Search Results (1,194)

Background/Objectives: Hutchinson–Gilford progeria syndrome (HGPS) is a rare and fatal genetic disease caused by a silent mutation in the LMNA gene, leading to the production of progerin, a defective prelamin A variant. Progerin accumulation disrupts nuclear integrity, alters chromatin organization, and drives systemic cellular dysfunction. While autophagy and inflammation are key dysregulated pathways in HGPS, the role of microRNAs (miRNAs) in these processes remains poorly understood. Methods: We performed an extensive literature review to identify miRNAs involved in autophagy and inflammation. Through stem-loop RT-qPCR in aging HGPS and control fibroblast strains, we identified significant miRNAs and focused on the most prominent one, miR-181a-5p, for in-depth analysis. We validated our in vitro findings with miRNA expression studies in skin biopsies from an HGPS mouse model and conducted functional assays in human fibroblasts, including immunofluorescence staining, β-Galactosidase assay, qPCR, and Western blot analysis. Transfection studies were performed using an miR-181a-5p mimic and its inhibitor. Results: We identified miR-181a-5p as a critical regulator of premature senescence in HGPS. miR-181a-5p was significantly upregulated in HGPS fibroblasts and an HGPS mouse model, correlating with Sirtuin 1 (SIRT1) suppression and induction of senescence. Additionally, we demonstrated that TGFβ1 induced miR-181a-5p expression, linking inflammation to miRNA-mediated senescence. Inhibiting miR-181a-5p restored SIRT1 levels, increased proliferation, and alleviated senescence in HGPS fibroblasts, supporting its functional relevance in disease progression. Conclusions: These findings highlight the important role of miR-181a-5p in premature aging and suggest its potential as a therapeutic target for modulating senescence in progeroid syndromes. Full article

Botryosphaeria dothidea is the causative agent of Chinese hickory trunk canker, which poses significant threat to the production of Chinese hickory (Carya cathayensis Sarg.). Previous studies reported that endophytic–pathogenic phase transition, also referred to as latent infection, plays an important role in the interaction of Botryosphaeria dothidea with various host plants, including Chinese hickory. However, the mechanism underlying this phase transition is not well understood. Here, we employed RNA-Seq to investigate transcriptional changes in B. dothidea during its phase transition upon interaction with Chinese hickory. A co-expression network was generated based on 6391 differentially expressed genes (DEGs) identified from different infection stages and temperature treatments. One co-expressed module was found that highly correlated with temperature treatments which simulated conditions of B. dothidea latent infection in the field. Subsequently, 53 hub genes were detected, and gene ontology (GO) enrichment analysis revealed three categories of enriched GO terms: transmembrane transport or activity, ion homeostasis or transport, and carbohydrate metabolism. One PacC transcriptional factor (BDLA_00001555, an ambient pH regulator), and one endo-β-1,3-glucanase (BDLA_00010249) were specifically upregulated under temperature treatments that corresponded with the activation stage of B. dothidea’s pathogenic state. The knockout mutant strain of BDLA_00001555 demonstrated defective capability upon the activation of the pathogenic state. This confirmed that BDLA_00001555, the PacC transcriptional factor, plays an important role in the latent infection phase of B. dothidea. Our findings provide insights into the pathogenic mechanism of Chinese hickory trunk canker disease. Full article

FeAl intermetallic compounds exhibit high application potential in high-voltage transmission lines to withstand external forces such as powerlines’ own gravity and wind force. The ordered crystal structure in FeAl intermetallic compounds endows materials with high strength, but the remarkable brittleness at room temperature restricts engineering applications. This contradiction is essentially closely related to the deformation mechanism at the nanoscale. Here, we performed molecular dynamics simulations to reveal anomalous grain size effects and deformation mechanisms in nanocrystalline FeAl intermetallic material. Models with grain sizes ranging from 6.2 to 17.4 nm were systematically investigated under uniaxial tensile stress. The study uncovers a distinctive inverse Hall-Petch relationship governing flow stress within the nanoscale regime. This behavior stems from high-density grain boundaries promoting dislocation annihilation over pile-up. Crucially, the material exhibits anomalous ductility at ultra-high strain rates due to stress-induced phase transformation dominating the plastic deformation. The nascent FCC phase accommodates strain through enhanced slip systems and inherent low stacking fault energy with the increasing phase fraction paralleling the stress plateau. Nanoconfinement suppresses the propagation of macroscopic defects while simultaneously suppressing room-temperature brittle fracture and inhibiting the rapid phase transformation pathways at extreme strain rates. These findings provide new theoretical foundations for designing high-strength and high-toughness intermetallic nanocompounds. Full article

Surface and sub-surface atomic configurations are critical for catalysis as they host the active sites governing electrochemical processes. This study employs density functional theory (DFT) calculations and Monte Carlo simulations combined with the cluster-expansion approach to investigate atom distribution and Pt segregation in Pt-Fe alloys across varying Pt/Fe ratios. Our simulations reveal a strong tendency for Pt atoms to segregate to the surface layer while Fe atoms enrich the sub-surface region. Crucially, the calculations predict the stability of a periodic Pt₂Fe alloy surface model, characterized by specific defect structures, at low platinum content and low annealing temperatures. Electronic structure analysis indicates that forming this Pt₂Fe surface alloy lowers the d-band center of Pt atoms, weakening CO adsorption and thereby enhancing resistance to CO poisoning. Although defect-induced strains can modulate the d-band center, crystal orbital Hamilton population (COHP) analysis confirms that such strains generally strengthen Pt-CO interactions. Therefore, the theoretical design of Pt₂Fe alloy surfaces and controlling defect density are predicted to be effective strategies for enhancing catalyst resistance to CO poisoning. This work highlights the advantages of periodic Pt₂Fe surface models for anti-CO poisoning and provides computational guidance for designing efficient Pt-based electrocatalysts. Full article

The constitutive model is widely employed to characterize the rheological properties of metallic materials under high-temperature conditions. It is typically derived from a series of high-temperature tests conducted at varying deformation temperatures, strain rates, and strains, including hot stretching, hot compression, separated Hopkinson pressure bar testing, and hot torsion. The original experimental data used for establishing the constitutive model serves as the foundation for developing phenomenological models such as Arrhenius and Johnson–Cook models, as well as physical-based models like Zerilli–Armstrong or machine learning-based constitutive models. The resulting constitutive equations are integrated into finite element analysis software such as Abaqus, Ansys, and Deform to create custom programs that predict the distributions of stress, strain rate, and temperature in materials during processes such as cutting, stamping, forging, and others. By adhering to these methodologies, we can optimize parameters related to metal processing technology; this helps to prevent forming defects while minimizing the waste of consumables and reducing costs. This study provides a comprehensive overview of commonly utilized experimental equipment and methods for developing constitutive models. It discusses various types of constitutive models along with their modifications and applications. Additionally, it reviews recent research advancements in this field while anticipating future trends concerning the development of constitutive models for high-temperature deformation processes involving metallic materials. Full article

Transition-metal and rare-earth element co-doped ZnO nanoparticles have attracted significant attention due to their potential applications in spintronics and optoelectronics. In this study, Zn_0.95Co_0.01EuxO (x = 0.01–0.05) nanoparticles were synthesized using the sol–gel technique. The estimated stress, strain, and crystallite sizes of the synthesized Co/Eu co-doped ZnO nanoparticles were calculated using the Williamson–Hall method, and their electron spin resonance (ESR) properties were investigated to examine the effect on their magnetic and structural properties. X-ray diffraction (XRD) analysis confirmed the presence of a single-phase structure. Surface morphology, elemental composition, crystal quality, defect types, density, and magnetic behavior were characterized using scanning electron microscope (SEM), electron-dispersive spectroscopy (EDS), and ESR techniques, respectively. The effect of Eu concentration on the linewidth (ΔBpp) and g-factor in the ESR spectra was studied. By correlating ESR results with the obtained structural properties, room-temperature ferromagnetic behavior was identified. Full article

Pile foundations are critical structural elements, and their integrity is essential for ensuring the stability and safety of construction projects. Low-strain pile integrity testing (LSPIT) is widely used for defect detection; however, conventional manual interpretation of reflectograms is both time-consuming and susceptible to human error. This study presents a deep learning-driven approach utilizing transfer learning with convolutional neural networks (CNNs) to automate pile defect detection. A dataset of 328 reflectograms collected from real construction sites, including 246 intact and 82 defective samples, was used to train and evaluate the model. To address class imbalance, oversampling techniques were applied. Several state-of-the-art pretrained CNN architectures were compared, with ConvNeXtLarge achieving the highest accuracy of 98.2%. The accuracy reported was achieved on a dedicated test set using real reflectogram data from actual construction sites, distinguishing this study from prior work relying primarily on synthetic data. The proposed novelty includes adapting pre-trained CNN architectures specifically for real-world pile integrity testing, addressing practical challenges such as data imbalance and limited dataset size through targeted oversampling techniques. The proposed approach demonstrates significant improvements in accuracy and efficiency compared to manual interpretation methods, making it a promising solution for practical applications in the construction industry. The proposed method demonstrates potential for generalization across varying pile lengths and geological conditions, though further validation with broader datasets is recommended. Full article

Phage therapy shows promise as an adjunct to antibiotics for treating Staphylococcus aureus infections. We previously reported a combined flucloxacillin/two-phage cocktail treatment selected for resistance to podovirus phage 66 in a rodent model of methicillin-susceptible S. aureus (MSSA) endocarditis. Here we show that resistant clones harbor mutations in tarS, which encodes a glycosyltransferase essential for β-GlcNAcylation of wall teichoic acid (WTA). This WTA modification has been described in vitro as critical for podoviruses adsorption. Transcriptomics confirmed continued tarS expression in resistant clones, supporting a loss-of-function mechanism. Accordingly, phage 66 binding and killing were restored by WT tarS complementation. In addition, we investigated the counterintuitive innate susceptibility to phage 66 of the tarM + Laus102 strain used in the endocarditis model. We show that it likely results from a significant lower tarM expression, in contrast to the innate resistant strain RN4220. Our findings demonstrate that tarS-mediated WTA β-GlcNAcylation is critical for podovirus infection also in vivo and identify tarM transcriptional defect as a new mechanism of podoviruses susceptibility in S. aureus. Moreover, and since tarS disruption has been previously shown to enhance β-lactam susceptibility, our results support the development of combined podovirus/antibiotic strategies for the management of MRSA infections. Full article

Listeria monocytogenes is a life-threatening bacterial foodborne pathogen that can persist in food-processing facilities for years. Although phages can control L. monocytogenes during food production, phage-resistant bacterial subpopulations can regrow in phage-treated environments. In this study, an L. monocytogenes hly defective strain, NJ05-Δhly, was produced, which considerably regulated the interactions between L. monocytogenes and phages. Specifically, we observed a 76.92-fold decrease in the efficiency of plating of the defective strain following infection with the Listeria phage vB-LmoM-NJ05. The lytic effect was notably diminished at multiplicities of infection of 1 and 10. Furthermore, the inactivation of LLO impaired biofilm formation, which was completely suppressed and eliminated following treatment with 10⁸ PFU/mL of phage. Additionally, phages protected cells from mitochondrial membrane damage and the accumulation of mitochondrial reactive oxygen species induced by L. monocytogenes invasion. Transcriptomic analysis confirmed these findings, revealing the significant downregulation of genes associated with phage sensitivity, pathogenicity, biofilm formation, and motility in L. monocytogenes. These results underscore the vital role of LLO in regulating the pathogenicity, phage susceptibility, and biofilm formation of L. monocytogenes. These observations highlight the important role of virulence factors in phage applications and provide insights into the potential use of phages for developing biosanitizers. Full article

This study investigates the influence of die design parameters on forging forces and thermomechanical responses during near-solidus forging (NSF) of complex steel components. Finite element simulations using Forge NxT analyzed six die configurations varying geometry orientation, gating system design (conical, cylindrical, curvilinear), and draft angles (20° and 30°), with 42CrMo4E steel modeled at 1360 °C. Key responses including punch and lateral forces, temperature distribution, strain localization, and die stress were evaluated to assess design effects. Results showed that the gating system geometry critically controls material flow and load requirements. The conical gating design with a 30° draft angle yielded the lowest punch (141.54 t) and lateral (149.44 t) forces, alongside uniform temperature and strain distributions, which improve product quality by minimizing defects and incomplete filling. Lower lateral forces also reduce die opening risk, enhancing die life. In contrast, the base case with a 20° draft angle exhibited higher forces and uneven strain, increasing die stress and compromising part quality. These findings highlight the importance of selecting appropriate gating systems and draft angles to reduce forming loads, increase die life, and improve uniform material flow, contributing to better understanding of die design in NSF of complex steel components. Full article

In this study, we investigated the mitochondrial defects resulting from the deletion of GCN5, a lysine-acetyltransferase, in the yeast Saccharomyces cerevisiae. Gcn5 serves as the catalytic subunit of the SAGA acetylation complex and functions as an epigenetic regulator, primarily acetylating N-terminal lysine residues on histones H2B and H3 to modulate gene expression. The loss of GCN5 leads to mitochondrial abnormalities, including defects in mitochondrial morphology, a reduced mitochondrial DNA copy number, and defective mitochondrial inheritance due to the depolarization of actin filaments. These defects collectively trigger the activation of the mitophagy pathway. Interestingly, deleting CSN5, which encodes to Csn5/Rri1 (Csn5), the catalytic subunit of the COP9 signalosome complex, rescues the mitochondrial phenotypes observed in the gcn5Δ strain. Furthermore, these defects are suppressed by exogenous ergosterol supplementation, suggesting a link between the rescue effect mediated by CSN5 deletion and the regulatory role of Csn5 in the ergosterol biosynthetic pathway. Full article

The application of additive manufacturing technology in the field of nuclear power is becoming increasingly promising. The low-cycle fatigue behavior of Z2CN19-10 controlled-nitrogen-content stainless steel (SS) was investigated by fatigue equipment, scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), and transmission electron microscopy (TEM), including additive manufactured (AM) and forged materials. The results showed that the microstructure of the AM material exhibited anisotropy for the X, Y, and Z directions. The tensile and impact properties of the X, Y, and Z directions in AM material were similar. The fatigue life (N_f) of X- and Y-direction specimens was better than that of Z-direction specimens. The tensile, impact, and fatigue properties of all AM materials were lower than those of the forged specimens. The Z direction specimens of AM material showed the best plastic strain by the highest transition fatigue life (N_T) during the fatigue strain amplitude at 0.3% to 0.6%. The forged specimens showed the best fatigue properties under the plastic strain amplitude control mode. Fatigue fracture surfaces of AM and forged materials exhibited multi- and single-fatigue crack initiation sites, respectively. This could be attributed to the presence of incompletely melted particles and manufacturing defects inside the AM specimens. The dislocation morphology of AM and forged fatigue specimens was observed to study the low-cycle fatigue behaviors in depth. Full article

Thermomechanical processing has a significant impact on the porosity and mechanical properties of AISI 316L stainless steel produced by laser powder bed fusion (L-PBF). This work evaluated the effect of three heat treatment conditions: as-built (HT0), annealed at 650 °C for 3 h with air cooling (HT1), and annealed at 1050 °C for 1 h followed by water quenching (HT2), combined with cold and hot rolling at different strain levels. The most pronounced improvement was observed after 20% hot rolling followed by water quenching (HR + WQ), which reduced porosity to 0.05% and yielded the most spherical pores, with a circularity factor ($f_{circle}$) of 0.90 and an aspect ratio (AsR) of 1.57. At elevated temperatures, the matrix becomes more pliable, which promotes pore closure and helps reduce stress concentrations. On the other hand, applying heat treatment without causing deformation resulted in the pores growing and increasing porosity in the build direction. The fractography supported these findings, showing a transition from brittle to more ductile fracture surfaces. Heat treatment combined with plastic deformation effectively reduced internal defects and improved both structural integrity and strength. Full article

This study aimed to verify, under real operating conditions, the effectiveness of protective lactic acid bacteria (LAB) culture in counteracting the development of late blowing defects in Valtellina Casera PDO cheese and its impact on product sensory characteristics. Thirty-four LAB isolated from Bitto and Valtellina Casera PDO cheeses were screened for anti-Clostridium activity. Lacticaseibacillus casei VC201 was able to inhibit all the indicator strains through organic acid production. Valtellina Casera PDO cheese-making was performed twice in three dairy farms using a commercial autochthonous starter culture with and without the addition of the protective culture VC201. Cheese was ripened both at 8 °C and 12 °C and analyzed after 70 and 180 days for LAB population, proteolysis, and lipolysis evolution as well as sensory impact. Cheeses with the addition of the VC201 strain showed higher contents of rod-shaped LAB throughout the ripening at both temperatures. The protective culture decreased the production of butyric acid at 70 days, especially at 8 °C (−15.4%), while butyric fermentation was occasionally lightly observed at 12 °C. The sensory profile was favorably impacted by the higher relative proportion of short-chain fatty acids (SCFFAs, C2–C8), which was especially pronounced at 8 °C and persisted for 180-day ripening (23.91% vs. 18.84% at 70 days and 23.84 vs. 21.71 at 180 days of ripening). The temperature and time of ripening had a significant effect on the free fatty acid content of the cheese samples in all three classes (SCFFA, MCFFA, and LCFFA). The cheese made with Lcb. casei VC201 was preferred, according to the sensory evaluation, being perceived as less acidic, less bitter, tastier, and with more intense flavor. Protective cultures can represent a practical way to reduce late blowing defects in Valtellina Casera cheese production while maintaining adherence to its PDO regulatory requirements. Full article

Background/Objectives: Localized provoked vulvodynia (LPV) is characterized by chronic vulvar pain upon light touch to the vestibule, a specialized ring of tissue immediately surrounding the vaginal opening. LPV affects about 14 million people in the US, yet the etiopathology of the disease is unknown. In LPV, the vestibule expresses elevated levels of the pro-nociceptive pro-inflammatory mediators prostaglandin E₂ (PGE2) and interleukin-6 (IL-6), which corresponds to lower pain thresholds. Previous studies have shown reduced amounts of arachidonic acid (AA)-derived pro-resolving lipid mediators in tissue biopsies from LPV patients that might impede the resolution of inflammation. AA is obtained from dietary linoleic acid, pointing to a defect in the metabolism of dietary polyunsaturated fatty acids in LPV. We aimed to further explore the involvement of AA metabolism in LPV, which appears dysregulated in the vestibule of LPV patients and culminates in chronic inflammation and chronic pain. Methods: Vestibular and vulvar tissue biopsies obtained from LPV and non-LPV patients were used to generate fibroblast strains and assessed for COX/LOX expression using qRT-PCR. Fibroblast strains were treated with inflammatory stimuli, and then COX-1 and COX-2 expression was assessed using Western blot analysis. Pro-inflammatory mediator production was assessed using enzyme-linked immunosorbent assays (ELISAs). ALOX5 and ALOX12 expression was assessed using qRT-PCR. Finally, lipidomic analysis was carried out to screen for 143 lipid metabolites following inflammatory challenge. Results: Tissue and fibroblasts from LPV patients exhibited altered expression of COX/LOX enzymes and production of AA-derived lipid mediators compared to non-LPV patients. Conclusions: Lipid profiles of tissue and vestibular fibroblasts from LPV patients differed from non-LPV patients, and this difference was attributed to differential COX/LOX expression and activity, which metabolizes AA derived from dietary linoleic acid. This dysregulation fosters chronic inflammation and reduced resolution capacity in LPV patients, causing chronic pain. While further work is needed, these findings suggest that dietary modifications could impact the LPV mechanism. Full article