Search Results (13,971)

Spodoptera littoralis (Boisd.) (Lepidoptera: Noctuidae) is a major insect pest that severely affects various crops. Our study provides new insights by combining field efficacy trials with enzymatic analysis to evaluate the effects of emamectin benzoate mixtures with other insecticides (lufenuron, cypermethrin, chlorpyrifos, and spinosad) against S. littoralis. The aim of our work was to investigate the effectiveness of five insecticides, i.e., emamectin benzoate, lufenuron, cypermethrin, chlorpyrifos, and spinosad, for controlling this pest under field conditions during two consecutive seasons (2023–2024). Each insecticide was applied individually at the recommended rate, while some were mixed with emamectin benzoate at half its recommended rate. The results indicated that emamectin benzoate was the most effective insecticide, followed by lufenuron. The joint action of emamectin benzoate (LC₂₅) and its mixtures with other insecticides (chlorpyrifos, spinosad, cypermethrin, and lufenuron) at various concentrations (LC₅₀) against second- and fourth-instar S. littoralis larvae was evaluated. Results showed additive effects with chlorpyrifos, lufenuron, and cypermethrin, while potentiation occurred with cypermethrin (LC₅₀) and chlorpyrifos (LC₅₀). Antagonistic effects were observed in the combination of emamectin benzoate with spinosad (LC₂₅ and LC₅₀). This study concluded that applying insecticides individually is more cost-effective for managing cotton leafworm infestations in cotton crops. Additionally, enzyme activity analysis showed significant changes in alpha-esterase, beta-esterase, carboxylesterase, acetylcholinesterase, and glutathione S-transferase levels in larvae treated with different insecticide combinations. Full article

Background: We aimed to explore the mechanism by which extracellular-5′-nucleotidase (NT5E) regulates macrophage polarization via regenerating islet-derived protein 3 beta (Reg3β) and other plasma proteins that mediate immune-cell effects on myocarditis. Methods: The involvement of NT5E in Reg3β-induced macrophage polarization was first analyzed using RNA sequencing, Western blotting, and quantitative polymerase chain reaction. Mendelian randomization was employed to identify NT5E and various plasma proteins as potential therapeutic targets for myocarditis. Mediation analysis, enrichment analysis, protein–protein interaction network analysis, drug prediction, molecular docking, and single-cell RNA sequencing were integrated to further evaluate the biological functions and pharmacological potential of the identified targets. Finally, phenome-wide association studies were conducted to assess the safety of targeting these proteins. Results: NT5E expression was elevated in Reg3β-stimulated M2 macrophages. The expression of Arg-1, a marker of M2 macrophages, decreased upon NT5E knockdown, suggesting that NT5E is involved in the Reg3β-mediated polarization of macrophages to the M2 phenotype. Mendelian randomization analysis identified NT5E and 80 other plasma proteins as being causally associated with myocarditis. Mediation analysis revealed 12 immune-cell types were mediators of the effects of plasma protein on myocarditis progression. Drug prediction identified candidates such as ICN 1229 and chrysin, which showed strong binding affinities in molecular docking analyses. These findings may contribute to the development of effective treatments for myocarditis. Conclusions: NT5E plays a dual role in Reg3β-induced macrophage polarization and in interacting with plasma proteins that influence the onset and progression of myocarditis through immune-cell pathways. Full article

Recent studies have demonstrated that the coumarin derivative 4-Methylumbelliferone (4MU) has an antidiabetic effect in rodent models. 4MU is known to decrease the availability of hyaluronan (HA) substrates and inhibit the activity of different HA synthases. Nevertheless, it has been observed that 4MU may also affect cellular metabolism. In this study, we utilize the rat insulinoma beta cell line (INS-1E) cultured in both two-dimensional (2D) and three-dimensional (3D) experimental settings (pseudo islets), as an in vitro model to study beta cell functionality. For the first time, we observed that treating INS1E cells with 4MU results in improved insulin secretion. Additionally, we discovered that 4MU treatment elicited morphological changes from multilayer to monolayer conditions, along with a varied distribution of insulin granules and cell adhesion properties. Notably, we found that insulin secretion is not correlated with HA production. The same result was observed in co-culture experiments involving INS-1E cells and stromal vascular fraction (SVF) from adipose tissue. These experiments aim to investigate the effects of 4MU on beta cells in the context of its potential use in early-stage type 1 diabetes and in enhancing islet transplantation outcomes. Full article

Introduction: The combination of ceftazidime−avibactam (CAZ-AVI) with aztreonam (ATM) may be an option for the treatment of infections due to metallo-β-lactamases (MBLs) producing bacteria, as recommended by current guidelines. MBLs protect the pathogen from any available β-lactam/β-lactamase inhibitor (BL/BLI). Moreover, in vitro and clinical data suggest that double carbapenem therapy (DCT) may be an option for such infections. Materials and Methods: This retrospective study was conducted in two mixed intensive care units (ICUs) at the University Hospital of Larissa, Thessaly, Greece, and the General Hospital of Larissa, Thessaly, Greece, during a three-year period (2022−2024). Mechanically ventilated patients with bloodstream infection (BSI) caused by K. pneumoniae resistant to all BL/BLI combinations were studied. Patients were divided into three groups: in the first, patients were treated with CAZ-AVI + ATM; in the second, with DCT; and in the third, with antibiotics other than BL/BLIs that presented in vitro susceptibility. The primary outcome of the study was the change in Sequential Organ Failure Assessment (SOFA) score between the onset of infection and the fourth day of antibiotic treatment. Secondary outcomes were SOFA score evolution during the treatment period, total duration of mechanical ventilation (MV), ICU length of stay (LOS), and ICU mortality. Results: A total of 95 patients were recruited. Among them, 23 patients received CAZ-AVI + AZT, 22 received DCT, and 50 patients received another antibiotic regimen which was in vitro active against the pathogen. The baseline characteristics were similar. The mean (SE) overall age was 63.2 (1.3) years. Mean (SE) Acute Physiology and Chronic Health Evaluation II (APACHE II) and SOFA scores were 16.3 (0.6) and 7.6 (0.3), respectively. The Charlson Index was similar between groups. The control group presented a statistically lower SOFA score on day 4 compared to the other two groups [mean (SE) 8.9 (1) vs. 7.4 (0.9) vs. 6.4 (0.5) for CAZ-AVI + ATM, DCT and control group, respectively (p = 0.045)]. The duration of mechanical ventilation, ICU LOS, and mortality were similar between the groups (p > 0.05). Comparison between survivors and non-survivors revealed that survivors had a lower SOFA score on the day of BSI, higher PaO₂/FiO₂ ratio, higher platelet counts, and lower lactate levels (p < 0.05). Septic shock was more frequent among non-survivors (60.3%) in comparison to survivors (27%) (p = 0.0015). Independent factors for mortality were PaO₂/FiO₂ ratio and lactate levels (p < 0.05). None of the antibiotic regimens received by the patients was independently associated with survival. Conclusions: Treatment with CAZ-AVI + ATM or DCT may offer similar clinical outcomes for patients suffering from BSI caused by K. pneumoniae strains resistant to all available BL/BLIs. However, larger studies are required to confirm the findings. Full article

Introduction: Osteoarthritis (OA), a leading cause of disability among the elderly, is characterized by progressive joint tissue destruction. Fucoidan, a sulfated polysaccharide with known anti-inflammatory and antioxidant properties, has been investigated for its potential to protect against interleukin-1 beta (IL-1β)-induced articular tissue damage. Methods: Human primary chondrocytes and synovial fibroblasts were pre-treated with 100 μg/mL fucoidan before stimulation with 1 ng/mL of IL-1β. The protective effects of fucoidan were assessed by measuring oxidative stress markers and catabolic enzyme levels. These in vitro findings were corroborated using a rat anterior cruciate ligament transection-induced OA model. To explore the underlying mechanisms, particularly the interaction between microRNAs (miRs) and heme oxygenase-1 (HO-1), five candidate miRs were identified in silico and experimentally validated. Luciferase reporter assays were used to confirm direct interactions. Results: Fucoidan exhibited protective effects against IL-1β-induced oxidative stress and catabolic processes in both chondrocytes and synovial fibroblasts, consistent with in vivo observations. Fucoidan treatment restored HO-1 expression while reducing inducible nitric oxide synthase and matrix metalloproteinase levels in IL-1β-stimulated cells. Notably, this study revealed that fucoidan modulates the miR-22/HO-1 pathway, a previously uncharacterized mechanism in OA. Specifically, miR-22 was upregulated by IL-1β and subsequently attenuated by fucoidan. Luciferase reporter assays confirmed a direct interaction between miR-22 and HO-1. Conclusion: The results demonstrate that fucoidan mitigates OA-related oxidative stress in chondrocytes and synovial fibroblasts through the novel modulation of the miR-22/HO-1 axis. The miR-22/HO-1 pathway represents a crucial therapeutic target for OA, and fucoidan may offer a promising therapeutic intervention. Full article

Quinoa (Chenopodium quinoa), a stress-tolerant pseudocereal ideal for studying abiotic stress responses, was used to systematically identify optimal reference genes for qPCR normalization under gradient stresses: low temperatures (LT group: −2 °C to −10 °C), heat (HT group: 39° C to 45 °C), and drought (DR group: 7 to 13 days). Through multi-algorithm evaluation (GeNorm, NormFinder, BestKeeper, the ΔCt method, and RefFinder) of eleven candidates, condition-specific optimal genes were established as ACT16 (Actin), SAL92 (IT4 phosphatase-associated protein), SSU32 (Ssu72-like family protein), and TSB05 (Tryptophan synthase beta-subunit 2) for the LT group; ACT16 and NRP13 (Asparagine-rich protein) for the HT group; and ACT16, SKP27 (S-phase kinase), and NRP13 for the DR group, with ACT16, NRP13, WLIM96 (LIM domain-containing protein), SSU32, SKP27, SAL92, and UBC22 (ubiquitin-conjugating enzyme E2) demonstrating cross-stress stability (global group). DHDPS96 (dihydrodipicolinate synthase) and EF03 (translation elongation factor) showed minimal stability. Validation using stress-responsive markers—COR72 (LT), HSP44 (HT), COR413-PM (LT), and DREB12 (DR)—confirmed reliability; COR72 and COR413-PM exhibited oscillatory cold response patterns, HSP44 peaked at 43 °C before declining, and DREB12 showed progressive drought-induced upregulation. Crucially, normalization with unstable genes (DHDPS96 and EF03) distorted expression profiles. This work provides validated reference standards for quinoa transcriptomics under abiotic stresses. Full article

Contextual multi-armed bandits (CMABs) are vital for sequential decision-making in areas such as recommendation systems, clinical trials, and finance. We propose a simulation framework integrating Gaussian Process (GP)-based CMABs with vine copulas to model dependent contexts and GARCH processes to capture reward volatility. Rewards are generated via copula-transformed Beta distributions to reflect complex joint dependencies and skewness. We evaluate four policies—ensemble, Epsilon-greedy, Thompson, and Upper Confidence Bound (UCB)—over 10,000 replications, assessing cumulative regret, observed reward, and cumulative reward. While Thompson sampling and LLM-guided policies consistently minimize regret and maximize rewards under varied reward distributions, Epsilon-greedy shows instability, and UCB exhibits moderate performance. Enhancing the ensemble with copula features, GP models, and dynamic policy selection driven by a large language model (LLM) yields superior adaptability and performance. Our results highlight the effectiveness of combining structured probabilistic models with LLM-based guidance for robust, adaptive decision-making in skewed, high-variance environments. Full article

Background/Objectives: Clinically significant portal hypertension (CSPH) in cirrhotic patients impacts mortality rates and quality of life. CSPH increases the risk of systemic decompensation and could predispose to the deterioration of portal hypertension (PH)–gastric complications, such as portal hypertensive gastropathy (PHG) and portal hypertensive polyps (PHPs). In the management of CSPH with high-risk varices, endoscopic band ligation (EBL) is effective in preventing variceal bleeding. However, this procedure has several drawbacks, ranging from its inability to treat PH to the potential development of significant PH–gastric complications. The aim of our study is to evaluate endoscopic changes in PHG, PHPs, and gastric varices before and after the obliteration of esophageal varices, highlighting the potential risks of EBL. Methods: We retrospectively evaluated forty-four patients who underwent EBL for esophageal varices in emergency and elective settings, according to Baveno VII guidelines. We assessed the presence and severity of PHG, the status of gastric varices, and the number of PHPs before and after the eradication of esophageal varices. We used Fisher’s exact test and t-tests to compare the endoscopic and clinical-laboratory data statistically. A p-value < 0.05 was considered statistically significant. Results: This study found that after the eradication of varices, there was a significant worsening of PHG in 28 patients (63%) compared to before the procedure (p < 0.05). The condition remained stable in 14 patients (31%). However, it is worth noting that 90% of the patients exhibited severe PHG at baseline. Additionally, the absence of ascites and the non-administration of beta blockers at baseline were independent risk factors for worsening PHG (p < 0.05). Along with the deterioration of PHG, three patients (7%) developed gastric varices, all classified as type 1 gastroesophageal varices, and in two patients (4.5%), PHPs were formed. In particular, out of these two cases, the number of PHPs increased from one to two compared to the baseline. Conclusions: Our study underscores the association of EBL with a general worsening of PH–gastric complications and the protective effect of beta blockers in this context. Despite these promising results, future studies are needed to assess whether the worsening of PH–gastric complications is sustained over time and whether it is associated with a deterioration in clinical outcomes in patients with cirrhosis. Such evidence could help guide a more informed therapeutic decision between EBL and beta blockers. Full article

Human milk bacteria contribute to gut microbiome establishment in breastfed infants. Although breastfeeding is recommended throughout infancy, temporal variation in the milk microbiome—particularly beyond solid food introduction—remains understudied. We analyzed 539 milk samples from 83 mother–infant dyads between 1 week and 12 months postpartum using full-length 16S rRNA gene sequencing. The microbiota was dominated by Streptococcus (34%), Cutibacterium (12%), and Staphylococcus (9%), with marked inter-individual variation. Microbiome profiles remained largely stable across lactation, with only six taxa showing temporal fluctuations, including increases in typical oral bacteria such as Streptococcus salivarius, Streptococcus lactarius, Rothia mucilaginosa, and Granulicatella adiacens. Richness and evenness were higher at 1 week compared to 1 month postpartum (p = 0.00003 and p = 0.007, respectively), then stabilized. Beta diversity also remained stable over time. Maternal pre-pregnancy BMI was positively associated with Gemella haemolysans (p = 0.016), while Haemophilus parainfluenzae was more abundant in milk from mothers with allergies (p = 0.003) and those who gave birth in autumn or winter (p = 0.006). The introduction of solid food was linked to minor taxonomic shifts. Overall, the milk microbiome remained robustly stable over the first year of lactation, with limited but notable fluctuations in specific taxa. This study supports the role of human milk as a consistent microbial source for infants and identifies maternal BMI, allergy status, and birth season as key variables warranting further investigation. Full article

Saffron (Crocus sativus L.) contains bioactive compounds with potential health benefits, including modulation of protein function and gene expression. However, their ability to tune the epigenetic machine remains poorly understood. This study employs molecular docking (AutoDock Vina 1.4), dynamics simulations, and MM/PBSA calculations to investigate the interactions between four saffron-derived molecules—crocetin, beta-D-glucosyl trans-crocetin, picrocrocin and safranal—and four epigenetic enzymes—DNMT1, DNMT3a, HDAC2, and SIRT1. Our in silico screening identifies beta-D-glucosyl trans-crocetin, one of the saffron’s crocins, as a potential DNMT1 inhibitor. Along with crocetin, it also shows the ability to inhibit HDAC2 and activate SIRT1. Picrocrocin displays a resveratrol-like ability to activate SIRT1. None of the saffron-derived compounds effectively bind or inhibit DNMT3a. Among the tested molecules, safranal shows no interaction with the selected epigenetic targets. These findings highlight saffron’s nutriepigenomic potential and emphasize the need for functional validation within relevant in vitro and in vivo experimental methodologies. Full article

Antimicrobial resistance (AMR) is a growing global health threat, with wild birds increasingly recognized as potential reservoirs of resistant pathogens and as sentinels of environmental AMR. This study investigated the occurrence and AMR profiles of Gram-negative bacteria isolated from wild birds that died at the Wildlife Rescue Center in Vanzago, Lombardy, in 2024. Cloacal swabs were collected from 112 birds representing various ecological categories. A total of 157 Gram-negative bacteria were isolated and identified, including clinically relevant genera and species, such as Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Salmonella spp., Pseudomonas aeruginosa, and Acinetobacter baumannii. Antimicrobial susceptibility testing revealed resistance to first-line and critically important antimicrobials, including those exclusively authorized for human use. Notably, a phenotype compatible with Extended-Spectrum Beta-Lactamase (ESBL) production was detected in four out of ten (40%) K. pneumoniae isolates. In addition, 20 out of the 157 (12.7%) isolated bacteria phenotypically exhibited a resistance profile indicative of AmpC beta-lactamase (AmpC) production, including Enterobacter spp. and P. aeruginosa. Resistance patterns were particularly interesting in birds with carnivorous, scavenging, or migratory-associated behaviors. These findings highlight the role of wild birds in the ecology and dissemination of antimicrobial-resistant bacteria (ARB) and highlight the need for wildlife-based AMR monitoring programs as part of a One Health approach. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and neuronal dysfunction. It is driven by the accumulation of amyloid-beta (Aβ) plaques, Tau protein hyperphosphorylation, oxidative stress, and neuroinflammation. Resveratrol (RSV) is a natural polyphenolic compound found in grapes, berries, and red wine that has garnered attention for its potential neuroprotective properties in combating AD. The neuroprotective effects of RSV are mediated through the activation of sirtuins (SIRT1), inhibition of Aβ aggregation, modulation of Tau protein phosphorylation, and the attenuation of oxidative stress and inflammatory responses. RSV also enhances mitochondrial function and promotes autophagy, which are important processes for maintaining neuronal health. Preclinical studies have demonstrated its efficacy in reducing Aβ burden, improving cognitive performance, and mitigating synaptic damage; however, challenges such as poor bioavailability, rapid metabolism, and limited blood–brain barrier penetration restrict its clinical applicability. Recent technological advances and selected modifications are being explored to overcome these limitations and enhance its therapeutic efficacy. This review summarizes the multifaceted neuroprotective mechanisms of RSV, the synergistic potential of natural compounds in enhancing neuroprotection, and the advancements in formulation strategies aimed at mitigating AD pathology. Leveraging the therapeutic potential of natural compounds represents a compelling paradigm shift for AD management, paving the way for future clinical applications. Full article

While the gut microbiota of obese children in Mexico has been studied, its relationship with depressive and anxiety symptoms in obese adults remains unexplored. The aim of this study was to describe the gut microbiota profile of Mexican adults with obesity and its association with depression and anxiety. We sequenced the V3-V4 region of the 16S rRNA gene from stool samples of obese adults categorized into four groups: control (OCG), with depressive symptoms (OD), with anxiety symptoms (OAx), or with both (ODAx). Alpha diversity was assessed using t-tests, beta diversity was assessed with PERMANOVA, and taxonomic differences was assessed with LEfSe. Associations between bacterial genera and clinical variables were analyzed using the Maaslin2 library. Bacteroidota was the most prevalent phylum, and Prevotella was the dominant enterotype across all groups. Although overall diversity did not differ significantly, 30 distinct taxonomic biomarkers were identified among groups as follows: 4 in OCG (Firmicutes), 5 in OD (Firmicutes, Bacteroidota), 13 in OAx (Firmicutes, Bacteroidetes, Fusobacteroidota, Proteobacteria), and 8 in ODAx (Firmicutes). This is the first study to identify distinct gut microbiota profiles in obese Mexican adults with depressive and anxiety symptoms. These findings suggest important microbial biomarkers for improving the diagnosis and treatment of mental health conditions in obesity. Full article

Background: Despite the survival benefit of ICDs in patients with HFrEF, most recipients do not receive appropriate therapy during follow-up. Existing risk models based on echocardiographic and clinical parameters show limited predictive accuracy for arrhythmic events. This study aimed to assess whether ECG-derived markers outperform conventional measures in predicting appropriate ICD shocks. Methods: This retrospective observational study included 375 patients with HFrEF who underwent ICD implantation for primary prevention at least six months before study enrollment. Twelve-lead surface ECGs were analyzed for a QTc interval, Tp-e/QT ratio, frontal QRS-T angle, and maximum deflection index (MDI). Clinical, echocardiographic, and arrhythmic event data obtained from device interrogations were evaluated. Receiver operating characteristic (ROC) curve analysis and multivariate logistic regression were performed to identify independent predictors of appropriate ICD shocks. Results: Patients who experienced appropriate ICD shocks had significantly higher rates of a complete bundle branch block, digoxin use, QRS duration, QTc, Tp-e/QT ratio, frontal QRS-T angle, MDI, and right-ventricular pacing ratio. Conversely, beta-blocker use was significantly lower in this group. In multivariate analysis, independent predictors of appropriate shocks included the patient’s digoxin use (OR = 2.931, p = 0.003), beta-blocker use (OR = 0.275, p = 0.002), frontal QRS-T angle (OR = 1.009, p < 0.001), QTc interval (OR = 1.020, p < 0.001), and Tp-e/QT ratio (OR = 4.882, p = 0.050). The frontal QRS-T angle had a cutoff value of 105.5° for predicting appropriate ICD shocks (sensitivity: 73.6%, specificity: 85.2%, AUC = 0.758, p < 0.001). Conclusions: Electrocardiographic markers, particularly the frontal QRS-T angle, QTc interval, and Tp-e/QT ratio, demonstrated superior predictive power for appropriate ICD shocks compared to conventional echocardiographic and clinical measures. These easily obtainable, non-invasive ECG parameters may improve current risk stratification models and support more individualized ICD implantation strategies. Full article

Background/Objectives: Dietary patterns have changed over time, characterising a process of nutritional transition that reflects socioeconomic and demographic inequalities among different populations. This study assessed changes in dietary consumption patterns and the associated social determinants, comparing two time periods in a sample of individuals from a state in the Northeast Region of Brazil. Methods: Data from the 2008–2009 and 2017–2018 Household Budget Survey for the state of Paraíba were analysed, totalling 951 and 1456 individuals, respectively. Foods were categorised according to the NOVA classification and compared based on sociodemographic and economic variables. To determine the factors that most strongly explain the contribution of each NOVA food group to the diet, beta regression analysis was conducted. Results: Differences were observed between the two periods regarding the dietary contribution of the NOVA food groups, with a decrease in consumption of unprocessed foods and an increase in ultra-processed foods. Living in urban areas, being an adolescent, and having an income above the minimum wage were associated with reduced intake of unprocessed foods in both periods. Additionally, being an adolescent and having more than eight years of schooling were associated with higher consumption of ultra-processed foods. Conclusions: The population under study showed changes in food consumption, reflecting a transition process that is occurring unevenly across socioeconomic and demographic groups, thereby reinforcing social inequalities. These findings can guide priorities in food and nutrition policies, highlighting the need for intervention studies to evaluate the effectiveness of such actions. Full article