Search Results (23,340)

DEAD-box (DDX) RNA helicases are essential regulators of RNA metabolism and gene expression. Among them, DDX10 remains poorly characterized despite growing evidence supporting its involvement in human diseases. This review provides a comprehensive analysis of DDX10, from its structural and functional features to its emerging roles in solid tumors and hematologic malignancies. We discuss how DDX10, through its conserved domains, contributes to pre-rRNA processing, ribosome biogenesis, and cell proliferation, and explore potential links between DDX10 and processes such as liquid–liquid phase separation (LLPS) and epigenetic regulation, which may underlie its roles in cancer cell plasticity and stress response. We argue that the dysregulation of these fundamental cellular processes positions DDX10 as a focal point where aberrant RNA metabolism and altered molecular condensates converge to disrupt transcriptional homeostasis and drive oncogenic transformation. Aberrant DDX10 expression is a recurrent feature across multiple cancers, where it promotes tumor progression, therapy resistance, and poor prognosis. Moreover, DDX10 participates in oncogenic fusion events, most notably the NUP98::DDX10 fusion identified in a subset of acute myeloid leukemias, which drives leukemogenesis by disrupting transcriptional regulation and cellular differentiation. Given its tumor-associated expression and diverse biological functions, DDX10 is increasingly recognized as a potential diagnostic biomarker and a promising target for therapeutic strategies. By consolidating current knowledge under this unifying framework, this review highlights the multifaceted roles of DDX10 in cancer biology, advocating further research into its molecular functions and translational potential. Full article

Soil erosion poses a significant environmental challenge in semi-arid and Mediterranean regions, jeopardizing the sustainability of land and water resources. This study explores the spatio-temporal dynamics of water erosion within the Tafna watershed in Algeria, which encompasses an area of approximately 7200 km². Utilizing the Revised Universal Soil Loss Equation (RUSLE) integrated with Geographic Information Systems (GIS), the assessment relies on bias-corrected simulated rainfall data that offers consistent spatial coverage over the past four decades (1983–2023). Additionally, the rainfall asymmetry coefficient (Cs) was calculated to evaluate the impact of temporal rainfall variability on soil loss. The results indicate significant spatial and temporal variability; average erosion rates vary from less than 6 t/ha/year in stable areas to 23–27 t/ha/year in steep, sparsely vegetated regions. Overall, soil erosion has increased by approximately 16% during the study period, driven by heightened rainfall aggressiveness and an intensification of erosive potential. Correlation analysis underscores the intricate relationships between rainfall, topography, and erosive dynamics, highlighting the exacerbating effect of irregular rainfall patterns (Cs). These findings underscore the Tafna watershed’s high vulnerability to both natural and human-induced pressures, reinforcing the necessity for differentiated land management and targeted soil and water conservation strategies. The methodology developed in this study provides a transferable approach for assessing water erosion in other semi-arid and Mediterranean watersheds facing similar data limitations and hydro-climatic variability. Full article

The patch-clamp technique is widely regarded as the gold standard in cellular electrophysiology and can be applied in several configurations. In the cell-attached (C-A) mode, it enables the recording of single-channel currents, whereas the whole-cell (W-C) mode allows for the measurement of macroscopic currents, representing the collective activity of many channels. When the recording configuration was switched from C-A to W-C on the same cell, the current amplitude increased dramatically, while action currents (ACs) were completely abolished, indicating a profound alteration in the cell’s electrophysiological response under the new setup. In excitable cells, the occurrence of ACs, representing propagated action potentials, can interfere with C-A single-channel recordings. To address this, a high-K⁺ solution is typically applied to the bath to suppress the ACs. The inwardly rectifying K⁺ (Kir), ATP-sensitive K⁺ (K_ATP) and large-conductance Ca²⁺-activated K⁺ (BK_Ca) channels are crucial members of the K⁺ channel family that facilitate the efflux of K⁺ ions, driven by the K⁺ electrochemical gradient. These channels are primarily distinguished by their rectification properties and gating kinetics. For instance, K_ATP channels exhibit a bursting kinetic pattern with inward rectifying property, while BK_Ca channels display strong outward rectification. Mitoxantrone, which belongs to a class of drugs called anthracenediones, can suppress the activity of Kir channels in differentiated RAW 264.7 cells, with no change in single-channel conductance. The respiratory stimulator GAL-021 acts as a BK_Ca channel inhibitor, and it suppresses channel activity and shifts the activation curve to the right, suggesting a voltage-dependent blockade that stabilizes the channel in a closed state. GAL-021 does not change the single-channel conductance, indicating it is a gating modifier rather than an open-pore blocker. The functional roles of ion channels are fundamentally important. Correspondingly, the field is transitioning to artificial intelligence for automated single-cell patch-clamp experiments, though brain slice recordings still require manual techniques. Full article

Background/Objectives: First row transition metal ions have recently regained attention in coordination chemistry as alternatives to gadolinium-based paramagnetic contrast agents, motivated by emerging safety concerns associated with certain Gd³⁺-based contrast agents. In this study, we report the development of a novel homoleptic diketonate Fe³⁺ complex functionalized with biocompatible indole moieties. We investigate its potential as a paramagnetic relaxation agent by evaluating its ability to modulate the T₁ and T₂ relaxation times of water proton. Methods: Iron(III) tris-1,3-(1-methylindol-3-yl)propanedionate [Fe(BIP)₃] was synthesized via a thermal method from bis(1-methylindol-3-yl)-1,3-propanedione (HBIP) using Fe(ClO₄)₃∙6 H₂O as the metal source. The complex was characterized by UV-Vis, IR and NMR spectroscopy, differential scanning calorimetry–thermogravimetric analysis, and single-crystal X-ray diffraction. Fe(BIP)₃ aggregation behavior in aqueous environment, including size and morphology of aggregates, was investigated using dynamic light scattering and scanning electron microscopy. Incorporation of the aggregates into phospholipid vesicles was evaluated by fluorescence resonance energy transfer and fluorescence correlation spectroscopy. The paramagnetic properties of monomeric Fe(BIP)₃ were probed in solution by nuclear magnetic resonance recurring to the Evans bulk magnetization method. Results: The designed synthetic procedure successfully afforded Fe(BIP)₃, which was fully characterized by UV-Vis and IR spectroscopy, as well as single-crystal X-ray diffraction. Aqueous solutions of Fe(BIP)₃ spontaneously formed rice-grain-shaped nanoscale aggregates of hydrodynamic radius ≈ 30 nm. Incorporation of these aggregates into phospholipid vesicles enhanced their stability. The longitudinal r₁ and transverse r₂ relaxivities of Fe(BIP)₃ aggregates were assessed to be 1.92 and 52.3 mM⁻¹s⁻¹, respectively, revealing their potential as paramagnetic relaxation agents. Conclusions: Fe(BIP)₃ aggregates, stabilized through incorporation into phospholipid vesicles, demonstrate promising potential as novel paramagnetic relaxation agents in aqueous environments. Full article

Purpose: Despite existing signatures, there remains a lack of robust autophagy-based biomarkers validated across multi-omics datasets and independent clinical cohorts in ESCC. The aim of our study was to develop an autophagy-related prognostic model for ESCC. Methods: Using transcriptomic data of ESCC from GEO/TCGA and autophagy-related genes (ARGs) from five autophagy-specific datasets, we identified the intersection between ARGs and tumor-normal differentially expressed genes (DEGs). We constructed a prognostic model using stepwise multivariate Cox regression based on these genes in GSE53625 (n = 179), validated in TCGA-ESCC (n = 94) through survival analysis and ROC curve, and analyzed the prognostic value of candidate genes in in-house ESCC samples. Results: We successfully established a robust prognostic 4-ARGs model comprising NBEA, CLOCK, NLRX1, and MAGEA3 (training: p < 0.0001, validation: p = 0.013). In the in-house ESCC cohort (n = 14), NLRX1 was verified as a reliable prognostic factor for disease-free survival (p = 0.043). Significant correlations were observed between signatures and the immune microenvironment, and the model effectively predicted patients’ responses to immunotherapy. Conclusion: We developed a novel 4-ARGs prognostic model and identified NLRX1 as a potential autophagy-dependent biomarker. These findings underscore its utility as a valuable tool for prognosis, risk stratification, and therapy guidance in ESCC. Full article

Liver cirrhosis (LC) is a complex pathological condition characterized by extensive transcriptomic reprogramming, yet the regulatory role of non-coding RNAs in disease progression remains poorly understood. This study aimed to systematically investigate long non-coding RNA (lncRNA)-messenger RNA (mRNA) interaction networks in LC through weighted gene co-expression network analysis (WGCNA). Gene expression profiles from datasets GSE197406, GSE107170, and GSE17548 were retrieved from the Gene Expression Omnibus (GEO) database, and differentially expressed lncRNAs and mRNAs were identified. Co-expression modules were constructed using WGCNA. Furthermore, functional enrichment analyses were conducted and drug repurposing opportunities were evaluated. Additionally, lncRNA-mRNA co-expression networks and lncRNA-mRNA-pathway networks were constructed to identify key regulatory relationships. Molecular docking simulations were subsequently performed to validate potential drug–target interactions. The results revealed several co-expression modules significantly associated with LC, particularly the turquoise module (r = 0.81). Genes within this module were enriched in several biological pathways, including the PI3K-Akt signaling pathway, NF-κB signaling pathway, and chemokine signaling pathway. The hub lncRNA in the turquoise module, NONHSAT134945.2, was found to be co-expressed with mRNAs involved in inflammasome-mediated pyroptosis and hepatocyte activation, such as CSF1R, HCK, and CASP1. Based on this hub gene signature, AB-1010, GW768505A, and Dasatinib were identified as potential therapeutic candidates. Molecular docking analysis confirmed that these compounds exhibit high binding affinity to CSF1R and HCK, with all interatomic distances maintained below 3.5 Å. These findings provide new insights into the molecular mechanisms underlying LC and suggest that the NONHSAT134945.2–CSF1R/HCK axis may serve as a valuable target for future translational research and therapeutic development. Full article

This study focuses on obtaining lignin-based hydrogels from pruning residues of orange trees in the Safor region (Valencia) using an alkaline extraction method. The structural analysis of the obtained lignin was carried out using Fourier-transform infrared spectroscopy (FTIR), which revealed the characteristic functional groups of lignin, as well as its structural monolignols: syringyl and guaiacyl. The thermal properties were analyzed using differential scanning calorimetry (DSC) and thermogravimetric analysis. The DSC thermogram revealed a relatively low glass transition temperature (T_g) of 67 °C, which may be attributed to partial lignin chain degradation during alkaline extraction. Soda lignin was obtained at 190 °C with an approximate yield of 10.8% relative to the initial biomass and subsequently used to synthesize poly(vinyl alcohol) (PVA)-based hydrogels for ibuprofen encapsulation. Finally, the release experiments of the encapsulated ibuprofen were carried out in an aqueous phosphate buffer medium (pH = 7) at room temperature. A multi-curve response analysis (MCR) algorithm using the Korsmeyer–Peppas (KP) concentration model was used to analyze the release curves, which concluded that the drug and water-soluble lignin fraction (SLF) were released at different rates. For both components, a good correlation was obtained between the measured responses and those provided by the KP model. The release profile indicated that approximately 87% of the initial ibuprofen load was released from the hydrogel within 5 h, highlighting the promising potential of lignin-based hydrogels for drug delivery applications. Full article

The expanding insect farming industry generates up to 67,000 tons of frass per year. Its potential use as fertilizer is promising, but has not yet been widely studied. This study aimed to characterize the chemical composition, organic matter structure, ecotoxicity, and phytotoxicity of frass from four insect species in order to evaluate its potential as a fertilizer. We compared four types of insect frass (IF) (Tenebrio molitor, Galleria mellonella, Hermetia illucens, and Acheta domesticus) to Eisenia fetida vermicompost (EFV). We used physicochemical analyses (pH, electrical conductivity (EC), macro-micronutrients and dissolved organic carbon (DOC), spectroscopy (solid-state ¹³C nuclear magnetic resonance (NMR), and Fourier-transform infrared spectroscopy (FTIR)) and thermogravimetry/differential scanning calorimetry (TGA/DSC: R₁, R₂, Tmax), together with phytotoxicity (germination index, %GI) and ecotoxicity (toxicity units, TU) bioassays. Composition was species-dependent: A. domesticus showed the highest levels of nitrogen (N), phosphorus (P), and potassium (K); the concentration of DOC was higher in insect frass (IF) than in EFV, with the highest concentration found in IF of T. molitor. ¹³C NMR/FTIR profiles distinguished between frass (carbohydrates/proteins and chitin signals) and EFV (humified, oxidized matrix). Thermal stability followed: G. mellonella (R₁ ≈ 0.88) ≥ A. domesticus (0.79) > H. illucens (0.73) > EFV (0.67) > T. molitor (0.50). In bioassays, T. molitor and A. domesticus exhibited phytotoxicity (%GI < 30), whereas G. mellonella and H. illucens did not. EFV exhibited the highest %GI. Dilution increased %GI in all materials, especially in T. molitor and A. domesticus, and reduced acute risk (TU). Frass is not a uniform input: its agronomic performance emerges from the interaction between EC (ionic stress), the availability of labile C (DOC, C/N and low-temperature exotherms), and structural stability (R₁/R₂ and aromaticity). In terms of formulation, IF can provide nutrients that mineralize rapidly, whereas EFV contributes stability. Controlling the inclusion and dilution of materials (e.g., limiting the amount of T. molitor in blends) and considering the mixing matrix helps to manage phytotoxicity and ecotoxicity, and realize the fertilizer value of the product. Full article

Objectives: We aimed to investigate the effects of 6 weeks of leucine supplementation on athletic performance, central fatigue, and serum metabolome in endurance athletes, and to provide valuable insights into nutritional strategies for endurance athletes. Methods: Twenty cross-country skiers were recruited and randomized into 2 groups: the placebo (PLA) group and the leucine (LEU) group. Subjects were given leucine (8.5 g) + sucrose (14 g) or only sucrose (14 g) supplements twice each day from Monday to Saturday for 6 weeks. Test parameters include body composition, aerobic capacity, isokinetic muscle strength, blood biochemistry, and targeted metabolomics. Results: After intervention, compared to the PLA group (1) the ankle muscle strength (p = 0.01), VO₂max (p = 0.01) and valine in serum (p = 0.03) were increased in the LEU group. (2) Targeted metabolomics results showed that the differential metabolites were enriched in the branched chain amino acids (BCAAs) biosynthesis and degradation. (3) The LEU group had a significant increase in α-ketoisovaleric acid (p = 0.03), which can reduce the continuous decomposition of BCAAs. Conclusions: In conclusion, a six-week intervention of leucine supplementation significantly enhanced ankle muscle strength in endurance athletes, likely through a reduction in BCAA catabolism. Additionally, this combined supplementation strategy demonstrated potential benefits in improving aerobic endurance and may contribute to the attenuation of exercise-induced central fatigue. Full article

Drug resistance is an important challenge in medical research and clinical practice, posing a serious threat to the effectiveness of current therapeutic strategies. Transcriptomics has played a crucial role in analyzing resistance-related genes and pathways, while the application of machine learning in high-throughput data analysis and prediction has also opened up new avenues in this field. However, existing studies mostly focus on a single drug or specific categories, and their conclusions are limited in applicability across drug categories, while studies on drugs beyond antibacterial and antitumor categories remain limited. In this study, we systematically analyzed the transcriptomic data of resistant cell lines treated with 1738 drugs spanning 82 categories and identified core genes through an integrated analysis of three classical machine learning methods. Using the antibacterial drug salinomycin as an example, we established a resistance prediction model that demonstrated high predictive accuracy, indicating the significant value of the selected core genes in prediction. Meanwhile, some of the core genes identified through the protein–protein interaction (PPI) network overlapped with those derived from machine learning analysis, further supporting the reliability of these core genes. Pathway enrichment analysis of differential genes revealed potential resistance mechanisms. This study provides a new perspective for exploring resistance mechanisms across drug categories and highlights potential directions for resistance intervention strategies and novel drug development. Full article

In this study, semi-interpenetrating polymer network (semi-IPN) hydrogels based on methacrylated dextran and native inulin were designed as biodegradable carriers for the colon-specific delivery of uracil as a model antitumor compound. The hydrogels were synthesized via free-radical polymerization, using diethylene glycol diacrylate (DEGDA) as a crosslinking agent at varying concentrations (5, 7.5, and 10 wt%), and their structural, thermal, and biological properties were systematically evaluated. Fourier transform infrared spectroscopy (FTIR) confirmed successful crosslinking and physical incorporation of uracil through hydrogen bonding. Concurrently, differential scanning calorimetry (DSC) revealed an increase in glass transition temperature (T_g) with increasing crosslinking density (149, 153, and 156 °C, respectively). Swelling studies demonstrated relaxation-controlled, first-order swelling kinetics under physiological conditions (pH 7.4, 37 °C) and high gel fraction values (84.75, 91.34, and 94.90%, respectively), indicating stable network formation. SEM analysis revealed that the hydrogel morphology strongly depended on crosslinking density and drug incorporation, with increasing crosslinker content leading to a more compact and wrinkled structure. Uracil loading further modified the microstructure, promoting the formation of discrete crystalline domains within the semi-IPN hydrogels, indicative of physical drug entrapment. All formulations exhibited high encapsulation efficiencies (>86%), which increased with increasing crosslinker content, consistent with the observed gel fraction values. Simulated in vitro gastrointestinal digestion showed negligible drug release under gastric conditions and controlled release in the intestinal phase, primarily governed by crosslinking density. Antimicrobial assessment against Escherichia coli and Staphylococcus epidermidis, used as an initial or indirect indicator of cytotoxic potential, revealed no inhibitory activity, suggesting low biological reactivity at the screening level. Overall, the results indicate that DEGDA-crosslinked dextran/inulin semi-interpenetrating (semi-IPN) hydrogels represent promising carriers for colon-targeted antitumor drug delivery. Full article

The management of lung cancer (LC) in patients with interstitial lung diseases (ILDs) presents significant challenges, particularly with the increasing use of immunotherapy (IT). Immunotherapy-related pneumonitis (ICIP) is a potential complication of immune checkpoint inhibitors (ICIs) that can be difficult to differentiate from pre-existing or treatment-induced ILD. The incidence of treatment-related pneumonitis is higher in patients with pre-existing ILD, which complicates the therapeutic approach. Moreover, antifibrotic drugs have shown potential in reducing the incidence of post-operative acute exacerbations in IPF patients undergoing surgery and radiotherapy. ILDs in LC patients can either develop ab initio, linked to environmental exposures, autoimmune diseases, or emerge because of cancer therapies. Although large-scale clinical trial evidence remains limited, careful therapy selection, early detection of pneumonitis, and close monitoring are crucial. Further prospective studies are needed to refine therapeutic strategies, particularly regarding the role of IT in this sensitive population and the role of combination therapies with antifibrotics and ICIs to optimize outcomes for patients with both LC and ILDs. This review summarizes the available evidence on the safety and efficacy of IT in this population, emphasizing the importance of personalized treatment approaches and vigilant monitoring. Full article

Chronic kidney disease (CKD) afflicts 850 million people worldwide, with an estimate that it is the 5th highest cause of years of life lost (YLLs). Standard confirmatory procedures for disease are blood and urine analysis with ultrasound for confirmation. Neutrophil gelatinase-associated lipocalin (NGAL) has been established as a prognostic biomarker, especially for the pre-clinical stages of CKD, thus presenting itself as a dependable predictor of the progression. With the aim of designing diagnostics, fatty acids were explored as potential biorecognition elements for the selective capture of NGAL. Three fatty acids—linoleic acid, arachidonic acid, and retinoic acid—were shortlisted as plausible candidates based on their known affinity toward lipocalin family proteins. Docking followed by molecular dynamics simulations were employed to evaluate the binding affinity and stability of each complex. Among them, linoleic acid exhibited the most favorable interaction, as evidenced by the lowest binding free energy. Subsequently, fluorescence and electrochemical techniques—square-wave voltammetry, differential pulse voltammetry, cyclic voltammetry, and electrochemical impedance spectroscopy (EIS)—were systematically compared for qualitative and quantitative checking of the accuracy of NGAL detection. Amongst the electrochemical techniques, differential pulse voltammetry DPV demonstrated superior analytical performance with an LOD of 0.05 ng/mL with a sensitivity of 23.2 µA/cm²/pg. To the best of our knowledge, this is the first report of a fatty acid-based biosensor platform for NGAL detection, presenting a novel approach for CKD diagnostics. The sensitivity obtained is comparable with available NGAL detection methods yet cost-effective and robust. Full article

Baroclinic wave resonance, particularly Rossby waves, has attracted great interest in ocean and atmospheric physics since the 1970s. Research on Rossby wave resonance covers a wide variety of phenomena that can be unified when focusing on quasi-stationary Rossby waves traveling at the interface of two stratified fluids. This assumes a clear differentiation of the pycnocline, where the density varies strongly vertically. In the atmosphere, such stationary Rossby waves are observable at the tropopause, at the interface between the polar jet and the ascending air column at the meeting of the polar and Ferrel cell circulation, or between the subtropical jet and the descending air column at the meeting of the Ferrel and Hadley cell circulation. The movement of these air columns varies according to the declination of the sun. In oceans, quasi-stationary Rossby waves are observable in the tropics, at mid-latitudes, and around the subtropical gyres (i.e., the gyral Rossby waves GRWs) due to the buoyant properties of warm waters originating from tropical oceans, transported to high latitudes by western boundary currents. The thermocline oscillation results from solar irradiance variations induced by the sun’s declination, as well as solar and orbital cycles. It is governed by the forced, linear, inviscid shallow water equations on the β-plane (or β-cone for GRWs), namely the momentum, continuity, and potential vorticity equations. The coupling of multi-frequency wave systems occurs in exchange zones. The quasi-stationary Rossby waves and the associated zonal/polar and meridional/radial geostrophic currents modify the geostrophy of the basin. Here, it is shown that the ubiquity of resonant forcing in (sub)harmonic modes of Rossby waves in stratified media results from two properties: (1) the natural period of Rossby wave systems tunes to the forcing period, (2) the restoring forces between the different multi-frequency Rossby waves assimilated to inertial Caldirola–Kanai (CK) oscillators are all the stronger when the imbalance between the Coriolis force and the horizontal pressure gradients in the exchange zones is significant. According to the CK equations, this resonance mode ensures the sustainability of the wave systems despite the variability of the forcing periods. The resonant forcing of quasi-stationary Rossby waves is at the origin of climate variations, as well-known as El Niño, glacial–interglacial cycles or extreme events generated by cold drops or, conversely, heat waves. This approach attempts to provide some new avenues for addressing climate and weather issues. Full article

Biomorphic hydroxyapatite scaffolds derived from rattan wood (GreenBone) show significant promise in bone tissue engineering due to their inherent structural similarity to natural bone. Laser-drilled GreenBone scaffolds were studied for enhanced porosity, nutrient diffusion, cellular infiltration, and vascularisation. Patient-derived bone marrow mesenchymal stromal/stem cells (BMMSCs) and culture-expanded mesenchymal stem cells (cMSCs) demonstrated high cell viability (>90%), considerable adhesion, and extensive cytoskeletal organisation. Trilineage differentiation confirmed the multipotency of BMMSCs, with osteogenic, adipogenic, and chondrogenic markers being successfully expressed. BMMSCs and cMSCs exhibited enhanced differentiation and gene expression profiles. At week 4, key osteogenic and angiogenic genes such as BMP2, VEGFC, RUNX2, and COL1A1 showed elevated expression, indicating improved bone formation and vascularisation activity. Markers associated with extracellular matrix (ECM) remodelling, including MMP9 and TIMP1, were also upregulated, suggesting active tissue remodelling. ELISA analysis for VEGF further demonstrated increased VEGF secretion, highlighting the scaffold’s angiogenic potential. The improved cellular response and vascular signalling emphasise the translational relevance of laser-modified GreenBone scaffolds for bone tissue engineering, particularly for critical-sized defect repair requiring rapid vascularised bone regeneration. Full article