Browse Articles
Discover research articles across all indexed journals
Exosomal miRNA expression profiling in patients with imatinib resistant Chronic myeloid leukemia: A pilot study
Chronic myeloid leukemia (CML) is a hematologic malignancy originating from hematopoietic stem cells and driven by the BCR-ABL fusion oncogene. Imatinib (IM), a tyrosine kinase inhibitor, is commonly used as a frontline therapy for CML. However, some patients exhibit primary resistance or show persistent molecular evidence of disease despite treatment. Emerging studies indicate that exosome-derived microRNAs (miRNAs) play a role in mediating drug resistance and may serve as promising biomarkers for cancer diagnosis and predicting therapeutic response. This study aimed to investigate the plasma exosomal miRNA expression profiles in CML patients to identify potential biomarkers associated with IM resistance. Exosomes were isolated from plasma samples of both IM-sensitive and IM-resistant CML patients. The exosomal miRNA content was analyzed using RNA sequencing, followed by differential expression analysis, which revealed 13 upregulated and 21 downregulated miRNAs in IM-resistant patients. Subsequent bioinformatics analysis indicated significant enrichment in pathways related to autophagy and PI3K-Akt signaling. Notably, miR-451a and miR-16–2-3p were among the most significantly upregulated miRNAs in exosomes from IM-resistant individuals. Interestingly, miR-16–2-3p expression showed a strong inverse correlation with clinical laboratory results, specifically blood urea nitrogen and creatinine levels. This pilot study identified plasma exosomal miRNAs, particularly miR-451a and miR-16–2-3p, as potential biomarkers for imatinib resistance in chronic myeloid leukemia. Target gene prediction was performed to explore their regulatory roles. Despite the limited sample size, these findings enhance our understanding of drug resistance mechanisms and warrant further validation in larger cohorts to assess their clinical relevance and therapeutic potential.
A comparative study of flaxseed gum effect on Lactobacillus acidophilus genes expression, and textural, sensory, structural, and microbiological properties of synbiotic Iranian white cheese
Abstract Flaxseed gum (FG), a natural polysaccharide with prebiotic potential, may enhance probiotic functionality by modulating bacterial gene expression and improving viability in synbiotic dairy matrices. This study evaluated the effect of FG (2.5% and 5%) on Lactobacillus acidophilus gene expression, viability, sensory properties, texture, and microstructure in Iranian white cheese. Four functional genes were selected for their roles in amino acid biosynthesis, stress adaptation, metabolic regulation, and cell wall integrity. Gene expression was assessed on days 15 and 60 using real-time PCR, while bacterial viability was measured by PMA-qPCR and plate count methods. Significant differences in relative gene expression were observed across all treatments and both time points (day 15 and day 60), with distinct fold-change values for each gene. All gene expressions peaked on day 15 and declined by day 60, possibly due to adaptive stress responses or diminishing FG effect. On day 60, the FG 5% treatment exhibited the highest L. acidophilus viability (1.55 × 107 CFU/g), outperforming both the control and other treatments, and highlighting its superior protective effect during cheese ripening. Sensory analysis revealed FG 5% had the highest general acceptance score, with textural and structural parameters (springiness, chewiness, and porosity) comparable to or improved over control. SEM and ImageJ analyses confirmed enhanced matrix cohesion, reduced porosity (7%), and finer fat dispersion (10 μm) in FG 5%. These findings show that FG may support probiotic viability and cheese quality, offering new insight into the molecular basis of probiotic survival and a promising strategy for developing functional dairy products.
Digital product success under the microscope: When artificial intelligence in projects helps — and when it hurts
As organizations navigate an increasingly dynamic digital landscape, the challenge of achieving consistent product success has intensified. This study investigates how key management factors—customer-driven product development, open innovation networks, organizational digital agility, and AI-integrated project management—influence digital product outcomes. Special attention is given to the dual role of artificial intelligence: as a potential enabler of innovation and a possible constraint when applied in rigid or misaligned ways. A quantitative survey was conducted among 239 professionals engaged in product-related roles across diverse industries and regions. Data were analyzed using linear regression, moderation analysis, and non-parametric testing to assess both direct and interaction effects among the variables. The results reveal that customer-driven product development, open innovation networks, and organizational digital agility each have a statistically significant positive impact on product success, with customer-driven development emerging as the strongest predictor. In contrast, AI-integrated project management does not demonstrate a significant direct effect. Notably, AI negatively moderates the relationship between open innovation networks and product success, suggesting that while AI may enhance structured knowledge-sharing, it can also diminish the creative and collaborative elements essential for innovation if not carefully managed. These findings highlight the strategic complexity of integrating AI into digital product development. While AI can enhance operational efficiency and knowledge flows, its impact on innovation outcomes is context-dependent and may disrupt the balance between human creativity and automated decision-making. The study underscores the need for hybrid models in which AI complements—not replaces—human expertise. Insights from this research offer valuable guidance for organizations aiming to design resilient, customer-centric, and innovation-driven digital product strategies in an AI-enhanced environment.
Multiple model visual feature embedding and selection method for an efficient pest classification supporting precision agriculture
Evaluation of methods for the measurement of antibody-dependent enhancement of dengue virus infection using different FcγRIIa expressing cell lines
Background Pre-existing dengue antibodies could potentially exacerbate disease severity through antibody-dependent enhancement (ADE). Current serological assays focus on measuring neutralizing antibodies for vaccine evaluation, but don’t measure sub-neutralizing antibodies that enhance infection via Fcγ receptors. Consensus on a standardized system for measuring dengue virus ADE remains elusive. Methods In this study, we compared and evaluated ADE responses using two different methodologies in healthy blood donors (n = 12) and secondary dengue patients’ (n = 12) samples with pre-existing IgG antibodies to dengue virus (DENV). We performed an ADE-infection assay in FcγRIIa-expressing U937, K562, and Vero-CD32a cells. Foci-reduction neutralization test (FRNT) was performed simultaneously in Vero and Vero-CD32a cells, and reduction in neutralization titres was examined in Vero-CD32a cells. Results Out of 12 blood donors, all 9 anti-dengue IgG-positive donors demonstrated ADE through infection-enhancement assay against DENV-2 and DENV-4 serotypes in U937 and K562 cells, but not in Vero-CD32a cells. None of the anti-dengue IgG-negative donor samples exhibited ADE against DENV in all three cell lines. Fold-enhancement of DENV-2 infection was comparable in the two cell lines whereas, fold-enhancement of DENV-4 infection was significantly higher in K562 than in U937 cells. Comparable neutralizing antibody titres in Vero and Vero-CD32a cells against DENV-2 and DENV-4 serotypes suggest that donor samples did not exhibit any enhancing activity in Vero-CD32a cells. Comparable DENV-2 titres and significantly lower DENV-4 titres were obtained in Vero-CD32a than in Vero cells in secondary dengue patient samples, indicating that enhancing activity was influenced by DENV serotypes. Conclusion In summary, infection-enhancement assay using K562 cells was superior to U937 and Vero-CD32a cells in evaluating ADE. Samples with high neutralizing activity demonstrated very low levels of infection-enhancing activity in Vero-CD32a cells. Comparison of FRNT titres in Vero and Vero-CD32a cells is not suitable for detecting ADE. Our findings suggest that infection-enhancing activities are apparent at sub-neutralizing concentrations of dengue virus antibodies in all individuals exposed to dengue virus.
A comprehensive study on damage prediction of pile foundations of inclined high rise buildings and the effect of compaction grouting
The positive effect of moral self-concept on fraudulent behavior and the need for moral cleansing
Abstract Both moral cleansing and moral licensing theories suggest that moral self-concept positively influences subsequent engagement in fraudulent behavior. Specifically, a decrease in moral self-concept reduces dishonesty (moral cleansing), while an increase promotes it (moral licensing). However, within these theoretical frameworks, prior research has rarely measured moral self-concept directly, and even fewer studies have manipulated it experimentally. As a result, a direct test of the role of self-concept in these theories is still lacking. This study addresses this gap by experimentally manipulating and directly measuring moral self-concept to examine its relation to subsequent fraudulent behavior. A large-scale randomized experiment was conducted among Hungarian university students, using a subtle priming intervention that urged participants to recall their past moral transgressions. This manipulation effectively lowered moral self-concept, which in turn reduced dishonest behavior, as measured by the fraudulent misreporting of numbers rolled in a monetarily incentivized “die-under-the-cup” task. This causal chain aligns with the theory of moral cleansing. Using the randomized treatment as an instrument, the study has identified a positive causal effect of moral self-concept on fraudulent behavior, indicating that a decrease in moral self-concept reduces fraudulent behavior.
Period-doubling cascade to chaos and optimal quadratic harvesting in a prey–predator–scavenger model using Crowley–Martin functional response
Abstract In the present article, a prey–predator–scavenger model is proposed and investigated with quadratic harvesting of predator and scavenger populations. The system is assumed to follow the Crowley–Martin functional response to describe the interaction between prey and predator populations. The positivity and boundedness of the system with respect to positive initial conditions are established. The analysis included determining all feasible equilibrium points and assessing their local stability under appropriate conditions. The system exhibits limit cycles around the interior equilibrium point. It is also observed that the solution of the system undergoes a period-doubling route to chaos. The existence of local bifurcation around the equilibrium points is investigated. It is shown that the system admits a transcritical bifurcation and a Hopf point for certain parameter values. The system also undergoes a global bifurcation, i.e., a generalized Hopf bifurcation, with respect to different parametric planes. The uniform persistence of the system is derived under specific conditions. Furthermore, an optimal harvesting problem is proposed and analyzed to determine the optimal harvesting pathways that not only maximize net revenue but also effectively manage harvesting efforts. The existence and characterization of optimal controls are discussed using Pontryagin’s maximum principle to balance the implementation of harvesting efforts. Extensive numerical simulations, including time series, phase portraits, and bifurcation diagrams, are performed to illustrate the theoretical results.
Proanthocyanidins inhibit CYP1B1 through mixed-type kinetics and stable binding in molecular dynamics simulations
Abstract Cytochrome P450 1B1 (CYP1B1) is a heme-containing enzyme involved in procarcinogen activation and estrogen metabolism, contributing to tumor progression. This study investigates the inhibitory effects of proanthocyanidin (PA) on CYP1B1-catalyzed reactions and its underlying mechanisms. Enzyme kinetics revealed that PA exerts mixed-type inhibition with an IC₅₀ of 2.53 ± 0.01 μM. Molecular docking demonstrated that PA binds to key residues (Phe231, Gly329, Ala330, Asn228, Asn265) and the heme cofactor through hydrogen bonding and π–π stacking, interfering with substrate binding and electron transfer. Molecular dynamics simulations over 200 ns confirmed the stability of the PA-CYP1B1 complex. To validate the stability and inhibitory relevance of the simulation results, berberine, a known CYP1B1 inhibitor, was used as a positive control in parallel analyses. In silico ADMET prediction indicated high intestinal absorption and a favorable safety profile, with no significant CYP inhibition or mutagenicity. However, low membrane permeability and multiple drug-likeness violations suggest limited oral bioavailability. These findings support the potential of PA as a natural CYP1B1 inhibitor for cancer prevention and treatment. Further structural optimization or formulation strategies may enhance its pharmacokinetic properties and clinical applicability.
Regulation of divergent epithelial-to-mesenchymal transition responses via the CDK4/6-USP51 pathway through ZEB1 protein stabilization
Arbuscular mycorrhizal fungi enhance soybean phosphorus uptake and soil fertility under saline-alkaline stress
Learning and criticality in a self-organizing model of connectome growth
Reduced field-of-view DWI outperforms conventional DWI in assessing tumor heterogeneity and HPV status in head and neck cancer
Machine learning approaches for predicting the construction time of drill-and-blast tunnels
Accelerometry is a valid method to distinguish between healthy and 6-OHDA-lesioned parkinsonian rats
Abstract In Parkinson’s disease (PD), continuous sensor-based evaluation of motor symptom severity, e.g., using accelerometry, has become an emerging field of interest in clinical research. Continuous symptom monitoring would also be of interest in preclinical disease models; however, such devices are far less established in animal models, most likely due to additional requirements in size, energy consumption, and impairment-free attachment. In contrast, accelerometers manufactured in micro-electro-mechanical systems (MEMS) technology are promising sensor devices, which allow for space-saving and energy-efficient monitoring of movements. In the present study, we aim to extend the state of the art by establishing wireless accelerometer measurements as a simple and energy-efficient method to distinguish between healthy rats and the 6-hydroxydopamine (6-OHDA) PD animal model. Male Wistar-Han rats were assessed either three weeks after unilateral 6-OHDA or sham lesioning within their home cages with an extracorporeal accelerometer placed in a rodent backpack for 12 h during their active phase. The data was transmitted wirelessly to a computer, preprocessed, and a statistical analysis was performed to find differences between the datasets of 6-OHDA and sham-lesioned rats. The statistical analysis showed significant differences in the variances of the magnitude of the acceleration vectors between the two classes. In conclusion, accelerometry is a valid method to distinguish between 6-OHDA-lesioned rats with unilateral dopaminergic deficiency and their healthy counterparts. The presented method represents a first step towards automated symptom severity monitoring and provides a framework to expand the application to on-implant integrated accelerometers for continuous monitoring of symptom manifestations in rodent models of neurodegenerative diseases. Future studies are required to expand accelerometry to assess symptom severity to ultimately utilize it for preclinical research on adaptive therapies.