Search Results (7,651)

Protein misfolding diseases are characterized by structurally abnormal proteins that lose their functionality, resulting in cellular and tissue dysfunction. Neurodegenerative diseases, including Parkinson’s disease, Alzheimer’s disease and Huntington’s disease, share a common etiopathogenesis characterize by the accumulation of misfolded proteins. These proteins autonomously aggregate within neuronal cells, triggering inflammation and cell death. The accumulation of misfolded proteins triggers endoplasmic reticulum (ER) stress, leading to alter Ca²⁺ homeostasis. This prolonged stress condition induces the cleavage of procaspase 4 which is resident in ER and activates NF-kB pathway activation, leading to inflammatory responses and cell death. In this study, the efficacy of the drug Vx-445 (Elexacaftor), used in the pharmacological treatment of cystic fibrosis, was assessed in human adenocarcinomic basal alveolar epithelial (A549) and neuronal (SH-SY5Y) cell lines, where ER stress was induced by Thapsigargin. The aim was to assess whether the corrector was able to reduce ER stress by restoring cellular homeostasis and, probably, the proper folding of misfolded proteins and reducing the inflammatory response triggered by these events. Therefore, protein levels of IkBα, p-STAT 3 and COXII were analyzed by flow cytofluorimetry, while Ca²⁺ content was measured by spectrofluorimetry. The results obtained suggest a significant effect of Vx-445 in restoring cellular homeostasis, leading to reduced expression of inflammation-related proteins, such as IL-6, tested by ELISA. Although preliminary, these results encourage further studies to explore the potential repurpose of Vx-445 as a therapeutic candidate for conditions involving ER stress and chronic inflammatory diseases associated with protein misfolding, beyond its current use in cystic fibrosis. Full article

The calorific value of coal is a key parameter for pricing, trade, and combustion management. Conventional bomb calorimetry provides accurate results but is time-consuming, labor-intensive, and destructive. Near-infrared (NIR) spectroscopy offers a rapid and non-destructive alternative, yet its application is limited by strong band correlations, nonlinear spectral responses, and the lack of interpretability in many predictive models. In this study, the Kolmogorov–Arnold Network (KAN) is applied to the prediction of coal calorific value, demonstrating its capability to describe nonlinear spectral relationships within an interpretable mathematical structure. Based on this framework, a Radial Basis Function KAN (RBF-KAN) is further developed by replacing the B-spline bases in the KAN with radial basis functions, allowing improved representation of localized and irregular spectral variations while maintaining model transparency. Using 671 coal-powder samples measured by a portable MicroNIR spectrometer, the RBF-KAN achieved an RMSE of 1.35 MJ/kg and an MAE of 0.92 MJ/kg under five-fold cross-validation, outperforming conventional regression models, deep neural networks, and other KAN variants. Analysis of RBF activations and spectral attribution maps indicates that the model consistently responds to characteristic O-H and C-H overtone regions, which correspond to known absorption features in coal. These results suggest that the RBF-KAN provides a practical and interpretable framework for on-site estimation of coal calorific value, complementing traditional calorimetric analysis. Full article

This bioinformatic study provides a comprehensive theoretical assessment of oxalate-degrading enzymes in probiotics. Kidney stone disease is a common urological disorder with rising global incidence, largely driven by the precipitation of insoluble calcium oxalate salts. Current treatments—including thiazides, lithotripsy, or ultrasound fragmentation—often show variable outcomes and high recurrence rates. Here, we systematically assessed the oxalate-degrading potential of 38 probiotic species listed in the List of Cultures Available in Food (China National Health Commission) along with selected next-generation probiotics. Using BLASTp homology searches, we identified seven strains carrying both oxalyl-CoA decarboxylase (OXC) and formyl-CoA transferase (FRC) genes, one encoding oxalate decarboxylase (OXDC), and three harboring subunits of oxalate oxidoreductase (OOR). Additionally, seven species from international probiotic lists (EFSA QPS and AEProbio) were analyzed, among which two carry both OXC and FRC genes. We prioritized strains with the coupled OXC-FRC pathway or OOR enzymes, examined catalytic site conservation by multiple sequence alignment, and performed AlphaFold-based structural prediction with Template Modeling (TM)-align scoring. Species with TM-scores >0.8 exhibited highly conserved folds, suggesting functional oxalate degradation capacity. These findings provide theoretical guidance for identifying probiotic candidates with oxalate-degrading activity and establish a framework for developing next-generation functional probiotics to alleviate kidney stone disease. Full article

Atmospheric deposition is considered a source of heavy metals in plants. However, research on the uptake pathways of atmospheric particulate matter by leaves and the subsequent translocation of heavy metals within plants remains limited. In this study, the foliar uptake and translocation of heavy metals in two maize cultivars (fresh corn and silage corn cultivars, called Baiyunuo909 and Qingzhu932, respectively) were investigated through foliar exposure using soil from a mining area to simulate dry deposition under controlled chamber conditions. The height and biomass of maize were inhibited after three and five exposures to fallout deposition, and this inhibitory effect became increasingly pronounced with prolonged exposure. Furthermore, the activities of catalase (CAT) and superoxide dismutase (SOD), along with the malondialdehyde (MDA) content, significantly decreased in both cultivars relative to the control. This decrease was more significant in fresh maize, with the reduction ranges being 94.3%, 42.1%, and 40.8%, respectively. Fallout exposure elevated the contents of cadmium, lead, arsenic and zinc in the leaves, stems, and sheaths of both cultivars, despite no significant increase in the roots. The bioconcentration factors of leaves for heavy metals ranged from 0.0002 to 0.0007, representing a 3.5–fold variation; however, the overall low values showed no significant differences. Scanning electron microscopy with energy-dispersive spectroscopy revealed the accumulation of particulate matter on the leaf surface, with a higher density around the cuticle and stomata. Additionally, the fresh corn cultivar demonstrated greater sensitivity to fallout than the silage corn cultivar. In summary, heavy metals present in atmospheric particulate matter can be absorbed by leaves and subsequently translocated to other plant tissues. This study provides a theoretical foundation for understanding the mechanisms of foliar heavy metal uptake in maize. Full article

Acrylamide (AA), a well-known neurotoxin, shows obvious damage to the nervous system. Cyanidin-3-O-glucoside (C3G), a representative anthocyanin, is identified as a promising neuroprotective agent as its excellent antioxidant capacity. This study evaluated the mitoprotective effects of C3G against AA-mediated neurotoxicity. The results showed that pretreatment with C3G (10 μmol/L) significantly lessened the reduction in AA-induced cell survival rate, increasing cell viability by 1.31 times compared to the AA-only group. C3G reduced intracellular ROS and MDA level accumulation by 84.0% and 61.9%, respectively. Furthermore, C3G suppressed the activation of NLRP3 inflammasome and Caspase-3-dependent apoptosis pathways induced by AA. Further mitochondrial analysis revealed that C3G pretreatment enhanced mitochondrial membrane potential recovery by 1.50 times and preserved the mitochondrial ultrastructure, while also restoring the aerobic respiratory capacity. PCR array demonstrated that C3G reversed the AA-induced downregulation of mitochondrial biogenesis genes PGC-1α and TFAM by 2.67-fold and 1.88-fold, respectively, and mitochondrial dynamics genes Mfn2 and Opa1 by 2.76-fold and 3.08-fold. Further in vivo studies confirmed that the blueberry anthocyanin extracts, which are mainly composed of C3G, showed neuroprotective function through maintaining mitochondrial function, alleviating inflammation, and apoptosis. This article provides new insights into the neuroprotective effects of C3G. Full article

Monitoring respiratory activity is a key indicator of physiological health and an essential component in smart textile systems for unobtrusive vital sign assessment. In this work, we present a one-dimensional convolutional recurrent neural network (1D-CRNN) for automatic classification of breathing activity from inertial data acquired by a smart e-textile of 59 subjects. The proposed method integrates convolutional layers for local feature extraction with recurrent layers for temporal context modeling, enabling robust segmentation of breathing and noise segments. The model was trained and evaluated using a stratified five-fold cross-validation scheme to account for inter-subject variability and class imbalance. Across different window sizes, the classifier achieved a mean accuracy of 0.88 and an F1-score of 0.92 at a window size of 2000 samples. The best-performing configuration for a single fold, reached an accuracy of 0.995 and an F1-score of 0.99. Furthermore, near-real-time feasibility was demonstrated, with a total processing time—including data loading, classification, segmentation, and visualization—of only 1.76 s for a 250 s measurement, corresponding to more than 100× faster than the recording time. These results indicate that the proposed approach is highly suitable for embedded, on-device inference within wearable systems. Full article

Background: Ozonation is a non-thermal process that can remodel the chemistry and bioactivity of plant extracts. We evaluated whether ozonating green tea extract enhances its phenolic composition and in vitro bioactivity in relation to nutrition and food applications, with potential clinical applications. Methods: Ethanolic green tea extract (GTE) was exposed to ozone (0–7 L/min, 5 h) to yield an ozonated extract (GTOE). Phenolics were quantified by the HPLC. Bioactivities included antimicrobial testing (agar diffusion; MIC/MBC/MFC), antibiofilm formation, time-kill kinetics (0–180 min), bacteria-induced hemolysis in human RBCs, DPPH radical scavenging, pancreatic lipase inhibition, and scratch-wound closure in human fibroblasts. Data from n = 3 independent experiments were analyzed by one-way ANOVA with Tukey’s post hoc test (α = 0.05). Results: Ozonation increased gallic acid (3150.92 to 3229.69 µg/g) and ellagic acid (2470.66 to 2789.40 µg/g), while catechin decreased slightly (2634.09 to 2535.09 µg/g). Compared with GTE, GTOE produced larger inhibition zones and lower MIC/MBC/MFC against Candida albicans, Bacillus subtilis, Staphylococcus aureus, Klebsiella pneumoniae, and Salmonella typhi; Aspergillus niger remained unsusceptible. For example, inhibition zones for S. aureus and K. pneumoniae increased by 2–4 mm and MIC/MBC values were 2-8-fold lower. Candida albicans showed marked sensitivity (MFC 500 to 125 µg/mL). GTOE exhibited superior, dose-dependent antibiofilm activity across all tested strains, reaching up to 97.82% inhibition, (highest for S. aureus and S. typhi, at 75% MBC). GTOE reduced bacterial counts more rapidly than GTE across all tested strains, achieving full eradication within 150 min. Bacteria-induced hemolysis was inhibited by 97% at 75% MIC with GTOE, versus 93–96% with GTE. Antioxidant capacity improved (DPPH IC₅₀ 3.31 vs. 5.54 μg/mL), as did lipase inhibition IC₅₀ 6.06 vs. 17.69 μg/mL). Wound closure at 48 h increased (GTOE 61.1%; GTE 56.8%; control 50.8%). Conclusions: Controlled ozonation of green tea extract remodeled phenolics and consistently enhanced antimicrobial, antibiofilm, antioxidant, potential anti-obesity, and wound-healing activities in vitro. These results support food-grade optimization and safety/by-product profiling, followed by in vivo validation at diet-relevant doses, to enable nutrition, food, and potential clinical applications. Full article

Rehabilitation of upper extremity (UE) impairments after stroke requires regular evaluation, with standard methods typically being time–consuming and relying heavily on manual assessment by therapists. In our study, we propose automating these assessments using electromyography (EMG) as a core indicator of muscle activity, correlating passive and active EMG signals with clinical motor impairment scores. UE motor function in 25 patients was evaluated using the Fugl–Meyer Assessment for UE (FMA–UE), the Modified Ashworth Scale (MAS), and the Brunnstrom Recovery Stages (BRS). EMG data were processed via feature extraction and linear discriminant analysis (LDA), with 10-fold cross–validation for binary classification based on clinical score thresholds. The LDA classifier accurately distinguished impairment categories, achieving area under the receiver operating characteristic curve (AUC–ROC) scores of 0.897 ± 0.272 for FMA–UE > 33, 0.981 ± 0.103 for FMA–UE > 44, 0.890 ± 0.262 for MAS > 0, 0.968 ± 0.130 for BRS > 3, and 0.987 ± 0.085 for BRS > 4. Notably, resting–state EMG alone yielded comparable classification performance. These findings demonstrate that EMG–driven assessments can reliably classify motor impairment levels, offering a pathway to objective clinical scoring that can streamline rehabilitation workflows, reduce therapists’ manual burden, and prioritize patient recovery over assessment procedures. Full article

This research characterized a novel Komagataella phaffii strain generated through intraspecific crossing between a wild isolate and a laboratory strain. This segregant, called S467, expressed 2.2-fold more secreted recombinant β-glucosidase than its parental strains in microtiter scale, which suggested that S467 could be an attractive host for bioprocess optimization. S467 was grown alongside the laboratory strain CBS7435 expressing β-glucosidase (CBS_BGL9), as a control, in a 1.5 L bioreactor to determine kinetics parameters, and similar cell growth rate (0.12 h⁻¹) but higher recombinant protein activity, measured as enzymatic activity, was observed in S467. The effect of specific cell growth rate was studied using continuous cultures (chemostat) at different dilution rates, identifying conditions that provided up to a twofold increase in enzymatic activity in S467. RT-qPCR was conducted on key genes associated with the genetic background of S467, in order to clarify differences at the transcriptomic level that render S467 as a potential superior host for recombinant protein production. Overall, this study provides quantitative evidence of the positive effect of the natural isolate IRA1 allele for the generation of recombinant β-glucosidase and highlights the usability of natural genetic diversity in K. phaffii. Full article

Grapefruit is rich in flavanones, particularly naringin and narirutin. This study investigated the effects of temperature, time, and solid-to-liquid ratio on microwave-assisted pressurized CO₂–H₂O (MWP-CO₂-H₂O) extraction of flavonoids from grapefruit and optimized the parameters for maximum total flavonoid content (TFC) using response surface methodology. Independent variable ranges were 110–160 °C, 4.00–14.00 min, and 1:10.00–1:40.00 g/mL. Optimum conditions were 128 °C, 13.88 min, and 1:31.35 g/mL, yielding a TFC of 27.96 ± 1.29 mg naringin equivalent/g dry weight. Under these conditions, extraction yield, total phenolic content, ferric reducing ability of plasma, cupric reducing antioxidant capacity, and DPPH IC₅₀ were 55.17 ± 1.90% (dry basis), 25.42 ± 1.39 mg gallic acid equivalent/g, 39.16 ± 1.61 µmol trolox equivalent/g, 81.64 ± 0.29 µmol trolox equivalent/g, and 1.60 ± 0.01 mg/mL, respectively. Compared to conventional extraction (CE), MWP-CO₂-H₂O produced higher TFC, phenolic content, and antioxidant activity, while reducing extraction time by 13.68-fold. These results highlight grapefruit peel waste as a sustainable source of bioactive compounds and demonstrate that MWP-CO₂-H₂O is an environmentally sustainable, efficient alternative to conventional methods. Full article

In patients with inflammatory bowel disease (IBD), colorectal cancer (CRC) occurs with 20-to-30-fold higher frequency, is more advanced at diagnosis, and has a worse prognosis than in the general population. To improve their treatment options, we determined if targeting STAT3 with TTI-101, a small-molecule STAT3 inhibitor, was beneficial in the azoxymethane (AOM)-disodium sulfate (DSS) mouse model of colitis-associated CRC. C57BL/6 mice received a single intraperitoneal injection of AOM followed by three cycles of 5% DSS in drinking water before receiving TTI-101 (50 mg/kg by oral gavage, OG, and daily) or vehicle for 28 days. TTI-101 treatment reduced adenoma numbers by 89% from 1.14 ± 1.07 in vehicle-treated mice to 0.13 ± 0.35 in TTI-101-treated mice (p ≤ 0.05, Kruskal–Wallis test). Levels of activated STAT3 (pY-STAT3) were increased 3.3-fold in the epithelium and stroma of dysplastic mucosa (147 ± 46; mean ± SD; and n = 4) vs. normal mucosa (45 ± 26; n = 7; and p ≤ 0.05, Kruskal–Wallis test) and were correlated with the adenoma number. TTI-101 was detected at pharmacologically relevant levels in the plasma and colons of TTI-101-treated AOM-DSS mice and was concentrated within colon tissue; plasma TTI-101 levels inversely correlated to pY-STAT3 levels. Importantly, TTI-101 normalized the colon transcriptome of AOM-DSS mice and reduced the expression of STAT3- and STAT1-upregulated genes associated with CRC oncogenesis. Thus, TTI-101 treatment may benefit IBD patients with CRC. Full article

Olive leaf tea (OLT), rich in phenolics, exhibits antioxidant, anti-inflammatory, and potential anticancer effects; however, the in vivo efficacy remains unclear. This study evaluated the chemopreventive and systemic effects of OLT in a murine Ehrlich Ascites Tumor (EAT) model, with a focus on the treatment timing. OLT was prepared by aqueous infusion and characterized for total phenolic content (TPC: 25.74 mg GAE/g), DPPH scavenging (197.88 µmol TE/g), FRAP activity (81.23 µmol Fe²⁺/g), and LC-MS/MS profile (oleuropein 77.6%). Mice received OLT orally before or after tumor inoculation. Prophylactic OLT reduced EAT cell counts (from 31.48 × 10⁷ to 21.15 × 10⁷), ascites volume (from 4.58 to 2.98 mL), elevated miR-155-5p (14.34-fold), normalized ALT/AST, and restored hepatic antioxidants without histopathological damage. Co-treatment with 5-FU preserved efficacy while reducing hepatotoxicity. In conclusion, OLT provides timing-dependent anticancer and systemic protective effects in the EAT model, supporting its potential as a cost-effective nutraceutical for cancer prevention and adjunctive therapy. Full article

Sodium butyrate has been documented to support gut function and help control pathogens in the gastrointestinal tract. However, the precise mechanisms of dietary sodium butyrate’s control over enteric pathogens in chickens remain unclear. Our study demonstrated that priming chicken bone marrow-derived macrophages (BMDMs) or the HD11 cell line with 1 mM sodium butyrate significantly enhanced their antimicrobial capacity against key bacterial pathogens (Escherichia coli, Salmonella Typhimurium, Pseudomonas aeruginosa, and Staphylococcus aureus) in gentamicin protection assays (p < 0.05; ≥1 log reduction in CFU/mL). This in vitro enhancement was associated with increased production of reactive oxygen species (ROS), as detected by DCFH-DA assays, showing approximately a 30% increase in HD11 cells and a 12% increase in BMDMs. Butyrate priming was observed to result in autophagy activation, potentially through mTOR pathway inhibition, evidenced by changes in related gene expression using RT-qPCR assay and a 2.5-fold increase in GFP-LC3B accumulation. Supporting this, pharmacological inhibition of ROS using the ROS scavenger N-acetyl-L-cystine (NAC) or autophagy with chloroquine reduced the butyrate-enhanced bacterial clearance. Furthermore, the mTOR inhibitor rapamycin synergized with butyrate priming, whereas the mTOR activator L-leucine counteracted enhanced antimicrobial activity. These findings offer crucial insights for improving host defence against bacterial infections and developing novel therapeutic strategies in chickens. Full article

Hair follicle stem cells (HFSCs) are resident stem cells within hair follicles (HFs) that possess self-renewal and differentiation capacities, serving as a critical model for regenerative medicine research. Their dynamic interaction with dermal papilla cells (DPCs) plays a decisive role in HF development and cycling. FGF22 is a paracrine fibroblast growth factor that can regulate the proliferation, differentiation and migration of epithelial cells. This study established a DPC-HFSC co-culture system, revealing that FGF22 overexpression in DPCs significantly upregulated FGFR1/FGFR2 mRNA expression levels in HFSCs (p < 0.05), with a 1.67-fold increase in EdU-positive cell proportion (p < 0.01). CCK-8 assays demonstrated markedly enhanced HFSC viability (p < 0.01), with a 17% reduction in HFSC apoptosis (p < 0.05). Conversely, FGF22 knockout downregulated FGFR1/FGFR2 expression (p < 0.05), reduced HFSC proliferation capacity by 25% (p < 0.01), and increased HFSC apoptosis levels by 1.81-fold (p < 0.05). In addition, FGF22 overexpression promotes the proliferation and differentiation of HFSCs by activating Wnt/β-Catenin, Sonic Hedgehog (Shh) and Notch signaling pathways, or inhibiting BMP signaling pathways. Knockout of FGF22 weakens these processes and inhibits the activation and differentiation of HFSCs. This study, through the DPCs-HFSCs co-culture system, revealed the regulatory mechanism of FGF22 secreted by DPCs on the proliferation and differentiation of HFSCs, thereby providing theoretical references for fields such as fine-wool sheep breeding, human regenerative medicine, and hair loss treatment. Full article

Background: Subclinical hyperthyroidism grade 1 (SCH G1, TSH > 0.1 mU/L) is common in patients with thyroid unifocal autonomy (UFA) and associated with cardiovascular risks and increased mortality. While ¹³¹I radioiodine therapy (¹³¹I-RIT) effectively treats UFA, it frequently induces hypothyroidism, partly due to extra-nodular absorbed dose (AD) enhanced by residual TSH stimulation. Objective: We hypothesized that short-term LT3-induced TSH suppression at the time of RIT would promote long-term euthyroidism. Patients and Methods: A retrospective study was conducted on 95 UFA patients with SCH G1 (2001–2024). Patients underwent baseline and post-LT3 thyroid scintigraphy, and then received ¹³¹I-RIT with individualized dosimetry. Long-term bioclinical follow-up was achieved. Results: Short-term low-dose LT3 suppression caused no adverse events and significantly reduced TSH (0.45 to 0.047 mU/L). Whole-gland ¹²³I uptake decreased moderately (11.0 to 8.4%), while extra-nodular lobe uptake dropped markedly (1.77 to 0.73%) (all p < 0.0001). This focused activity on the UFA (2.5-fold increase), maintaining mean UFA AD (about 260 Gy) but reducing extra-nodular AD (61 to 37 Gy, p < 0.0001). Despite low ¹³¹I doses (mean 181 MBq), a dose–response relationship was observed: higher AD correlated with greater nodular lobe volume reduction (p < 0.033). At the 88-month follow-up, 93% of patients achieved normal thyroid function; one had persistent SCH G1, two were borderline hypothyroid, and two required LT4. Conclusions: ¹³¹I-RIT under brief LT3-induced TSH suppression induces sustained euthyroidism in SCH G1 with UFA. This simple, low-risk strategy reduces radioprotection concerns and is under evaluation to determine cardiovascular benefits. Full article