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Given the profound multiple myeloma (MM) heterogeneity in clonal proliferation of malignant plasma cells (PCs) and anti-MM therapeutic potential of nanotherapies, it is inevitable to develop treatment plan for patients with MM. Two composite nanoparticles (NPs), As 4 S 4 /Fe 3 O 4 (4:1) and As 4 S 4 /Fe 3 O 4 (1:1) demonstrated effective anti-MM activity in in vitro, ex vivo, and in vivo in xenograft mouse model. Composite NPs triggered activation of p-ERK1/2/p-JNK, and downregulation of c-Myc, p-PI3K, p-4E-BP1; G 2 /M cell cycle arrest with increase in cyclin B1, histones H2AX/H3, activation of p-ATR, p-Chk1/p-Chk2, p-H2AX/p-H3; and caspase- and mitochondria-dependent apoptosis induction. NPs attenuated the stem cell-like side population in MM cells, both alone and in the presence of stroma. For a higher clinical response rate, As 4 S 4 /Fe 3 O 4 (4:1) observed synergism with dexamethasone and melphalan, while As 4 S 4 /Fe 3 O 4 (1:1) showed synergistic effects in combination with bortezomib, lenalidomide and pomalidomide anti-MM agents, providing the framework for further clinical evaluation of composite NPs in MM., Competing Interests: Declaration of competing interest The authors declare the following competing interests: K.C.A. declares advisory role (Pfizer, Amgen, Astrazeneca, Janssen, Precision Biosciences), board membership (C4 Therapeutics, Raqia, NextRNA, Window, Mana, Starton) and ownership interests (C4 Therapeutics, Oncopep, NextRNA, Raqia). Other authors declare no competing financial interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The profile of secondary metabolites present in the apple cuticular layer is not only characteristic of a particular apple cultivar; it also dynamically reflects various external factors in the growing environment. In this study, the possibility of authenticating apple samples by analyzing their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled with high-resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. A total of 274 authentic apple samples from four cultivars harvested in the Czech Republic and Poland between 2020 and 2022 were analyzed. The complex data generated, processed using univariate and multivariate statistical methods, enabled the building of classification models to distinguish apple cultivars as well as their geographical origin. The models showed very good performance in discriminating Czech and Polish samples for three out of four cultivars: "Gala", "Golden Delicious" and "Idared". Moreover, the validity of the models was tested over several harvest seasons. In addition to metabolites of the triterpene biosynthetic pathway, the diagnostic markers were mainly wax esters. "Jonagold", which is known to be susceptible to mutations, was the only cultivar for which an unambiguous classification of geographical origin was not possible.

Incineration is currently the standard way of disposing of municipal waste. It uses components protected by high-temperature-resistant layers of materials, such as Inconel alloys. Therefore, the objective of the current paper is to study the mechanical properties and structure of a bimetallic Inconel 625-16Mo3 steel tube. The Inconel 625 layer was 3.5 mm thick and was applied to the surface of the tube with a wall thickness of 7 mm via the cold metal transfer method. The bimetallic tube was bent using a supercritical bend (d ≤ 0.7D). This paper is focused on the investigation of the material changes in the Inconel 625 layer areas influenced by the maximum tensile and compressive stresses after the bend. The change in layer thickness after the bend was evaluated and compared to the non-deformed tube. In addition, the local mechanical properties (nanohardness, Young modulus) across the indicated interfacial areas using quasistatic nanoindentation were investigated. Subsequently, a thorough microstructure observation was carried out in areas with maximum tensile and compressive stresses to determine changes in the morphology and size of dendrites related to the effect of tensile or compressive stresses induced by bending. It was found that the grain featured a stretched secondary dendrite axis in the area of tensile stress, but compressive stress imparted a prolongation of the primary dendrite axis.

Centrosomes play an important role in the microtubule organization of a cell. The sperm's specialized centrosome consists of the canonical barrel-shaped proximal centriole, the funnel-shaped distal centriole, and the pericentriolar material known as striated columns (or segmented columns). Here, we examined the localization of the centriole proteins CEP135 and CP110 in cattle and human spermatozoa. In canonical centrioles, CP110 is a centriole tip protein that controls cilia formation, while CEP135 is a structural protein essential for constructing the centriole. In contrast, we found antibodies recognizing CEP135 and CP110 label near the proximal and distal centrioles at the expected location of the striated columns and capitulum in cattle and humans in an antibody and species-specific way. These findings provide a pathway to understanding the unique functions of spermatozoan centrosome., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2023 by the authors.)

Drilling into the solid material is one of the basic technological operations, which creates a cylindrical hole in an appropriate time with required quality. Drilling operation demands a favourable removal of chips from the cutting area because a creation of an undesirable shape of chips can impart a lower quality of the drilled hole corresponding with the generation of excess heat due to the intense contact of the chip with drill. The solution for a proper machining is a suitable modification of the drill geometry i.e., point and clearance angles as presented in current study. The tested drills are made of M35 high-speed steel characterized by a very thin core at the point of the drill. An interesting feature of the drills is the use of cutting speed higher than 30 m min -1 , with the feed of 0.2 mm per revolution. The surface roughness (Ra and Rz lower than 1 µm and 6 µm respectively), cylindricity (0.045 mm), roundness (0.025 mm), perpendicularity of the hole axis (0.025 mm), diameters and position of the individual holes were achieved for a drill with point angle 138.32°and clearance angle 6.92 respectively. The increase of the drill point angle by 6° resulted in the decrease in the feed force of more than 150 N. In addition, an increase of the clearance angle by 1° resulted with a decrease in the feed force of 70 N. The results of the experiment showed that with the correct geometry of the tool the effective machining without using internal cooling can be realised., (© 2023. The Author(s).)

The Fused Filament Fabrication (FFF) method is an additive technology that is used for the creation of prototypes within Rapid Prototyping (RP) as well as for the creation of final components in piece or small-series production. The possibility of using FFF technology in the creation of final products requires knowledge of the properties of the material and, at the same time, how these properties change due to degradation effects. In this study, the mechanical properties of the selected materials (PLA, PETG, ABS, and ASA) were tested in their non-degenerate state and after exposure of the samples to the selected degradation factors. For the analysis, which was carried out by the tensile test and the Shore D hardness test, samples of normalized shape were prepared. The effects of UV radiation, high temperature environments, high humidity environments, temperature cycles, and exposure to weather conditions were monitored. The parameters obtained from the tests (tensile strength and Shore D hardness) were statistically evaluated, and the influence of degradation factors on the properties of individual materials was assessed. The results showed that even between individual manufacturers of the same filament there are differences, both in the mechanical properties and in the behavior of the material after exposure to degradation effects.