Search Results (3,663)

Thyroid hormones (thyroxine, T₄, and triiodothyronine, T₃) are indispensable for sustaining vertebrate life, and their deficiency gives rise to a wide range of symptoms characteristic of hypothyroidism, affecting 5–10% of the world’s population. The precursor for thyroid hormone synthesis is thyroglobulin (Tg), a large iodoglycoprotein consisting of upstream regions I-II-III (responsible for synthesis of most T₄) and the C-terminal CholinEsterase-Like (ChEL) domain (responsible for synthesis of most T₃, which can also be generated extrathyroidally by T₄ deiodination). Using CRISPR/Cas9-mediated mutagenesis, we engineered a knock-in of secretory ChEL into the endogenous TG locus. Secretory ChEL acquires Golgi-type glycans and is properly delivered to the thyroid follicle lumen, where T₃ is first formed. Homozygous knock-in mice are capable of thyroidal T₃ synthesis but largely incompetent for T₄ synthesis such that T₄-to-T₃ conversion contributes little. Instead, T₃ production is regulated thyroidally by thyrotropin (TSH). Compared to cog/cog mice with conventional hypothyroidism (low serum T₄ and T₃), the body size of ChEL-knock-in mice is larger; although, these animals with profound T₄ deficiency did exhibit a marked elevation of serum TSH and a large goiter, despite normal circulating T₃ levels. ChEL knock-in mice exhibited a normal expression of hepatic markers of thyroid hormone action but impaired locomotor activities and increased anxiety-like behavior, highlighting tissue-specific differences in T₃ versus T₄ action, reflecting key considerations in patients receiving thyroid hormone replacement therapy. Full article

In familial Alzheimer’s disease (FAD), presenilin 1 (PSEN1) E280A cholinergic-like neurons (ChLNs) induce aberrant secretion of extracellular amyloid beta (eAβ). How PSEN1 E280A ChLNs-eAβ affects microglial activity is still unknown. We obtained induced microglia-like cells (iMG) from human peripheral blood cells (hPBCs) in a 15-day differentiation process to investigate the effect of bolus addition of Aβ42, PSEN1 E280A cholinergic-like neuron (ChLN)-derived culture supernatants, and PSEN1 E280A ChLNs on wild type (WT) iMG, PSEN1 E280A iMG, and sporadic Alzheimer’s disease (SAD) iMG. We found that WT iMG cells, when challenged with non-cellular (e.g., lipopolysaccharide, LPS) or cellular (e.g., Aβ42, PSEN1 E280A ChLN-derived culture supernatants) microenvironments, closely resemble primary human microglia in terms of morphology (resembling an “amoeboid-like phenotype”), expression of surface markers (Ionized calcium-binding adapter molecule 1, IBA-1; transmembrane protein 119, TMEM119), phagocytic ability (high pHrodo™ Red E. coli BioParticles™ phagocytic activity), immune metabolism (i.e., high generation of reactive oxygen species, ROS), increase in mitochondrial membrane potential (ΔΨm), response to ATP-induced transient intracellular Ca²⁺ influx, cell polarization (cluster of differentiation 68 (CD68)/CD206 ratio: M1 phenotype), cell migration activity according to the scratch wound assay, and especially in their inflammatory response (secretion of cytokine interleukin-6, IL-6; Tumor necrosis factor alpha, TNF-α). We also found that PSEN1 E280A and SAD iMG are physiologically unresponsive to ATP-induced Ca²⁺ influx, have reduced phagocytic activity, and diminished expression of Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) protein, but when co-cultured with PSEN1 E280A ChLNs, iMG shows an increase in pro-inflammatory phenotype (M1) and secretes high levels of cytokines IL-6 and TNF-α. As a result, PSEN1 E280A and SAD iMG induce apoptosis in PSEN1 E280A ChLNs as evidenced by abnormal phosphorylation of protein TAU at residue T205 and cleaved caspase 3 (CC3). Taken together, these results suggest that PSEN1 E280A ChLNs initiate a vicious cycle between damaged neurons and M1 phenotype microglia, resulting in excessive ChLN death. Our findings provide a suitable platform for the exploration of novel therapeutic approaches for the fight against FAD. Full article

This study explored the potential of chitosan (CH)/bacterial cellulose (BC) complexes (0.5% w/v) as novel emulsifiers to stabilize oil-in-water (o/w) Pickering emulsions (20% v/v sunflower oil), with a focus on their gel-like behavior. Emulsions were prepared using CH combined with BNC derived via H₂SO₄ (BNC1) or H₂SO₄-HCl (BNC2) hydrolysis. Increasing BNC content improved stability by reducing phase separation and enhancing viscosity, while CH contributed interfacial activity and electrostatic stabilization. CH/BNC1_25:75 emulsions showed the highest stability, maintaining an emulsion stability index (ESI) of up to 100% after 3 days, with minimal change in droplet size (R_h ~8.5–8.8 μm) and a positive ζ-potential (15.1–29.8 mV), as confirmed by dynamic/electrophoretic light scattering. pH adjustment to 4 and 10 had little effect on their ESI, while ionic strength studies showed that 0.1 M NaCl caused only a slight increase in droplet size combined with the highest ζ-potential (−35.2 mV). Higher salt concentrations led to coalescence and disruption of their gel-like structure. Rheological analysis of CH/BNC1_25:75 emulsions revealed shear-thinning behavior and dominant elastic properties (G′ > G″), indicating a soft gel network. Incorporating sunflower-seed protein isolates into CH/BNC1 (25:75) emulsions led to coacervate formation (three-layer system), characterized by a decrease in droplet size and an increase in ζ-potential (up to 32.8 mV) over 7 days. These findings highlight CH/BNC complexes as sustainable stabilizers for food-grade Pickering emulsions, supporting the development of biopolymer-based emulsifiers aligned with bioeconomy principles. Full article

Background/Objectives: A nanostructured membrane of polycaprolactone (a synthetic polymer) was synthesized using an electrospinning technique aiming to enhance its hydrophilicity and rate of degradation by surface modification via aminolysis. Since polycaprolactone nanofibrous films are naturally hydrophobic and with slow degradation, which restricts their use in biological systems, amino groups were added to the fiber surface using the aminolysis technique, greatly increasing the wettability of the membranes. Methods: Polycaprolactone nanofibrous membranes were synthesized via the electrospinning technique and surface modification by aminolysis. Trypsin, pepsin, and pancreatin were conjugated onto the aminolyzed PNF surface to further strengthen biocompatibility by enhancing the hydrophilicity, porosity, and biodegradation rate. SEM, FTIR, EDX, and liquid displacement method were performed to investigate proteolytic efficiency and morphological and physical characteristics such as hydrophilicity, porosity, and degradation rates. Results: Enzyme activity tests, which showed a zone of clearance, validated the successful enzyme conjugation and stability over a wide range of pH and temperatures. Scanning electron microscopy (SEM) confirms the smooth morphology of nanofibers with diameters ranging from 150 to 950 nm. Fourier transform infrared spectroscopy (FTIR) revealed the presence of O–H, C–O, C=O, C–N, C–H, and O–H functional groups. Energy-dispersive X-ray (EDX) elemental analysis indicates the presence of carbon, oxygen, and nitrogen atoms owing to the presence of peptide and amide bonds. The liquid displacement technique and contact angle proved that Pepsin-PNFs possess notably increased porosity (88.50% ± 0.31%) and hydrophilicity (57.6° ± 2.3 (L), 57.9° ± 2.5 (R)), respectively. Pancreatin-PNFs demonstrated enhanced enzyme activity and degradation rate on day 28 (34.61%). Conclusions: These enzyme-conjugated PNFs thus show improvements in physicochemical properties, making them ideal candidates for various biomedical applications. Future studies must aim for optimization of enzyme conjugation and in vitro and in vivo performance to investigate the versatility of these scaffolds. Full article

Background/Objectives: Concussions have been associated with deficits in attentional control. The current work examined whether attentional correlates could be enhanced following acute aerobic exercise in those with a history of concussion (CH). Methods: EEG was collected as participants completed a flanker task to evoke stimulus-locked (N2, P3) and response-locked error-related (ERN, Pe) ERPs, before and after participants completed a bout of acute aerobic exercise at moderate intensity. Conflict was modulated with distance (close/far) and congruency (incongruent/congruent) of the distractors relative to the targets. Results: CH individuals had reduced accuracy in high-conflict conditions, with improvements following exercise. No differences were observed in attentional cognitive control across the four conditions (close/far congruent, close/far incongruent); however, reduced interference control was shown in far conditions, when compared to close conditions. When compared to non-concussed controls, increased accuracy with increased response time in individuals with a concussion history was likely attributed to the speed–accuracy trade-off. Close conditions highlighted a decreased Pe amplitude in CH individuals (as opposed to the active controls), suggesting CH individuals may present with challenges when evaluating an error with working memory. Conclusions: The findings demonstrated acute exercise improved accuracy among CH individuals, and performance monitoring is impacted negatively long term following a concussion. Full article

The mixed oxides of Ni/ZrO₂, Ni-Ca/ZrO₂, Ni-Ba/ZrO₂, and Ni-Ba-Ca/ZrO₂ were prepared using the co-precipitation method at a pH of precisely 8.3. The catalytic mixed oxides of Ni/ZrO₂, Ni-Ca/ZrO₂, Ni-Ba/ZrO₂, and Ni-Ba-Ca/ZrO₂ were characterized using x-ray diffraction XRD, Brunauer Emmett Teller (BET), scanning electron microscopy (SEM), and metal dispersion for the screening of phase purity, surface area, and morphology. The mixed oxides are subjected to CO₂-TPD to quantify the basicity of every composition. The mixed oxide catalysts of Ni/ZrO₂, Ni-Ca/ZrO₂, Ni-Ba/ZrO₂, and Ni-Ba-Ca/ZrO₂ were screened for oxythermal reforming of CH₄ with CO₂ in a fixed bed tubular reactor at 800 °C. Among all catalysts, the Ba- and Ca- loaded Ni-Ba-Ca/ZrO₂ showed high conversion by the decomposition of methane and CO₂ disproportionation throughout the time on stream of 29 h. The high activity with stability led to less coke formation over Ni-Ba-Ca/ZrO₂ over the surface. The stable syngas production with an active catalyst bed contributed to the improved bimetallic synergy. The high surface basicity of Ni-Ba-Ca/ZrO₂ may keep actively gasifying the formed soot and allow for further stable reforming reactions. Full article

Cold environments challenge the structural and functional integrity of membrane proteins, requiring specialized adaptations to maintain activity under low thermal energy. Here, we investigate the molecular basis of cold tolerance in the peptide transporter PepT1 from the Antarctic icefish (Chionodraco hamatus, ChPepT1) using molecular dynamics simulations, binding free energy calculations (MM/GBSA), and dynamic network analysis. We compare ChPepT1 to its human ortholog (hPepT1), a non-cold-adapted variant, to reveal key features enabling psychrophilic function. Our simulations show that ChPepT1 displays enhanced global flexibility, particularly in domains adjacent to the substrate-binding site and the C-terminal domain (CTD). While hPepT1 loses substrate binding affinity as temperature increases, ChPepT1 maintains stable peptide interactions across a broad thermal range. This thermodynamic buffering results from temperature-sensitive rearrangement of hydrogen bond networks and more dynamic lipid interactions. Importantly, we identify a temperature-responsive segment (TRS, residues 660–670) within the proximal CTD that undergoes an α-helix to coil transition, modulating long-range coupling with transmembrane helices. Dynamic cross-correlation analyses further suggest that ChPepT1, unlike hPepT1, reorganizes its interdomain communication in response to temperature shifts. Our findings suggest that cold tolerance in ChPepT1 arises from a combination of structural flexibility, resilient substrate binding, and temperature-sensitive interdomain dynamics. These results provide new mechanistic insight into thermal adaptation in membrane transporters and offer a framework for engineering proteins with enhanced functionality in extreme environments. Full article

Cholinergic neuron impairment is a significant cause of cognitive decline in Alzheimer’s disease (AD), making acetylcholinesterase (AChE) a key therapeutic target. AChE inhibitors are principal drugs prescribed to alleviate symptoms in AD patients, while up to 50% of these individuals also suffer from depression, frequently treated with selective serotonin reuptake inhibitors (SSRIs). Due to the multisymptomatic nature of AD, there is a growing interest in developing multitargeted ligands that simultaneously enhance cholinergic and serotonergic tone. This study presents the synthesis of novel ligands based on functionalized piperidines, evaluated through radioligand binding assays at the serotonin transporter (SERT) and AChE and butyrylcholinesterase (BuChE) inhibition. The pharmacological results showed that some compounds exhibited moderate inhibitory activity against AChE, with one compound 19 standing out as the most potent, also displaying a moderate BuChE inhibitory activity, while showing low affinity for SERT. On the other hand, compound 21 displayed an interesting polypharmacological profile, with good and selective activity against BuChE and SERT. The results underscore the difficulty of designing promiscuous ligands for these targets and suggest that future structural modifications could optimize their therapeutic potential in AD. Full article

The biomass-to-liquid process is a promising alternative for sustainably meeting the growing demand for liquid fuels. This study focuses on the fabrication, characterization, and performance of a structured iron catalyst for producing hydrocarbons through Fischer–Tropsch synthesis (FTS). The catalyst was designed to address some drawbacks of conventional supported catalysts, such as low utilization, poor activity, and instability. The experimental investigation involved the manufacturing and characterization of both promoted and unpromoted iron-based catalysts. The performance of the structured iron catalyst was assessed in a fixed-bed reactor under relevant industrial conditions. Notably, the best results were achieved with a syngas ratio typical of the gasification of lignocellulosic biomass, where the catalyst exhibited superior catalytic activity and selectivity toward desired hydrocarbon products, including light olefins and long-chain paraffins. The resulting structured catalyst achieved up to 95% CO conversion in a single pass with 5% selectivity for CH₄. The results indicate that the developed structured iron catalyst has considerable potential for efficient and sustainable hydrocarbon production via the Fischer–Tropsch synthesis. The catalyst’s performance, enhanced stability, and selectivity present promising opportunities for its application in large-scale hydrocarbon synthesis processes. Full article

The Carbohydrate-Responsive Element-Binding Protein (ChREBP) is a glucose-sensitive transcription factor that regulates the carbohydrate and lipid metabolism. We investigated its cell-type-specific role in hepatocarcinogenesis using a chemically induced mouse model. Additionally, we examined the functions of its isoforms, ChREBPα and ChREBPβ. After the diethylnitrosamine (DEN) administration, we analyzed hepatocellular adenomas and carcinomas in systemic ChREBP-knockout (KO), hepatocyte-specific ChREBP-KO (L-KO), and wildtype (WT) mice at 4, 12, and 36 weeks using histology, morphometry, proliferation measurements, immunohistochemistry, a Western blot, and a quantitative PCR. Tumors developed 36 weeks after the DEN administration in 27% of WT mice but less frequently in KO (18%) and L-KO (9%) mice. However, preneoplastic foci were less common in KO mice but not in L-KO mice (39% vs. 9%; p < 0.05). L-KO hepatocytes exhibited lower proliferation, while KO tumors showed the downregulation of AKT/mTOR signaling, glycolysis, and lipogenesis compared to WT tumors. Our results showed that the liver-specific loss of ChREBPα, while ChREBPβ remained active, significantly reduced the tumor progression, suggesting an oncogenic role for ChREBPα. In contrast, the systemic knockout of both ChREBPα and ChREBPβ reduced the tumor initiation but did slightly prevent tumor progression, indicating that ChREBPβ may exert tumor-suppressive functions. Full article

Background: COVID-19 led to social isolation, potentially reducing physical activity (PA), increasing sedentary time, and lowering quality of life (QoL). This study investigated the association between these factors in patients with Chagas disease (ChD) during the pandemic. Methods: This cross-sectional study included 187 patients with ChD. PA and sedentary time were assessed by the IPAQ-short and QoL by the WHOQOL-Bref. The relationship between PA levels and sedentary time with QoL were assessed using unadjusted and adjusted generalized linear models. Results: The highest tertile of total PA was positively associated with the psychological (Exp β = 1.11; 95% CI: 1.02–1.22) and environmental (Exp β = 1.12; 95% CI: 1.01–1.23) QoL domains. The intermediate (Exp β = 1.12; 95% CI: 1.01–1.25) and highest (Exp β = 1.14; 95% CI: 1.02–1.27) tertiles of moderate-to-vigorous PA were positively associated with the physical domain. Similarly, both the intermediate (Exp β = 1.11; 95% CI: 1.01–1.22) and highest (Exp β = 1.12; 95% CI: 1.01–1.21) tertiles of moderate-to-vigorous PA were positively associated with the psychological domain. The highest tertile of sedentary time was associated with a decrease in the physical domain (Exp β = 0.88; 95% CI: 0.79–0.98). Conclusions: Higher levels of total and moderate-to-vigorous PA were associated with better QoL, while greater sedentary time was associated with poorer QoL. Full article

Background/Objectives: HIF-1α and ERRα are both implicated in breast cancer progression, yet their functional interplay remains poorly understood. This study investigates their molecular crosstalk in the context of hypoxia-induced drug resistance. Methods: MCF-7 (estrogen receptor, ER-positive) spheroids and CoCl₂-treated SK-BR-3 (ER-negative) cells were used to model tumor hypoxia. Protein expression, coimmunoprecipitation, chromatin immunoprecipitation (ChIP), pharmacological inhibition, and siRNA-mediated gene silencing were employed to assess physical and functional interactions. Immunohistochemistry (IHC) on a tissue microarray (TMA) of 168 invasive breast carcinomas was performed to evaluate clinical relevance. Results: ERRα levels remained unchanged under hypoxia, while its coactivator, Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 α (PGC-1α), was upregulated. ERRα physically interacted with HIF-1α and was required for HIF-1 transcriptional activity under hypoxic conditions. ChIP assays showed that ERRα-driven overexpression of Permeability glycoprotein 1 (P-gp) and Vascular Endothelial Growth Factor (VEGF) was mediated by HIF-1α binding to the MDR1 and VEGF promoters. Inhibition or silencing of ERRα reversed P-gp overexpression and restored intracellular doxorubicin. TMA analysis confirmed the clinical correlation between ERRα, HIF-1α, and P-gp expression, highlighting the role of ERRα in hypoxia-induced drug resistance. ERRα expression was independent of ER status, suggesting an estrogen-independent function. Conclusions: This study identifies a novel physical and functional interaction between ERRα and HIF-1α that promotes chemoresistance in hypoxic breast tumors. Targeting ERRα may represent a promising therapeutic strategy to overcome drug resistance in aggressive, ER-independent breast cancer subtypes. Full article

This study evaluates the agronomic and environmental performance of pelletized compost derived from olive mill waste as a sustainable alternative to mineral fertilizers for cultivating wheat (Triticum turgidum L.) under conventional tillage methods. A field experiment was conducted in semi-arid Spain, employing three fertilization strategies: inorganic (MAP + Urea), sewage sludge (SS), and organic compost pellets (OCP), each providing 150 kg N ha⁻¹. The parameters analyzed included wheat yield, grain quality, soil properties, and greenhouse gas (GHG) emissions. Inorganic fertilization yielded the highest productivity and nutrient uptake. However, the OCP treatment reduced grain yield by only 15%, while improving soil microbial activity and enzymatic responses. The SS and OCP treatments showed increased CO₂ and N₂O emissions compared to the control and inorganic plots. However, the OCP treatment also acted as a CH₄ sink. Nutrient use efficiency was greatest under mineral fertilization, though the OCP treatment outperformed the SS treatment. These results highlight the potential of OCP as a circular bio-based fertilizer that can enhance soil function and partially replace mineral inputs. Optimizing application timing is critical to aligning nutrient release with crop demand. Further long-term trials are necessary to evaluate their impact on the soil and improve environmental outcomes. Full article

Reclaimed fields have a low soil fertility and low productivity compared to conventional arable land, necessitating research on productivity enhancement. The rice–frog co-culture model is an ecologically intensive practice that combines biodiversity objectives with agricultural production needs, offering high ecological and economic value. However, there is a lack of research on this model that has focused on factors other than soil nutrient levels. The present study evaluated the rice–frog co-culture model in a reclaimed paddy field across three experimental plots with varying frog stocking densities: a rice monoculture (CG), low-density co-culture (LRF), and high-density co-culture (HRF). We investigated the effects of the frog density on greenhouse gas emissions throughout the rice growth. The rice–frog co-culture model significantly reduced methane (CH₄) emissions, with fluxes highest in the CG plot, followed by the LRF and then HRF plots. This reduction was achieved by altering the soil pH, the cation exchange capacity, the mcrA gene abundance, and the mcrA/pmoA gene abundance ratio. However, there was a contrasting nitrous oxide (N₂O) emission pattern. The co-culture model actually increased N₂O emissions, with fluxes being highest in the HRF plots, followed by the LRF and then CG plots. The correlation analysis identified the soil nosZ gene abundance, redox potential, urease activity, nirS gene abundance, and ratio of the combined nirK and nirS abundance to the nosZ abundance as key factors associated with N₂O emissions. While the co-cultivation model increased N₂O emissions, it also significantly reduced CH₄ emissions. Overall, the rice–frog co-culture model, especially at a high density, offers a favorable sustainable agricultural production model. Full article

The conversion of CO₂ into CH₄ through the Sabatier reaction is one of the key processes that can reduce CO₂ emissions into the atmosphere. This work aims to develop Ni-Al aerogel-based thermo-photocatalysts with large specific surface areas prepared using a sol–gel method and subsequent supercritical drying in CO₂. Different Al/Ni molar ratios were selected for the development of the catalysts, characterized using ICP-OES, N₂ adsorption–desorption isotherms, XRD, H₂-TPR, TEM, UV-Vis DRS, and XPS techniques. Thermo-photocatalytic activity tests were performed in a photoreactor with two different light sources (λ = 365 nm, λ = 470 nm) at a temperature range from 300 °C to 450 °C and a pressure of 10 bar. The catalyst with the highest Ni loading (AG 1/3) produced the best catalytic results, reaching CO₂ conversion and CH₄ selectivity levels of 82% and 100%, respectively, under visible light at 450 °C. In contrast, the catalysts with the lowest nickel loading produced the lowest results, most likely due to their low amounts of active Ni. These results suggest that supercritical drying is an efficient method for developing active thermo-photocatalysts with high Ni dispersion, suitable for Sabatier reactions under mild reaction conditions. Full article