Search Results (1,088)

Rising temperatures and atmospheric CO₂ exert complex, interacting effects on plant carbon metabolism and volatile organic compound (VOC) emissions. This study investigated the physiological mechanisms underlying acute thermal tolerance in Populus nigra by integrating leaf gas exchange with high-resolution proton-transfer-reaction time-of-flight mass spectrometry (PTR-TOF-MS). We employed a factorial design (25–40 °C; 400 and 800 ppm CO₂) to examine how metabolic regulation and pulse-induced signalling interact across thermal gradients. Our results identify a critical metabolic tipping point around 40 °C, representing a transition toward a survival-orientated state. Isoprene emission decoupled from net photosynthesis at this threshold; while carbon assimilation collapsed, isoprene was maintained at near-maximal rates to prioritize thylakoid thermal protection. Under moderate temperatures (25–35 °C), emission capacity scaled linearly with the chloroplastic DMADP pool, but this relationship broke down at 40 °C. Notably, elevated CO₂ sustained the magnitude of stress-related “bursts” at the thermal limit, suggesting that increased carbon availability provides the metabolic stamina required to fuel emergency defence and fermentative pathways. These findings demonstrate that acute thermal exposure triggers a metabolic reconfiguration, shifting resources from growth-oriented processes toward survival-based stabilization mechanisms. Full article

Respiratory syncytial virus (RSV) is a major pathogen responsible for severe lower respiratory tract infections in infants, the elderly, and immunocompromised individuals. Because the RSV F protein mediates viral entry and 15-lipoxygenase (15-LOX) amplifies virus-induced inflammatory responses, dual targeting of these proteins may provide both antiviral and anti-inflammatory benefits. In this study, we combined computational prediction with experimental validation to identify natural dual-target inhibitors from the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP). A total of 13,131 natural compounds were screened by drug-likeness evaluation, molecular docking, ADME assessment, and molecular dynamics simulations, yielding 31 potential dual-target candidates with favorable drug-like properties. Among them, rhoeadine (MOL001473) maintained stable binding conformations with both targets throughout 100 ns simulations. In BEAS-2B cells, rhoeadine exhibited significant anti-RSV activity (EC50 = 1.82 µM), low cytotoxicity (IC50 = 34.50 µM), and a selectivity index (SI) of 18.97. Time-of-addition experiments suggested that rhoeadine primarily acts at the early stage of viral infection. Additionally, ELISA results indicated that rhoeadine significantly inhibited RSV-induced secretion of CCL5 and IL-6, highlighting its anti-inflammatory potential. In summary, this study identified rhoeadine as a promising natural compound with antiviral and anti-inflammatory activities against RSV. Computational analyses suggested its potential association with RSV F protein and 15-LOX, although direct target-level validation is still required. Full article

Climate change-induced abiotic stress, particularly heat and drought during olive oil accumulation, significantly threatens the productivity and oil quality of olive trees (Olea europaea L.). This study investigated the efficacy of pre-harvest elicitation using the biostimulants harpin and chitosan (both as commercially available products) under summer conditions in Greece, in commercially productive rainfed groves of cv. ‘Megaritiki’. Multivariate analysis (PCA and factor analysis) revealed that pre-harvest application of these elicitors successfully balanced the trade-off between oil yield and quality. Both harpin and chitosan maintained hydrolytic (free acidity—0.25 and 0.29 g oleic acid 100 g⁻¹, respectively, compared to 0.56 g oleic acid 100 g⁻¹ in the control) and primary oxidative markers (peroxides—4.16 and 4.16 meq O₂ kg⁻¹, respectively, compared to 5.20 meq O₂ kg⁻¹ in the control) at exceptionally low levels compared to untreated trees. The treatments induced a distinctive metabolic shift regarding volatile compounds governed by the lipoxygenase (LOX) pathway. Harpin application was strongly associated with complex floral and fruity volatile compounds (2-hexen-1-ol and trans-2-hexenal) and a high α-tocopherol concentration (38.58 mg kg⁻¹ compared to 23.12 mg kg⁻¹ in the control), suggesting an enhanced physiological response in favor of oil quality attributes. Conversely, chitosan elevated the oxidative stability of the oil by increasing total phenol concentration (by almost 97% compared to the control) and prioritizing the accumulation of the stable monounsaturated fatty acids (oleic acid—increased by 12.5% compared to the control) over polyunsaturated ones (linoleic acid), while endowing the oil with desirable “green freshness” aromas (cis-3-hexenal). These results demonstrate that elicitation with harpin and chitosan is a potent tool for sustainably enhancing extra virgin olive oil quality under rainfed conditions in Greece, steering fruit metabolism toward a premium nutraceutical and sensory profile and enhancing the functional properties of the oil (phenol content, antioxidant capacity, monounsaturated fatty acids, α-tocopherol and squalene). Full article

Acute coronary syndrome patients undergoing percutaneous coronary intervention remain at high risk for major adverse cardiovascular events (MACE: cardiovascular mortality, non-fatal myocardial infarction, and stroke). Inflammatory–oxidative stress biomarkers are potential prognostic tools; however, the influence of sampling timing—pre-procedural versus post-procedural—remains unclear. This meta-analysis evaluated six biomarkers: sST2, GDF-15, OPG, sLOX-1, H-FABP, and Galectin-3. Pooled Hazard Ratios (HRs) for time-to-event outcomes and Standardized Mean Differences (SMDs) between event and non-event groups were synthesized using random-effects models involving 40 studies (18,933 patients). Elevated pre-procedural levels of sST2 (HR = 3.32, p < 0.0001), GDF-15 (HR = 3.00, p < 0.0001), sLOX-1 (HR = 2.61, p = 0.0023), and OPG (HR = 1.79, p = 0.0206) significantly predicted MACE. Notably, pre-PCI sST2 strongly predicted heart failure hospitalization (HR = 6.30, p < 0.0001). Additionally, pre-PCI H-FABP demonstrated a moderate significant effect on adverse outcomes (SMD = 0.67, p < 0.0001). While pre-PCI Galectin-3 was not significant, its post-procedural levels showed a large significant effect (SMD = 1.15, p < 0.0001). In conclusion, inflammatory and oxidative stress biomarkers, particularly sST2 and GDF-15, demonstrate consistent associations with adverse outcomes in ACS patients undergoing PCI, offering more reliable baseline risk stratification than post-procedural measurements. Full article

Background/Objectives: The significant negative correlation between protein and oil content in soybean seeds is a long-standing bottleneck for conventional breeding. Its root cause lies in insufficient understanding of related molecular regulatory processes. Methods: We selected the CSSL_R19, a chromosome segment substitution line, to thoroughly investigate the intrinsic effects of the substituted segment on the high seed storage protein (SSP) and low fatty acid (FA) phenotype. Transcriptomic, proteomic, and metabolomic analyses were performed on the recurrent parent and R19. Results: A total of 1821 differentially expressed genes (DEGs), 12 differentially expressed proteins (DEPs), and 10 differentially accumulated metabolites (DEMs) were detected. Subsequently, an integrative examination of the data demonstrated that 28 DEGs, 5 DEPs, and 4 DEMs participated in biological processes such as carbohydrate metabolism, lipid degradation, as well as protein synthesis and transport. Mechanistically, down-regulation of PGM reduces the carbon source supply for FA synthesis; up-regulation of LOX, LACS, ACX, and KAT promotes FA degradation. SRP, SAR1, and HSP70 are involved in the synthesis and transport of SSP. Crucially, qRT-PCR validation performed on all 28 core DEGs showed that their expression trends were highly consistent with the transcriptome data, confirming the reliability of the findings. Conclusions: In conclusion, we propose a potential regulatory network that enhances SSP accumulation and reduces FA content. Altogether, these findings advance our understanding of storage compound accumulation in soybeans and guide future breeding strategies. Full article

Osteoporosis is characterized by reductions in bone mineral density (BMD) and bone quality. While gut-derived signaling has been increasingly studied in relation to BMD, its contribution to molecular factors associated with bone quality remains less defined. Here, we investigated whether a heat-inactivated, freeze-dried, non-viable preparation of Levilactobacillus brevis AS-1 modulates intestinal epithelial-like cells and thereby promotes lysyl oxidase (LOX), a key enzyme involved in collagen cross-linking. Caco-2 cells were treated using 1 mM sodium butyrate and subsequently stimulated with 100 μg/mL L. brevis AS-1. Supernatants were collected and applied to MG63 cells. Cytokine mRNA expression in Caco-2 cells and LOX responses in MG63 cells were analyzed by qRT-PCR, and bone morphogenetic protein (BMP-1) and transforming growth factor-β (TGF-β)1 protein levels in the supernatant were measured by ELISA. L. brevis AS-1 stimulation up-regulated BMP-1 and TGF-β1 mRNA expression in SB-treated Caco-2 cells and increased BMP-1 protein secretion into the supernatant. LOX mRNA expression and total LOX activity were increased in MG63 cells treated with the conditioned supernatant, and inhibition of BMP-1/procollagen C-proteinase activity (UK383367) attenuated LOX mRNA induction. Collectively, these results suggest that L. brevis AS-1 stimulates intestinal epithelial-like cells to secrete BMP-1, which in turn promotes LOX mRNA expression in osteoblast precursor cells. This in vitro mechanism supports the concept of gut–bone crosstalk regulating molecular factors associated with bone quality. Full article

The increasing demand for continuous physiological monitoring has accelerated the development of high-sensitivity wearable electrochemical platforms. This study reports the fabrication of a multi-analyte electrochemical sensor based on single-walled carbon nanotubes (SWCNTs) for the detection of sweat-associated metabolites. To facilitate efficient heterogeneous electron transfer, glucose oxidase (Gox), lactate oxidase (Lox), and urease (Ure) were immobilized onto the SWCNT network through π–π interaction using 1-pyrenebutanoic acid succinimidyl ester (PBSE), followed by additional stabilization via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS) coupling. The developed platform exhibited concentration-dependent resistance responses within the ranges of 0.02–0.20 mM for glucose, 20–100 mM for lactate, and 50–400 mM for urea under controlled experimental conditions. The resistance-based configuration enabled stable and reproducible signal modulation across these concentration intervals. Although direct testing with human sweat was not performed, the electrochemical behavior of key sweat-related metabolites was systematically evaluated as a preparatory step toward future wearable integration. Full article

Background/Objectives: Congenital anomalies of the kidney and urinary tract (CAKUTs) represent the leading cause of pediatric chronic kidney disease, yet the molecular mechanisms underlying these malformations remain incompletely understood. While genetic studies have identified numerous CAKUT-associated genes, conventional knockout approaches often result in embryonic lethality or fail to reveal tissue-specific gene functions. This review aims to synthesize findings from conditional knockout mouse studies that have elucidated the spatiotemporal requirements of key signaling pathways during kidney development. Methods: We conducted a narrative synthesis of studies employing Cre-loxP conditional gene targeting in mouse models, identified through systematic searches of PubMed and cross-referencing of key primary research. Studies were selected based on their use of lineage-specific Cre drivers (Six2-Cre, Hoxb7-Cre, Foxd1-Cre) to investigate nephron progenitor maintenance, ureteric bud branching morphogenesis, and stromal–epithelial interactions. Results: Conditional knockout studies have redefined CAKUT pathogenesis as a disorder of dose-dependent signaling, temporal regulation, and inter-compartmental communication. WNT/β-catenin signaling operates in a biphasic, dose-dependent manner in nephron progenitors, with Six2-Cre-mediated β-catenin deletion causing premature progenitor depletion. BMP and FGF pathways demonstrate dose-dependent and context-specific functions in progenitor maintenance, while GDNF/RET signaling is essential for ureteric bud outgrowth and branching. Importantly, stromal-specific deletions have uncovered non-cell-autonomous mechanisms regulating nephron formation. Haploinsufficiency studies demonstrate that partial pathway disruption can reduce nephron endowment without overt CAKUT, predisposing to adult-onset hypertension and chronic kidney disease. Conclusions: Conditional gene targeting has mechanistically redefined CAKUT from a collection of structural malformations to a spectrum of disorders arising from quantitative perturbations in lineage-specific signaling networks. These findings establish that phenotypic severity is determined by the degree of pathway disruption, the developmental timing of insult, and the compartment affected, providing a framework for interpreting oligogenic interactions and variable penetrance in human CAKUTs. Full article

Background/Objectives: Floral bud morphogenesis is a critical developmental process determining yield potential in blueberry, yet the molecular regulatory mechanisms in leaves during this phase remain poorly understood. Methods: In this study, we employed a time-series transcriptomic approach to investigate leaf gene expression dynamics during floral bud morphogenesis in rabbiteye blueberry. Leaves were sampled at six time points spanning the critical developmental window from the cessation of summer shoot growth to bud swell and dormancy onset. Results: RNA-seq analysis generated 121.68 Gb of clean data, and weighted gene co-expression network analysis (WGCNA) identified four stage-specific modules (brown, red, blue, turquoise) significantly associated with distinct morphogenetic phases. The brown module (0–6W) was enriched in photosynthesis and hormone signaling pathways, while the red (9W) and blue (12W) modules featured protein processing, stress and hormone signaling, and carbohydrate metabolism. The turquoise module (15W) was dominated by carbon metabolism and flavonoid biosynthesis genes. Key flowering-related genes exhibited dynamic expression patterns: FT was specifically upregulated at the late stage (15W), AP2 genes peaked at mid-stage (9–12W), and COL9 showed early high expression (0–3W). Hormone-related gene analysis revealed extensive involvement of multiple pathways, with brassinosteroid (BR) signaling comprising the largest number of genes (101). Co-expression networks further identified hub genes, including FT, COL9, AP2, ERF1, SR160, LOX3-1, and transcription factor genes like MYB-related, as potential central regulators. Conclusions: Our findings demonstrate that blueberry leaves undergo a phased functional transition from a photosynthetic source to a hub for signal integration and metabolic support during floral bud morphogenesis, actively contributing to reproductive development through systemic signaling. This study provides novel insights into flowering regulation in woody perennials and establishes a foundation for marker-assisted breeding and cropping season management in blueberry. Full article

Mitochondria comprise ~1/3rd of the volume of an adult ventricular cardiomyocyte. The gene Immt encodes the Mic60/Mitofilin protein that is hypothesized to organize the mitochondrial contact site and cristae organization system (MICOS) complex that generates mitochondrial cristae junctions between the inner and outer membranes. To investigate the function of the Immt gene in the mouse heart, we generated and characterized mice in which this gene was specifically deleted in the mouse heart using a loxP-targeted allele (Immt^fl/fl) and either the constitutive heart-specific Myh6-Cre transgene or the conditional Myh6-MerCreMer transgene, each of which showed lethality in several weeks. Hearts from these mice showed progressive hypertrophic cardiomyopathy and failure with lost contractility and lung edema. At the ultrastructural level, hearts from these mice showed extreme abnormalities in mitochondrial architecture characterized by lost cristae junctions, stacking of the inner mitochondrial membranes, mitophagy and areas with complete absence of mitochondria. Analysis of mitochondria showed loss of the MICOS complex of proteins as well as loss of mitochondrial membrane potential (Δψ) and increased expression of mitophagy proteins and mitochondrial biogenesis transcription factors. Hearts from these mice also showed widespread cardiomyocyte necrosis and induction of the universal mitochondrial stress response at the mRNA level, as well as major alterations in cardiac metabolites, suggesting greater use of glucose, ketones and amino acids. We conclude that the Immt gene is required for cardiac mitochondrial structure and function, although the ensuing mitochondrial stress response provides molecular clues as to how the heart can compensate metabolically and maintain viability for weeks after mitochondria are absent or unfunctional. Full article

Imide derivatives constitute an interesting group of compounds exhibiting broad biological activity. Structures containing the imide moiety [–CO–N(R)–CO–] occur in both natural and synthetic compounds. Several drugs containing an imide moiety are in therapeutic use. In this review, we present the structures and describe the effects of cyclic imide derivatives, which primarily exhibit anti-inflammatory activity. Some of the presented derivatives have been studied in detail, and their additional analgesic, anticancer, and antibacterial effects have been described. The relative neuroprotective properties of imide derivatives are also described, as are reports of their effect on lowering cholesterol and triglyceride levels. In this review, we discuss monocyclic imide derivatives (succinimide, glutarimide, maleimide, and hydantoin), bicyclic derivatives (e.g., phthalimide), and polycyclic imides. Full article

The present study reports, for the first time, the chemical composition of the leaf essential oil (LEO) from Aspilia rudis as well as its antioxidant and anti-inflammatory activities. Analysis combining GC(RI), GC-MS and ¹³C-NMR of 36 samples identified 58 compounds representing 96.7–99.3% of the whole composition. Statistical analyses revealed chemical variability in three clusters, each composed of samples from the same sampling site. Cluster I is dominated by germacrene D (27.2 ± 2.7%), α-pinene (24.0 ± 2.9%) and (E)-β-caryophyllene (13.1 ± 1.7%), cluster II by α-pinene (38.9 ± 2.4%) and germacrene D (19.1 ± 3.6%), while the prevalent compound of cluster III is α-pinene (51.9 ± 5.3%), followed by β-pinene (11.7 ± 1.7%) and germacrene D (10.7 ± 2.2%). The oil samples S10, S26 and S36 demonstrated antioxidant activity (DPPH: EC₅₀ = 43.8 ± 1.0, 28.5 ± 1.0 and 38.8 ± 1.0 µg/mL, respectively; ABTS: TEAC = 17.16 ± 0.70, 23.35 ± 1.32 and 18.76 ± 0.64 µmol TE/mg EO, respectively) and anti-inflammatory activity through the LOX inhibition assay (IC₅₀ = 34.9 ± 1.0, 32.1 ± 1.0 and 22.2 ± 1.0 µg/mL, respectively). The activities of A. rudis LEO may be related to its main compounds and thymol, all known for their various pharmacological and biological properties, and probably to synergistic effects. Full article

Background: Etoricoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is widely prescribed for the management of inflammatory conditions. Despite its extensive clinical use, evidence regarding its hepatic safety profile remains limited and incompletely characterized. Aims: This study aimed to systematically evaluate the hepatic effects of etoricoxib in a murine model by integrating histopathological assessment with analysis of mRNA expression of key enzymes involved in arachidonic acid metabolism Methods: Male BALB/c mice (n = 7 per group) received either low or high doses of etoricoxib (10.5 or 21 mg/kg/day) or celecoxib (35 or 70 mg/kg/day) for 28 consecutive days. Liver tissues were examined histologically using hematoxylin and eosin staining, while molecular alterations were assessed by quantitative PCR targeting representative cyclooxygenase (COX), lipoxygenase (LOX), and cytochrome P450 (CYP450) isoforms involved in arachidonic acid metabolism. Results: High-dose etoricoxib exposure was associated with pronounced hepatic histopathological alterations, including hepatocellular necrosis, inflammatory cell infiltration, and sinusoidal congestion. In contrast, low-dose treatment resulted in only mild vascular and cellular changes. At the molecular level, etoricoxib administration was associated with marked downregulation of several arachidonic acid–metabolizing genes (including Cyp4a12 and Alox12), whereas Cox2 expression was significantly upregulated (p < 0.05), indicating a shift toward a pro-inflammatory transcriptional profile. Conclusions: Etoricoxib exposure is associated with dose-dependent hepatic injury in mice, accompanied by coordinated transcriptional alterations in arachidonic acid–metabolizing pathways. Notably, molecular changes were detectable even at low doses in the absence of overt histological damage, suggesting potential early indicators of hepatic stress. These findings underscore the importance of cautious dose optimization and further translational studies to clarify the long-term hepatic safety of etoricoxib in clinical settings. Full article

Virgin olive oil (VOO) quality is strongly influenced by olive cultivar and fruit maturity stage, yet their combined effects remain insufficiently characterized in many traditional olive-growing regions. This study evaluated the physicochemical parameters, phenolic compounds content, antioxidant activity, fatty acid profile, volatile compounds, and sensory attributes of VOOs obtained from five autochthonous cultivars of Extremadura (Spain)—‘Corniche’, ‘Manzanilla Cacereña’, ‘Morisca’, ‘Pico Limón’, and ‘Verdial de Badajoz’—harvested at three ripening stages (Green, Verging-on-ripe, and Ripe). Early harvest oils exhibited significantly higher total phenolic content (up to 478 mg/kg expressed by caffeic acid equivalent, CAE), oxidative stability (up to 188 h), intense green-fruity notes dominated by (E)-2-hexenal and (Z)-3-hexenal, and stronger bitterness and pungency. As ripening progressed, phenolic compounds and LOX-derived C6 volatiles markedly decreased, while oil yield, linoleic acid, saturated aldehydes, and oxidation markers increased in most cultivars. Cultivar-specific responses were evident: ‘Corniche’ and ‘Manzanilla Cacereña’ maintained higher oleic acid and stability, whereas ‘Morisca’ and ‘Pico Limón’ were more prone to phenolic compound loss and sensory deterioration at full ripeness. Multivariate analysis confirmed strong genotype × maturity interactions shaping oil quality. Optimal harvest timing must therefore be tailored to each cultivar to maximize phenolic content, oxidative stability, and sensory excellence while balancing industrial yield. Full article

Contagious bovine pleuropneumonia (CBPP) is a significant respiratory disease in cattle caused by Mycoplasma mycoides subsp. mycoides (Mmm). A better understanding of the pathogenesis of CBPP and the immune response of the host to infection will assist in the development of novel interventions to prevent disease progression. In this study, bovine lung explants (BLEs) were exposed to Mmm to investigate the upregulation and release of early inflammatory cytokines, mediators and receptors following tissue infection. Immunomodulatory molecules indicative of cell activation were investigated by immunoblotting on the BLEs and the tissue culture supernatants, and quantitative real-time PCR (RTq-PCR) was performed on the BLEs to determine the fold change in the expression of the respective mRNA. Immunoblotting indicated the production of inflammatory cytokines, mediators and receptors in Mmm-infected BLEs; however, this contrasted strongly with the mRNA expression profile, which did not show any significant fold increase. Infection of the BLEs with Mmm stimulated the production of some pro-inflammatory cytokines and mediators, including IL-1β, COX-2, 5-LOX and iNOS. Toll-like receptor proteins TLR2 and TLR4 were detected solely in the tissue culture supernatant of Mmm-infected BLEs. These receptors are considered to be involved in the recognition of Mmm by BLE tissue cells, thus triggering intracellular pathways that produce specific inflammatory cytokines and mediators, initiating the inflammatory response. Full article