Search Results (12,286)

Root plasticity is vital for crop survival amid global warming. Yet, the molecular mechanisms governing wheat root thermotolerance remain largely unknown. In this study, we combined phenomics, transcriptomics, and metabolomics with machine learning to analyze the performance of heat-tolerant cultivar YM158 and heat-sensitive cultivar YM15 under varying heat stress. While high temperatures (35 °C) severely inhibited root growth and caused oxidative damage in YM15, YM158 maintained robust root architecture and redox balance. Using weighted gene co-expression network analysis (WGCNA) alongside the random forest feature selection algorithm, we identified the flavonoid biosynthesis pathway as central to thermotolerance. Protein–protein interaction network analysis revealed that wheat root adaptability to high temperatures involves maintaining protein homeostasis via the endoplasmic reticulum protein processing system, specifically activating the flavonoid biosynthesis pathway and enhancing the antioxidant enzyme system. Furthermore, we identified a potential regulatory hub involving the cell wall sensor FERONIA (FER) and heat shock factors (HSFs), highlighting a complex interaction between hormonal signaling and secondary metabolism. Our study offers a detailed map of root heat adaptation and positions the flavonoid-mediated antioxidant system as a promising target for breeding climate-resilient crops. Full article

This study addresses the challenges associated with deep-well drilling mud cuttings, including large waste volumes, high transportation costs, and complex organic pollutants. A low-cost synergistic technology was developed for the resource utilization of pyrolyzed drilling waste residue (PDWR) and the in situ remediation of oil-contaminated drill cuttings. A ternary photocatalytic system consisting of PDWR, H₂O₂, and oxalic acid was proposed and demonstrated to effectively degrade total petroleum hydrocarbons (TPH) in drill cuttings under solar irradiation. Systematic optimization identified optimal dosages of PDWR, H₂O₂, and oxalic acid as 250 mg, 280 mg, and 90 mg, respectively. The addition of oxalic acid significantly enhanced photocatalytic oxidation performance, increasing H₂O₂ utilization by 63.8% and improving the TPH degradation rate by a factor of 3.03. Under optimal conditions and 7 days of solar irradiation, TPH degradation efficiencies of 65.19–88.66% were achieved for initial TPH concentrations ranging from 5000 to 12,000 mg kg⁻¹. Mechanistic analysis revealed that a Fenton-like reaction between transition metals in PDWR and H₂O₂ dominated the photocatalytic process, while oxalic acid facilitated metal redox cycling through coordination and electron transfer, promoting sustained generation of reactive oxygen species (·OH). This study demonstrates a feasible and sustainable approach for high-value utilization of drilling waste residue and solar-driven in situ remediation of oil-contaminated drill cuttings, highlighting its strong potential for practical application. Full article

L-glutamate (L-Glu) is the primary excitatory neurotransmitter in the mammalian central nervous system. Developing a real-time monitoring system is essential to understanding the onset and progression of related conditions. However, the absence of an L-Glu dehydrogenase that is insensitive to oxygen limits the development of oxygen-independent electrochemical enzymatic sensors. Additionally, the most commonly used L-Glu-specific oxidase requires site-specific proteolytic post-translational modifications in specific host microorganisms, which makes protein engineering difficult. To address these issues, L-Glu oxidase derived from Streptomyces mobaraensis (SmEOx), which does not require post-translational modifications, was engineered to function as a dehydrogenase. Residues crucial for the oxidative half reaction with oxygen in SmEOx were identified, and mutagenesis studies were conducted. Mutant SmEOx variants with suppressed oxidase activity and improved dye-mediated dehydrogenase activity compared to the wild-type enzyme were successfully obtained. The ratio of dehydrogenase activity to oxidase activity (Dh/Ox) increased ~2900-fold in mutant M117I and ~6700-fold in mutant M117F/K400N compared to wild-type recombinant SmEOx. The resulting virtually L-Glu dehydrogenases (vEDHs) were modified with a redox mediator and evaluated using transient open-circuit potential (OCP)-based L-Glu measurements. As a result, the vEDH (M117F/K400N mutant)-immobilized electrode enabled electrochemical L-Glu detection under ambient oxygen without the need for an external electron mediator, unlike the wild-type enzyme. The created vEDH, together with the OCP sensor developed using it, paves the way for future development of miniaturized, real-time L-Glu monitoring systems with high temporal and spatial resolution. Full article

Advanced-stage ovarian cancer remains a major clinical challenge because of its aggressive behavior and the frequent development of chemoresistance. The nuclear factor erythroid-derived 2–like 2 (NRF2) signaling pathway regulates cellular redox homeostasis. However, its role in ovarian cancer stem-like cells remains unclear. Therefore, we aimed to investigate the effects of NRF2 overexpression on acetaldehyde dehydrogenase (ALDH)⁺ KURAMOCHI ovarian cancer cells in vitro and in vivo. In particular, we investigated the effects of NRF2 on tumor-associated behaviors, chemoresistance, and signaling pathways. Lentivirus-mediated NRF2 overexpression activated extracellular signal-regulated kinase and AKT signaling. Moreover, it modulated tumor-associated phenotypes, including proliferation, migration, and invasion. NRF2-overexpressing cells exhibited significantly enhanced migratory and invasive capacities, increased resistance to paclitaxel and carboplatin, and reduced apoptosis. Furthermore, the expression of anti-apoptotic proteins was upregulated, and caspase-3 activation was attenuated. In xenograft models, NRF2 overexpression promoted tumor growth and increased the expression of antioxidant and angiogenic factors, including heme oxygenase-1 and vascular endothelial growth factor A. Collectively, these findings demonstrate that NRF2 regulates ovarian cancer aggressiveness and chemoresistance by coordinating stress response signaling, survival pathways, and tumor progression. Therefore, targeting NRF2-mediated signaling represents a promising therapeutic strategy for overcoming drug resistance and improving outcomes in patients with ovarian cancer. Full article

Cardiovascular disease remains the leading global cause of mortality, largely due to the limited regenerative capacity of adult human myocardium. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) offer a scalable platform for cardiac repair and disease modeling; however, their persistent metabolic immaturity—characterized by reliance on glycolysis, reduced oxidative phosphorylation (OXPHOS), and structurally underdeveloped mitochondria—limits functional integration and long-term therapeutic efficacy. Recent advances indicate that targeted metabolic reprogramming can enhance mitochondrial biogenesis, increase ATP production, and improve stress resilience in iPSC-CMs. This review examines the complementary integration of CRISPR-based metabolic engineering and extracellular vesicle (EV)-mediated metabolic modulation as a systems-level strategy for cardiac maturation. We discuss CRISPR activation, interference, and epigenome-editing approaches targeting regulators such as PGC-1α, TFAM, and PPARs to promote stable enhancement of mitochondrial networks and respiratory capacity. In parallel, engineered EVs delivering miRNAs, metabolic enzymes, and redox modulators provide non-genomic mechanisms to optimize bioenergetic function and mitigate oxidative stress. By synthesizing mechanistic insights, quantitative bioenergetic metrics, and translational considerations, we propose CRISPR-EV synergy as a precision framework for durable metabolic maturation of iPSC-CMs, with implications for regenerative therapy, pharmacologic screening, and myocardial repair. Full article

Extracellular vesicles (EVs), particularly exosomes, have emerged as critical mediators of intercellular communication, yet the metabolite fraction of their cargo remains substantially underexplored relative to proteins and nucleic acids. This review synthesizes current knowledge on the exosomal metabolome as a functionally distinct intercellular signaling system with unique biophysical properties. We review the mechanisms proposed to govern metabolite encapsulation into exosomes, encompassing membrane transporter involvement, lipid raft partitioning, and binding to luminal proteins, and discuss the unresolved question of whether metabolite loading is selective or stochastic. Critically, we present a quantitative framework evaluating whether delivered metabolite quantities are sufficient to alter recipient cell metabolic pools, distinguishing receptor-mediated signaling from bulk substrate delivery. We also address methodological considerations including contamination artifacts and isolation-method biases that complicate interpretation of EV metabolomics data. Exosomal metabolites are reviewed across four functional categories: energy substrates (ATP, lactate, amino acids), signaling molecules (TCA cycle intermediates, eicosanoids, nucleotides), redox cofactors and antioxidants (NADH, glutathione), and oncometabolites. For each category, available evidence is critically appraised, distinguishing metabolites with direct mass spectrometric detection from those whose roles are inferred from parent-cell biology. The review examines the roles of exosomal metabolites in tumor-stroma metabolic symbiosis, immunometabolic regulation, inter-organ crosstalk in metabolic diseases including type 2 diabetes and non-alcoholic fatty liver disease, cancer metastasis, viral infections, and immune evasion. A quantitative framework is discussed to evaluate whether delivered metabolite quantities are sufficient to alter recipient cell metabolic pools, distinguishing receptor-mediated signaling from bulk substrate delivery. Technical challenges in exosomal metabolomics are reviewed, including the impact of isolation method on data quality, contamination artifacts, and current standardization gaps. Therapeutic implications of exosomal metabolite signaling are discussed, encompassing metabolite-loaded exosomes as therapeutic vehicles and exosomal metabolite loading as a pharmacological target. Integration of single-vesicle technologies with systems biology approaches is highlighted as a promising direction for advancing this field toward precision medicine applications in oncological and metabolic disorders. Full article

Cellular therapy using human cardiac mesenchymal progenitor cells (hMPCs) for regenerative medicine is hindered by poor cell survival and senescence. Long non-coding RNAs (lncRNAs) are critical regulators of cellular processes, yet their role in cardiac aging remains underexplored. Here, lncRNA microarray profiling identified a novel lncRNA, XLOC_002543, upregulated in hMPCs preconditioned with cobalt protoporphyrin (CoPP), which was named CoPP-Induced and SFPQ-Associated RNA Transcript (CISAT) due to its interaction with splicing factor proline and glutamine rich (SFPQ), confirmed via RNA pull-down and immunoprecipitation. CISAT was the only highly expressed transcript among seven lnc-ANKMY1-5 variants in hMPCs, as shown by RT-PCR. Notably, CISAT expression decreased in aging/senescent hMPCs, correlating with elevated p16^INK4A, a senescence marker. Overexpression of CISAT reduced p16^INK4A levels; enhanced hMPC survival, proliferation, and migration; and increased antioxidant and anti-apoptotic protein expression, while CISAT knockdown reduced resistance to H₂O₂-induced oxidative stress. In vivo, intramyocardial transplantation of CISAT-overexpressed hMPCs in an immune-deficient murine myocardial infarction model reduced fibrosis, promoted angiogenesis, and preserved cardiac function. Mechanistically, CISAT interacts with SFPQ to regulate NRF2-mediated redox homeostasis and inhibits p38 MAPK phosphorylation, mitigating senescence and enhancing cell survival. These findings suggest that targeting CISAT to modulate redox signaling and p38 MAPK pathways in aging hMPCs could improve their therapeutic efficacy for myocardial repair in heart disease. Full article

The progression of prostate cancer to castration-resistant disease (CRPC) remains a clinical challenge in which oxidative stress intersects with the PI3K/AKT–androgen receptor (AR) axis. Quercetin (QRC) is a redox-active dietary flavonol, yet its mechanistic impact on CRPC is incompletely defined. Here, we tested whether QRC suppresses AR output by directly modulating AKT. C4-2B and 22Rv1 CRPC cell lines were treated with increasing QRC concentrations, with or without enzalutamide (Enz). Proliferation and viability were monitored by IncuCyte imaging and SYTOX Green incorporation. AKT phosphorylation (S473), AR phosphorylation (S210/213), AR abundance and localization, and prostate-specific antigen (PSA) secretion were assessed by immunoblotting, immunofluorescence, and dot blot, respectively. Docking and molecular dynamic simulations were performed to identify and evaluate a putative QRC-binding site on AKT. QRC produced a dose-dependent cytostatic effect (IC₅₀ 24.37 μM in C4-2B; 21.54 μM in 22Rv1) without marked cell death, reduced pAKT(S473) by up to 80%, decreased pAR(S210/213), and diminished nuclear AR and PSA secretion. Simulations suggested a putative druggable allosteric pocket in the AKT1 N-lobe, with G159 emerging as a potential anchor residue. Enz cotreatment with QRC did not produce additive effects, consistent with a model in which QRC acts upstream of ligand-driven AR activation and thereby limits the incremental benefit of AR antagonism under these conditions. These data support QRC as an AKT–AR axis modulator in CRPC and provide a target engagement framework beyond simple ROS scavenging. Full article

Background: Cryopreservation induces oxidative stress, membrane disruption, and mitochondrial injury in spermatozoa, leading to impaired motility and fertility. Selenium, as an essential trace element, protects cells from oxidative damage through selenoproteins such as glutathione peroxidase 4 (GPX4), a critical enzyme that detoxifies lipid hydroperoxides and inhibits ferroptosis. This study investigated whether supplementation with L-selenomethionine (L-SeMet), an organic selenium source with superior bioavailability and lower toxicity than inorganic forms, could alleviate cryo-induced sperm injury by suppressing ferroptosis. Methods & Results: Dairy goat sperm were cryopreserved with 0, 2, 4, 6, 8, 10 μM L-SeMet. Supplementation with 6 μM L-SeMet significantly improved motility, membrane and acrosome integrity, and mitochondrial membrane potential. Biochemical assays showed reduced iron, ROS, and MDA levels, alongside increased ATP, SOD, and GSH contents. Proteomic analysis identified 148 differentially expressed proteins, including up-regulation of GPX4, FTH1, VDAC2, and VDAC3—core ferroptosis regulators. Metabolomic profiling further revealed enrichment in unsaturated fatty acid biosynthesis, amino acid metabolism, and the TCA cycle, pathways closely linked to ferroptosis regulation. Transmission electron microscopy confirmed that L-SeMet preserved mitochondrial ultrastructure. Mechanistically, L-SeMet mirrored the ferroptosis inhibitor N-acetyl-L-cysteine and reversed RSL3-induced oxidative damage. Western blotting verified activation of the NRF2–SLC7A11–GPX4 antioxidant axis and inhibition of KEAP1 expression. Conclusions: Collectively, these findings demonstrate that L-SeMet protects spermatozoa from cryo-induced injury by stabilizing redox homeostasis, maintaining mitochondrial function, and inhibiting ferroptosis. The results highlight ferroptosis as a critical mechanism of sperm cryodamage and identify L-SeMet as a promising metabolic intervention to enhance post-thaw sperm quality and fertility. Full article

Diabetes mellitus (DM) is a major disorder contributing to human mortality and morbidity globally. The use of medicinal plants in the management of diabetes is gaining global popularity due to their accessibility and cost-effectiveness. In this study, we evaluated the ameliorative potential of Vernonia amygdalina leaves crude extract (CE), free phenol (FP), and bound phenol (BP) fractions (50 mg/kg body weight) in a rat model of streptozotocin (STZ)-induced type 1 diabetes (T1DM). The effects of these treatments for 28 days on glucose, insulin, glycated hemoglobin, hepatic injury indices, and lipid profile were assessed in the serum. Furthermore, redox biomarkers (liver) and inflammatory mediators (serum and liver) were analyzed. Our results indicated that CE, FP, and BP fractions of Vernonia amygdalina inhibited the deleterious effects of T1DM by attenuating hyperglycaemia, insulin deficiency, hepatic injury, and dyslipidemia. Also, CE, FP, and BP fractions differentially improved antioxidant enzymes activity and reduced oxidative and inflammatory markers production. Specifically, CE showed superior effects compared with FP, BP, and metformin across multiple biomarkers, including glycated hemoglobin, α-amylase, α-glucosidase, hepatic glycogen, total cholesterol, LDL-cholesterol, protein carbonyl, SOD, IL-1β, and IL-10. The antidiabetic effects produced by CE, FP, and BP fractions of Vernonia amygdalina may be ascribed to the presence of different bioactive phytochemicals as revealed by HPLC analysis. Overall, our data would suggest a potential therapeutic role for Vernonia amygdalina leaves extracts in addressing hepatic complications due to T1DM. Full article

The crosstalk between the endocannabinoid system (ECS) and reactive nitrogen species (RNS) has emerged as an important area of investigation in recent years. Although many aspects of this interaction remain elusive, accumulating evidence demonstrates that the ECS plays a critical role in regulating RNS-mediated signaling under physiological conditions. This modulation can be either inhibitory or stimulatory, depending on the specific receptor subtype, cell type, and tissue location involved. While ECS-RNS interactions support normal cellular homeostasis, their dysregulation contributes to various disease states, particularly neurodegenerative disorders. Studies in both rodent models and human subjects show that ECS modulation can reduce anxiety, attenuate neuroinflammatory responses, and slow disease progression in neurodegenerative conditions. This review examines how cannabinoid-based interventions modulate nitrosative stress and neuroinflammation in Alzheimer’s disease (AD) and Parkinson’s disease (PD), highlighting their potential as targeted therapeutics that address multiple pathological mechanisms simultaneously and may offer advantages over conventional treatment approaches. Full article

Pomegranate (Punica granatum L.) has attracted considerable attention for its anticancer potential; however, mechanistic studies employing bioactivity-guided fractions from geographically distinct landraces remain limited. Building on our previous report on the bioactivity and phytochemical profile of the Bidah pomegranate landrace, the present study applied bioactivity-guided fractionation to enrich biologically active constituents and investigate mitochondria-associated cellular responses in colorectal cancer cells (Caco-2 cells). A semi-polar fraction from Bidah pomegranate crude extract (B6) was evaluated for its antioxidant activity, cell viability, cell death morphology, mitochondrial membrane potential, transcriptional modulation of key regulatory genes, and phytochemical composition. High-performance liquid chromatography (HPLC) profiling of B6 revealed a chromatographic fingerprint with seven detectable peaks, including two major peaks at retention times of 7.577 and 8.602 min, together accounting for approximately 66% of the total chromatographic area, indicating the enrichment of major constituents. Consistent with this enrichment, the fraction exhibited potent DPPH radical scavenging activity at a microgram-range IC₅₀, suggesting the presence of redox-active phytochemicals. In cell-based assays, the fraction induced a dose-dependent reduction in metabolic viability, while acridine orange/propidium iodide (AO/PI) staining of Caco-2 cells revealed delayed, regulated cell death. JC-1 staining demonstrated a pronounced loss of mitochondrial membrane potential, consistent with early mitochondrial dysfunction. Gene expression analysis further revealed modulation of pro- and anti-apoptotic genes, alongside cell-cycle-associated and oxidative stress/inflammatory markers. Gas chromatography–mass spectrometry (GC–MS) profiling identified polyacetylenes, sterol derivatives, fatty acid esters, and terpenoids, providing chemical context for the observed mitochondrial perturbation. Collectively, the findings support a mitochondria-centered, regulated cell death response driven by a multi-component phytochemical matrix. This study advances mechanistic insight beyond crude extract analysis and highlights the sustainable biomedical value of the Bidah pomegranate landrace as an underutilized regional resource. Full article

The increasing integration of renewable energy sources, such as solar photovoltaics, requires low-cost, scalable energy storage solutions suitable for decentralized systems. This work experimentally evaluates an iron chloride concentration redox flow battery (FeCl-CFB) coupled to a photovoltaic system. The battery, which employs the Fe²⁺/Fe³⁺ redox couple to store energy through a chemical concentration gradient, was electrochemically characterized using different carbon-based electrode materials and operated under solar charging for 25 charge–discharge cycles. A maximum power density of 6.3 W·m⁻² was achieved at the cell level, with stable cycling behavior under variable solar irradiance. Coulombic and energy efficiencies remained within ranges of 63–72% and 20–28%, respectively, throughout the cycles. Despite these moderate efficiencies, the system demonstrated a consistent and functional usable capacity. The main limitation identified was a decrease in maximum power after prolonged cycling, attributable to resistance and polarization losses rather than electrolyte instability. These preliminary results characterize the initial performance of the FeCl-CFB under solar-driven conditions, highlighting significant efficiency and stability challenges that must be addressed through further optimization to determine the future potential for decentralized energy storage. Full article

Ochratoxin A (OTA) is a highly toxic mycotoxin commonly detected in food and agricultural products, requiring sensitive analytical methods for reliable monitoring. Herein, we report an ultrasensitive turn-on electrochemical aptasensor for OTA detection based on a target-induced displacement of an aptamer–complementary DNA (cDNA) duplex assembled on an electrochemically reduced graphene oxide (ERGO)-modified glassy carbon electrode (GCE). In the absence of OTA, a methylene blue (MB)-labeled aptamer hybridized with cDNA is immobilized on the ERGO surface via π–π stacking interactions, forming a rigid duplex that suppresses electron transfer and yields a low electrochemical signal. Upon OTA binding, the aptamer undergoes a conformational transition into a G-quadruplex structure, leading to dissociation of the cDNA strand. This target-induced folding brings the MB redox tag into close proximity to the ERGO surface, markedly accelerating electron transfer and enhancing the cathodic reduction current of MB, thereby producing a pronounced signal-on response in square-wave voltammetry (SWV). The ERGO-modified electrode provides a conductive and stable interface without chemical linkers. Under optimized conditions, the aptasensor shows a linear response to OTA from 10 fM to 100 pM with an ultralow LOD of 0.67 fM, together with high selectivity, good reproducibility, and satisfactory stability. This work demonstrates a simple and effective turn-on aptasensing strategy for sensitive electrochemical detection of OTA. Full article

The persistent discharge of refractory toxic organic pollutants poses a severe threat to aquatic environmental safety, driving the urgent demand for high-efficiency water treatment technologies in environmental engineering. Fenton and Fenton-like oxidation processes have garnered extensive attention due to their robust oxidizing capacity and environmental benignity; however, traditional Fenton systems are constrained by inherent limitations, including a narrow applicable pH range, potential secondary pollution, and cumbersome catalyst recovery. To address these challenges, Fenton-like catalysts have evolved progressively from single-metal systems to multi-metal alloy configurations. This review systematically elaborates on the fundamental principles and technical bottlenecks of classical Fenton and Fenton-like reactions, while comprehensively summarizing the research progress of multi-metal alloy catalysts—encompassing binary alloys, multi-component alloys, and high-entropy alloys. Special emphasis is placed on dissecting the core mechanisms through which multi-metal alloys optimize redox cycles and enhance structural stability, leveraging intermetallic synergistic effects, unique electronic structures, and lattice distortion. Furthermore, this work synthesizes key performance enhancement strategies for such catalysts, including co-catalyst synergy, external field assistance, and supported composite modification. Ultimately, this review aims to provide a scientific foundation and technical reference for the rational design, development, and engineering application of high-performance Fenton-like catalysts in sustainable wastewater remediation. Full article