Search Results (948)

The life cycle of the hepatitis C virus (HCV) is closely linked to lipid metabolism. Recently, the stress defence transcription factor, nuclear factor erythroid 2 related factor-1 (Nrf1), has been described as a cholesterol sensor that protects the liver from excess cholesterol. Nrf1, like its homologue Nrf2, further responds to oxidative stress by binding with small Maf proteins (sMaf) to the promotor antioxidant response element (ARE). Given these facts, investigating the crosstalk between Nrf1 and HCV was a logical next step. In HCV-replicating cells, we observed reduced levels of Nrf1. Furthermore, activation of Nrf1-dependent target genes is impaired due to sMaf sequestration in replicase complexes. This results in a shortage of sMaf proteins in the nucleus, trapping Nrf1 at the replicase complexes and further limiting its function. Weakened Nrf1 activity contributes to impaired cholesterol removal, which occurs alongside an elevated intracellular cholesterol level and inhibited LXRα promoter activation. Furthermore, inhibition of Nrf1 activity correlated with a kinome profile characteristic of steatosis and enhanced inflammation—factors contributing to HCV pathogenesis. Our results indicate that activation of Nrf1-dependent target genes is impaired in HCV-positive cells. This, in turn, favours viral morphogenesis, as evidenced by enhanced replication and increased production of viral progeny. Full article

This work investigates the impact of an internal electric field on the annihilation characteristics of positrons implanted in a $180\left(10\right)\mathrm{nm}$ SiO₂ layer of a Metal-Oxide-Silicon (MOS) capacitor, using Positron Annihilation Lifetime Spectroscopy (PALS). By varying the gate voltage, electric fields up to $1.72\mathrm{MV}/\mathrm{cm}$ were applied. The measurements reveal a field-dependent suppression of positronium (Ps) formation by up to $64\%$, leading to an enhancement of free positron annihilation. The increase in free positrons suggests that vacancy clusters are the dominant defect type in the oxide layer. Additionally, drift towards the SiO₂/Si interface reveals not only larger void-like defects but also a distinct population of smaller traps that are less prominent when drifting to the Al/SiO₂ interface. In total, by combining positron drift with PALS, more detailed insights into the nature and spatial distribution of defects within the SiO₂ network and in particular near the SiO₂/Si interface are obtained. Full article

Dendrons, also named dendritic wedges, are a kind of molecular tree, having a branched structure linked to a functional core. The functional core can be used in particular for the functionalization of materials. Different types of dendrons are known, synthesized either by a convergent process, from the external part to the core, or by a divergent process from the core to the external part. Polyphosphorhydrazone (PPH) dendrons are always synthesized by a divergent process, which enables a fine-tuning of both the core function and the external functions. They have been used for the functionalization of diverse materials such as silica, titanium dioxide, gold, graphene oxide, or different types of nanoparticles. Nanocomposites based on materials functionalized with PPH dendrons have been used in diverse fields such as catalysts, chemical sensors, for trapping pollutants, to support cell cultures, and against cancers, as will be emphasized in this review. Full article

Metastases are the leading cause of cancer-related deaths. The spread of neoplasms involves multiple mechanisms, with metastatic tumors exhibiting molecular behaviors distinct from their primary counterparts. The key hallmarks of metastatic lesions include chromosomal instability, copy number alterations (CNAs), and a reduced degree of subclonality. Furthermore, metabolic adaptations such as enhanced glycogen synthesis and storage, as well as increased fatty acid oxidation (FAO), play a critical role in sustaining energy supply in metastases and contributing to chemoresistance. FAO promotes the infiltration of macrophages into the tumor, where they polarize to the M2 phenotype, which is associated with immune suppression and tissue remodeling. Additionally, the tumor microbiome and the action of cytotoxic drugs trigger neutrophil extravasation through inflammatory pathways. Chemoresistant neutrophils in the tumor microenvironment can suppress effector lymphocyte activation and facilitate the formation of neutrophil extracellular traps (NETs), which are linked to drug resistance. This article examines the genomic features of metastatic tumors, along with the metabolic and immunological dynamics within the metastatic tumor microenvironment, and their contribution to drug resistance. It also discusses the molecular mechanisms underlying resistance to chemotherapeutic agents commonly used in the treatment of metastatic cancer. Full article

Ceramic dental prosthetics with internal metal structures are made from a cobalt–chromium alloy that is coated with ceramic. This study aims to validate surface treatments for the metal that enhance the adhesion of the ceramic coating under masticatory forces. Surface conditioning is performed using mechanical methods, like sandblasting (SB), and thermal methods, such as oxidation (O). The ceramic coating is applied to the metal component following the conditioning process, which can be conducted using either a single method or a combination of methods. Each conditioned sample undergoes characterization through various techniques, including drop shape analysis (DSA), scanning electron microscopy (SEM), X-ray diffraction (EDX), and atomic force microscopy (AFM). After the ceramic coating is applied and subjected to thermal sintering, the metal–ceramic samples are mechanically tested to assess the adhesion of the ceramic layer. The research findings, illustrated by scanning electron microscopy (SEM) images of the metal structures’ surfaces, indicate that alloy powder particles ranging from 10 to 50 µm were either adhered to the surfaces or present as discrete dots. Particles that exceed the initial design specifications of the structure can be smoothed out using sandblasting or mechanical finishing techniques. The energy-dispersive spectroscopy (EDS) results show that, after sandblasting, fragments of aluminum oxide remain trapped on the surface of the metal structures. These remnants are considered impurities, which can negatively impact the adhesion of the ceramic to the metal substrate. The analysis focuses on the exfoliation of the ceramic material from the deformed metal surfaces. The results emphasize the significant role of the sandblasting method and the micro-topography it creates, as well as the importance of the oxidation temperature in the treatment process. Drawing on 25 years of experience in dental prosthetics and the findings from this study, this publication aims to serve as a guide for applying the ceramic bonding layer to metal surfaces and for conditioning methods. These practices are essential for enhancing the adhesion of ceramic materials to metal substrates. Full article

Seven lager beers and seven non-alcoholic counterparts, marketed by the same producers, were analyzed for their total phenolic content (TPC), radical scavenging activity (RSA) towards the DPPH radical and ThioBarbituric Index (TBI). All beers were also subjected to spin trapping experiments at 60 °C in the presence of PBN. To our knowledge, this is the first time that non-alcoholic beers (NABs) have been subjected to spin trapping experiments coupled with Electron Spin Resonance (ESR) spectroscopy. The evolution of the intensity of the PBN radical adducts during the first 150 min was represented graphically and the intensity at 150 min (I₁₅₀) and the area under the curve (AUC), were measured. The I₁₅₀ and the AUC of lagers and NABs are significantly different, whereas the TPC, the EC₅₀ of the DPPH assay, and the TBI of the two groups are superimposed. A relationship, previously proposed by us, to correlate ESR spectroscopy parameters with others obtained from UV-Vis spectrophotometry, was also applied, demonstrating its practicability. Multivariate analysis shows that clustering in two separate groups occurs only if I₁₅₀ and AUC are included in the model. Based on these results, ESR spectroscopy can be applied to study the oxidative stability of NABs. Full article

In this paper, a series of polyaniline (PANI)/Ti₃C₂ MXene composites (PMCs) with a biomimetic structure were prepared and employed as an anticorrosion coating application. First, the PANI was synthesized by oxidative polymerization with ammonium persulfate as the oxidant. Then, 2D Ti₃C₂ MXene nanosheets were prepared by treating the Ti₃AlC₂ using the optimized minimally intensive layer delamination (MILD) method, followed by characterization via XRD and SEM. Subsequently, the PMC was prepared by the oxidative polymerization of aniline monomers in the presence of Ti₃C₂ MXene nanosheets, followed by characterization via FTIR, XRD, SEM, TEM, CV, and UV–Visible. Eventually, the PMC coatings with the artificial biomimetic surface structure of a macaw feather were prepared by the nano-casting technique. The corrosion resistance of the PMC coatings, evaluated via Tafel polarization and Nyquist impedance measurements, shows that increasing the MXene loading up to 5 wt % shifts the corrosion potential (E_corr) on steel from −588 mV to −356 mV vs. SCE, reduces the corrosion current density (I_corr) from 1.09 µA/cm² to 0.035 µA/cm², and raises the impedance modulus at 0.01 Hz from 67 kΩ to 3794 kΩ. When structured with the hierarchical feather topography, the PMC coating (Bio-PA-MX-5) further advances the E_corr to +103.6 mV, lowers the I_corr to 7.22 × 10⁻⁴ µA/cm², and boosts the impedance to 96,875 kΩ. Compared to neat coatings without biomimetic structuring, those with engineered biomimetic surfaces showed significantly improved corrosion protection performance. These enhancements arise from three synergistic mechanisms: (i) polyaniline’s redox catalysis accelerates the formation of a dense passive oxide layer; (ii) MXene nanosheets create a tortuous gas barrier that cuts the oxygen permeability from 11.3 Barrer to 0.9 Barrer; and (iii) the biomimetic surface traps air pockets, raising the water contact angle from 87° to 135°. This integrated approach delivers one of the highest combined corrosion potentials and impedance values reported for thin-film coatings, pointing to a general strategy for durable steel protection. Full article

The microstructure evolution and hardness variations of as-fabricated and recrystallized 12Cr oxide dispersion strengthened (ODS) steel after dual-ion (6.4 MeV Fe³⁺ and energy-degraded 1 MeV He⁺) irradiation at 973 K up to 10.6 displacements per atom (dpa) at peak damage and 8900 appm He are investigated. Results show that the oxide particles slightly shrink in the as-fabricated specimen, while they are stable in the recrystallized specimen. Furthermore, larger helium bubbles are trapped at the grain boundaries in the as-fabricated specimen, and the size of helium bubbles in the grains is almost the same for both as-fabricated and recrystallized specimens, indicating that reduction of grain boundaries would reduce the potential nucleation sites and suppress the helium segregation. Moreover, no obvious hardening occurs in the as-fabricated specimen, whereas the hardness increases a little in the recrystallized specimen. Based on the barrier model, the barrier strength factor of helium bubbles is calculated. The value is 0.077, which is much smaller and suggests that helium bubbles seem not to significantly induce irradiation hardening. Full article

This review highlights recent insights into the pathophysiology and therapeutic strategies for improving biocompatibility in hemodialysis. Hemodialysis activates the innate immune system, particularly the complement cascade and neutrophils, leading to acute microinflammation. Interleukin-8 (IL-8), which increases during dialysis, promotes neutrophil chemotaxis and neutrophil extracellular trap (NET) formation, triggering myeloperoxidase (MPO) release and oxidative stress. Neutrophil accumulation in atherosclerotic plaques exacerbates vascular inflammation through IL-6 upregulation. Elevated levels of IL-8, MPO, and NET-related biomarkers are associated with increased all-cause and cardiovascular mortality in dialysis patients. Strategies to mitigate these effects include the use of advanced membrane materials (e.g., AN69, vitamin E-coated, polymethyl methacrylate), novel dialysis modalities (e.g., high-volume online hemodiafiltration, cool dialysate, hydrogen-enriched dialysate), and citrate-based anticoagulation. These approaches aim to suppress complement activation, reduce oxidative stress, and limit neutrophil-induced damage. Enhancing biocompatibility is crucial for reducing cardiovascular complications and improving outcomes in dialysis patients. Suppressing the innate immune response during dialysis may become a future cornerstone in extracorporeal blood purification therapy. Full article

We report the first syntheses—from commercially available 3-chloro-2-fluoroprop-1-ene (9)—of key garlic-derived compounds containing sp²-fluorine. We also report synthesis of fluoro-5,6-dihydrothiopyrans by trapping 2-fluorothioacrolein (15). Thus, difluoroallicin (12, S-(2-fluoro-2-propenyl) 2-fluoroprop-2-ene-1-sulfinothioate) is prepared by peracid oxidation of 1,2-bis(2-fluoro-2-propenyl)disulfane (11). S-2-Fluoro-2-propenyl-l-cysteine (2-fluorodeoxyalliin, 13), synthesized from cysteine and characterized by X-ray crystallography, is oxidized to its S-oxide, 2-fluoroalliin (22). The latter, with alliinase-containing powdered fresh garlic, gives a mixture of 12, allicin (1), and isomers of monofluoroallicin (23), indicating that 22 serves as a substrate for garlic alliinase. Upon heating, 12 generates transient 15, which dimerizes giving difluoro vinyl dithiins 6 and 7. Ethyl acrylate trapping of 15 affords 5- and 6-substituted 3-fluoro-5,6-dihydro-4H-thiopyrans (19 and 20). In 1,1,1,3,3,3-hexafluoro-2-propanol (HEFP) as solvent, 12 is converted into trifluoroajoene ((E,Z)-1-(2-fluoro-3-((2-fluoro-2-propenyl)sulfinyl)prop-1-en-1-yl)-2-(2-fluoro-2-propenyl)disulfane; 18). Liquid sulfur converts 11 to a (CH₂=CFCH₂)₂S_n mixture (n = 4–15), characterized by UPLC-(Ag⁺)-coordination ion spray-mass spectrometry. Full article

The removal of partially hydrogenated fats, as well as the substitution of saturated fats with healthier alternatives, has become increasingly common due to their well-established association with adverse health effects. As a result, the demand for alternative formulations in the food industry has driven the development of a promising emerging technology: oleogels. Oleogels are a semi-solid material made by trapping liquid oil within a three-dimensional network formed by structuring agents. Within this context, this study aimed to develop and characterize margarines prepared with oleogels formulated from extra virgin olive oil, coconut oil, starch, and beeswax at varying concentrations. The proposed oleogel-based formulations exhibited a high melting temperature range and lower enthalpy. Although lipid oxidation levels differed between the commercial and oleogel-based margarines, they remained within acceptable limits. A significant difference in color was observed, with the oleogel formulations imparting a slight greenish hue compared to the commercial margarine. In terms of microstructure, the commercial margarine presented smaller and more uniformly distributed water droplets. Oleogel-based margarines demonstrated technological feasibility. Considering consumers’ growing interest in food innovation and health-conscious products, olive oil-based oleogel margarines represent a promising alternative, particularly due to the nutritional benefits associated with olive oil. Full article

This study explores the identification, characterization, and biological evaluation of angiotensin I-converting enzyme (ACE)-inhibitory peptides derived from enzymatic hydrolysates of crucian carp swim bladders. Following sequential purification by size-exclusion and reversed-phase chromatography, two bioactive peptides—Hyp-Gly-Ala-Arg (Hyp-GAR) and Gly-Ala-Hyp-Gly-Ala-Arg (GA-Hyp-GAR)—were identified using ultra-high-performance liquid chromatography coupled with linear ion trap–Orbitrap tandem mass spectrometry. The synthetic peptides demonstrated potent ACE-inhibitory activity in vitro, with IC₅₀ values of 12.2 μM (Hyp-GAR) and 4.00 μM (GA-Hyp-GAR). Molecular docking and enzyme kinetics confirmed competitive inhibition through key interactions with ACE active site residues and zinc coordination. In vivo antihypertensive activity was evaluated in spontaneously hypertensive rats, revealing that GA-Hyp-GAR significantly reduced systolic blood pressure in a dose-dependent manner. At a dose of 36 mg/kg, GA-Hyp-GAR reduced systolic blood pressure by 60 mmHg—an effect comparable in magnitude and timing to that of captopril. Mechanistically, GA-Hyp-GAR modulated levels of angiotensin II, bradykinin, endothelial nitric oxide synthase, and nitric oxide. A 90-day subchronic oral toxicity study in mice indicated no significant hematological, biochemical, or histopathological alterations, supporting the peptide’s safety profile. These findings suggest that GA-Hyp-GAR is a promising natural ACE inhibitor with potential application in functional foods or as a nutraceutical for hypertension management. Full article

Osteoarthritis (OA) is a prevalent and debilitating joint disease in older adults with a complex etiology. We investigated the role of SUMOylation, a post-translational modification, in OA pathogenesis, focusing on the mitochondrial chaperone Prohibitin (PHB1) and the cartilage homeostasis transcription factor PITX1. We hypothesized that oxidative stress-induced SUMOylation promotes PHB1 nuclear accumulation, leading to PITX1 downregulation and contributing to OA development. Analysis of cartilage specimens from 27 OA patients and 4 healthy controls revealed an increased nuclear accumulation of PHB1 in OA chondrocytes, accompanied by elevated levels of SUMO-1 and SUMO-2/3. Mechanistically, nuclear PHB1 interacted indirectly with SUMO-1 through a SUMO-interacting motif (SIM), and the deletion of this SIM prevented PHB1 nuclear trapping in OA cells. Furthermore, the SUMO-conjugating enzyme E2 (UBC9) encoded by the UBE2I gene was upregulated in knee OA cartilage, and its overexpression in vitro enhanced PHB1 nuclear accumulation. Consistently, transgenic mice overexpressing the Ube2i gene exhibited increased UBC9 in their knee cartilage, resulting in Pitx1 downregulation and the emergence of an early OA-like phenotype in articular chondrocytes. Our findings uncover a novel role for UBC9-mediated SUMOylation in primary knee and hip OA. This pathway enhances PHB1 nuclear accumulation, contributing to PITX1 repression and subsequent OA development. These results underscore the importance of SUMOylation in OA pathogenesis and suggest potential molecular targets for early diagnosis and therapeutic intervention. Full article

In this study, zinc–tin oxide (ZTO) thin films were prepared via radio-frequency magnetron sputtering to examine the influence of annealing temperature on the performance of thin-film transistors (TFTs) and their resistive-load inverters. The findings reveal that annealing modulates the concentration and spatial distribution of oxygen vacancies (V_O), which directly affect carrier density and interface trap density, ultimately determining the electrical behavior of inverters. At the optimal annealing temperature of 600 °C, the V_O concentration was effectively moderated, resulting in a TFT with a mobility of 12.39 cm² V⁻¹ s⁻¹, a threshold voltage of 6.13 V, an on/off current ratio of 1.09 × 10⁸, and a voltage gain of 11.77 in the corresponding inverter. However, when the V_O concentration deviated from this optimal range, whether in excess or deficiency, the gain was reduced and power consumption increased. This V_O engineering strategy enables the simultaneous optimization of both TFT and inverter performance without relying on rare elements, offering a promising pathway toward the development of low-cost, large-area, flexible, and transparent electronic devices. Full article

This study systematically investigates the mechanism by which total ionizing dose (TID) affects the lifetime degradation of NMOS devices induced by hot-carrier injection (HCI). Experiments involved Cobalt-60 (Co-60) gamma-ray irradiation to a cumulative dose of 500 krad (Si), followed by 168 h annealing at 100 °C to simulate long-term stability. However, under HCI stress conditions (V_D = 2.7 V, V_G = 1.8 V), irradiated devices show a 6.93% increase in threshold voltage shift (ΔV_th) compared to non-irradiated counterparts. According to the IEC 62416 standard, the lifetime degradation of irradiated devices induced by HCI stress is only 65% of that of non-irradiated devices. Conversely, when the saturation drain current (I_Dsat) degrades by 10%, the lifetime doubles compared to non-irradiated counterparts. Mechanistic analysis demonstrates that partial neutralization of E’ center positive charges at the gate oxide interface by hot electrons weakens the electric field shielding effect, accelerating ΔV_th drift, while interface trap charges contribute minimally to degradation due to annealing-induced self-healing. The saturation drain current shift degradation primarily correlates with electron mobility variations. This work elucidates the multi-physics mechanisms through which TID impacts device reliability and provides critical insights for radiation-hardened design optimization. Full article