Search Results (9,805)

Fungal skin infections caused by dermatophytes are of significant veterinary and zoonotic concern. This study investigated the prevalence, risk factors, and treatment outcomes of dermatophytosis in dogs and cats with skin lesions. A total of 140 animals (90 dogs and 50 cats) that presented with skin lesions (alopecia, crusts, pruritus, and scales) were examined. Identification of dermatophyte isolates relied on both phenotypic characteristics and molecular techniques. The molecular approach involved PCR and sequencing of ribosomal DNA regions (ITS1, ITS2, and 5.8S rDNA), complemented by Restriction Fragment Length Polymorphism (RFLP). Treatment regimens included topical clotrimazole, systemic itraconazole, supportive therapy, and a dermatophyte vaccine. Of the 90 dog samples examined, 47 (52.22%) were positive for fungal culture (p = 0.65). In cats, 35 samples (70%) were positive (p < 0.0001). Microsporum canis was the most significant (p < 0.0001) prevalent isolate (60%), followed by Trichophyton mentagrophytes (20%). This study reported the first isolation of T. indotineae in Egypt. Younger animals (<1 year) exhibited a significantly (p < 0.05) higher risk of infection compared with adults (>1 year). Indoor/outdoor housing in cats significantly reduced the risk of infection when compared with indoor housing (p < 0.0001; odds ratio = 0.05). Combination therapy using itraconazole, clotrimazole, supportive treatment, and a dermatophyte vaccine resulted in the fastest clinical recovery (p < 0.0001). These findings underscore the importance of accurate diagnosis and effective treatment strategies for managing dermatophytosis in pets and preventing zoonotic transmission. Full article

Background: Lennox–Gastaut syndrome (LGS) is a severe childhood-onset developmental and epileptic encephalopathy characterized by treatment-resistant seizures and significant morbidity. Despite multiple approved anti-seizure medications (ASMs), optimal seizure control remains elusive. This has led to ongoing interest in newer ASMs, including those not specifically approved for LGS. This review evaluates the emerging evidence on the use of these agents in LGS management. Methods: We conducted a comprehensive literature search of PubMed, Web of Science, and Embase to identify studies examining perampanel, brivaracetam, cenobamate, ganaxolone, and stiripentol in LGS populations. Both randomized controlled trials and observational studies were included. Results: Perampanel was studied in approximately 300 patients across one Phase 3 trial and seven observational studies, showing responder rates of 26–69% with particular efficacy for generalized tonic–clonic and myoclonic seizures, though behavioral side effects (irritability, aggression) were dose-related concerns. Brivaracetam demonstrated inconsistent efficacy in 59 patients across six studies (0–61.5% responder rates) but offered better behavioral tolerability than levetiracetam. Cenobamate showed exceptional promise in 223 patients across seven studies with 50–85% responder rates and significant polypharmacy reduction, though requiring careful titration. Ganaxolone demonstrated efficacy in LGS-like CDKL5 deficiency phenotypes with 28.2% drop seizure reduction versus placebo. Stiripentol showed potential benefit for generalized seizures in limited LGS data. Conclusions: Several newer ASMs show therapeutic promise in LGS. Perampanel offers the most extensive evidence base, cenobamate demonstrates exceptional efficacy potential, while brivaracetam provides an alternative for levetiracetam-intolerant patients. Further controlled studies are needed to define optimal treatment algorithms. Full article

Background: Major depressive disorder (MDD) is a prevalent and disabling psychiatric illness with complex etiologies involving both genetic and environmental factors. While environmental stress is a known risk factor of MDD, the molecular mechanisms linking stress exposure to persistent depressive phenotypes remain incompletely understood. Methods: We established a 24-hour restraint stress-induced depression model in mice and performed integrated transcriptomic and proteomic analyses of the medial prefrontal cortex (mPFC) to investigate stress-related molecular alterations. Results: Behavioral assessments confirmed persistent depression-like phenotypes, including anhedonia and behavioral despair, lasting up to 35 days post-stress. RNA sequencing identified differentially expressed genes related to dopaminergic signaling and oxidative stress. Proteomic analysis identified 105 differentially expressed proteins involved in immune response and energy metabolism. Integrated multi-omics analysis highlighted convergent disruptions in immune regulation, metabolism, and epigenetic processes. Notably, clemastine exerts its antidepressant-like effects in part by mitigating neuroinflammation and preserving mitochondrial function. Conclusions: These findings provide novel insights into the molecular basis of stress-induced depression and suggest that clemastine is a potential therapeutic candidate. Full article

Diabetic keratopathy (DK) is a common ocular complication of diabetes mellitus (DM), affecting almost half of all diabetic patients. It is characterized by delayed healing of epithelial wounds, reduced corneal sensitivity, and persistent epithelial defects, which, in turn, significantly impair vision and quality of life. The limited understanding of its pathogenesis and the lack of effective treatments highlight the urgent need for more physiologically relevant experimental models. The three-dimensional (3D) models currently available provide valuable information on the pathophysiology of DK, although none of them yet fully reproduce the diabetic corneal phenotype complex. After a brief overview of corneal anatomy, the present review aims to systematically analyze the current 3D in vitro models developed for the study of DK, in terms of tissue architecture, presence of diabetic stimuli, and ability to replicate pathological traits. Full article

Juglans neotropica Diels, classified as endangered on the IUCN Red List, plays a crucial role in the resilience of Andean montane forests in southern Ecuador—a megadiverse region encompassing coastal, Andean, and Amazonian ecosystems. This study examines how climatic, edaphic, and topographic gradients influence the species’ phenotypic traits across six source localities—Tibio, Merced, Tundo, Victoria, Zañe, and Argelia—all of which are localities situated in the provinces of Loja and Zamora Chinchipe. By integrating long-term climate records, slope mapping, and soil characterization, we assessed the effects of temperature, precipitation, humidity, soil moisture, and terrain steepness on leaf presence, fruit maturation, and tree architecture. Over the past 20 years, temperature increased by 1.5 °C (p < 0.01), while precipitation decreased by 22%, disrupting local edaphoclimatic balances. More than 2000 individuals were measured in forest stands, with estimated ages ranging from 11 to 355 years. ANOVA results revealed that Tundo and Victoria exhibited significantly greater DBH, height, and volume (p ≤ 0.05), with Victoria showing a 30% larger DBH than Argelia, the lowest-performing provenance. Soils ranged from loam to sandy loam, with slopes exceeding 45% and pH levels from slightly acidic to neutral. These findings confirm the species’ pronounced phenotypic plasticity and ecological adaptability, directly informing site-specific conservation strategies and long-term forest management under shifting climatic conditions. Full article

Background: Intuitive inquiry meditation (Can-Hua-Tou) is a unique mental practice which differs from relaxation-based practices by continuously demanding intuitive inquiry. It emphasizes the doubt-driven self-interrogation, also referred to as Chan/Zen meditation. Nonetheless, its electrophysiological signature remains poorly characterized. Methods: We recorded 128-channel EEG from 20 male Buddhist monks (5–28 years Can-Hua-Tou experience) and 18 male novice lay practitioners (<0.5 year) during three counter-balanced eyes-closed blocks: Zen inquiry meditation (ZEN), a phonological control task silently murmuring “A-B-C-D” (ABCD), and passive resting state (REST). Power spectral density was computed for alpha (8–12 Hz), beta (12–30 Hz) and gamma (30–45 Hz) bands and mapped across the scalp. Mixed-design ANOVAs and electrode-wise tests were corrected with false discovery rate (p < 0.05). Results: Alpha power increased globally with eyes closed, but condition- or group-specific effects did not survive FDR correction, indicating comparable relaxation in both cohorts. In contrast, monks displayed a robust beta augmentation, showing significantly higher beta over parietal-occipital leads than novices across all conditions. The most pronounced difference lay in the gamma band: monks exhibited trait-like fronto-parietal gamma elevations in all three conditions, with additional, though sub-threshold, increases during ZEN. Novices showed negligible beta or gamma modulation across tasks. No significant group × condition interaction emerged after correction, yet only experts expressed concurrent beta/gamma amplification during meditative inquiry. Conclusions: Long-term Can-Hua-Tou practice is associated with frequency-specific neural adaptations—stable high-frequency synchrony and state-dependent beta enhancement—consistent with Buddhist constructs of citta-ekāgratā (one-pointed concentration) and vigilance during self-inquiry. Unlike mindfulness styles that accentuate alpha/theta, Chan inquiry manifests an oscillatory profile dominated by beta–gamma dynamics, underscoring that different contemplative strategies sculpt distinct neurophysiological phenotypes. These findings advance contemplative neuroscience by linking intensive cognitive meditation to enduring high-frequency cortical synchrony. Future research integrating cross-frequency coupling analyses, source localization, and behavioral correlates of insight will further fully delineate the mechanisms underpinning this advanced contemplative expertise. Full article

Lipids and polar metabolites are emerging as promising indicators of the brain’s molecular phenotype in both clinical and fundamental research. However, the impact of postmortem delay on these compounds, unavoidable in human brain studies, remains insufficiently understood. In this study, we examined the postmortem stability of lipids and polar metabolites over a 48-h interval in the brains of three species: humans, rats, and mice. We show that the abundance levels of 23% of the 867 studied lipids and 75% of the 104 studied polar metabolites were affected significantly by postmortem delay in at least one species. The postmortem effects correlated positively and significantly among the species, while showing an approximately tenfold slower rate in humans compared to rodents. The only exception to the postmortem rates deceleration was a group of oxidized fatty acids, which accumulated at similar speed in both humans and rodents. These findings provide valuable insights for improving reproducibility and refining the interpretation of human and rodent brain lipidome and metabolome data in future studies. Full article

Low-density lipoprotein receptor-related protein 5 (LRP5) is a multifunctional transmembrane coreceptor that plays a pivotal role in development and disease. Wnt/β-catenin signaling is the primary downstream signaling pathway activated by LRP5. Furthermore, some LRP5 functions are mediated by noncanonical pathways, such as AKT/P21 and TGF-β/Smad signaling. Pathologically, both loss-of-function and gain-of-function mutations in LRP5 produce distinct phenotypes, ranging from osteoporosis-pseudoglioma syndrome to high bone mass disorders. Beyond the skeletal system, LRP5 has emerged as a key regulator of retinal angiogenesis, vascular integrity, renal tubular function, neurodevelopment, and lipid metabolism. Its physiological functions are highlighted by its ability to influence adipocyte differentiation, insulin sensitivity, and neuronal synaptic plasticity. Moreover, LRP5 displays a dual role in development and disease progression. Although it plays a protective role in acute injuries such as myocardial infarction and acute kidney injury, LRP5 also contributes to chronic pathologies such as tubulointerstitial fibrosis, polycystic kidney disease, and atherosclerosis through fibrotic and inflammatory pathways. Recent therapeutic interest has focused on modulating LRP5 activity using agents such as anti-Dickkopf-related protein 1 antibody, sclerostin inhibitors, polyclonal antibodies, CRISPR/Cas9 knockout, and some natural products. This review discusses the current understanding of LRP5's physiological and pathological roles across organ systems and highlights its therapeutic potential, emphasizing the need for targeted approaches considering its context-dependent effects. Full article

Flight altitude is a critical parameter influencing both the spatial resolution and operational efficiency of UAV multispectral imaging; however, its quantitative effects on crop monitoring accuracy remain insufficiently characterized. This study investigated maize in the Yuci District, Jinzhong, China, using multispectral imagery and ground measurements of soil moisture, SPAD, leaf water content (LWC), leaf area index (LAI), plant height (PH), and aboveground biomass (AGB) collected at eight altitudes (65–200 m). Correlation analysis and three modeling approaches were applied: stepwise linear regression (SLR), random forest (RF), and back-propagation neural network (BPNN). Accuracy decreased with altitude. At 65–100 m, the correlations were strongest: LAI–NDVI/GNDVI ranged from 0.818 to 0.938, and SPAD–NDVI/GNDVI exceeded 0.816. At 80–100 m, RMSE values for LAI, SPAD, and LWC were 0.05, 10.37, and 0.67, with RE below 15%. At 200 m, the lowest R² dropped to 0.23, with errors rising sharply. RF and BPNN outperformed SLR, with BPNN yielding the highest accuracy for LAI and AGB. Overall, 65–100 m is optimal for precision monitoring, 120–160 m balances accuracy and efficiency, and 180–200 m suits large-scale reconnaissance. These findings provide methodological guidance for UAV flight parameter optimization in precision agriculture. Full article

Cardiovascular diseases are the leading cause of human death worldwide. The role of the female hormone estrogen (E2) in this context is subject of debate. E2 might counteract inflammation by acting on macrophages; however, the underlying cellular mechanisms remain poorly understood. In the current study, we used primary human macrophages to investigate the effects of E2 on the NAD⁺-dependent deacetylase Sirt1, protein acetylation, and pro-inflammatory phenotype. Male and female primary monocytes from healthy adult individuals were polarized into pro-inflammatory M1 macrophages via treatment with LPS and IFN-γ followed by treatment with E2 for 24 h. While E2 treatment had no effect on the Sirt1 protein expression, it significantly increased the acetylation state of nuclear proteins p53 and Ku70. In addition, E2 increased NFκB-p65 expression exclusively in male M1 macrophages, while TNF-α was reduced in female M1 macrophages following E2 treatment. In male monocyte-like cells, E2 significantly reduced nuclear Sirt1 expression and increased Ku70 acetylation. The current study demonstrated that E2 treatment of human M1 macrophages leads to downregulation of nuclear Sirt1 and hyperacetylation of corresponding nuclear proteins. These molecular changes are associated with an enhancement of the pro-inflammatory phenotype in male primary macrophages, while an attenuation of inflammation was observed in female cells. Full article

Endothelial-to-mesenchymal transition (EndMT) is associated with various pathologies including cardiovascular, inflammatory, and fibrotic diseases or neoplasia. Concerning COVID-19, multiple organ dysfunctions and long COVID syndrome are mediated by microvascular damage and, recently, the role of SARS-CoV-2 peptide fragments in the induction of EndMT was demonstrated. Here, we investigated the immune-mediated effects of Spike S1 of SARS-CoV-2 on EndMT and demonstrated that cytokines secreted by S1-activated macrophages, mainly TNFα + IFNγ, also induce the phenotypical switch in HUVECs. In particular, a loss of the typical cobblestone morphology is observed, along with a huge reduction in endothelial adhesion molecules, such as vWF, CD31, and VE-cadherin, and a concomitant acquisition of mesenchymal markers, such as N-cadherin and FSP1 protein. In addition, the combined use of the drug infliximab, targeting TNFα, and baricitinib, an inhibitor of the JAK-STAT pathway, hinders the phenotypical changes by restoring the proper expression of endothelial markers. The protective effect of these drugs is evident not only when they are added to the culture medium together with the trigger, but also when added later, i.e., once EndMT has been started. These findings reinforce the role of COVID-19-associated cytokine storm in endothelial dysfunction and in the onset of the fibrotic process and sustain the clinical relevance of infliximab and baricitinib for the prevention of vascular damage. Full article

Macrophages are essential for immune homeostasis, playing crucial roles in immune responses from initiation to resolution. They trigger acute inflammation to promote elimination of pathogens and regulate excessive immune reactions to prevent chronic inflammation and autoimmune diseases. Consequently, macrophage dysfunction contributes to the progression of many disorders that involve inflammation. Cannabinoid Receptor 2 (CB2) has emerged as a promising therapeutic target due to its role in regulating macrophage-mediated immune functions, including via modulation of cytokine secretion, migration, phagocytosis, and polarisation. CB2 activation can produce beneficial outcomes via suppressing macrophage-mediated inflammatory pathways in animal models for various diseases that involve acute or chronic central or peripheral inflammation, whereas blocking CB2 may have utility when macrophage polarisation to a “resolving” phenotype is deleterious, such as in tumour-associated macrophages. However, despite abundant promising preclinical results, the relatively few CB2-selective agonists tested in clinical trials to date have exhibited limited efficacy. Here, we provide an overview of the roles of macrophages in health and disease, thoroughly review in vitro and in vivo preclinical findings on CB2-mediated modulation of macrophage function, summarise current progress in clinical trials for CB2-targeted compounds, and discuss approaches for addressing current challenges in ongoing efforts toward developing safe and effective CB2-targeted therapeutics. Full article

Acute lymphoblastic leukemia (ALL) remains a formidable therapeutic challenge, particularly within high-risk cohorts. Advances in next-generation sequencing have elucidated critical mutations that significantly influence prognosis and therapeutic decision-making. Tyrosine kinase inhibitors (TKIs) have significantly improved treatment outcomes in Philadelphia chromosome-positive (Ph+) ALL. Meanwhile, emerging therapies such as monoclonal antibodies and chimeric antigen receptor (CAR) T-cell therapies show promise for B-cell ALL, although they are associated with considerable toxicities. These developments underscore the persistent need for alternative therapeutic strategies that can benefit a wider range of patients. In this study, human ALL cell lines—characterized by either wild-type or mutant tumor protein p53 (TP53) status—were treated with RG7388 (an MDM2 (mouse double minute 2 homolog) inhibitor) and BBI608 (a STAT3 (signal transducer and activator of transcription 3) inhibitor), both as single agents and in combination. Cell viability was quantified using XTT assays, while apoptosis was assessed via flow cytometry. Additionally, immunoblotting and qRT-PCR were employed to evaluate changes in protein and gene expression, respectively. RG7388 demonstrated potent growth inhibition in the majority of ALL cell lines, with p53-mutant cell lines exhibiting resistance. BBI608 reduced cell viability across all tested cell lines, though with variable sensitivity. Notably, the combination of RG7388 and BBI608 elicited synergistic anti-proliferative effects in p53 wild-type and partially functional p53-mutant cells, enhancing apoptosis and stabilizing p53 protein levels. In contrast, MOLT-4 cells, which harbor concurrent TP53 and STAT3 mutations, did not benefit from the combination treatment, indicating an inherent resistance phenotype within this subset. Collectively, these findings highlight the therapeutic potential of combined MDM2 and STAT3 inhibition in ALL, particularly in p53 wild-type and partially functional p53-mutant contexts. This combinatorial approach augments apoptosis and tumor growth suppression, offering a promising avenue for expanding treatment options for a broader patient population. Further investigation is warranted to validate these preclinical findings and to explore translational implications in genetically diverse ALL subsets. Full article

The safety profile of Lentilactobacillus buchneri KU200793, which has neuroprotective effects, was comprehensively evaluated through both phenotypic and genotypic analyses. Phenotypically, the strain exhibited no β-hemolysis, mucin degradation, indole production, gelatin liquefaction, urease activity, or β-glucuronidase activity. Additionally, it did not produce D-lactate, and only trace amounts of spermidine were detected among the biogenic amines. Furthermore, L. buchneri KU200793 did not exhibit bile salt deconjugation, further supporting its safety profile. However, its tetracycline resistance exceeded the threshold set by the European Food Safety Authority. Genotypic analysis using the HGTree program identified tetA(58) and nalD genes with sequence similarities of 33.64% and 30.17%, respectively, indicating a low level of homology. These findings suggest that tetracycline resistance in L. buchneri KU200793 is unlikely to have been acquired through horizontal gene transfer, thereby minimizing the risk of resistance gene dissemination. This study underscores the importance of comprehensive safety assessments to evaluate the suitability of L. buchneri KU200793 for probiotic applications. Full article

Background: Accurate and early diagnosis of autism spectrum disorder (ASD) is essential for timely intervention. Structural magnetic resonance imaging (sMRI) and functional magnetic resonance imaging (fMRI) provide complementary insights into brain structure and function. Most deep learning approaches rely on a single modality, limiting their ability to capture cross-modal relationships. Methods: We propose DAGMNet, a dual-branch attention-pruned graph neural network for ASD prediction that integrates sMRI, fMRI, and phenotypic data. The framework employs modality-specific feature extraction to preserve unique structural and functional characteristics, an attention-based cross-modal fusion module to model inter-modality complementarity, and a phenotype-pruned dynamic graph learning module with adaptive graph construction for personalized diagnosis. Results: Evaluated on the ABIDE-I dataset, DAGMNet achieves an accuracy of 91.59% and an AUC of 96.80%, outperforming several state-of-the-art baselines. To validate the method’s generalizability, we also validate it on ADNI datasets from other degenerative diseases and achieve good results. Conclusions: By effectively fusing multimodal neuroimaging and phenotypic information, DAGMNet enhances cross-modal representation learning and improves diagnostic accuracy. To further assist clinical decision making, we conduct biomarker detection analysis to provide region-level explanations of our model’s decisions. Full article