Search Results (265)

In recent years, the expansion of the illicit market for Novel Psychoactive Substances (NPS) has resulted in the emergence of numerous synthetic recreational drugs specifically designed to evade legal control and analytical detection. Among these, nitazenes represent one of the most potent classes of new synthetic opioids, although information regarding their toxicological properties remains limited. The present study aimed to assess the genotoxic potential of four nitazenes: clonitazene, etonitazene, isotonitazene and metonitazene in human lymphoblastoid TK6 cells using a flow cytometric version of the In Vitro Mammalian Cell Micronucleus Test, following OECD Guideline No. 487. Cells were exposed to concentrations ranging from 12.5 to 100 μM, and cytotoxicity, cytostasis, and apoptosis were evaluated to identify appropriate doses for micronucleus frequency assessment. Vinblastine, a well-established mutagen, was included as positive control. Our findings demonstrated that clonitazene and isotonitazene exhibit mutagenic potential, suggesting an increased long-term risk of developing chronic degenerative diseases. Furthermore, the results revealed that structurally related molecules can induce markedly different cellular effects, underscoring the importance of compound-specific toxicological evaluations to achieve a comprehensive understanding of the risks associated with their illicit use—risks often presumed to involve only addiction or acute toxicity. Full article

The LATERAL ORGAN BOUNDARIES DOMAIN (LBD) gene family encodes plant-specific transcription factors that play vital roles in plant growth, development, and stress responses. Rice (Oryza sativa L.), a staple food for more than half of the world’s population, also serves as an important model organism for monocot functional genomics. In this study, we conducted a comprehensive genomic survey of the OsLBD gene family in Oryza sativa ssp. japonica using the latest genomic sequence data. A total of 35 members of this family were identified through systematic characterization of their gene structures, conserved domains, phylogenetic relationships, and chromosomal distributions. Our analysis indicated that the expansion of OsLBD genes may have resulted mainly from segmental duplication, with these duplicated genes exhibiting diverse evolutionary fates ranging from functional conservation to expression divergence. Phylogenetic analysis further classified the OsLBD genes into two major groups: Class I and Class II. Expression profiling across various developmental stages demonstrated dynamic spatiotemporal regulation, with certain genes exhibiting tissue-specific expression, particularly in reproductive tissues. Furthermore, a comprehensive co-expression analysis of OsLBD genes and their co-regulators revealed multiple modules with tissue-specific roles in pollen cell wall synthesis and endosperm glycogen biosynthesis. Promoter analysis identified several cis-regulatory elements associated with hormone responses, stress adaptation, and developmental processes, consistent with the observed expression patterns under phytohormone treatments. Comparative genomics revealed a higher degree of synteny between rice and barley than between rice and Arabidopsis, highlighting the evolutionary conservation within the Poaceae family. This study provides a foundational framework for understanding the biological functions of OsLBD genes in rice and identifies promising candidate genes involved in vegetative and reproductive growth, development, and stress responses. Full article

The phase-pure cubic pyrochlore of the Bi₂Cr_0.5Co_0.5Nb₂O_9+Δ composition can be successfully synthesized by a modified sol–gel method (Pecini method-PM) and a traditional solid-phase method (SPM). A feature of the solid-phase synthesis method is the formation of bismuth(VI) chromates as intermediate synthesis products, which is confirmed by X-ray spectroscopy data (NEXAFS). During the sol–gel synthesis method, bismuth chromates are not formed due to the formation of the Bi₂₈O₃₂(SO₄)₁₀ salt, which is thermally stable up to 880 °C, preventing the interaction of bismuth(III) and chromium(III) oxides. The temperature of the final pyrochlore calcination during sol–gel synthesis is reduced by 100 °C (950 °C) compared to the solid-phase method. The crystal structure of pyrochlore (sp. gr. Fd-3m, PM, a = 10.49360(5) Å, Z = 4) was refined by the Rietveld method based on X-ray powder diffraction (XRD) data. NEXAFS Cr2p and Co2p spectra of ceramics synthesized at 1050 °C correspond to the charge states of Cr(III), Co(II) and Co(III) ions. The thermal expansion coefficient of the cell was calculated from high-temperature X-ray diffraction measurements in the range of 20–1200 °C. The thermal expansion coefficient (TEC) monotonically increases from 3.92 × 10⁻⁶ °C⁻¹ (20 °C) to 9.89 × 10⁻⁶ °C⁻¹ (1020 °C). Above 1110 °C, TEC decreases due to thermal dissociation of Bi₂Cr_0.5Co_0.5Nb₂O_9+Δ with the formation of CoNb₂O₆, Bi₂O₃. The mixed pyrochlore (PM) exhibits a moderately high permittivity of ∼97, and low dielectric losses of ∼2 × 10⁻³ at 1 MHz and ∼30 °C. The activation energy of conductivity of the high-temperature region is 0.89 eV. The electrical properties of pyrochlore were synthesized by the ceramic (SPM) and Pechini methods (PM) were analyzed. The electrical properties of the samples up to 400 °C were modeled using equivalent electrical circuits Full article

As a process fluid in oil reservoirs, carbon dioxide plays a dominant role in enhanced oil recovery by increasing volume and decreasing interfacial tension. To study the volume expansion behavior of a CO₂–oil system under reservoir conditions, ten hydrocarbon components with carbon numbers ranging from 8 to 26 were selected to represent crude oil. Systems of CO₂ with normal alkanes, cycloalkanes, and aromatic hydrocarbons were measured using a self-assembled high-pressure visible cell, with a temperature range of 313.15 K to 353.15 K and a pressure up to 25 MPa. Experimental results demonstrate that pressure and temperature significantly influence the relative volumetric expansion behavior. The expansion rate exhibits a positive correlation with pressure, whereas it shows a negative correlation with temperature. Among different molecular configurations, normal alkanes exhibit the most pronounced swelling effect. This study establishes that the volumetric expansion behavior of crude oil under CO₂ exposure is predominantly governed by n-alkane components with carbon numbers less than 16. In the heavy hydrocarbon (carbon number > 16) and CO₂ system, the influence of hydrocarbon structure and carbon number on the expansion extent is considerably reduced. This paper delivers critical theoretical foundations for elucidating the microscopic interaction mechanisms in CO₂ enhanced oil recovery and optimizing injection parameter strategies. Full article

Bone metastases continue to be a major cause of morbidity and mortality in patients with advanced cancers, driven by the dynamic remodeling of the bone marrow niche. Traditionally viewed as passive space-fillers, bone marrow adipocytes (BMAs) are now recognized as active regulators of tumor growth, therapeutic resistance, and skeletal pathology. BMAs comprise a significant portion of the adult marrow space, particularly in aging and obesity, and facilitate metastatic colonization through various mechanisms. These include metabolic coupling, where adipocyte-derived fatty acids fuel tumor oxidative phosphorylation; the secretion of adipokines such as leptin and IL-6, which promote epithelial-to-mesenchymal transition, invasion, and immune evasion; regulation of osteoclastogenesis via RANKL expression; and the release of extracellular vesicles that reprogram cancer cell metabolism. Clinical and experimental studies show that BMA expansion correlates with increased tumor burden and poorer outcomes in breast, prostate, lung cancers, and multiple myeloma. Additionally, BMAs actively promote therapeutic resistance through metabolic rewiring and drug sequestration. Experimental models, ranging from in vitro co-cultures to in vivo patient-derived xenografts, demonstrate the complex roles of BMAs and also reveal important translational gaps. Despite promising preclinical approaches such as metabolic inhibitors, PPARγ modulation, adipokine blockade, and lifestyle changes, no therapies directly targeting BMAs have yet reached clinical practice. This review compiles current evidence on the biology of BMAs, their tumor-promoting interactions, and potential therapeutic strategies, while also highlighting unresolved questions about BMA heterogeneity, lipid flux, and immunometabolic crosstalk. By revealing how bone marrow adipocytes actively shape the metastatic niche through metabolic, endocrine, and immunological pathways, this review highlights their potential as novel biomarkers and therapeutic targets for improving the management of bone metastases. Full article

Background/Objectives: Biological aging phenotypes in coronary artery disease (CAD) include coronary atherosclerosis, vascular aging, and endothelial dysfunction. The aim of the present study was to investigate the potential links between aging phenotypes, regulatory immune cells, and features of the thymus in patients with CAD. Methods: A single-center, cross-sectional, comparative study was conducted. Patients were stratified according to the severity of coronary atherosclerosis: patients with a Gensini score ≥ 65 points and patients with a Gensini score < 65 points. Peripheral blood and thymus biopsy were obtained. Imaging flow cytometry, ELISA, and immunohistochemical analysis were used for analysis. Results: Thymic morphology ranged from total fatty involution to a preserved structure of the thymus (20–80% area in 31% of obtained samples) but was not associated with the severity of atherosclerosis. Meanwhile, patients with a Gensini score ≥ 65 had impaired thymus cellular composition compared to patients with a Gensini score < 65 points; increased frequency of CD8+ T lymphocytes and NK cells; and decreased frequency of CD4 + CD8+ T lymphocytes. In peripheral blood, the main determinants of a Gensini score ≥ 65 points were low absolute counts of eMDSCs and CD25^low Tregs with FoxP3 nuclear translocation, while advanced vascular aging was associated with elevated eMDSC absolute counts. Advanced coronary atherosclerosis was also associated with decreased numbers of endothelial progenitor cells in circulation. Conclusions: Thymus dysfunction accompanies CAD progression and is manifested in changes in cellular composition rather than morphology. In CAD patients, MDSC and Treg lymphocytes are equally involved in the progression of coronary atherosclerosis, which is aggravated by the decreased regulatory potential of the endothelium. Vascular aging represents a distinct phenotype of biological aging in CAD patients, characterized by the expansion of eMDSCs. Full article

Background/Objectives: Chimeric Antigen Receptor (CAR)-T cell therapy has demonstrated impressive clinical results against hematological malignancies. However, currently commercialized CAR-T therapies are designed for autologous use, which entails some disadvantages, including high costs, manufacturing delays, complex standardization, and frequent production failures due to patient T cell dysfunction. Moreover, their CARs target one specific antigen, increasing the probability of antigen-negative tumor relapses. To overcome these limitations, we developed a novel NKG2D CAR-T cell therapy for allogeneic use with broad target specificity, as this CAR targets eight different ligands commonly upregulated in both solid and hematological tumors. Additionally, the manufacturing process was optimized to improve the phenotypic characteristics of the final product. Methods: Multiplex CRISPR/Cas9 technology was applied to eliminate the expression of TCR and HLA class I complexes in healthy donor T cells to reduce the risk of graft-versus-host disease and immune rejection, respectively, as well as lentiviral transduction for introducing the second-generation NKG2D-CAR. Moreover, we sought to optimize this manufacturing process by comparing the effect of different culture interleukin supplementations (IL-2, IL-7/IL-15 or IL-7/IL-15/IL-21) on the phenotypic and functional characteristics of the product obtained. Results: Our results showed that the novel CAR-T cells effectively targeted cervicouterine and colorectal cancer cells, and that those manufactured with IL-7/IL-15/IL-21 supplementation showed the most suitable characteristics among the conditions tested, considering genetic modification efficiency, cell proliferation, antitumor activity and proportion of the stem cell memory T cell subset, which is associated with enhanced in vivo CAR-T cell survival, expansion and long-term persistence. Conclusions: In summary, this new prototype of NKG2D CAR-T cell therapy for allogeneic use represents a promising universal treatment for a wide range of tumor types. Full article

This study investigates the acoustic performance of Ecoflex™ 00-35, a highly flexible silicone rubber, for use in soft and adaptable vibration and noise control systems. Under normal conditions, Ecoflex™ 00-35 consists of two components—Part A and Part B—which are mixed and cured at room temperature to form an elastomer. In this study, curing parameters such as the A/B mixing ratio, thinning agent addition, and curing pressure were varied to examine their effects on acoustic behavior. The microstructure of the prepared samples was analyzed using scanning electron microscopy (SEM), while sound absorption properties were measured using impedance tubes. Test results demonstrated that modifying curing parameters, applying vacuum, and incorporating a thinning agent increased the average cell diameter, leading to the fabrication of a moderate sound absorber with a sound absorption coefficient ranging from 0.35 to 0.60 in the low- to mid-frequency ranges. Further enhancement in low-frequency absorption was achieved by applying low pressure for a short duration, allowing cell expansion. In contrast, the addition of a thinning agent significantly improved absorption at higher frequencies. These findings highlight the influence of processing conditions on the acoustic behavior of soft silicone elastomers and provide valuable insights into their structure–property relationships. Ultimately, this study contributes to the development of advanced materials for acoustic damping and noise control applications. Full article

Copper is a vital micronutrient for animals and plants acting as a crucial cofactor in the synthesis of numerous metabolic enzymes and contributing to mitochondrial respiration, metabolism, oxido-reductive reactions, signal transmission, and oxidative and nitrosative damage. In the cells, copper may exist in the Cu⁺ and Cu⁺⁺ oxidation states and the interconversion between these two states may occur via various redox reactions regulating cellular respiration, energy metabolism, and cell growth. The human body maintains a low level of copper, and copper deficiency or copper excess may adversely affect cellular functions; therefore, regulation of copper levels within a narrow range is important for maintaining metabolic homeostasis. Recent studies identified a new copper-dependent form of cell death called cuproptosis. Cuproptosis occurs due to copper binding to lipoylated enzymes (for instance, pyruvate dehydrogenase and α-ketoglutarate dehydrogenase) in the tricarboxylic acid Krebs cycle. In recent years, extensive studies on copper homeostasis and copper-induced cell death in degenerative disorders, like Menkes, Wilson, Alzheimer, Parkinson’s, Huntington’s diseases, and Amyotrophic Lateral Sclerosis, have discussed the therapeutic potential of targeting cuproptosis. Copper contamination in the environment, which has increased in recent years due to the expansion of agricultural and industrial activities, is associated with a wide range of human health risks. Soil used for the cultivation of grapes has a long history of copper-based fungicide application (the Bordeaux mixture is rich in copper) resulting in copper accumulation at levels capable of causing toxicity in plants that co-inhabit the vineyards. Phytoremediation, which uses plants and biological solutions to remove toxic heavy metals and pesticides and other contaminants from soil and water, is an environmentally friendly and cost-effective technology used for the removal of copper. It requires plants to be tolerant of high levels of copper and capable of accumulating metal copper in plants’ aerial organs and roots. This review aims at highlighting the importance of copper as an essential metal, as well as its involvement in cuproptosis and neurodegenerative diseases. Full article

Background/Objectives: Hematogones, B cell precursors, are considered a clock of bone marrow reconstitution after chemotherapy and hematopoietic stem cell transplantation (HSCT). Methods: In this retrospective observational monocentric study, we investigated the prognostic role of hematogone expansion after allogeneic HSCT and its association with clinical and molecular features. Results: Using a cut-off value of 0.1%, hematogones were detected in 60% of patients at the first re-evaluation after HSCT (median, 2.4%; range, 0.2–9.0%) and in 63% of subjects at the most recent evaluation (MRR) (median, 1.4%; range, 0.1–5.1%). In particular, prolonged hematogone expansion was associated with longer overall survival (p = 0.0043) and relapse-free survival (p = 0.0002). No associations were described between hematogone frequency and stem cell sources or acute or chronic graft versus host disease incidence. Conclusions: In conclusion, our results confirmed that hematogones mirrored bone marrow fitness and reconstitution ability; thus, they could be used as a prognostic marker of HSCT outcomes. Full article

The rapid expansion of broadband wireless communication systems, including 5G, satellite networks, and next-generation IoT platforms, has created a strong demand for antenna architectures capable of real-time beam control, compact integration, and broad frequency coverage. Traditional reflectarrays, while effective for narrowband applications, often face inherent limitations such as fixed beam direction, high insertion loss, and complex phase-shifting networks, making them less viable for modern adaptive and reconfigurable systems. Addressing these challenges, this work presents a novel wideband planar metasurface that operates as a polarization rotation reflective metasurface (PRRM), combining 90° polarization conversion with 1-bit reconfigurable phase modulation. The metasurface employs a mirror-symmetric unit cell structure, incorporating a cross-shaped patch with fan-shaped stub loading and integrated PIN diodes, connected through vertical interconnect accesses (VIAs). This design enables stable binary phase control with minimal loss across a significantly wide frequency range. Full-wave electromagnetic simulations confirm that the proposed unit cell maintains consistent cross-polarized reflection performance and phase switching from 3.83 GHz to 15.06 GHz, achieving a remarkable fractional bandwidth of 118.89%. To verify its applicability, the full-wave simulation analysis of a 16 × 16 array was conducted, demonstrating dynamic two-dimensional beam steering up to ±60° and maintaining a 3 dB gain bandwidth of 55.3%. These results establish the metasurface’s suitability for advanced beamforming, making it a strong candidate for compact, electronically reconfigurable antennas in high-speed wireless communication, radar imaging, and sensing systems. Full article

The commercialization of proton-conducting fuel cells (PCFCs) is hindered by the limited electroactivity and durability of cathodes at intermediate temperatures ranging from 400 to 700 °C, a challenge exacerbated by an insufficient understanding of high-entropy perovskite (HEP) materials for oxygen reduction reaction (ORR) optimization. This study introduces an yttrium-doped HEP to address these limitations. A comparative analysis of Ce_0.2−xY_xBa_0.2Sr_0.2La_0.2Ca_0.2CoO_3−δ (x = 0, 0.2; designated as CBSLCC and YBSLCC) revealed that yttrium doping enhanced the ORR activity, reduced the thermal expansion coefficient (19.9 × 10⁻⁶ K⁻¹, 30–900 °C), and improved the thermomechanical compatibility with the BaZr_0.1Ce_0.7Y_0.1Yb_0.1O_3−δ electrolytes. Electrochemical testing demonstrated a peak power density equal to 586 mW cm⁻² at 700 °C, with a polarization resistance equaling 0.3 Ω cm². Yttrium-induced lattice distortion promotes proton adsorption while suppressing detrimental Co spin-state transitions. These findings advance the development of durable, high-efficiency PCFC cathodes, offering immediate applications in clean energy systems, particularly for distributed power generation. Full article

Bacteriophages (phages), the most abundant biological entities on Earth, have long served as both model systems and therapeutic tools. Recent advances in synthetic biology and genetic engineering have revolutionized the capacity to tailor phages with enhanced functionality beyond their natural capabilities. This review outlines the current landscape of synthetic and functional engineering of phages, encompassing both in-vivo and in-vitro strategies. We describe in-vivo approaches such as phage recombineering systems, CRISPR-Cas-assisted editing, and bacterial retron-based methods, as well as synthetic assembly platforms including yeast-based artificial chromosomes, Gibson, Golden Gate, and iPac assemblies. In addition, we explore in-vitro rebooting using TXTL (transcription–translation) systems, which offer a flexible alternative to cell-based rebooting but are less effective for large genomes or structurally complex phages. Special focus is given to the design of customized phages for targeted applications, including host range expansion via receptor-binding protein modifications, delivery of antimicrobial proteins or CRISPR payloads, and the construction of biocontained, non-replicative capsid systems for safe clinical use. Through illustrative examples, we highlight how these technologies enable the transformation of phages into programmable bactericidal agents, precision diagnostic tools, and drug delivery vehicles. Together, these advances establish a powerful foundation for next-generation antimicrobial platforms and synthetic microbiology. Full article

Meloidogyne incognita (M. incognita) is a devastating root-knot nematode that parasitizes a broad range of crop species by inducing the formation of giant cells (GCs) in host roots, thereby facilitating nutrient acquisition. This process profoundly alters host sugar metabolism, yet the molecular regulators underlying sugar dynamics during infection remain poorly understood in cucumber. In this study, we investigated the role of the cucumber alkaline α-galactosidase gene (CsAGA1) in M. incognita-infected roots. Histochemical analysis of proCsAGA1::GUS transgenic lines demonstrated that CsAGA1 is spatially localized to nematode-induced feeding sites, with its expression markedly induced in GCs and phloem-adjacent tissues during infection. Functional analyses revealed that silencing CsAGA1 impaired root and gall development. CsAGA1-silenced plants exhibited increased gall numbers (per gram root) but significantly reduced root growth and smaller galls compared to controls. These results indicate that CsAGA1 is required for proper gall expansion and root growth during M. incognita infection. This study provides novel insight into the sugar-mediated regulation of host–nematode interactions, and CsAGA1 emerges as a potential target for the biological control of M. incognita. Full article

Epigeal cotyledons with excised embryonic axes are often used as a model system to study the processes of cell division and expansion. These processes are regulated by diverse phytohormones and signaling molecules. Phytohormones modulate antioxidant defense systems and interact with reactive oxygen species (ROS) to synchronize normal plant cell growth. This study provides new information concerning alterations in enzymatic antioxidants linked to the production and scavenging of ROS in excised epigeal cotyledons of zucchini grown on solutions of methyl jasmonate (MeJA) and cytokinins (CKs)—N⁶-benzyl adenine and N₁-(2-chloropyridin-4-yl)-N₂-phenylurea—in the presence or absence of light under laboratory conditions. The cotyledon material was used to determine the dynamics of selected biochemical parameters starting from the 2nd to the 6th day of incubation. In general, our results revealed that exogenous MeJA caused a reduction in the content of hydrogen peroxide (H₂O₂) and free proline, as well as in the activity of superoxide dismutase (SOD), guaiacol peroxidase (POX) and catalase (CAT) in dark-grown cotyledons. Applied alone, both cytokinins increased most of the parameters studied, except proline and protein levels. However, when MeJA was combined with CKs, it acted in a diverse manner, ranging from antagonistic to synergistic depending on the cytokinin type, parameter measured and light regime. Similar alterations were also found in the levels of leaf pigments in the cotyledons grown under light conditions. In general, the changes in the antioxidant enzyme activities due to light were more intense than those observed in dark-grown cotyledons. The data obtained show, for the first time, the involvement of the hormonal interplay between MeJA and CKs on the biochemical changes in antioxidant defense during cotyledon growth under different light conditions. Full article