Search Results (70,012)

Background: Mesenchymal stem cells (MSCs) exhibit a high capacity for differentiation, possess anti-inflammatory and proangiogenic properties, and stimulate the growth and proliferation of neighboring cells. MSCs are a promising tool in regenerative medicine. However, the molecular mechanisms underlying the properties of these cells are not yet fully understood. Gene expression in MSCs influences their characteristics and differentiation potential. Therefore, it is essential to investigate factors affecting gene expression as well as those activating signaling pathways, which will enable more effective and individualized applications of MSCs. In this study, we aimed to identify signaling pathways involved in gene expression in umbilical cord-derived MSCs (UC-MSCs) that may be altered by maternal diabetes and hypothyroidism during pregnancy. Methods: The research material consisted of UC-MSCs. Samples obtained from nine participants were analyzed. UC-MSCs were isolated and cultured, and RNA was extracted. The isolated RNA was used for microarray-based gene expression analysis. Subsequently, pathway enrichment analysis was performed to identify the signaling pathways involved. Results: In the diabetes group, 340 genes (0.71%) were upregulated, while 268 genes (0.56%) were downregulated compared with UC-MSCs from the control group. In the diabetes group, the most compact module was composed of proteins associated with WNT/planar cell polarity (WNT/PCP) signaling. The second module included genes related to smooth muscle activity. In the hypothyroidism group, an association was identified between the extracellular matrix organization pathways (GO:0030198) and the extracellular structure organization (GO:0043062) pathways. Moreover, in this group, increased expression of MMP1, MMP10, and GREM1 was observed. Conclusions: In summary, our study demonstrated the impact of diabetes and hypothyroidism on gene expression in UC-MSCs. We also observed the activation of distinct signaling pathways depending on the presence of these conditions. However, this work represents a preliminary screening, and the results should be validated by PCR in a larger cohort. Full article

Wildfire monitoring in tropical regions requires robust frameworks capable of transforming heterogeneous satellite detections into consistent, event-level information suitable for decision support. This study presents the DescrEVE Fogo (Descrição de Eventos de Fogo) framework, a relational and scalable system that models daily fire events in Brazil by integrating Advanced Very High Resolution Radiometer (AVHRR), Moderate-Resolution Imaging Spectroradiometer (MODIS), and Visible Infrared Imaging Radiometer Suite (VIIRS) active-fire detections within a unified Structured Query Language (SQL)/PostGIS environment. The framework formalizes a mathematical and computational model that defines and tracks fire fronts and multi-day fire events based on explicit spatio-temporal rules and geometry-based operations. Using database-native functions, DescrEVE Fogo aggregates daily fronts into events and computes intrinsic and environmental descriptors, including duration, incremental area, Fire Radiative Power (FRP), number of fronts, rainless days, and fire risk. Applied to the 2003–2025 archive of the Brazilian National Institute for Space Research (INPE) Queimadas Program, the framework reveals that the integration of VIIRS increases the fraction of multi-front events and enhances detectability of larger and longer-lived events, while the overall regime remains dominated by small, short-lived occurrences. A simple, prototype fire-type rule distinguishes new isolated fire events, possible incipient wildfires, and wildfires, indicating that fewer than 10% of events account for more than 40% of the area proxy and nearly 60% of maximum FRP. For the 2025 operational year, daily ignition counts show strong temporal coherence with the Global Fire Emissions Database version 5 (GFEDv5), albeit with a systematic positive bias reflecting differences in sensors and event definitions. A case study of the 2020 Pantanal wildfire illustrates how front-level metrics and environmental indicators can be combined to characterize persistence, spread, and climatic coupling. Overall, the database-native design provides a transparent and reproducible basis for large-scale, near-real-time wildfire analysis in Brazil, while current limitations in sensor homogeneity, typology, and validation point to clear avenues for future refinement and operational integration. Full article

The genus Calliandra (Leguminosae: Mimosoideae) encompasses over 200 species, many of which hold significant ethnobotanical value. However, a critical and comprehensive review consolidating their phytochemical and pharmacological knowledge is currently lacking. This article aims to provide a detailed and analytical overview of the traditional uses, phytochemistry, and pharmacological properties of the most studied Calliandra species, identifying trends, gaps, and future research priorities. A systematic literature search was conducted using Google Scholar, Scopus, Web of Science, and PubMed from 1986 to 2025. The review focuses on Calliandra portoricensis, Calliandra haematocephala, and Calliandra surinamensis due to the relative abundance of scientific literature concerning their medicinal applications. These species produce a diverse array of secondary metabolites, including distinctive galloylated flavonoids, phenolic acids, and triterpenes. Extracts and isolated compounds demonstrate a wide range of pharmacological activities, such as antioxidant, antimicrobial, anti-inflammatory, antidiabetic, and anticancer effects, providing a scientific basis for their traditional uses. The genus Calliandra represents a promising source of bioactive compounds. However, future research must focus on compound isolation, mechanistic studies, rigorous toxicological profiling, and clinical trials to fully realize its therapeutic potential. Full article

Mycobacterium bovis is the causative agent of tuberculosis (TB) infecting a wide range of animal hosts, including humans. Domestic pigs (Sus scrofa domestica) are susceptible to different mycobacteria, particularly species within the Mycobacterium avium complex (MAC). However, in countries where bovine TB is endemic, such as Argentina, M. bovis is the most frequently reported species in pigs. This study aimed to evaluate the immune response and disease progression of a local strain (MB894) isolated from pigs and compare its pathogenicity with the highly virulent strain MB303, isolated from wild boar. Additionally, we sought to explore the genomic basis underlying the virulent phenotype of MB894. For this purpose, a murine infection model was used to assess pathogenicity, organ colonization, dissemination and cytokine induction. Whole-genome sequencing was performed to identify genetic features, including non-synonymous SNPs and INDELs, potentially associated with virulence. The severe immunopathogenesis produced by MB894, the higher multiplication rate in the evaluated organs, and the greater dissemination to other organs compared to MB303, combined with the cytokine levels induced by this strain, prompted us to classify MB894 as a hypervirulent strain. Genomic analysis revealed candidate genes that may be virulence factors contributing to this phenotype. In summary, MB894 represents a hypervirulent M. bovis strain with distinct pathogenic and genomic characteristics. These findings provide insights into the molecular determinants of virulence and highlight the need for further evaluation of identified gene candidates. Full article

Collaborative control of multiple surface vessels remains a significant challenge in autonomous maritime operations, particularly within environments characterized by sparse rewards. Conventional Multi-Agent Proximal Policy Optimization (MAPPO) often suffers from inefficient credit assignment and slow convergence in such scenarios. To address these limitations, this paper proposes an enhanced MAPPO framework that integrates a counterfactual baseline—derived from Counterfactual Multi-Agent Policy Gradients (CMAPG)—into the Generalized Advantage Estimation (GAE) formulation. Furthermore, a Prioritized Experience Replay (PER) mechanism with importance sampling is incorporated to improve sample efficiency. The counterfactual baseline is necessary to provide precise, agent-specific learning signals within the on-policy paradigm, directly tackling the credit assignment problem. The PER mechanism, carefully adapted with importance sampling, is essential to break the sample-inefficiency barrier by strategically reusing valuable past experiences without compromising stability. This synergistic approach refines credit assignment by isolating individual contributions and maximizes the utility of valuable historical experiences. Simulation results and comparisons validate the enhanced control performance of the proposed controller. Full article

This paper addresses the stringent requirements of high-precision equipment for broadband, contactless active vibration isolation by tackling three key research gaps: the lack of an integrated design deeply coupling vertical and lateral subsystems, the absence of explicit characterization of the base-to-load vibration transmission chain in dynamic models, and the disconnect between theory and application due to spatial sensor–actuator mismatch. To bridge these gaps, a novel five-degree-of-freedom active magnetic levitation vibration isolation system is proposed. Its core contributions are threefold. First, an electromagnetic-structure co-design method based on the equal magnetic reluctance principle is introduced, enabling a globally optimized, integrated actuator layout that maximizes force density within spatial constraints. Second, a dynamic model incorporating explicit base kinematic excitation is established, clearly revealing the complete physical mechanism of vibration transmission through the suspension gap and providing an accurate foundation for model-based control. Third, a coordinate reconstruction control model is constructed, which transforms the ideal center-of-mass-based dynamics into a design model using only measurable gap signals via systematic coordinate transformations, thereby fundamentally eliminating control deviations from physical spatial mismatch. This work provides a comprehensive theoretical framework and solution for next-generation high-performance active vibration isolation platforms, encompassing integrated design, precise modeling, and engineering implementation. Full article

There is a strong need for nanobodies that target novel cancer-associated antigens to advance radioligand imaging and antibody-based therapeutics. In this study, we investigated whether non-targeted llama immunization using tumor cells, combined with non-targeted phage-display panning of human cell lines, could yield nanobodies specific to Prostate-Specific Membrane Antigen (PSMA). Nanobody selection using both classical three-round PSMA negative–positive panning and single-round panning of cell lines (positive or negative) for PSMA showed clear enrichment for PSMA binders in both strategies. Using shRNA knockdown, flow cytometry, cell-ELISA, immunohistochemistry and structural modeling and docking, we confirmed the PSMA-targeting of selected nanobodies. Two distinct epitopes were predicted to be bound by nanobodies PSMANb9 and A7 (JVZ-007), and this was corroborated by epitope competition assays. These findings support the feasibility of non-targeted immunization and panning strategies for isolating antigen-targeting cancer nanobodies. Full article

Cinnamaldehyde (CIN) is a natural organic compound known for its antimicrobial and antioxidant properties. However, its susceptibility to environmental degradation has restricted its practical application. This study aimed to microencapsulate CIN using soy protein isolate hydrolysates and maltodextrin as wall materials through emulsion preparation and spray drying, and to characterize the microstructure, controlled-release properties, antibacterial efficacy, and preservation performance of the resulting microcapsules. Under optimized condition, the encapsulation efficiency reached 70.72%. The microcapsules displayed smooth spherical structures, improved thermal stability, and an average particle size of 291.01 ± 33.64 nm. They demonstrated enhanced storage stability and sustained-release characteristics. Furthermore, the microcapsules exhibited significant antibacterial and antioxidant activity, which effectively delayed lipid and protein oxidation in pork loin for up to 6 days. Collectively, the results confirm the successful encapsulation of CIN and indicate the strong potential of these microcapsules for food industry applications requiring preservative and controlled-release functions. Full article

Steep slope failures adjacent to residential areas are becoming an increasingly serious hazard. However, satellite-based monitoring is often limited by revisit time and spatial resolution, which can impede the timely identification of small, precursory deformations. To support dense in situ surveillance, embedded glass fiber-reinforced polymer (GFRP) sensor rods were installed in a susceptible slope, and ground-displacement data were recorded at 5 min intervals for five months. Based on these multivariate time series, we propose PRISM-TAD, a masked Transformer-based anomaly detection approach that integrates kinematic priors computed from displacement and velocity to model normal slope dynamics and detect departures from typical behavior. The proposed method was benchmarked against six baselines: robust velocity threshold screening, PCA-based reconstruction, Isolation Forest, one-class SVM, a 1D convolutional autoencoder, and a standard Transformer reconstructor. In a field test using a documented slope failure case in Seocheon, PRISM-TAD generated an alert approximately 22 h before collapse while yielding the lowest false alarm rate. Although some baseline methods showed longer nominal lead times, they produced substantially more false positives. Overall, the results suggest that coupling high-frequency IoT displacement sensing with domain-informed deep learning can enhance the operational reliability of early warning for slope failures. Full article

The overuse of antibiotics in animal husbandry is a primary driver of antimicrobial resistance, creating a pressing need for safe and effective natural alternatives. This study systematically evaluated the potential of the edible aromatic plant Elsholtzia cypriani as a comprehensive alternative by investigating its chemical composition, bioactivities, and preliminary safety. Methods included solvent extraction and systematic chromatographic fractionation from the plant aerial parts, complemented by a series of in vitro assays assessing anti-inflammatory, antioxidant, and antibacterial properties, along with an acute toxicity study. A total of thirty compounds were isolated and their structures were elucidated, including two new and twenty-eight known compounds reported for the first time in this species. Key isolates, such as ethyl caffeate and luteolin, demonstrated significant anti-inflammatory activity, antioxidant capacity, and antibacterial action against pathogens like Escherichia coli. Acute toxicity assessment revealed no adverse effects at the tested dosage. In conclusion, E. cypriani is rich in diverse bioactive compounds which exhibit direct antimicrobial, anti-inflammatory, and antioxidant activities in vitro, and shows a favorable preliminary safety profile. This work systematically establishes the chemical and pharmacological basis for this plant, highlighting its potential for further development and evaluation as a multifunctional natural feed additive. Full article

Background: Although elevated triglyceride (TG) levels are consistently associated with hypertension in observational studies, whether TGs have a causal effect on hypertension remains uncertain, and evidence in East Asian populations is limited. Methods: We analyzed 2159 Korean adults (20–86 years) whose individual-level genetic and phenotypic data were obtained from a cross-sectional health check cohort. Candidate TG-associated genetic variants were identified using genome-wide association analysis and evaluated as instrumental variables (IVs). An individual-level, two-stage IV Mendelian randomization (MR) framework was applied to assess the potential effect of TGs on hypertension, alongside conventional observational analyses using logistic regression. Results: Three candidate TG-associated single-nucleotide polymorphisms (SNPs)—rs78115082 (TRPC7), rs117867615 (TTLL1), and rs34463296 (LINC03019)—were identified and combined to construct a weighted genetic risk score (GRS). Although all the instruments met the conventional strength criteria (F statistics > 10), they explained only a modest proportion of the Genes and species should be in italics, while proteins and enzymes are shown in normal format. Please check and keep them in correct format in the whole main text.variance in TG levels (partial R², 0.008–0.020). Observational analyses showed a strong positive association between TG levels and hypertension (crude odds ratio [OR] = 2.12; 95% confidence interval [CI]: 1.76–2.54; adjusted OR = 1.43; 95% CI: 1.16–1.75). In contrast, MR estimates based on individual SNPs and the GRS were directionally positive but statistically nonsignificant, with wide CIs crossing the null, indicating limited precision. Conclusions: In this Korean cohort, observational analyses demonstrated a robust association between TG levels and hypertension, whereas individual-level MR provided inconclusive genetic evidence for a causal effect under the available instruments. The difference between the observational and genetic estimates is compatible with the finding that TG levels reflect broader cardiometabolic dysregulation rather than acting as an isolated causal determinant of hypertension. These findings underscore the need for larger studies with stronger, externally derived instruments to refine the causal inference in East Asian populations. Full article

Candida albicans is an opportunistic fungus capable of forming biofilms that are resistant to conventional antifungal treatments. This study evaluated the antibiofilm activity of an ethanolic extract from Mexican oregano (Lippia graveolens Kunth) stem and its impact on the protein composition of the C. albicans cell wall (CW). The proteomic analysis was restricted to the adherent cells that persisted after treatment, representing the more tolerant subpopulation. First, the biofilm-forming capacity of 18 clinical isolates was characterized. Subsequently, the effect of the Lippia graveolens Kunth stem extract on biofilm formation was assessed in clinical isolates of C. albicans with high and moderate biofilm-forming capacities. The results showed an MIC₉₀ of 16 mg/mL against C. albicans isolates in planktonic growth. Furthermore, the extract exhibited an antibiofilm effect, showing a 77% inhibition in the highly biofilm-forming C. albicans 2400H strain at 1.6 mg/mL. To assess how the extract influences CW composition, we analyzed the CW proteome of the adherent biofilm cells of C. albicans that persisted after exposure to the stem extract. Mass spectrometry identified 1006 total proteins, where 156 were up-regulated, and 94 were down-regulated. Of the differentially expressed proteins, we identify 40 CW proteins (CWP’s) associated with dimorphic transition, adhesion, oxidative stress, and biofilm formation. These findings provide the potential of the L. graveolens Kunth stem as a natural antifungal agent against C. albicans biofilms. In addition, we identified CWP’s associated with tolerance to the extract’s antibiofilm activity, offering mechanistic insight into persistence and potential targets for improving antibiofilm interventions. Full article

Background: Carbapenem-resistant Gram-negative bacilli (CR-GNB) represent a critical threat to patients in intensive care units (ICUs), where limited therapeutic options contribute to elevated mortality. In Latin America and the Caribbean (LAC), the epidemiological burden of CR-GNB remains insufficiently characterized due to fragmented surveillance systems. This systematic review aimed to synthesize pooled prevalence estimates of CR-GNB among Gram-negative isolates recovered from ICUs across LAC countries. Methods: This systematic review was prospectively registered with PROSPERO (CRD420251177826), followed PRISMA 2020 guidelines and the JBI Manual for prevalence reviews. We searched PubMed, Scopus, LILACS, and SciELO from January 2015 to October 2025 without language restrictions. Observational studies reporting phenotypic carbapenem resistance data from ICUs in LAC countries were eligible. Two reviewers independently screened studies and extracted data. A two-level multilevel generalized linear mixed model (GLMM) with logit transformation was employed using a random-effects approach. Risk of bias was assessed using the JBI critical appraisal checklist. Results: Of 25 eligible studies spanning eight countries, 12 contributed 49 observations to quantitative synthesis. Overall pooled prevalence of CR-GNB was 28.88% (95% CI: 17.32–44.05%), with considerable heterogeneity (I² = 95.24%). Species-specific prevalence was highest for Acinetobacter baumannii (72.58%), followed by Klebsiella pneumoniae (37.48%) and Pseudomonas aeruginosa (29.93%). Regional stratification revealed higher prevalence in South America (31.81%) compared to North America (22.65%) and the Caribbean (11.63%). Conclusions: Nearly one-third of Gram-negative isolates from LAC ICUs exhibit carbapenem resistance, with A. baumannii predominating. Substantial inter-study heterogeneity underscores the need for standardized regional surveillance networks and coordinated antimicrobial stewardship initiatives. Full article

The S-100 standard for Electronic Chart Display and Information Systems (ECDIS) uses Lua scripts to render electronic charts, yet lacks security specifications for script execution. This paper evaluates automated Static Application Security Testing (SAST) tools versus expert manual review for S-100-compliant software. Four SAST tools were applied alongside an expert review of OpenS100, a reference implementation for next-generation ECDIS. While automated tools identified numerous defects, they failed to detect 83% (19/23) of expert-identified vulnerabilities, including an unrestricted Lua interpreter flaw with a Common Vulnerability Scoring System (CVSS) score of 9.3. This vulnerability enables Remote Code Execution (RCE) via malicious portrayal catalogues, verified through Proof of Concept (PoC) development. The analysis demonstrates that SAST tools are constrained by limited maritime domain knowledge and challenges in analyzing cross-language semantic risks at the C++–Lua interface. The findings establish that identified vulnerabilities stem from specification gaps in the S-100 standard rather than isolated coding errors. These results indicate that functional safety certifications require supplementation to address design-level security risks. The evidence supports that the International Hydrographic Organization (IHO) incorporate security controls, such as script sandboxing and library restrictions, into the S-100 framework before the 2029 mandatory adoption deadline. Full article

Background: Klebsiella pneumoniae is a World Health Organization-listed critical priority pathogen and a major cause of healthcare-associated infections, driven by the global emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) lineages and their alarming convergence with hypervirulence. Methods: In this study, 152 clinical specimens, including urine, blood, pus, wound swabs, and respiratory samples, were collected from tertiary care hospitals in Peshawar, Pakistan. Standard microbiological and biochemical methods identified 55 K. pneumoniae isolates. Antimicrobial susceptibility testing (AST) was performed using the Kirby–Bauer disk diffusion and broth microdilution methods, with results interpreted according to Clinical and Laboratory Standards Institute (CLSI) guidelines. MDR and XDR phenotypes were defined based on European Centre for Disease Prevention and Control (ECDC) criteria. Whole-genome sequencing (WGS) was conducted on 16 phenotypically confirmed MDR/XDR isolates, followed by comprehensive bioinformatic analyses to characterize sequence types (STs), acquired antimicrobial resistance genes, resistance-associated chromosomal mutations, virulence determinants, plasmid replicons, and phylogenetic relationships. Results: Among 55 confirmed K. pneumoniae isolates, 19 (34.5%) were classified as MDR and 10 (18.2%) as XDR. WGS revealed substantial genomic heterogeneity, identifying 11 distinct STs, with ST39 being the most prevalent. Resistance to multiple antibiotic classes was mediated by the combined presence of plasmid-borne carbapenemases and extended-spectrum β-lactamases, alongside chromosomal mutations affecting outer membrane porins (OmpK35/OmpK36), fluoroquinolone targets (gyrA/parC), efflux regulation (ramR, marR), and lipid A modification pathways associated with colistin resistance (mgrB, pmrA/pmrB, arnC, crrB). IncF-family plasmids predominated and frequently co-occurred with additional resistance-associated replicons. Notably, one isolate exhibited an expanded virulence gene repertoire, including multiple siderophore systems and a complete type II secretion system, consistent with a hypervirulence-associated genomic profile. Phylogenetic analyses demonstrated close relatedness to international lineages from Asia, the Middle East, and Europe, indicating regional and transnational dissemination. Conclusions: This study highlights the complex interplay between plasmid-mediated gene acquisition and chromosomal adaptive mutations driving MDR and XDR phenotypes in K. pneumoniae circulating in Peshawar, Pakistan. The identification of hypervirulence-associated genetic features within an MDR background underscores the growing threat posed by convergent lineages and emphasizes the need for sustained WGS-based surveillance to inform infection control and antimicrobial stewardship strategies. Full article