Search Results (1,330)

Drawing on experience–satisfaction–loyalty, this study models how specific digital retail interface attributes translate into behavioural outcomes. Survey data from Portuguese online shoppers were analysed with PLS-SEM to test a formative–reflective framework linking Interactivity and Technologies, Trust–Security–Privacy, Fulfilment and Service Quality, Usability and Web Design, Personalisation and Customisation and Omnichannel Integration to customer experience (CX), customer satisfaction (CS), customer loyalty (CL) and electronic word of mouth (eWOM). The model explains 62.6% of CX, 70.1% of CS and 66.7% of CL. CX is strongly associated with CS and CS, in turn, with CL; associations with eWOM are non-significant, revealing a theoretical blind spot around advocacy. Interactivity and Technologies, Trust–Security–Privacy and Fulfilment and Service Quality emerge as the most significant antecedents of CX, whereas Omnichannel Integration is inert. The findings advance digital commerce theory by decoupling advocacy from evaluative satisfaction and by reconceptualising integration as multidimensional. Practically, they prioritise investment in interactive, secure and fulfilment capabilities while signalling that loyalty is not associated with advocacy. This study concludes by outlining measurement refinements and longitudinal avenues to capture social–motivational drivers of eWOM. Full article

Introduction: Neuroinflammation is a common pathological hallmark of Coronavirus Disease 2019 (COVID-19) and epilepsy; however, their shared immunogenomic mechanisms remain poorly defined. This study explores shared immune-inflammatory transcriptomic signatures and identifies potential repositioning therapeutics. Methods: We integrated single-cell RNA-seq data from peripheral blood mononuclear cells (PBMCs) of COVID-19 patients and healthy donors (GSE149689), and bulk RNA-seq data from hippocampal tissue of patients with Temporal Lobe Epilepsy with Hippocampal Sclerosis (TLE-HS) and healthy controls (GSE256068). Common Differentially Expressed Genes (DEGs) were identified and subjected to GO/KEGG enrichment, a PPI network, hub gene detection (cytoHubba), and transcriptional regulation analysis (ENCODE-based TF/miRNA networks). Drug repositioning was performed using the LINCS L1000 database. Results: We identified 25 DEGs shared across datasets, including 22 upregulated genes enriched in cytokine–cytokine receptor interaction, NF-κB, and Toll-like receptor pathways. PPI analysis revealed a CX3CR1–TLR4-centered immune module. Gabapentin emerged as a promising repositioning candidate with potential to downregulate CX3CR1, TLR4, and selectin P ligand (SELPLG). Receiver Operating Characteristic (ROC) analysis confirmed the diagnostic value of these targets (AUC > 0.90 in epilepsy). A mechanistic model was proposed to illustrate Gabapentin’s dual action on microglial polarization and cytokine suppression. Conclusions: Our results reveal a shared CX3CR1–TLR4–NF-κB inflammatory axis in COVID-19 and epilepsy, supporting Gabapentin as a potential dual-action immunomodulator. These findings reveal a previously underappreciated immunomodulatory role for Gabapentin, providing mechanistic rationale for its repositioning in neuroinflammatory conditions beyond seizure control. Full article

The dynamics of the HIV reservoir during antiretroviral therapy (ART) exhibit variability, with a pronounced decline during the initial years of treatment. However, the identification of biomarkers and host factors associated with the decay of the different forms of HIV proviruses remains to be fully elucidated. We conducted a longitudinal study on people with HIV provided by the Spanish National HIV cohort. We assessed the HIV-DNA levels by Intact Proviral DNA Assay, and inflammatory markers using the Proximity Extension Assay, before and after ART initiation. A multivariate linear regression model was employed to identify potential predictive markers. Our results highlight the identification of novel inflammatory markers, such as ADA, DNER, CDCP1, SCF, among others, that varied significantly over ART initiation. In addition, we observed several markers associated with intact HIV-DNA before ART initiation (CD8A, CX3CL1, and ST1A1) or during undetectable viral load post-ART (IL-10). Moreover, up to five markers were able to predict the intact HIV reservoir decay over ART. The strongest predictor was Stem Cell Factor (SCF), where higher baseline levels of this marker were associated with a greater decline in the intact HIV reservoir. In conclusion, we have identified inflammatory markers associated with the size and dynamics of the HIV-DNA reservoir. These findings provide new insights that could contribute to the development of multi-targeted intervention strategies aimed at modulating or monitoring the HIV reservoir size. Full article

Background: Chemokines play a pivotal role in the progression of osteoarthritis (OA), but their exact mechanisms remain unclear. This study aimed to identify potential chemokine-associated biomarkers and investigate their causal relationships with OA. Methods: Transcriptome and genome-wide association study (GWAS) data were obtained from public databases, while chemokine-related genes (CRGs) were sourced from the literature. Initially, CRGs were expanded, followed by Mendelian randomization (MR) analysis, differential expression analysis, machine learning, and receiver operating characteristic (ROC) curve plotting to identify potential biomarkers. The causal relationships between these biomarkers and OA, as well as their biological functions, were further explored. Results: Fourteen candidate genes were identified for machine learning analysis, with DDIT3, CEBPB, CX3CR1, and ARHGAP25 emerging as feature genes. CEBPB and CX3CR1, which exhibited AUCs > 0.7 in the GSE55235 and GSE55457 datasets, were selected as potential biomarkers. Notably, CEBPB expression was lower, while CX3CR1 expression was elevated in the case group. Furthermore, both genes were co-enriched in spliceosome, lysosome, and cell adhesion molecule pathways. MR analysis confirmed that CEBPB and CX3CR1 were causally linked to OA and acted as protective factors (IVW model for CEBPB: OR = 0.9051, p = 0.0001; IVW model for CX3CR1: OR = 0.8141, p = 0.0282). Conclusions: CEBPB and CX3CR1 were identified as potential chemokine-related biomarkers, offering insights into OA and suggesting new avenues for further investigation. Full article

Rhabdomyolysis is characterized by the breakdown of skeletal muscle tissue, frequently leading to acute kidney injury (AKI). Traditional conservative treatments have shown limited effectiveness in modifying the disease course, thereby necessitating targeted pharmacological approaches. Zileuton (Z), a selective inhibitor of 5-lipoxygenase (5-LOX), has demonstrated efficacy in enhancing renal function recovery in animal models of AKI induced by agents such as cisplatin, aminoglycosides, and polymyxins. The present study aimed to evaluate the therapeutic potential of a single dose of Z in mitigating rhabdomyolysis-induced AKI (RI-AKI) via modulation of myeloid-derived suppressor cells (MDSCs). Male C57BL/6 mice were assigned to four experimental groups: Sham (intraperitoneal administration of 0.9% saline), Z (single intraperitoneal injection of Z at 30 mg/kg body weight), glycerol (Gly; single intramuscular dose of 50% glycerol at 8 mL/kg), and glycerol plus Z (Z + Gly; concurrent administration of glycerol intramuscularly and Z intraperitoneally). Animals were sacrificed 24 h post-glycerol injection for analysis. Zileuton administration significantly improved renal function, as indicated by reductions in blood urea nitrogen (BUN) levels (129.7 ± 17.9 mg/dL in the Gly group versus 101.7 ± 6.8 mg/dL in the Z + Gly group, p < 0.05) and serum creatinine (Cr) levels (2.2 ± 0.3 mg/dL in the Gly group versus 0.9 ± 0.3 mg/dL in the Gly + Z group p < 0.05). Histopathological assessment revealed a marked decrease in tubular injury scores in the Z + Gly group compared to the Gly group. Molecular analyses demonstrated that Z treatment downregulated mRNA expression of macrophage-inducible C-type lectin (mincle) and associated macrophage infiltration-related factors, including Areg-1, Cx3cl1, and Cx3CR1, which were elevated 24 h following glycerol administration. Furthermore, the expression of NLRP-3, significantly upregulated post-glycerol injection, was attenuated by concurrent Z treatment. Markers of mitochondrial biogenesis, such as mitochondrial DNA (mtDNA), transcription factor A mitochondrial (TFAM), and carnitine palmitoyltransferase 1 alpha (CPT1α), were diminished 24 h after glycerol injection; however, their expression was restored upon simultaneous Z administration. Additionally, Z reduced protein levels of BNIP3, a marker of mitochondrial autophagy, while enhancing the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), suggesting that Z ameliorates RI-AKI severity through the regulation of mitochondrial quality control mechanisms. Zileuton also decreased infiltration of CD11b(+) Gr-1(+) MDSCs and downregulated mRNA levels of MDSC-associated markers, including transforming growth factor-beta (TGF-β), arginase-1 (Arg-1), inducible nitric oxide synthase (iNOS), and iron regulatory protein 4 (Irp4), in glycerol-injured kidneys relative to controls. These markers were elevated 24 h post-glycerol injection but were normalized following concurrent Z treatment. Collectively, these findings suggest that Zileuton confers reno-protective effects in a murine model of RI-AKI, potentially through modulation of mitochondrial dynamics and suppression of MDSC-mediated inflammatory pathways. Further research is warranted to elucidate the precise mechanisms by which Z regulates MDSCs and to assess its therapeutic potential in clinical contexts. Full article

Combined oxidative phosphorylation deficiency type 8 (COXPD8) is an autosomal recessive mitochondrial disorder caused by a mutation of the nuclear encoded mitochondrial alanyl-tRNA synthetase gene (AARS2). Clinical manifestations of COXPD8 include lethal infantile hypertrophic cardiomyopathy, pulmonary hypoplasia, generalized muscle weakness, and neurological involvement. We report a patient with COXPD8 caused by two mutations in the AARS2 gene. The c.1738 C>G mutation has not been previously reported, while the c.2872 C>T mutation has been associated with pulmonary hypoplasia and hypertrophic cardiomyopathy. Cardiac tissue, obtained through the LungMAP program, showed that, compared to other patients of similar ages, these two mutations affect not only the assembly of functional monomeric complexes (Cx) I and IV of the electron transport chain (ETC) but also limit the formation of respiratory supercomplexes. This patient had altered expression of some ETC proteins but normal expression of several enzymes of the tricarboxylic acid cycle. We also show that one of the control/comparison patients had an undiagnosed ETC Cx IV deficiency. In conclusion, our data demonstrate that the two mutations of the AARS2 gene are associated with failed assembly of Cx I and Cx IV and reduced formation of respiratory supercomplexes of the ETC, likely leading to acute bioenergetic stress. Full article

Extended-reach drilling (ERD) offers substantial economic and operational benefits by accessing extensive reservoir sections with fewer surface facilities, yet poses significant frictional challenges due to complex wellbore geometries and extreme operating conditions. This study introduces a multi-interface lubrication evaluation framework. It systematically assesses oil-based drilling fluids (OBDFs) across three downhole contact scenarios: metal–rock, metal–mud cake, and metal–metal interfaces under HTHP conditions. We developed a quantitative, normalized scoring system. Benchmarked against distilled water (score 0) and W1-110 mineral oil (score 100), it integrates frictional data from various tests into a unified metric for lubricant comparison. Three candidate lubricants—PF-LUBE EP, PF-LUBE OB, and CX-300—were evaluated at varying dosages, lithologies, and applied loads. Results show that at 2 wt%, PF-LUBE EP achieved the most consistent performance, reducing friction coefficients by 36.8% (metal–rock), 27.5% (metal–mud cake), and 32.5% (metal–metal), with a normalized average score of 155.39, outperforming PF-LUBE OB and CX-300 by 12.5% and 18.3%, respectively. Its superior performance is attributed to a bionic dual-layer film formed by organophosphorus anchoring and alkyl slip layers, enabling self-healing and stability under cyclic loading and HTHP environments. PF-LUBE OB and CX-300 also demonstrated friction reduction but with lower normalized scores (138.06 and 131.27), reflecting less stability across varied conditions. The proposed framework bridges the gap between laboratory testing and field-scale application by capturing multi-interface behaviors, enabling objective lubricant selection and dosage optimization for complex ERD operations. These findings not only validate PF-LUBE EP as a robust additive but also establish a scalable methodology for the development and optimization of next-generation OBDF formulations aimed at reducing torque, drag, and equipment wear in challenging drilling environments. Full article

This work focused on the photocatalytic performance enhancement of titanium dioxide (TiO₂) nanotubes decorated by gold nanoparticles. The surface of the nanotubes synthesized using the anodization technique was modified with subsequent deposition of gold nanoparticles (Au-NPs) via electrophoretic deposition. The impact of electrophoretically deposited gold nanoparticles (Au-NPs) on TiO₂ nanotubes, with varying deposition times (5 min, 8 min and 12 min), was investigated in the degradation of amido black (AB) dye. The morphological analysis using scanning electron microscopy (SEM, TESCAN VEGA3, TESCAN Orsay Holding, Brno, Czech Republic) and transmission electron microscopy (TEM, JEM—100CX2, JEOL Japan). revealed a well-organized nanotubular structure of TiO₂, with a wall thickness of 25 nm and an internal diameter of 75 nm. Optical study, including photoluminescence and diffuse reflectance spectroscopy, provided evidence of charge transfer between the Au-NPs and the TiO₂-NTs. Furthermore, the photocatalytic measurements showed that the enhanced photocatalytic activity of the TiO₂-NTs resulted from successful Au deposition onto their surface, surpassing that of the pure sample. This improvement is attributed to the higher work function of gold nanoparticles, which effectively promoted the separation of photogenerated electron–hole pairs. The sample Au-NPs/TiO₂-NTs with a deposition time of 5 min exhibited the best photocatalytic efficiency, achieving an 85% degradation rate after 270 min under UV irradiation. Moreover, the enhancement obtained was also attributed to the plasmonic effect induced by Au-NPs. Kinetic investigations revealed that the photocatalytic reaction followed apparent first-order kinetics, highlighting the efficiency of Au-NPs/TiO₂-NTs as a photocatalyst for dye degradation. Full article

Background/Objectives: To design the pDNA delivery carrier for delivery into skeletal muscle, a total of twelve terminal-alkylated PEGs (Cx-I-PEGy) with four alkyl groups of different carbon numbers (Cx: x = 4, 8, 12, 16) modified via an imine spacer at the ends of three methoxy PEGs of different molecular weights (PEGy: y = 500, 2k, 5k) have been synthesized. Methods: Among them, four Cx-I-PEG5k formed an imine-mediated complex formation with pDNA, as assessed by agarose gel electrophoresis, defined as an iminium mono-ion complex (I-MIC) without multivalent electrostatic interaction by minimizing potential toxic cations. Results: Most resulting I-MICs maintained the flexible structure of pDNA and promoted the binding to pDNA. The expression of pDNA by intramuscular injection with the resulting I-MICs was the highest by using I-MICs with C4-I-PEG5k and was observed extensively by the in vivo imaging system (IVIS). Conclusions: These results suggest that the I-MICs with C4-I-PEG5k are promising for pDNA transfection into skeletal muscle, offering the alkyl iminium for the pDNA binding group to demonstrate the factor of pDNA’s flexible structure as one of the key parameters for in vivo local pDNA transfection. Full article

This study presents an integrated workflow for the characterization of fault-controlled fractured–vuggy reservoirs, demonstrated through a comprehensive analysis of the TP12CX fault zone in the Tahe Oilfield. The methodology establishes a four-element structural model—comprising the damage zone, fault core, vuggy zone, and cavern system—coupled with a multi-attribute geophysical classification scheme integrating texture contrast, deep learning, energy envelope, and residual impedance attributes. This framework achieves a validation accuracy of 91.2%. A novel structural element decomposition–integration approach is proposed, combining deterministic structural reconstruction with facies-constrained petrophysical modeling to quantify reservoir properties. The resulting models identify key heterogeneities, including caverns (Φ = 17.8%, K = 587 mD), vugs (Φ = 3.5%, K = 25 mD), and fractures (K = 1400 mD), with model reliability verified through production history matching. Field application of an optimized nitrogen foam flooding strategy, guided by this workflow, resulted in an incremental oil recovery of 3292 tons. The proposed methodology offers transferable value by addressing critical challenges in karst reservoir characterization, including seismic resolution limits, complex heterogeneity, and late-stage development optimization in fault-controlled carbonate reservoirs. It provides a robust and practical framework for enhanced oil recovery in structurally complex carbonate reservoirs, particularly those in mature fields with a high water cut. Full article

Background and Aim: The immunological interactions between soil-transmitted helminths (STHs) and herpes simplex virus type 2 (HSV-2), particularly in the context of co-infection, are poorly understood. Next-generation sequencing (NGS) offers a powerful approach to explore these complex immune responses and uncover potential therapeutic targets. This study leveraged NGS and bioinformatic tools to investigate transcriptional changes and immunological pathways in female genital tract (FGT) tissues of BALB/c mice acutely infected with Nippostrongylus brasiliensis (Nb), HSV-2, or co-infected. Methods: Total RNA was harvested from FGT tissues of BALB/c mice infected with Nb, HSV-2, co-infected with both pathogens, and uninfected controls. Differentially expressed genes (DEGs) were identified by comparing uninfected versus infected FGT tissues in R using edgeR and limma packages. Immune-related genes were identified by intersecting DEGs in each group-wise comparison with immune function gene sets derived from the Mouse Genome Informatics (MGI) database. Functional and pathway enrichment analyses were performed with g: Profiler and protein–protein interaction networks were built using the STRING database and visualized with Cytoscape. Key hub genes and significant gene modules were identified using the Cytoscape plugins CytoHubba and MCODE, followed by further functional analysis of these modules. Results: NGS analysis revealed distinct gene expression profiles in response to single infection with Nb or HSV-2, with both showing significant differences when uninfected controls were compared to infected FGT tissues at a 5% false discovery rate. Notably, there were no significant differences in gene expression profiles between uninfected and co-infected FGT tissues. In the comparison of uninfected versus Nb-infected FGT tissues, 368 DEGs were identified, with 356 genes upregulated and 12 downregulated. Several immune-related genes, such as Ptprc, Ccl11, Ccr2, and Cx3cr1, were significantly altered. Pathway analysis of DEGs, hub genes, and significant modules indicated modulation of immune and defense responses. Notably, Nb infection induced a robust Th2-dominant immune response in the FGT, with downregulation of pro-inflammatory genes. This likely reflects helminth-driven modulation that may impair protective Th1 responses and highlights the systemic impact of Nb on the FGT immunity. In the comparison of uninfected versus HSV-2-infected FGT tissues, 140 DEGs were identified, with 121 upregulated and 19 downregulated. Immune-related genes, including Ldlr, Camk1d, Lrp8 and Epg5, were notably altered. HSV-2 infection led to early and predominant downregulation of immune genes, consistent with viral immune evasion strategies. In addition, functional analysis revealed enrichment in cell cycle and sterol biosynthesis pathways, suggesting that HSV-2 modulates host metabolism to support viral replication while influencing immune responses. In co-infection, no significant transcriptional changes were observed, potentially reflecting immune antagonism where Nb-induced Th2 responses may suppress HSV-2-driven Th1 immune responses. Conclusions: This preliminary study offers insights into the gene expression responses in the FGT to acute single and co-infection with Nb and HSV-2. Together, these findings reveal distinct transcriptomic changes in the FGT following Nb and HSV-2 infection, with co-infection potentially leading to immune antagonism and transcriptional equilibrium. This highlights the complex interplay between helminth- and virus-induced immune modulation in shaping FGT immunity. By leveraging NGS, this study highlights important immune-related pathways and serves as a foundation for further investigations into the mechanistic roles of DEGs in immunity to these pathogens, with potential implications for developing novel therapeutic strategies. Full article

We report about the effect of nitrogen and carbon concentration on the superconducting transition temperature T_C of (NbMoTaW)₁C_xN_y carbonitride films deposited using reactive DC magnetron sputtering. By measuring the temperature dependence of electrical resistance and magnetization of these carbonitrides, with 0.20 ≤ x ≤ 1.17 and 0 ≤ y ≤ 0.73, we observe a T_C enhancement that occurs especially at high (x ≥ 0.76) carbon concentrations, with the largest T_C = 9.6 K observed in the over-doped fcc crystal structure with x = 1.17 and y = 0.41. The reason why the largest T_C appears at high C concentrations is probably related to the lower atomic mass of carbon compared to nitrogen and to the increase in the electron–phonon interaction due to different bonding of carbon (compared to nitrogen) to the Nb-Mo-Ta-W metallic sublattice. However, for concentrations where y > 0.71 and x + y > 1.58, two structural phases begin to form. Additionally, the proximity to structural instability may play a role in the observed B_C2 enhancement. Further measurements in a magnetic field show that the upper critical fields B_C2 of (NbMoTaW)₁C_xN_y carbonitrides provide B_C2/B_C2 < 2 T/K, which falls within the weak-coupling pair breaking limit. Full article

The aim of this study was to develop a mathematical model to predict the body weight of tilapia fingerlings using variables obtained through computer vision. A total of 2092 tilapia fingerlings and juveniles, weighing between 10 and 100 g, were fasted for 12 h, anesthetized, weighed, and photographed using an iPhone 12 Pro Max at 33 cm height in a closed container with different bottom colors. Images were segmented using Roboflow’s instance segmentation model, achieving 99.5% mean average precision, 99.9% precision, and 100% recall. From the segmented images, area, perimeter, major axis (MA), minor axis (SA), X and Y centroids, compactness, eccentricity, and the MA/SA ratio were extracted. Seventy percent of the data was used to build the model, and 30% for validation. Stepwise multiple regression (backward selection) was performed, using body weight as the dependent variable. The prediction model was: −17.7677 + 0.0007539(area) – 0.0848303 (MA) – 0.108338(SA) + 0.0034496(CX). The validation model showed similar coefficients and R² = 0.99. The second validation, using observed versus predicted values, also yielded an R² of 0.99 and a mean absolute error of 1.57 g. Correlation and principal component analyses revealed strong positive associations among body weight, area, axes, and predicted values. Computer vision proved effective for predicting tilapia fingerlings’ weight. Full article

In the last decades, numerous approaches have been explored for the cross-coupling of biaryl building blocks depending on the presence of boron sources. In fact, these changes have been catalyzed by transition metal complexes. This review focuses on the progress of the last decade in transition metal-catalyzed C–X borylation and direct C–H borylation, with emphasis on nickel-catalyzed C–H borylation, as effective and affordable protocols for the borylation of aryl substrates. In addition, Suzuki-type cross-coupling by activation of C–H, C–C, or C–N bonds is also reported. This study then offers an overview of recent advances for the synthesis of bi- and multi-aryls found in synthetic molecular complexes and natural products using the transition metal-catalyzed one-pot Miyaura-type C–X and C–H borylation–Suzuki coupling sequence. Full article

Murine microglia exhibit rapid self-renewal upon removal from the postnatal brain. However, the signaling pathways that regulate microglial repopulation remain largely unclear. To address this knowledge gap, we depleted microglia from mixed glial cultures using anti-CD11b magnetic particles and cultured them for 4 weeks to monitor their repopulation ability in vitro. Flow cytometry and immunocytochemistry revealed that anti-CD11b bead treatment effectively eliminated >95% of microglia in mixed glial cultures. Following removal, the number of CX3CR1-positive microglia gradually increased; when a specific threshold was reached, repopulation ceased without any discernable rise in cell death. Cell cycle and 5-ethynyl-2′-deoxyuridine incorporation assays suggested the active proliferation of repopulating microglia at d7. Time-lapse imaging demonstrated post-removal division of microglia. Colony-stimulating factor 1 receptor-phosphoinositide 3-kinase-protein kinase B signaling was identified as crucial for microglial repopulation, as pharmacological inhibition or neutralization of the pathway significantly abrogated repopulation. Transwell cocultures revealed that resident microglia competitively inhibited microglial proliferation probably through contact inhibition. This in vitro microglial removal system provides valuable insights into the mechanisms underlying microglial proliferation. Full article