity of BSA decreased regularly and significantly under the action of the surfactants added, the fluorescence quenching mechanism was analyzed thoroughly with the use of the Stern–Volmer equation (and its modification) and attributed to the formation of BSA–surfactant complexes. The binding efficiency and mode of interactions were evaluated among others by the determination, comparison, and discussion of the values of binding (association) constants of the newly formed complexes and the corresponding thermodynamic parameters (ΔG, ΔH, ΔS). Furthermore, the influence of the structure of the chosen surfactants (charge of hydrophilic head and length of hydrophobic chain) as well as different environmental conditions (pH, temperature) on the binding mode and the strength of the interaction has been investigated and elucidated.     

Why Do We Need More Active ATRP Catalysts?

Atom transfer radical polymerization (ATRP) is a staple technique for the preparation of polymers with well-defined architecture. In ATRP, the catalyst governs the equilibrium between propagating radicals and dormant species, thus affecting the polymerization control for a range of monomers and transferable atoms employed in the process. The design and the use of highly active catalysts could diminish the amount of transition metal complexes, extend ATRP to less active monomers and give access to new chain-end functionalities. At the same time, very active catalysts can be involved in formation of organometallic species. Herein, the role of the catalyst on the ATRP equilibrium is carefully elucidated, together with recent observations on the impact of the catalyst nature on formation of organometallic species and relevant side reactions. Based on this knowledge, a perspective on the benefits and challenges that derive from the use of highly active ATRP catalysts is presented.     

Solvent‐Assisted Low‐Temperature Crystallization of SnO2 Electron‐Transfer Layer for High‐Efficiency Planar Perovskite Solar Cells

A high‐quality polycrystalline SnO₂ electron‐transfer layer is synthesized through an in situ, low‐temperature, and unique butanol–water solvent‐assisted process. By choosing a mixture of butanol and water as a solvent, the crystallinity is enhanced and the crystallization temperature is lowered to 130 °C, making the process fully compatible with flexible plastic substrates. The best solar cells fabricated using these layers achieve an efficiency of 20.52% (average 19.02%) which is among the best in the class of planar n–i–p‐type perovskite (MAPbI₃) solar cells. The strongly reduced crystallization temperature of the materials allows their use on a flexible substrate, with a resulting device efficiency of 18%.     

Measurement of mechanical properties in a 316L stainless steel welded joint

The aim of this study was to measure the mechanical properties of weld material taken from a single weld bead laid down on a 316L steel plate. Due to the low available volume of weld material, microsamples with a total length of 5.5 mm were used. The Digital Image Correlation method (DIC), which enables measurement of mechanical properties of very small samples, was employed for the strain measurements in a uniaxial tensile test. Samples were cut out from three different zones of the specimen: plate, weld, and the heat affected zone. The material from heat affected zone showed the highest value of the Ultimate Tensile Strength (UTS) (580 ± 7 MPa) and yield strength (339 ± 6 MPa). Plate material had lower UTS (559 ± 5 MPa) and yield strength (304 ± 7 MPa). The lowest values of UTS (526 ± 6 MPa) and yield strength (291 ± 8 MPa) have been revealed for the weld. The values obtained for UTS, yield strength and elongation to failure for the plate material were compared with data obtained using standard test specimens. No significant differences between results obtained for the microsamples and standard samples have been found.     

Evaluation of the mechanical behavior of W7-X central support connections by means of semi-automated FE analysis

The stellarator Wendelstein 7-X is under construction at the Max-Planck-Institut für Plasmaphysik in Greifswald. Its superconducting coil system is fixed by a massive structure. During machine operation the coils exert high forces and moments against each other and the central support structure (CSS). Therefore, the detailed analysis of the coil to CSS connections, the so-called central support elements (CSE), is a critical item. The major details of the design have been frozen; nevertheless, there is still need for detailed analysis of the CSEs due to assembly issues, and later on for exploring operational limits of the machine. These analyses have to be performed quickly, reliably, and shall provide results in a standardized form to enable timely responses to the assembly team. Special numerical tools – finite element (FE) parametric models of CSEs – have been developed for the purpose of such analyses. In the models, the geometry, material properties, contact conditions, loads as well as results presentation are defined in a parametric way. The use of the developed models for the definition of the final weld parameters, bolt preloads, assessment of acceptable tolerances, and optimal positions of the CSE-wedges before welding is also discussed.     

Freshness and quality attributes of cold stored Atlantic bonito (Sarda sarda) gravad

Quality and safety parameters of Atlantic bonito gravad during 42 days of storage at 7 ± 1 °C were analysed using monitoring sensory quality, microbial contamination, nucleotide degradation products, biogenic amines (BA), trimethylamine (TMA) and thiobarbituric acid reactive substances (TBARS). The shelf‐life of vacuum packed Atlantic bonito gravad was found to be 28 days. Total viable count (TVC) did not exceed 6 log CFU g^?1. Malonodialdehyde (MDA) content did not surpass 10 mg kg^?1. Nine biogenic amines were detected. Histamine level at the end of the storage was 355.3 mg kg^?1. TMA increased from 53.9 to 619.1 mg kg^?1. Among indicators based on the products of nucleotide degradation, the H value is best correlated with the sensory assessment. It can be concluded that the storage temperature of bonito gravad must be below 7 °C to prevent the threat to safety and quality posed by biogenic amines, especially histamine.     

Finishing works after welding of structures made of rust-resistant,high-alloy steels

In this paper, problems that occur when working with welds formed of high-alloy steels to restore their passive layers, damaged as a result of temperature impact, are discussed. Particular attention was paid to the procedures concerning aggressive etching agents during and after completion of the passivation processes (waste neutralization and utilization).