Search Results (212)

The DNA methyltransferases inhibitor 5-azacytidine (5AzC), clinically used to treat hematopoietic malignancies, can elevate genomic mutational burden, raising safety concerns. To define the epigenetic specificity and mutagenic consequences of 5AzC, we performed multi-omics analyses in Neurospora crassa. Our data showed that 5AzC caused a non-selective, genome-wide reduction in both 5-methylcytosine (5mC; ~50% decrease) and the heterochromatin mark H3K9me3 (~65% decrease), indicating broad off-target demethylation that may transiently benefit therapy yet compromise genome stability. Whole-genome sequencing (WGS) revealed a ~290-fold increase in mutation rate under 5AzC, with a pronounced C->G transversion bias, a spectrum typically associated with higher functional burden. Strikingly, 5AzC-induced mutations were enriched in H3K9me3-marked domains, particularly pericentromeric regions characterized by low 5mC but high H3K9me3. Genetic analyses showed that the loss of DNA methyltransferase DIM-2 reduced 5AzC-induced mutations by ~64%, while individual or combined knockout of the histone methyltransferase DIM-5 with DIM-2 led to an 85% reduction. Thus, mutagenesis was markedly amplified by DIM-2 and DIM-5, with DIM-2 activity dependent on DIM-5. Collectively, DIM-2 and DIM-5 accounted for nearly all A/T-site and ~80% of G/C-site mutations. These results reveal that 5AzC drives genome-wide loss of 5mC and H3K9me3, with mutagenesis preferentially targeting H3K9me3-enriched regions via DIM-2 and DIM-5. This work clarifies a mechanistic basis for 5AzC-associated genomic risk and highlights strategies for next-generation epigenetic therapies that preserve heterochromatin integrity while minimizing mutational load. Full article

The rapid advancement and widespread application of telecommunication technologies have significantly increased human exposure to electromagnetic waves, thereby intensifying the demand for effective electromagnetic shielding materials. Beyond potential health concerns, ensuring the stable performance of highly integrated electronic devices also necessitates protection against electromagnetic interference (EMI). In this study, the effects of processing conditions on the EMI shielding effectiveness (SE) of AZ61 magnesium alloy sheets were systematically investigated. Aging treatment of rolled AZ61 alloy promoted the formation of Mg₁₇Al₁₂ lamellae. Transmission Kikuchi diffraction analysis revealed that plate-like Mg₁₇Al₁₂ precipitates preferentially formed on the (0001) planes of the Mg matrix, contributing to improved EMI shielding. The rolled AZ61 sheet exhibited the highest SE in both the as-rolled state (83.1 dB at 900 MHz) and after aging for 131 h at 250 °C (76.2 dB at 900 MHz). The superior shielding performance of the as-rolled sheet is attributed to its high density of deformation-induced defects such as dislocations and twins, which induce lattice distortions and impede wave propagation. Meanwhile, the enhanced SE from the 131 h-aged condition results from multiple reflections of incident electromagnetic waves facilitated by the matrix–precipitate lamellar microstructure. Full article

Brown spot, caused by the fungus Bipolaris oryzae, has led to significant yield losses in rice production worldwide. This study hypothesized that azelaic acid (AzA) could reduce brown spot symptoms in rice leaves by potentiating biochemical defense reactions. A 2 × 2 factorial experiment was arranged in a completely randomized design with five replications per sampling time. The factors studied were plants sprayed with water (control) or AzA (10 mM; 7.5 mL per plant), either non-inoculated or inoculated with B. oryzae. In the in vitro assay, conidia exposed to AzA solutions at rates of 2.5, 5, 7.5, and 10 mM and to the fungicide solution did not form germ tubes compared to those in the control (water) treatment. The area of fungal colonies on oat–agar medium was reduced for the fungicide and AzA (rates increasing from 2.5 to 10 mM) treatments compared to the control (water) treatment. The EC₅₀ value was 3.8 mM AzA. Brown spot severity significantly decreased by 57, 48, 52, and 58% at 36, 60, 84, and 108 h after inoculation (hai) for AzA-sprayed plants compared to water-sprayed ones. The area under brown spot progress curve significantly decreased by 53% for AzA-sprayed plants compared to water-sprayed ones. Greatest activities of defense-related enzymes (chitinase at 108 hai, β-1,3-glucanase at 60 hai, phenylalanine ammonia-lyase at 60 and 108 hai, and lipoxygenase at 84 and 108 hai), a higher concentration of lignin at 84 and 108 hai, and a more robust antioxidative metabolism (higher activities of ascorbate peroxidase at 36 hai, catalase at 84 and 108 hai, and superoxide dismutase at 84 hai) were obtained for AzA-sprayed infected plants. The higher concentration of the superoxide anion radical in AzA-sprayed infected leaves helped to intensify the cell defense reactions against fungal infection and had a fungistatic effect against its hyphae and conidia germination. The findings of this study provide valuable insights into using AzA to potentiate foliar defense reactions in rice plants to hamper the infection by B. oryzae. Full article

Background: Autologous arteriovenous fistula (AVF) is the most commonly used vascular access for end-stage renal disease patients. However, during the maturation process following AVF surgery, insufficient initial venous diameter often results in inadequate blood flow, leading to fistula maturation failure. Studies have indicated that implanting stents can enlarge the initial venous diameter and improve the success rate of AVF surgeries. However, stents made from metallic materials remain permanently in the body after implantation, posing risks such as in-stent restenosis. Methods: Our development and testing of magnesium alloy stents with a layered double hydroxide (LDH) coating to assist AVF maturation is presented in this paper. Firstly, AZ31 alloy was used as a benchmark to screen coating technologies, including anodizing, alkaline films, and LDH coatings. ZM21 tubes were then utilized to verify the transferability of optimized parameters across different substrates. Finally, the optimized coating was applied to ZM21 stents, followed by validation through in vitro degradation tests and biochemical simulations. Results: The results showed that LDH-coated AZ31 samples exhibited a 95% reduction in average corrosion rate compared to untreated samples. Additionally, the anion exchange property of the LDH layer effectively reduced the pH of the saline solution. Subsequently, LDH coatings were applied to ZM21 magnesium alloy stents, followed by in vitro degradation and biochemical simulation. Compared to untreated ZM21 stents, LDH-coated stents demonstrated a 94.9% reduction in average corrosion rate and significantly reduced the generation of soluble magnesium chloride, maintaining the solution pH below 8.0 and the Mg²⁺ concentration below 300 μg/mL. Conclusions: The results show LDH is the most effective corrosion-resistant coating and can control the degradation rate of magnesium alloy stents to enhance their support duration and biocompatibility. Full article

This study examined cast AZ31 magnesium alloy and its variant containing micro-alloying elements of Y and Ca (AZXW alloy), evaluating their potential as anode materials in magnesium–air batteries. The AZXW alloy was fabricated via two manufacturing techniques: casting and extrusion. The synergistic influence of Y and Ca, in conjunction with the production procedure, on the microstructure, electrochemical characteristics, and anodic discharge behavior of the examined alloys was investigated. The addition of Y and Ca results in the formation of secondary phases that affect grain size, particle size, and distribution, as well as the electrochemical performance and discharge properties of the Mg–air battery constructed for this study, over 24 h or until fully discharged. This work demonstrates the potential to enhance discharge performance and electrochemical behavior by adjusting the aqueous electrolyte solution in the battery through the incorporation of Citric Acid (C.A) at varying concentrations. The incorporation of citric acid into the aqueous electrolyte improves battery stability and specific energy as long as citric acid is present in the solution. Magnesium hydroxide (Mg(OH)₂) begins to form on the anode surface as its concentration progressively decreases due to complexation with dissolved magnesium ions. This diminishes the effective anode area over time, ultimately resulting in the distinctive “knee-type” collapse characteristic of electrolytes containing citric acid. Full article

Fluorination has been proposed as an effective surface modification method for magnesium. The high-temperature oxidation behavior and protective mechanism of fluorinated AZ31 magnesium alloys, especially under prolonged isothermal conditions, have not been systematically investigated. In this study, an efficient and safe surface fluorination method that requires no post-treatment was developed to directly fluorinate the surface of AZ31 machining chips using F₂ gas. By adjusting the fluorination parameters, including fluorine gas pressure, temperature, and reaction time, the content and uniformity of the surface MgF₂ layer were effectively improved. High-temperature isothermal oxidation tests demonstrated a remarkable enhancement in oxidation resistance after fluorination; specifically, the weight change of the fluorinated samples decreased from 64.65% for the untreated alloy to 0.68% after oxidation at 450 °C for 12 h. To verify the formation of the MgF₂ layer and its protective mechanism, all samples were systematically characterized before and after heat treatment using XPS, SEM/EDS, and XRD. The results confirm that direct fluorination with F₂ is an effective approach for improving the high-temperature stability of AZ31 magnesium alloy. Full article

Controlled-release technologies based on natural clays offer a sustainable approach to enhance the efficacy and environmental compatibility of agrochemicals. This study reports the development and evaluation of clay-based azoxystrobin (Az) formulations for controlling Magnaporthiopsis maydis, the causal agent of maize late wilt disease. Among six carriers tested, raw bentonite and sepiolite were selected for their comparable adsorption capacity (9.5% Az loading efficiency) and ease of preparation. A novel mycelial plug-immersion bioassay was established and calibrated (R² = 0.92–0.95) to assess release kinetics and antifungal efficacy, showing approximately tenfold higher sensitivity than conventional disk-diffusion or mycelial-growth inhibition assays. Sequential wash and extended incubation experiments demonstrated sustained Az release equivalent to ≥1 mg L⁻¹ over 144 h, resulting in approximately 50% (p < 0.05) fungal growth suppression. A comparative analysis of particle suspensions and supernatants revealed formulation-specific release behaviors, which differed among clay carriers. Overall, bentonite and sepiolite acted as efficient carriers that prolonged fungicide bioavailability, minimized leaching losses, and preserved biological activity. These findings provide proof of concept for clay–Az formulations as eco-friendly and cost-effective tools for late wilt management and advance understanding of clay–fungicide interactions that support sustainable, integrated disease-control strategies. Full article

The SNF2-related chromatin remodeler Srcap is the principal ATPase responsible for the deposition of the histone variant H2A.Z at promoters and regulatory chromatin regions. Although this activity is known to modulate transcription, its contribution to DNA replication remains unexplored. Here we show that Srcap is required for efficient replication fork progression and origin firing in mammalian cells. Using RNA interference in human PC3 cells, we found that Srcap depletion leads to a ~25% reduction in fork elongation rate, decreased replication fork density, accumulation of the replication-stress marker γH2AX, and reduced chromatin-bound H2A.Z. High-resolution expansion microscopy further revealed diminished intensity and increased spacing of replication foci, consistent with reduced origin activation. Transcriptomic analysis of published data identified broad downregulation of replication-associated genes. These data uncover a dual mechanism by which Srcap sustains replication efficiency—through both H2A.Z-dependent chromatin organization and transcriptional maintenance of the replication machinery. Our findings establish Srcap as an important coordinator of replication dynamics, with implications for genome stability. Full article

Magnesium alloys are promising biodegradable orthopedic implant materials, but their clinical translation is hindered by rapid, unregulated corrosion in physiological environments. Polyvinylidene fluoride (PVDF) coating has attracted substantial attention for addressing the issue above. However, it suffers from insufficient interfacial adhesion to Mg alloy substrates. In this work, we propose a Zr-based pretreatment strategy to enhance PVDF coatings. The pretreatment was performed via a chemical conversion deposition method, which fabricated a Zr-based film on AZ31 magnesium alloy and greatly promoted the adhesion of the following PVDF coating. Interface analysis showed that coating adhesion was improved from 0.44 MPa to 2.48 MPa. In light of this, corrosion protection performance was significantly improved. Electrochemical tests in simulated body fluid revealed the enhanced PVDF coating shifted the corrosion potential from −1.594 V to −1.392 V and reduced the corrosion current density by over five orders of magnitude. Immersion tests also showed stable pH level, low weight loss, and good hydrophobicity with the enhanced PVDF coating. In summary, the enhanced PVDF coating provides excellent corrosion protection for magnesium alloys, thus boosting their biomedical use. Full article

Biodegradable magnesium (Mg) alloys are promising materials for temporary orthopaedic implants, combining favourable mechanical properties and superplastic behaviour with in vivo resorption. This enables (i) prolonged implant duration, (ii) fabrication of complex-shaped prostheses via superplastic forming (SPF), (iii) elimination of removal surgery, and (iv) reduced risk of long-term complications. However, rapid corrosion under physiological conditions remains a major limitation, highlighting the need for surface treatments that slow degradation while preserving implant integrity. This study investigates the effects of hydrothermal surface treatment on MgAZ31-SPF alloys, focusing on immunomodulatory responses, antibacterial potential, and degradation behaviour. Hydrothermally treated MgAZ31-SPF (MgAZ31-SPF-HT) extracts released lower Mg²⁺ concentrations (29.2 mg/dL) compared to untreated MgAZ31-SPF (47.5 mg/dL) while maintaining slightly alkaline pH (7–8.7), indicating improved control of early degradation. In vitro assays with human peripheral blood mononuclear cells (hPBMCs) and normal human dermal cells (NHDCs) showed that MgAZ31-SPF-HT extracts maintained higher cell viability over 24–72 h. Gene expression analysis revealed significant downregulation of pro-inflammatory markers CTSE and TNF-α, while protein quantification via ELISA and BioPlex confirmed reduced secretion of TNF-α, TGF-β1, TGF-β2, IL-6, and IL-8, suggesting mitigation of early immune activation. Antibacterial assays demonstrated limited Staphylococcus aureus colonisation on both MgAZ31-SPF and MgAZ31-SPF-HT scaffolds, with CFU counts (~10⁵–10⁶) well below the threshold for mature biofilm formation (~10⁸), and SEM analysis confirmed sparse bacterial distribution without dense EPS-rich layers. Overall, hydrothermal treatment improves Mg alloy biocompatibility by controlling Mg²⁺ release, modulating early immune responses, and limiting bacterial adhesion, highlighting its potential to enhance clinical performance of Mg-based implants. Full article

This review presents soybean responses to drought, heat, and salinity within a signal–transcript–chromatin framework. In this framework, calcium/reactive oxygen species and abscisic acid cues converge on abscisic acid-responsive element binding factor (ABF/AREB), dehydration-responsive element binding protein (DREB), NAC, and heat shock factor (HSF) families. These processes are modulated by locus-specific chromatin and non-coding RNA layers. Base-resolved methylomes reveal a high level of CG methylation in the gene body, strong CHG methylation in heterochromatin, and dynamic CHH ‘islands’ at the borders of transposable elements. CHH methylation increases over that of transposable elements during seed development, and GmDMEa editing is associated with seed size. Chromatin studies in soybean and model species implicate the reconfiguration of salt-responsive histone H3 lysine 27 trimethylation (H3K27me3) in G. max and heat-linked H2A.Z dynamics at thermoresponsive promoters characterized in Arabidopsis and other plants, suggesting that a conserved chromatin layer likely operates in soybean. miR169–NF-YA, miR398–Cu/Zn Superoxide Dismutases(CSD)/copper chaperone of CSD(CCS), miR393–transporter inhibitor response1/auxin signaling F-box (TIR1/AFB), and miR396–growth regulating factors (GRF) operate across leaves, roots, and nodules. Overexpression of lncRNA77580 enhances drought tolerance, but with context-dependent trade-offs under salinity. Single-nucleus and spatial atlases anchor these circuits in cell types and microenvironments relevant to stress and symbiosis. We present translational routes, sentinel epimarkers (bisulfite amplicons, CUT&Tag), haplotype-by-epigenotype prediction, and precise cis-regulatory editing to accelerate marker development, genomic prediction and the breeding of resilient soybean varieties with stable yields. Full article

The initial formation of corrosion products in pure humid air on magnesium alloys AZ91 and AZ31 was studied using infrared reflection absorption spectroscopy (IRRAS), infrared spectroscopic imaging, and SEM-EDS. The kinetics of corrosion product formation were monitored in situ with IRRAS during exposure to humid air (95% relative humidity) under two different CO₂ concentrations: low (≤1 ppm) and ambient (400 ppm). For low CO₂ concentrations, the primary corrosion product detected on both alloys was magnesium hydroxide (Mg(OH)₂). In contrast, under ambient CO₂ conditions (400 ppm), magnesium hydroxy carbonate was the dominant product. After 16 h of exposure, the amount of magnesium converted into corrosion products was approximately 8–10 times higher under low-CO₂ conditions compared to ambient levels. The smaller formation of corrosion products but increased magnesium carbonate formation on AZ91D is attributed to its higher aluminium content compared to AZ31. Corrosion attack and product formation were largely localised to the centre of the α-phase in AZ91D, with the β-phase likely serving as sites for cathodic reactions. Full article

Yeast +1 nucleosomes positioned at transcription start sites must be reorganized to allow transcription initiation. Nucleosome reorganization involves multiple factors including histone chaperone FACT (FAcilitates Chromatin Transcription), histone acetylation, and histone variant H2A.Z; however, the mechanism of this process is not fully understood. Here we investigated nucleosome unfolding in the presence of these factors by combining biochemical assays with single-particle Förster resonance energy transfer (spFRET) microscopy. The presence of the H3:K56Ac mimic (H3:K56Q) alone or together with H2A.Z (but not H2A.Z alone) facilitates the Nhp6-dependent unfolding of nucleosomes by FACT. In contrast to canonical nucleosomes, the unfolding of nucleosomes with the studied variant histones promotes the eviction of core histones from nucleosomal DNA. Furthermore, H2A.Z alone or in synergy with H3:K56Q facilitates transcription through a nucleosome as efficiently as FACT facilitates transcription through canonical nucleosomes. The data suggest that FACT, together with H3:K56 acetylation and H2A.Z, unfold promoter nucleosomes and participate in the eviction of histones to increase the accessibility of the transcription start site, thereby stimulating transcription initiation and possibly early elongation. Full article

The TIP60/NuA4 complex is a large, multifunctional histone acetyltransferase assembly of ~1.7 megadaltons, composed of 17–20 subunits, which plays a central role in epigenetic regulation. Through recognition of H3K4me3 by the ING3 reader, TIP60/NuA4 is recruited to sites of active transcription, where it remodels chromatin to regulate gene expression. Its activities include histone acetylation, histone variant exchange, transcriptional co-activation, and regulation of the cell cycle and apoptosis. In this review, we examine how altered subunit levels or mutations impact the chromatin structure and transcriptional activity, and how these changes influence differentiation across diverse cell types. We emphasize the molecular mechanisms by which TIP60/NuA4 shapes lineage specification, including histone H2A and H4 acetylation by the KAT5 catalytic subunit, H2A.Z incorporation by EP400, and interactions with transcription factors such as MyoD, PPARγ, and Myc. By integrating mechanistic and functional insights, we highlight how TIP60/NuA4 acts as a central epigenetic hub in differentiation and contributes to proper developmental transitions. Full article

The olive fruit is recognized for being a significant source of phenolic compounds, including hydroxytyrosol (H-tyr), tyrosol (Tyr), oleuropein (Ole), and verbascoside (Verb). The maturity index (MI) significantly influences the phenolic profile, which is a cultivar-specific trait. A study was conducted to assess the evolution of the phenolic profile in seven olive cultivars during ripening: ‘Galega vulgar’ (Gv), ‘Azeiteira’ (Az), ‘Cobrançosa’ (Cob), ‘Picual’ (Pic), ‘Carrasquenha’ (Car), ‘Redondil’ (Red), and ‘Arbequina’ (Arb). The results indicate a declining trend in total phenolic compounds (TPC) across all cultivars, with Cob and Car exhibiting the highest values, over 60 g GAE kg⁻¹ at T1 and above 30 g GAE kg⁻¹ at T7, respectively. In Ole quantitation, Red demonstrated the highest values, recording 39 g kg⁻¹ in T1 and 15 g kg⁻¹ at T7, with per olive fruit unit measurements ranging from 19.7 mg at T1 to 22.7 mg at T7. These findings underscore olive fruit as an exceptional source of bioactive compounds and their advantageous health-promoting effects, which might be utilized as a functional food source, validating the unique phenolic profiles of each cultivar in relation to ripening. Full article