Search Results (82)

Neuroinflammation is determinant in the progression of neurodegenerative diseases. One of the main mechanisms underlying this process involves the persistent activation of glial cells. Persistent activation of glial cells induces proinflammatory transcription factors and the release of cytokines, chemokines, and reactive oxygen species that exacerbate cellular dysfunction. This neurotoxic environment promotes neuronal death, while the products of cellular damage feed back into glial activation, establishing a self-sustaining pathogenic cycle that drives neurodegeneration. Alkaloids present in Amaryllidaceae plants support the use of this resource in folk medicine, displaying potent effects as acetylcholinesterase inhibitors and allosteric modulators of nicotinic receptors (nAChR). In this study, a murine microglial cell (IMG) model of LPS-induced inflammation was used to evaluate the involvement of α7 and α4β2 nAChRs in glioprotection and neuroprotection of SH-SY5Y cells against 6-hydroxydopamine (OHDA). GC-MS analysis revealed differences in the alkaloid profile between in vitro cultures with fructose and wild-type Rhodophiala pratensis. Homolycorine-type, norbelladine-type and crinine-type alkaloids produced in vitro reduced LPS-induced inflammation (5 µg/mL), possibly via α7 and α4β2 nAChRs, and showed a protective effect against OHDA-induced oxidative stress (1–3 µg/mL) and inhibited AChE and BuChE (24–78 µg/mL). Full article

Global Solar Radiation (Rs) is essential for ecological and climatic modeling, yet its spatialization is often hampered by sparse observation networks. Conventional methods demand a well-distributed set of stations with global representativeness—a requirement rarely met in practice. To address this gap, we propose a spatialization method based on environmental similarity and spatial proximity (ES-SP), which integrates the Law of Geographic Similarity and Tobler’s First Law of Geography. Using monthly Rs data from 11 stations in Tropical China (2015), we evaluated ES-SP against Ordinary Kriging (OK) and Local Polynomial Interpolation (LP) through leave-one-out cross-validation (LOOCV), with root mean square error (RMSE), relative RMSE, and mean absolute percentage error (MAPE) as accuracy metrics. Topographic and monthly meteorological covariates were selected dynamically via random forest (RF), and the performance differences among the three methods were tested statistically using the Wilcoxon signed-rank test. Results show that ES-SP outperforms both OK and LP in accuracy and stability, achieving the lowest error metrics in most months—e.g., RMSE as low as 37.23 MJ·m⁻² in December and MAPE as low as 4.34% in August—along with a narrow interquartile range, indicating consistent performance across seasons. Spatially, ES-SP accurately reproduces the coastal–inland gradient during the rainy season (May) and the latitudinal gradient in the dry season (January), whereas OK yields overly smooth distributions that obscure local details, and LP exhibits extreme instability and unrealistic spatial discontinuities. The study demonstrates that the ES-SP method effectively overcomes the reliance on globally representative station samples, providing a robust technical pathway for generating continuous Rs datasets in data-sparse regions such as Tropical China. Further research should focus on extending the geographic scope and refining the covariate set to enhance generalizability. Full article

Terrace construction is a critical engineering practice for soil and water conservation as well as sustainable agricultural development on the Loess Plateau (LP), China, where high-precision dynamic monitoring is essential for informed regional ecological governance. To address the challenges of inadequate extraction accuracy and poor model generalization in time-series terrace mapping amid complex terrain and spectral confounding, this study proposes a novel Swin Transformer-based Terrace Dual-Branch Deformable Boundary Network (STDBNet) that seamlessly integrates multi-source remote sensing (RS) data with deep learning (DL). The STDBNet model integrates the Swin Transformer architecture with a dual-branch attention mechanism and introduces a boundary-assisted supervision strategy, thereby significantly enhancing terrace boundary recognition, multi-source feature fusion, and model generalization capability. Leveraging Sentinel-2 multi-temporal optical imagery and terrain-derived features, we constructed the first 10-m-resolution spatiotemporal dataset of terrace distribution across the LP, encompassing nine annual periods from 2017 to 2025. Performance evaluations demonstrate that STDBNet achieved an overall accuracy (OA) of 95.26% and a mean intersection over union (MIoU) of 86.84%, outperforming mainstream semantic segmentation models including U-Net and DeepLabV3+ by a significant margin. Further analysis reveals the spatiotemporal evolution dynamics of terraces over the nine-year period and their distribution patterns across gradients of key terrain factors. This study not only provides robust data support for research on terraced ecosystem processes and assessments of soil and water conservation efficacy on the LP but also lays a scientific foundation for informing the formulation of regional ecological restoration and land management policies. Full article

Microorganism employs sophisticated strategies to adapt to acidic environments, with transcription factors occupying pivotal nodes within their hierarchical regulatory networks. In this study, we performed functional characterization of the AraR transcription factor LP_RS14895 via integrated multiomics approaches. RNA sequencing revealed 40 acid-responsive targets that were enriched in pathways related to pentose/glucuronate interconversions and amino sugar and nucleotide sugar metabolism. A genome-wide binding analysis via DAP-seq identified 1279 interaction sites and the most significantly enriched motif is “ARCCMATMAHC”. The results revealed that AraR plays a crucial role in regulating acid tolerance and metabolizable sugar (including arabinose, glucose, fructose, ribose, mannose, and trehalose). Overall, these findings offer mechanistic insights into microbial stress responses and provide a valuable method for addressing inhibitory processes of carbohydrate metabolizability under high-acid conditions. Full article

Hemorrhagic septicemia (HS) is a fulminant bovine disease across Asia and Africa, yet Pasteurella multocida (P. multocida) isolated from yak is poorly reported. We isolated strain NQ01 from a fatal HS case in Xizang, China and identified it as P. multocida B:2 by morphology, Gram stain, and PCR (kmt1⁺, bcbD⁺, LPS L2). NQO1 formed smooth, non-hemolytic colonies. After Gram staining, the cells appeared as red rods with bipolar staining. Antimicrobial testing showed broad susceptibility to β-lactams, aminoglycosides, tetracyclines, fluoroquinolones, midecamycin, florfenicol, polymyxin, and vancomycin, with resistance to metronidazole, trimethoprim sulfamethoxazole, and clindamycin. Streptomycin and ofloxacin had intermediate activity. In mice, the intraperitoneal and intranasal LD₅₀ values were 40.64 CFU/mL and 9.53 × 10⁶ CFU/mL, respectively. The intranasal fatal cases were characterized by bacteremia with multifocal disseminated intravascular coagulation involving lung, liver, and spleen. The complete genome comprises a single 2.33 Mb chromosome (40.47% GC, 2115 CDS, no plasmids) with only one resistance gene (Eco_EFTu_PLV) and 28 virulence genes spanning adhesion (tadA, rcpA, ppdD, pilB, tuf/tufA, htpB, PM_RS00430, PM_RS00425, PM_RS08640), immune modulation (lpxB/C/D, msbB, manB, rfaE/F, gmhA/lpcA, kdsA, pgi, wecA, galE, bexD’, ABZJ_RS06285, ABD1_RS00310), and nutritional/metabolic factor (hgbA, hemR, hemN), plus a YadA-like factor. Phylogenetically, NQ01 clusters with regional B:2 bovine/yak isolates. Collectively, these data define NQ01 as a highly virulent, low-resistance yak isolate and a practical model for natural-route HS pathogenesis and targeted control in high-altitude pastoral settings yaks. Full article

Background: Inflammasomes regulate the activation of caspases resulting in inflammation; inflammasome activation is dysregulated in Alzheimer’s disease (AD) and plays a role in the pathogenesis of this condition. Glibenclamide, an anti-inflammatory drug, could be an interesting way to down-modulate neuroinflammation. Methods: In this pilot study we verified with ex vivo experiments whether a glibenclamide-loaded nanovector (GNV) could reduce the NLRP3-inflammasome cascade in cells of AD patients. Monocytes isolated from healthy controls (HC) and AD patients were cultured in medium, alone or stimulated with LPS + nigericin in presence/absence of GNV. ASC-speck positive cells and inflammasome-related genes, proteins, and miRNAs expressions were measured. The polymorphisms of ApoE (Apolipoprotein E), specifically rs7412 and rs429358, as well as those of NLRP3, namely rs35829419, rs10733113, and rs4925663, were also investigated. Results: Results showed that ASC-speck+ cells and Caspase-1, IL-1β, and IL-18 production was significantly reduced (p < 0.005 in all cases) by GNV in LPS + nigericin-stimulated cells of both AD and HC. Notably, the NLRP3 rs10733113 AG genotype was associated with excessive inflammasome-related gene and protein expression. GNV significantly down-regulates inflammasome activation in primary monocytes, at least at protein levels, and its efficacy seems to partially depend on the presence of the NLRP3 rs10733113 genotype. Conclusions: All together, these results showed that GNV is able to dampen inflammation and NLRP-3 inflammasome activation in an ex vivo monocyte model, suggesting a possible role for GNV in controlling AD-associated neuroinflammation. Full article

Dysregulated inflammatory processes contribute to depression, and gene–environment interactions may influence an individual’s risk and resilience. Reduced brain-derived neurotrophic factor (BDNF) expression increases susceptibility for developing depressive symptoms, and the Val66Met (rs6265) single-nucleotide polymorphism (SNP) on the BDNF gene is linked to mood disorders. However, whether Val66Met confers increased vulnerability to inflammation-induced depressive tendencies is unknown. Here, we tested the hypothesis that the Val66Met SNP increases vulnerability to inflammation-induced depressive symptoms in a mouse model of lipopolysaccharide (LPS)-induced depression-like behavior. Behavior and neuroinflammation, following a 24 h LPS challenge, were measured in mice expressing the human BDNF Val66Met gene variant or Val66Val littermates (control). The Val66Met genotype did not affect the peripheral inflammatory response, acute neuroinflammation, or the acute sickness behavior response. Val66Met mice exhibited anhedonia-like behavioral responses following LPS challenge, and we found increased mRNA expression of IL-1β and TNFα in the cerebrum compared to controls. The mRNA expression of IL-1β and TNFα in the hippocampus and the nucleus accumbens of Val66Met mice was increased following LPS, and a significant genotype × LPS interaction was detected for CD68 expression in the nucleus accumbens. In summary, these data suggest that immune activation in Val66Met mice increased susceptibility to anhedonic behavior and dysregulated negative regulation of inflammation. Full article

Periodontitis is a multifactorial disease linked to host immune response and genetic predisposition. The TLR4 Asp299Gly single-nucleotide polymorphism (SNP, rs4986790) has been associated with altered responses to bacterial lipopolysaccharide (LPS) and may influence susceptibility to inflammatory diseases. Given the central role of TLR4 in innate immune recognition of periodontal pathogens, this study investigates the role of rs4986790 in modulating susceptibility to periodontal inflammatory destruction. A total of 1410 individuals from four populations were genotyped, with findings indicating a significant protective effect of the polymorphic allele. Functional assays demonstrated enhanced IL-8 secretion and increased sensitivity to CD14 inhibition in cells expressing the variant receptor. These results suggest that rs4986790 modifies the LPS response via TLR4, potentially offering protection against periodontal breakdown. Full article

Background/Objectives: Obesity is associated with cardiovascular disease worldwide. An increased lipoprotein A (LpA) level is an independent risk factor for cardiovascular disease in children. Genetic polymorphisms of the LPA gene may play an important role in susceptibility to obesity. The aim of this study was to investigate the association of LPA rs10455872 polymorphism with the risk and clinical phenotypes of childhood obesity. Methods: This study included 103 children with obesity and 77 healthy controls. Genotyping of the LPA rs10455872 polymorphism was performed using real-time PCR. Results: The genotype distributions of the LPA rs10455872 polymorphism did not differ significantly between children with obesity and healthy children (p = 0.563). A marked difference in insulin levels was observed between children with obesity carrying the AG (16.90 IU/mL) and AA (25.57 IU/mL) genotypes. A marked difference was also observed in CRP levels between children with obesity with the AG (2.31 mg/L) and AA (4.25 mg/L) genotypes. After correcting for multiple comparisons using the false discovery rate (FDR), significant differences were found between AG and AA genotypes in vitamin B12 (adjusted p = 0.024). Serum iron showed a borderline association (adjusted p = 0.072). A statistically significant correlation was found between the metabolic syndrome index and body fat ratio among children with obesity with the AA genotype (p = 0.028). Conclusions: Although limited by the small number of children with obesity with the AG genotype, some differences were noted between the AG and AA genotypes. These exploratory findings require further investigation in adequately powered studies. In children with obesity with the AA genotype, the metabolic syndrome index increases as the body fat ratio increases. Full article

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS), unlike pediatric acute-onset neuropsychiatric syndrome (PANS), is triggered by infections. This study aimed to assess the differences in low-grade endotoxemia and oxidative stress between these conditions. A cross-sectional study compared serum levels of soluble NOX2-dp (sNOX-2-dp), isoprostanes, lipopolysaccharide (LPS), and zonulin in 30 PANDAS, 21 PANS, and 30 control (CT) children matched for age and gender. Zonulin was used to assess gut permeability. Patients with PANDAS showed significantly higher serum levels of sNOX2-dp, isoprostanes, LPS, and zonulin than PANS and controls, while no significant differences were found between PANS and controls. sNOX2-dp correlated with isoprostanes (Rs = 0.708; p < 0.001), LPS (Rs = 0.584; p < 0.001), and zonulin (Rs = 0.662; p < 0.001). Multiple regression identified isoprostanes (β = 0.599; p < 0.001) and zonulin (β = 0.295; p = 0.01) as independent predictors of sNOX2-dp (R² = 81%). PANDAS and PANS showed distinct profiles of LPS, zonulin, NOX2, and isoprostanes. Future research should explore therapies targeting endotoxemia and oxidative stress for potential clinical benefits. Full article

α7 nAChRs are known to modulate several physiological and pathological functions in glial cells, and their selective activation might have anti-inflammatory effects in the central and peripheral nervous system. OL progenitors (OPCs) respond to cholinergic stimuli via muscarinic receptors that are mainly involved in the modulation of their proliferation. Conversely, the role of nicotinic receptors, particularly α7 nAChRs, has been poorly investigated. In this study, we evaluated the expression of α7 nAChRs in a model of OPCs (Oli neu) and the potential effects mediated by their selective activation. Methods: Oli neu cells were used as a murine immortalized OPCs model. The effects of α7 nAChRs stimulation on cell proliferation and survival were assessed by the MTT assay. RT-PCR and Western blot analysis were used to analyze the expression of α7 nAChRs and proliferative and differentiative markers (PCNA, MBP). LPS exposure was used to induce the environment in which the antioxidant and anti-inflammatory properties of α7 nAChRs were analyzed, evaluating NFR2 and TNF-α expression, ROS levels through DCFDA staining while Oil Red O staining was used for the analysis of lipid droplet content as a marker of cellular inflammation response. Results: The α7 nAChR is expressed both in OPCs and OLs, and its stimulation by the selective agonist ICH3 increases cell proliferation without modifying the OLs’ differentiation capability. Moreover, ICH3 showed anti-inflammatory and antioxidant effects against LPS exposure. Conclusions: The results herein obtained confirm the role of α7 nAChR in the modulation of neuroinflammatory processes as well as their protective effects on OLs. Full article

There are well-known issues in conjunction with eliciting probabilities, utilities, and criteria weights in real-life decision analysis. This article explores various computationally efficient methods for generating weights in multi-criteria decision support systems. Therefore, it constitutes an aid for MCDA modellers and tool designers in selecting surrogate methods for criteria weights. Given the challenges in eliciting precise criteria weights from decision-makers, this study evaluates a range of techniques for automatically generating surrogate weights, focusing on both ordinal and cardinal ranking approaches. With a thorough inquiry methodology never before used, we examine automatic multi-criteria weight-generating algorithms in this article. The methods tested include traditional rank-based models such as rank sum (RS), rank reciprocal (RR), and rank order centroid (ROC), alongside newer approaches like the sum reciprocal (SR) and cardinal sum reciprocal (CSR). The results show that the SR approach for the ordinal case and the CSR method for the cardinal case perform better in terms of robustness than other methods, even including the promising new geometric class of methods. It is also shown that linear programming (LP) performs poorly when compared to surrogate weight models. Additionally, as expected, the cardinal models perform better than the ordinal models. Unexpectedly, though, the well-established LP model’s performance is worse than previously thought. Full article

Background/Objectives: A novel ophthalmic formulation, XanterDES, containing 0.2% xanthan gum and 0.025% desonide sodium phosphate (DES), was developed to alleviate ocular surface discomfort and irritation. This study aimed to evaluate its pharmacodynamic properties and to characterize its rheological behavior and mucoadhesive characteristics, compared to another formulation containing 0.2% hyaluronic acid and 0.001% hydrocortisone (HYD). Methods: A rabbit (New Zealand White) model of LPS-induced uveitis was used to test different concentrations of DES on ocular markers of inflammation. The efficacy of XanterDES and HYD on induced dry eye was evaluated by assessing tear volume and corneal damage in C57BL/6 mice exposed to a controlled environmental chamber. The rheological and mucoadhesive properties of XanterDES and HYD were assessed using a HAAKE RheoStress RS600 rheometer and a TA-XT2 texture analyzer, respectively. Results: In the uveitis model, unlike DES 0.25%, a low concentration of 0.025% DES showed a significant inhibitory activity localized to the eye surface and effectively reduced corneal edema. In the dry eye model, XanterDES demonstrated superior efficacy compared to HYD, effectively preventing both tear volume reduction and corneal damage. XanterDES also demonstrated pseudoplastic and enhanced mucoadhesive properties compared to HYD. Conclusions: The ancillary anti-inflammatory effects of a low dose of DES combined with the biophysical properties of xanthan gum are supportive of a favorable therapeutic profile, promoting the maintenance or restoration of ocular surface homeostasis while minimizing the risk of adverse effects typically associated with standard-dose corticosteroids. The comparison with another low-dose corticosteroid highlights the superiority of XanterDES in pharmacodynamic and biophysical performance. Full article

Background/Objectives: Lipoprotein (a) [Lp(a)] plays a significant role in atherosclerosis and cardiovascular disease (CVD). Genetic regulation of Lp(a) involves variations in the apo(a) LPA gene, as specific polymorphisms like rs10455872 and rs3798220, both linked to higher Lp(a) levels and CVD. CVD remains the leading global cause of death, with high Lp(a) levels increasingly recognized as a significant factor in younger patients with no other CVD risk factors. We aimed to evaluate the association of LPA genetic variations with Lp(a) levels and its effect on cardiovascular risk as there are existing inconsistent findings. Methods: This case–control study included 251 subjects with a median age of 52 years (interquartile range, IQR = 17) and elevated Lp(a) levels. Cases were subjects who experienced early cardiovascular incidents (women < 65, men < 55 years old), and the control group included subjects without such history. Genotyping of LPA gene polymorphisms (rs10455872 and rs3798220) was performed, and demographic data with Lp(a) levels were collected. To evaluate the association between the LPA genotypes and the risk of cardiovascular incidents (CVI), several logistic regression models were performed. The cut-off points for Lp(a) levels were determined using diagnostic test accuracy measures. Results: The rs3798220-C allele was associated with higher Lp(a) levels (288 ± 166 nmol/L in cases vs. 189 ± 102 nmol/L in controls, p < 0.001) and myocardial infarction (53% in cases vs. 36% in controls, p = 0.036). Among cases, 28.9% carried the rs3798220-C allele, compared to 18.7% in controls. The rs10455872-G allele was slightly more prevalent in controls (34.15% vs. 29.69%) but without further significant associations. In this study, the cut-off Lp(a) value of 151 nmol/L, for patients with a positive family history of early CVD, is associated with a higher chance of developing CVI. Conclusions: This study demonstrates an association between the LPA rs3798220-C allele and higher Lp(a) levels, as well as an increased risk of early onset myocardial infarction. However, the obtained association should further be evaluated at a much larger scale. Full article

In low-permeability sandstone reservoirs (LPSR), impermeable interlayers significantly challenge carbon capture, utilization, and storage (CCUS) and enhance oil recovery (CO₂-EOR) processes by creating complex, discontinuous flow units. This study aims to address these challenges through a comprehensive multi-faceted approach integrating geological and microscopic analyses, including core analysis, reservoir petrography, field emission-scanning electron microscopy (FE-SEM), energy dispersive spectroscopy (EDS), and well-logging response analysis, and utilizing three-dimensional (3D) geological modeling. The current comprehensive investigation systematically characterizes interlayer types, petrophysical properties, thickness, connectivity, and their spatial distribution in the reservoir unit. Numerical simulations were conducted to assess the sealing efficiency and the impact of various interlayer materials on CO₂ flooding over a 10-year period. Results indicate the presence of petrophysical and argillaceous interlayers, with optimal sealing occurring in petrophysical barriers ≥ 4 m and argillaceous barriers ≥ 1.5 m thick. CO₂ leakage occurs through preferential pathways that emerge in a side-to-middle and bottom-to-top direction in interbeds, with multidirectional pathways showing greater leakage at the bottom compared to the upper side within barriers. Increased interlayer thickness constraints CO₂ breakthrough but reduces vertical flooding area and production ratio compared to homogeneous reservoirs. Augmented interbed thickness and area mitigate CO₂ breakthrough time while constraining gravity override and dispersion effects, enhancing horizontal oil displacement. These novel findings provide crucial insights for optimizing CCUS-EOR strategies in LPSR, offering a robust theoretical foundation for future applications and serving as a key reference for CO₂ utilization in challenging geological settings of LPSR worldwide. Full article