Search Results (15,804)

The development of sustainable and functional nanocomposites has attracted considerable attention in recent years due to their broad spectrum of potential applications, including wood preservation. Also, a global goal is to reuse the large volumes of waste for environmental issues. In this context, the aim of the study was to obtain soda lignin particles, to graft ZnO nanoparticles onto their surface and to apply these hybrids, embedded into a biodegradable polymer matrix, as protection/preservation coating for oak wood. The organic–inorganic hybrids were characterized in terms of compositional, structural, thermal, and morphological properties that confirm the efficacy of soda lignin extraction and ZnO grafting by physical adsorption onto the decorating support and by weak interactions and coordination bonding between the components. The developed solution based on poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and lignin-ZnO was applied to oak wood specimens by brushing, and the improvement in hydrophobicity (evaluated by water absorption that decreased by 48.8% more than wood, humidity tests where the treated sample had a humidity of 4.734% in comparison with 34.911% for control, and contact angle of 97.8° vs. 80.5° for untreated wood) and UV and fungal attack protection, while maintaining the color and aspect of specimens, was sustained. L.ZnO are well dispersed into the polymer matrix, ensuring a smooth and less porous wood surface. According to the results, the obtained wood coating using both a biodegradable polymeric matrix and a waste-based preservative can be applied for protection against weathering degradation factors, with limited water uptake and swelling of the wood, UV shielding, reduced wood discoloration and photo-degradation, effective protection against fungi, and esthetic quality. Full article

Objective: Uncovering the renoprotective and anti-inflammatory effects of atorvastatin treatment in diabetic-and-obese rats by employing traditional renal function indicators (urea and creatinine) and four prototypical cytokines (IL-1β, il-6, IL-17α, TNFα). Method: Twenty-eight male Wistar rats, aged 6 months, 350–400 g, were randomized into four groups. The first group, G-I, the denominated control, were fed standard chow over the whole course of the experiments. The rodents in G-II were exposed to a High-Fat Diet. The last two groups were exposed to Streptozotocin peritoneal injection (35 mg/kg of body weight). A short biochemical assessment was performed before diabetes model induction to ensure appropriate glucose metabolism before experiments. Following model induction, only rodents in group G-IV were gradually introduced to the same High-Fat Diet as received by G-II. Model confirmation 10 days after injections marked the start of statin treatment in group G-IV, by daily gavage of atorvastatin 20 mg/kg of body weight/day for 21 days. At the end of the experiments, the biochemical profile of interest comprised typical renal retention byproducts (urea and creatinine) and the inflammatory profile described using plasma levels of TNFα, IL-17α, IL-6, and IL-1β. Results: Treatment with Atorvastatin was associated with a statistically significant improvement in renal function in G-IV compared to untreated diabetic rodents in G-III. Changes in inflammatory activity showed partial association with statin therapy, TNFα and IL-17α mirroring the trend in urea and creatinine values. Conclusions: Our results indicate that atorvastatin treatment yields a myriad of pleiotropic activities, among which renal protection was clearly demonstrated in this model of diabetic-and-obese rodents. The statin impact on inflammation regulation may not be as clear-cut, but the potential synergy of renal function preservation and partial tapering of inflammatory activity requires further research in severely metabolically challenged models. Full article

Federated learning (FL) enables collaborative model building among a large number of participants without sharing sensitive data to the central server. Because of its distributed nature, FL has limited control over local data and the corresponding training process. Therefore, it is susceptible to data poisoning attacks where malicious workers use malicious training data to train the model. Furthermore, attackers on the worker side can easily manipulate local data by swapping the labels of training instances, adding noise to training instances, and adding out-of-distribution training instances in the local data to initiate data poisoning attacks. And local workers under such attacks carry incorrect information to the server, poison the global model, and cause misclassifications. So, the prevention and detection of such data poisoning attacks is crucial to build a robust federated training framework. To address this, we propose a prevention strategy in federated learning, namely confident federated learning, to protect workers from such data poisoning attacks. Our proposed prevention strategy at first validates the label quality of local training samples by characterizing and identifying label errors in the local training data, and then excludes the detected mislabeled samples from the local training. To this aim, we experiment with our proposed approach on both the image and audio domains, and our experimental results validated the robustness of our proposed confident federated learning in preventing the data poisoning attacks. Our proposed method can successfully detect the mislabeled training samples with above 85% accuracy and exclude those detected samples from the training set to prevent data poisoning attacks on the local workers. However, our prevention strategy can successfully prevent the attack locally in the presence of a certain percentage of poisonous samples. Beyond that percentage, the prevention strategy may not be effective in preventing attacks. In such cases, detection of the attacked workers is needed. So, in addition to the prevention strategy, we propose a novel detection strategy in the federated learning framework to detect the malicious workers under attack. We propose to create a class-wise cluster representation for every participating worker by utilizing the neuron activation maps of local models and analyze the resulting clusters to filter out the workers under attack before model aggregation. We experimentally demonstrated the efficacy of our proposed detection strategy in detecting workers affected by data poisoning attacks, along with the attack types, e.g., label-flipping or dirty labeling. In addition, our experimental results suggest that the global model could not converge even after a large number of training rounds in the presence of malicious workers, whereas after detecting the malicious workers with our proposed detection method and discarding them from model aggregation, we ensured that the global model achieved convergence within very few training rounds. Furthermore, our proposed approach stays robust under different data distributions and model sizes and does not require prior knowledge about the number of attackers in the system. Full article

Flood control infrastructure is essential for the development of cities and the population’s well-being. The goal is to protect human and economic resources by reducing the inundation area and controlling the flood level and peak discharges. Detention basins can do this by storing a large volume of water to be released after the peak discharge. By doing this, a large amount of energy is stored, which can be recovered via micro-hydropower. In addition, as the release flow is controlled and almost constant, Pumps as Turbines (PAT) could be a feasible and economic option in these cases. Thus, this study investigates the feasibility of micro-hydropower (MHP) in urban detention basins, using the Santa Lúcia detention basin in Belo Horizonte as a case study. The methodology involved hydrological modeling, hydraulic analysis, and economic and environmental assessment. The results demonstrated that PAT selection has a crucial role in the feasibility of the MHP, and exploiting rainfall with lower intensities but higher frequencies is more attractive. Using multiple PATs with different operating points also showed promising results in improving energy production. In addition to the economic benefits, the MHP in the detention basin produces minimal environmental impact and, as it exploits a wasted energy source, it also reduces the carbon footprint in the urban water cycle. Full article

Background/Objectives: Environmental stressors, including spaceflight and altered gravity, can negatively affect the symbiotic relationship between the gut microbiome and host health. Dietary prebiotics, which alter components of the gut microbiome, show promise as an effective way to mitigate the negative impacts of stressor exposure. It remains unknown, however, if the stress-protective effects of consuming dietary prebiotics will extend to chronic altered-gravity exposure. Methods: Forty female C57BL/6 mice consumed either a control diet or a prebiotic diet containing galactooligosaccharides (GOS) and polydextrose (PDX) for 4 weeks, after which half of the mice were exposed to 3 times the gravitational force of Earth (3g) for an additional 4 weeks. Fecal microbiome samples were collected weekly for 8 weeks, sequenced, and analyzed using 16S rRNA gene sequencing. Terminal physiological endpoints, including immune and red blood cell characteristics, were collected at the end of the study. Results: The results demonstrate that dietary prebiotic consumption altered the gut microbial community structure through changes to β-diversity and multiple genera across time. In addition, consuming dietary prebiotics reduced the neutrophil-to-lymphocyte ratio (NLR) and increased red blood cell distribution width (RDW-CV). Importantly, the prebiotic diet prevented the impacts of altered-gravity on β-diversity and the bloom of problematic genera, such as Clostridium_sensu_stricto_1 and Turicibacter. Furthermore, several prebiotic diet-induced genera-level changes were significantly associated with several host physiological changes induced by 3g exposure. Conclusions: These data demonstrate that the stress-protective potential of consuming dietary prebiotics extends to environmental stressors such as altered gravity, and, potentially, spaceflight. Full article

Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids—bioactive compounds from Cannabis sativa—exhibit multi-target pharmacology, including interactions with cannabinoid receptors, Peroxisome Proliferator-Activated Receptors (PPARs), Transient Receptor Potential (TRP) channels, and potentially SGLT2. Objective: To evaluate the potential of phytocannabinoids as novel modulators of renal glucose reabsorption via SGLT2 and to compare their efficacy, safety, and pharmacological profiles with synthetic SGLT2 inhibitors. Methods: We performed a narrative review encompassing the following: (1) the molecular and physiological roles of SGLT2; (2) chemical classification, natural sources, and pharmacokinetics/pharmacodynamics of major phytocannabinoids (Δ⁹-Tetrahydrocannabinol or Δ⁹-THC, Cannabidiol or CBD, Cannabigerol or CBG, Cannabichromene or CBC, Tetrahydrocannabivarin or THCV, and β-caryophyllene); (3) in silico docking and drug-likeness assessments; (4) in vitro assays of receptor binding, TRP channel modulation, and glucose transport; (5) in vivo rodent models evaluating glycemic control, weight change, and organ protection; (6) pilot clinical studies of THCV and case reports of CBD/BCP; (7) comparative analysis with established synthetic inhibitors. Results: In silico studies identify high-affinity binding of several phytocannabinoids within the SGLT2 substrate pocket. In vitro, CBG and THCV modulate SGLT2-related pathways indirectly via TRP channels and CB receptors; direct IC₅₀ values for SGLT2 remain to be determined. In vivo, THCV and CBD demonstrate glucose-lowering, insulin-sensitizing, weight-reducing, anti-inflammatory, and organ-protective effects. Pilot clinical data (n = 62) show that THCV decreases fasting glucose, enhances β-cell function, and lacks psychoactive side effects. Compared to synthetic inhibitors, phytocannabinoids offer pleiotropic benefits but face challenges of low oral bioavailability, polypharmacology, inter-individual variability, and limited large-scale trials. Discussion: While preclinical and early clinical data highlight phytocannabinoids’ potential in SGLT2 modulation and broader metabolic improvement, their translation is impeded by significant challenges. These include low oral bioavailability, inconsistent pharmacokinetic profiles, and the absence of standardized formulations, necessitating advanced delivery system development. Furthermore, the inherent polypharmacology of these compounds, while beneficial, demands comprehensive safety assessments for potential off-target effects and drug interactions. The scarcity of large-scale, well-controlled clinical trials and the need for clear regulatory frameworks remain critical hurdles. Addressing these aspects is paramount to fully realize the therapeutic utility of phytocannabinoids as a comprehensive approach to T2DM management. Conclusion: Phytocannabinoids represent promising multi-target agents for T2DM through potential SGLT2 modulation and complementary metabolic effects. Future work should focus on pharmacokinetic optimization, precise quantification of SGLT2 inhibition, and robust clinical trials to establish efficacy and safety profiles relative to synthetic inhibitors. Full article

Intestinal alkaline phosphatase (IAP) is a brush border enzyme secreted by enterocytes, playing a crucial role in maintaining gut mucosal defense. This study investigated the expression dynamics of IAP in the small intestine of pigs challenged with Escherichia coli (E. coli) K88, compared to healthy controls. Five-week-old pigs (n = 8) were orally administered E. coli K88 at a concentration of 2 × 10⁸ CFU/mL, with a dose of 2 mL per pig at 0 and 24 h. Five days post-challenge, tissue samples from the duodenum, jejunum, and ileum were collected for mucosal morphometric analysis and evaluation of IAP expression via immunohistochemistry, Western blotting, and real-time PCR. The results revealed the presence of IAP on the apical surface of villi throughout the small intestine, along with significantly upregulated IAP expression in E. coli-challenged pigs compared to controls. These findings suggest that Gram-negative bacteria such as E. coli can induce IAP expression, likely through lipopolysaccharide (LPS) stimulation, thereby enhancing its enzymatic activity as part of the intestinal defense mechanism. This study provides insight into the protective role of IAP and highlights its potential as a biomarker for assessing gut health and diagnosing enteric infections in animals. Full article

Background and Aims: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease frequently associated with fatigue and mild cognitive impairment. Brain-derived neurotrophic factor (BDNF) plays key roles in neuroplasticity, immune regulation, and metabolism. This study aimed to evaluate plasma BDNF levels in early-stage PBC and examine their clinical and biochemical associations. Methods: In this observational study, plasma BDNF, IL-6, and IL-18 concentrations were measured by ELISA in 45 patients with early-stage PBC and 31 age- and sex-matched healthy controls (mean age 60.5 years; 96% women). All participants underwent liver elastography using point shear wave elastography (ElastPQ), Doppler ultrasound, laboratory testing, and assessment of cognitive function (PHES) and fatigue severity (MFIS). Non-invasive fibrosis scores (APRI, FIB-4) were calculated. Results: Median plasma BDNF concentrations were significantly higher in PBC patients than in controls [median: 21.04 ng/mL (IQR: 10.68–38.07) vs. 5.80 ng/mL (IQR: 4.58–7.54); p < 0.0001]. In PBC patients, higher BDNF levels correlated inversely with liver stiffness measured by ElastPQ (R = −0.39, p = 0.0258), spleen dimensions, splenic vein flow volume (R = −0.49, p = 0.0018), suggesting an association with milder liver fibrosis and early hemodynamic alterations. A trend toward association between BDNF and IL-6 levels was observed in multivariate analysis. No significant associations were found between BDNF concentrations and markers of hepatocellular injury, cognitive performance, or fatigue severity. Conclusions: Plasma BDNF concentrations are elevated in early-stage PBC and inversely correlate with liver fibrosis severity. No significant associations were found with hepatocellular injury, cognitive function, or fatigue. These findings suggest that BDNF may play a protective role against hepatic fibrogenesis, or alternatively, that BDNF concentrations may decline with advancing liver disease. Further studies are needed to clarify its significance in PBC. Full article

The COVID-19 pandemic accelerated the rapid development and distribution of various vaccine platforms, resulting in a significant reduction in disease severity, hospitalizations, and mortality. However, persistent challenges remain concerning the durability and breadth of vaccine-induced protection, especially in the face of emerging SARS-CoV-2 variants. This review aimed to evaluate the factors influencing the immunogenicity and effectiveness of COVID-19 vaccines to inform future vaccine advancement strategies. A narrative review with systematic approach was conducted following PRISMA guidelines for narrative review. Literature was sourced from databases including PubMed, Embase, and Web of Science for studies published between December 2019 and May 2025. Encompassed studies assessed vaccine efficacy, immunogenicity, and safety across various populations and vaccine platforms. Data were collected qualitatively, with quantitative data from reviews highlighted where available. We have uncovered a decline in vaccine efficacy over time and weakened protection against novel variants such as Delta and Omicron. Booster doses, specifically heterologous regimens, improved immunogenicity and increased protection. Vaccine-induced neutralizing antibody titers have been found to correlate with clinical protection, although the long-term correlates of immunity remain poorly defined. The induction of IgG4 antibodies after repeated mRNA vaccinations raised concerns about potential modulation of the immune response. COVID-19 vaccines have contributed significantly to pandemic control; however, their efficacy is limited by the evolution of the virus and declining immunity. Forthcoming vaccine strategies should focus on broad-spectrum, variant-adapted formulations and defining robust comparisons of protection. Recognizing the immunological basis of vaccine response, including the role of specific antibody subclasses, is fundamental for optimizing long-term protection. Full article

The mechanism by which quorum sensing (QS) enhances stress resistance in enterohemorrhagic Escherichia coli (E. coli) O157:H7 remains unclear. We employed optimized exogenous QS signal N-acyl-homoserinelactones (AHL) (100 μM 3-oxo-C6-AHL, 2 h) in EHEC O157:H7 strain EDL933, which was validated with endogenous yenI-derived AHL, to investigate QS-mediated protection against acid stress. RNA-seq transcriptomics identified key upregulated genes (e.g., rmf). Functional validation using isogenic rmf knockout mutants generated via λ-Red demonstrated abolished stress resistance and pan-stress vulnerability. Mechanistic studies employing qRT-PCR and stress survival assays established Ribosomal Hibernation Factor (RMF) as a non-redundant executor in a SdiA–RMF–RpoS axis, which activates ribosomal dormancy and SOS response to enhance EHEC survival under diverse stresses. For the first time, we define ribosomal hibernation as the core adaptive strategy linking QS to pathogen resilience, providing crucial mechanistic insights for developing EHEC control measures against foodborne threats. Full article

Background/Objectives: Patients with stage IV gastric cancer who develop chronic intestinal failure require home parenteral nutrition (HPN). This study aimed to evaluate the prognostic relevance of nutritional and immune–inflammatory biomarkers and to construct an individualised survival prediction model using machine learning techniques. Methods: A secondary analysis was performed on a cohort of 410 patients with TNM stage IV gastric adenocarcinoma who initiated HPN between 2015 and 2023. Nutritional and inflammatory indices, including the Controlling Nutritional Status (CONUT) score and lymphocyte-to-monocyte ratio (LMR), were assessed. Independent prognostic factors were identified using Cox proportional hazards models. A Random Survival Forest (RSF) model was constructed to estimate survival probabilities and quantify variable importance. Results: Both the CONUT score and LMR were independently associated with overall survival. In multivariate analysis, higher CONUT scores were linked to increased mortality risk (HR = 1.656, 95% CI: 1.306–2.101, p < 0.001), whereas higher LMR values were protective (HR = 0.632, 95% CI: 0.514–0.777, p < 0.001). The RSF model demonstrated strong predictive accuracy (C-index: 0.985–0.986) and effectively stratified patients by survival risk. The CONUT score exerted the greatest prognostic influence, with the LMR providing additional discriminatory value. A gradual decline in survival probability was observed with an increasing CONUT score and a decreasing LMR. Conclusions: The application of machine learning to immune–nutritional data offers a robust tool for predicting survival in patients with advanced gastric cancer requiring HPN. This approach may enhance risk stratification, support individualised clinical decision-making regarding nutritional interventions, and inform treatment intensity adjustment. Full article

Quercetin (QE) is a naturally occurring flavonoid found in many fruits, vegetables, and other plant-based foods. It is recognized for its diverse pharmacological activities. Among its many therapeutic potentials, its antidiabetic properties are of particular interest due to the growing worldwide prevalence of diabetes mellitus. QE improves glycemic control by enhancing insulin sensitivity, stimulating glucose uptake, and preserving pancreatic beta cell function. These effects are mediated by the modulation of key molecular pathways, including AMPK, PI3K/Akt, and Nrf2/ARE, as well as by the suppression of oxidative stress and pro-inflammatory cytokines, such as TNF-α and IL-6. Furthermore, QE mitigates the progression of diabetic complications such as nephropathy, retinopathy, and vascular dysfunction, reducing lipid peroxidation and protecting endothelial function. However, the clinical application of quercetin is limited by its low water solubility, poor bioavailability, and extensive phase II metabolism. Advances in formulation strategies, including the use of nanocarriers, co-crystals, and phospholipid complexes, have shown promise in improving its pharmacokinetics. This review elucidates the mechanistic basis of QE quercetin antidiabetic action and discusses strategies to enhance its therapeutic potential in clinical settings. Full article

Background/Objectives: Non-syndromic cleft lip with or without palate (NSCL/P) is a common, multifactorial congenital anomaly. As genetic associations can be population-specific, this study aimed to investigate single-nucleotide polymorphisms (SNPs) in the VAX1, MAFB, and WNT3 genes for association with NSCL/P in a Japanese cohort. Methods: A case–control study was conducted with 310 Japanese patients with NSCL/P and 308 ethnically matched healthy controls from Aichi Gakuin Dental Hospital. We genotyped SNPs rs7078160 (VAX1), rs13041247 (MAFB), and rs3809857 (WNT3) using TaqMan assays. Associations were assessed using chi-squared tests, with results stratified by sex and corrected for multiple comparisons using the Bonferroni method. Results: The VAX1 rs7078160 A allele was significantly associated with an increased risk for NSCL/P (OR = 1.67, p < 0.00001). The association was particularly strong in females (OR = 1.93, p < 0.00001) but not significant in males after correction. The MAFB rs13041247 variant showed a nominal protective association with the NSCLO subtype that was not significant after Bonferroni correction. No significant association was found for WNT3. A notable gene–gene interaction was observed, where carrying risk alleles for both VAX1 and MAFB significantly increased overall NSCL/P risk (OR = 2.65, p = 0.00008). Conclusions: VAX1 rs7078160 is a significant risk factor for NSCL/P in the Japanese population, with a pronounced female-specific effect. A synergistic interaction between VAX1 and MAFB elevates disease risk, whereas WNT3 was not implicated in this cohort. These findings underscore the population-specific genetic architecture of NSCL/P. Full article

Oxidized phospholipids (OxPLs) are increasingly recognized as biologically active lipids involved in various pathologies. Both exposure to pathogenic factors and the efficacy of protective mechanisms are critical to disease development. In this study, we characterized an immunoassay that quantified the total capacity of the plasma to degrade or mask OxPLs, thereby preventing their interaction with cells and soluble proteins. OxLDL-coated plates were first incubated with human blood plasma or a control vehicle, followed by an ELISA using a monoclonal antibody specific to oxidized phosphatidylethanolamine. Pretreatment with the diluted blood plasma markedly inhibited mAb binding. The masking assay was optimized by evaluating the buffer composition, the compatibility with various anticoagulants, potential interfering compounds, the kinetic parameters, pre-analytical stability, statistical robustness, and intra- and inter-individual variability. We propose that this masking assay provides a simple immunological approach to assessing protective mechanisms against lipid peroxidation products. Establishing this robust and reproducible method is essential for conducting clinical association studies that explore masking activity as a potential biomarker of the predisposition to a broad range of lipid-peroxidation-related diseases. Full article

Background. The STING protein is activated by the second messenger cGAMP to promote the innate immune response against infections. Beyond this role, a chronically overactive STING signaling has been described in several disorders. Patients with severe COVID-19 exhibit a hyper-inflammatory response (the cytokine storm) that is in part mediated by the cGAS-STING pathway. Several STING inhibitors may protect from severe COVID-19 by down-regulating several inflammatory cytokines. This pathway has been implicated in the establishment of an optimal antiviral vaccine response. STING agonists as adjuvants improved the IgG titers against the SARS-CoV-2 Spike protein vaccines. Methods. We investigated the association between two common functional STING1/TMEM173 polymorphisms (rs78233829 C>G/p.Gly230Ala and rs1131769C>T/p.His232Arg) and severe COVID-19 requiring hospitalization. A total of 801 non-vaccinated and 105 fully vaccinated (mRNA vaccine) patients, as well as 300 population controls, were genotyped. Frequencies between the groups were statistically compared. Results. There were no differences for the STING1 variant frequencies between non-vaccinated patients and controls. Vaccinated patients showed a significantly higher frequency of rs78233829 C (230Gly) compared to non-vaccinated patients (CC vs. CG + GG; p = 0.003; OR = 2.13; 1.29–3.50). The two STING1 variants were in strong linkage disequilibrium, with the rs78233829 C haplotypes being significantly more common in the vaccinated (p = 0.02; OR = 1.66; 95%CI = 1.01–2.55). We also studied the LTZFL1 rs67959919 G/A polymorphism that was significantly associated with severe COVID-19 (p < 0.001; OR = 1.83; 95%CI = 1.28–2.63). However, there were no differences between the non-vaccinated and vaccinated patients for this polymorphism. Conclusions. We report a significant association between common functional STING1 polymorphisms and the risk of developing severe COVID-19 among fully vaccinated patients. Full article