Search Results (4,405)

Osteocalcin (OCN) is increasingly recognized as a multifunctional hormone whose actions extend far beyond its traditional role as a marker of bone turnover. This review provides an integrated examination of the molecular, endocrine, and translational dimensions of osteocalcin biology, with emphasis on its bioactive undercarboxylated form (ucOCN), which links skeletal remodeling to systemic physiological processes. The structural determinants, biosynthetic pathways, and vitamin K-dependent carboxylation mechanisms underlying OCN isoform diversity are summarized, together with analytical limitations arising from assay variability and differences between N-MID and ucOCN-specific measurements. Mechanistic evidence demonstrates that ucOCN signals through GPRC6A and GPR158 to modulate insulin secretion, muscle glucose uptake, adipokine production, testosterone synthesis, neurocognitive function, hepatic lipid metabolism, and acute stress response. These receptor-level pathways position osteocalcin as a central regulator at the intersection of bone metabolism and whole-body homeostasis. The review synthesizes data across major clinical contexts, including metabolic syndrome, type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease–mineral and bone disorder (CKD-MBD), cardiovascular dysfunction, and neurodegeneration, highlighting the modifying influence of vitamin K status, circadian rhythms, renal clearance, and local tissue microenvironments. The need for biomarker standardization, methodological harmonization, and receptor-targeted translational strategies is emphasized, alongside emerging therapeutic concepts involving vitamin K supplementation and exercise-induced activation of OCN. Collectively, the evidence reframes osteocalcin as a versatile endocrine mediator at the interface of bone physiology, systemic metabolic regulation, and disease mechanisms. Full article

Background: Thrombosis in light chain amyloidosis (LCA) occurs in the context of multiple organ dysfunction and inflammation. Conventional coagulation tests (screening) may not sufficiently capture the procoagulant substrate in the inflammatory/therapeutic dynamics. Methods: A total of 61 consecutive patients with LCA were prospectively included in the study. Clinical data, including organ involvement, time of diagnosis, treatment phase, DOAC exposure and thrombosis history were systematically recorded and subjected to screening. Specialized hemostasis tests such as APTT/PT, fibrinogen, D-dimer, TEG and TGT were performed and conventional times were analyzed in the subgroup without DOAC. Results: The prevalence of documented thrombosis was 32.8%, and thrombosis status was associated with TEG positivity and more strongly with TGT positivity. Hypercoagulability was identified in 50.8% by TEG and 41.0% by TGT, regardless of whether APTT/PT were within the reference values. APTT/PT did not predict thrombosis recurrence (p > 0.05), which was predicted by TEG (p = 0.0027) and TGT (p = 0.0006). An inflammation/fibrin turnover panel (CRP, fibrinogen, D-dimer) predicted TEG positivity (p < 0.0001), but not TGT, and was correlated with assessment at diagnosis, daratumumab-based therapy, and cardiac involvement. Conclusions: Global tests (TEG/TGT) promptly correlate with thrombosis recurrence in our cohort and provide crucial information in addition to clotting times for thrombotic phenotyping. Inflammation can influence TEG, so the decision to recommend the tests and the timing of their performance should be adapted to the clinical, biological, and therapeutic context. Full article

WRKY is a crucial transcription factor involved in plant growth, development, and responses to abiotic stress. In the present study, a total of 182 AaWRKY transcription factor members were identified across the Artemisia argyi genome and found to be distributed across 17 chromosomes. Evolutionary analysis revealed that segmental duplication served as the primary driver for family expansion, with the evolutionary trajectory shaped by strong purifying selection (Ka/Ks < 1.0). Phylogenetic classification categorized these members into seven highly conserved subgroups, while physicochemical analysis indicated that most AaWRKYs are unstable, hydrophilic proteins, consistent with the rapid turnover required for transcriptional switches. Transcriptomic profiling unveiled significant tissue-specific expression patterns, with over 50% of the members predominantly enriched in roots and specific genes, such as AaWRKY11, implicated in the regulation of leaf senescence. Protein–protein interaction (PPI) network analysis identified AaWRKY110 as a central regulatory hub linking the MAPK signaling pathway with the isoflavonoid biosynthetic machinery. Furthermore, comparative transcriptomic analysis between aphid-resistant (Ai20K) and susceptible (Ai72G) cultivars demonstrated that resistance is conferred by a priming mechanism involving high basal expression of key candidates, including AaWRKY82, 108, 128, and 71. In contrast, the susceptible genotype exhibited a delayed and ineffective hypersensitive-like response. Collectively, these findings elucidate the evolutionary dynamics of the AaWRKY family and provide critical genetic targets for the concurrent improvement of medicinal metabolite accumulation and biotic stress resilience in Artemisia argyi via molecular breeding. Full article

Background: Epithelial-to-mesenchymal transition (EMT) is a cellular reprogramming process characterized by coordinated changes in signaling, membrane organization and metabolism. In a previously established and deeply characterized Huh7 EMT model, it was demonstrated that TGF-β stimulation induces a reproducible shift toward a mesenchymal state accompanied by lipidomic and metabolic remodeling. Building on this framework, the present study evaluates whether extracellular vesicles (EVs)-enriched fractions derived from Capparis spinosa can modulate these EMT-associated alterations. Methods: After detailed physicochemical, molecular, lipidomic and metabolomic characterization, C. spinosa EVs were applied to EMT-induced Huh7 cells. The vesicles were efficiently internalized and, while not inducing a complete epithelial reversion, they attenuated mesenchymal features, indicating a modulatory rather than inhibitory action. Results: Lipidomic profiling showed a partial correction of TGF-β-induced changes including diacylglycerols, phosphoinositides and triglycerides, suggesting interference with lipid signaling and membrane turnover. Metabolomic data further points to reduced mitochondrial and fatty acid oxidation stress, reflected in the re-equilibration of carnitine and acylcarnitine species. Conclusions: Together, these findings indicate that C. spinosa EVs are able to attenuate EMT-associated metabolic and membrane remodeling, positioning them as promising modulators of tumor cell plasticity. Full article

This paper develops an evaluation of profitability for firms in Greece and Cyprus from 2005 to 2020. More specifically, it contains an investigation of comparative relevance and dominance of accounting versus non-financial variables, which affect the daily operations of firms, on the firms’ level of profitability. Moreover, this research examines the impact of corruption, unemployment, part-time employment and Research and Development (R&D) on the performance of companies, in order to help managers by giving them more information and assisting in long-term strategic planning. The results indicate that these variables do not have a large effect on the firm-level profitability of these two countries, which is largely influenced by profit margin and other interaction variables, such as profit margin on asset turnover ratio and equity multiplier. The findings underline that internal operational efficiency acts as the primary driver of short-term profitability, whereas macro-level indicators display weaker immediate associations. However, managing these structural elements remains strategically relevant for long-term springiness. Full article

Background/Objectives: Nurses’ turnover intentions are strong predictors of actual turnover, which increases costs, reduces care quality, and destabilies the workforce. This study aimed to identify the key predictors of nurses’ turnover intentions using advanced machine learning methods and to explore how demographic, well-being, and work environment factors contribute to these intentions. Methods: Cross-sectional data were collected from 2459 nurses employed across various healthcare institutions. We used multichannel invitation and snowball sampling. An artificial neural network regression model was applied, combined with iterative feature selection and SHAP analysis, to identify the most important predictors of turnover intentions and to examine nonlinear and context-dependent relationships among variables. Results: Seven predictors explained 49.8% of the variance in turnover intentions, outperforming traditional linear models. Age was the strongest predictor, with younger nurses demonstrating a substantially higher likelihood of intending to leave; this association was nonlinear, with intentions decreasing more sharply at older ages. Job satisfaction and burnout were also strong predictors, particularly among younger nurses. Four work environment factors further contributed to turnover intentions: managerial support functioned as a protective factor, interpersonal conflict increased intentions to leave, limited professional development opportunities were strongly associated with higher turnover intentions, and role conflict showed heterogeneous effects. Conclusions: Machine learning approaches enhance understanding of complex workforce dynamics and enable more precise identification of high-risk groups. The findings support age-sensitive retention strategies, proactive monitoring of nurse well-being, and organizational interventions to strengthen managerial support and professional development, ensuring workforce stability and sustainable healthcare service delivery. Full article

Taste dysfunction, or dysgeusia, is a frequent symptom associated with infections and systemic diseases, yet its cellular and molecular basis remains poorly understood. The COVID-19 pandemic provided an opportunity to study dysgeusia as a “natural experiment” due to its high prevalence in those with acute and long COVID (LC). We investigated salivary epithelial cells (SECs) using single-cell RNA sequencing to elucidate molecular changes underlying taste dysfunction in LC. Functional enrichment analysis of SEC transcriptomes from individuals with bitter taste dysfunction (LC-D) revealed downregulation of genes involved in cytoskeletal dynamics and taste cell–nerve synapse assembly. Further, specific Type II and III taste receptor genes, critical for bitter taste perception, were reduced. Microbial defense markers such as Toll-like receptors TLR2 and TLR4 were also downregulated, suggesting chronic inflammation. These findings support a model of sustained dysregulated epithelial turnover due to impaired taste in LC-D. Saliva-based single-cell approaches offer promising tools for future diagnostics and mechanistic studies of taste systems. Full article

Sex determination in teleost fishes exhibits remarkable evolutionary plasticity; however, the underlying mechanisms remain largely elusive for many species of high economic importance. Herein, we provide the first genome-wide investigation of the genetic basis of sex determination in the European anchovy (Engraulis encrasicolus), an ecologically and commercially vital clupeiform fish. Using low-pass whole-genome resequencing of 100 sexually mature individuals (50 females and 50 males), we conducted a genome-wide association study (GWAS) and F_ST scans to identify sex-linked loci and characterize sex-determining regions (SDRs). Our analyses revealed two major candidate SDRs located on chromosomes 14 and 18, encompassing multiple sex-associated single-nucleotide polymorphisms (SNPs) and insertions/deletions (InDels). Among these, the amhr2 (anti-Müllerian hormone type 2 receptor) gene on Chr14 displayed the strongest and most consistent association with phenotypic sex, marked by several male-specific missense SNPs and InDel variants. Comparative and transcriptomic analyses confirmed sex-biased expression of amhr2 and other SDR-linked genes, potentially indicating a male heterogametic (XY-like) genetic sex determination system. These results provide the first molecular evidence for a candidate SDR in E. encrasicolus, raise the possibility of involvement of amhr2 and additional loci in sex determination, and highlight rapid sex chromosome turnover within Clupeiformes. Our findings not only expand the understanding of teleost sex determination evolution but also establish a genomic foundation for developing molecular tools for sex identification and population management in anchovy fisheries. Full article

Coprophagous flies can convert livestock manure into protein-rich larval biomass for animal feed, but manure-based rearing raises biosafety concerns. This study characterized the internal bacterial community dynamics across development in Aldrichina grahami and Boettcherisca peregrina reared on swine manure, aiming to identify developmental stages with a lower microbial hazard profile. Using 16S rRNA gene amplicon sequencing of pooled internal samples, we analyzed communities from third-instar larvae, dispersing-stage larvae, pupae at multiple time points, and newly emerged adults. Developmental stage strongly structured bacterial composition and altered richness in both species. Communities were dominated by Bacillota and Pseudomonadota, reflecting substrate origin, with pronounced turnover during metamorphosis and stage-specific dominance patterns, indicating developmental filtering rather than uniform microbial clearance. Crucially, dispersing larvae did not show the marked dominance signatures seen in later pupal or adult stages, supporting this stage as a pragmatic harvest window with a comparatively lower microbial-hazard indicator profile. Since downstream processing such as drying or heating will further reduce viable hazards, stage selection serves as an effective upstream control to lower the initial hazard burden entering production. Full article

Background and Objectives: Bone fragility in people living with HIV (PLWH) reflects both reduced bone mineral density (BMD) and impaired microarchitecture, while functional decline may further amplify fracture vulnerability. This study evaluated whether adding a pragmatic sarcopenia screen improves bone fragility characterization beyond DXA-BMD, trabecular bone score (TBS), calcaneal quantitative ultrasound (QUS), and biomarkers, and explored the relationship between tenofovir disoproxil fumarate (TDF) exposure and microarchitectural impairment. Materials and Methods: In this single-center cross-sectional study at Victor Babeș University of Medicine and Pharmacy Timișoara, 98 adults on stable ART underwent DXA (T-scores), lumbar TBS (reported as TBS × 100), calcaneal QUS (SOS/BUA), and bone turnover markers (CTX, P1NP, 25(OH)D). Sarcopenia screening used handgrip strength and 4 m gait speed. Associations were tested using group comparisons, correlations, and multivariable modeling for degraded TBS (TBS × 100 < 124.0). Results: Sarcopenia screen-positive participants (n = 28) had lower TBS (123.8 vs. 127.7, p = 0.02), lower lumbar T-score (−1.7 vs. −1.2, p = 0.014), lower SOS (1523.3 vs. 1548.8 m/s, p = 0.002), and higher CTX (0.6 vs. 0.4 ng/mL, p < 0.001), with less frequent viral suppression (60.7% vs. 85.7%, p = 0.006). With >5 years TDF exposure (n = 28), degraded TBS prevalence was 82.1% vs. 40.0% in never-exposed (p = 0.001), alongside lower TBS (123.1 vs. 129.8, p < 0.001) and higher CTX (0.6 vs. 0.4 ng/mL, p < 0.001). Viral suppression independently reduced odds of degraded TBS (aOR 0.3, 95% CI 0.1–0.9; p = 0.034). Conclusions: In PLWH, prolonged TDF exposure and functional impairment co-occur with worse densitometric and microarchitectural profiles; viral suppression shows an independent protective association with microarchitecture. Full article

Background: Congested tournament schedules impose substantial physiological stress in team sports; however, the integrated endocrine and inflammatory responses to real competitive match load in female handball players remain insufficiently characterized. Objective: This study aimed to characterize the acute biochemical responses, including hormonal, inflammatory, muscle damage, and bone metabolism markers, elicited by competitive tournament load in female handball players and to provide practical insights for optimizing recovery strategies and load management during short-term competitive periods. Methods: In a pre–post study design, venous blood samples were collected from competitive female athletes (n = 8; age 20.83 ± 2.93 years) before the first match and after the fourth consecutive match of an official university qualification tournament. Biochemical analyses included cortisol, insulin, IL-6, creatine kinase (CK), IGF-1, irisin, lactate dehydrogenase (LDH), osteocalcin, and testosterone. Pre-to-post changes were assessed using paired t-tests and effect sizes. Results: Tournament load induced substantial multisystem physiological perturbations. Significant increases were observed in cortisol (p < 0.001), insulin (p = 0.044), IL-6 (p < 0.001), CK (p < 0.001), and osteocalcin (p = 0.005), indicating activation of the hypothalamic–pituitary–adrenal axis, systemic inflammation, muscle membrane disruption, and enhanced bone turnover. Conversely, IGF-1 (p < 0.001) and testosterone (p = 0.004) significantly decreased, reflecting suppression of anabolic signaling and a shift toward a catabolic hormonal environment under cumulative match stress. LDH significantly decreased (p = 0.002), while irisin showed no significant change (p > 0.05). Conclusions: These findings demonstrate that congested tournament schedules provoke an integrated endocrine–inflammatory stress response in female handball players. Importantly, the observed anabolic–catabolic imbalance highlights the need for individualized recovery strategies, optimized load management, and adequate recovery periods to mitigate maladaptation and reduce injury risk during short-term competitive tournaments. Full article

The commercialization of V-based catalysts for the selective catalytic reduction of NOx by NH₃ (NH₃-SCR) is hindered by their narrow operating temperature window, insufficient low-temperature (LT) activity, and severe SO₂-to-SO₃ oxidation. To bridge this gap, we herein introduced Nb and hexagonal BN into a VW/TiO₂ system to simultaneously enhance its LT SCR activity, suppress undesired side reactions, and improve durability. Nb incorporation promoted V⁵⁺/V⁴⁺ redox cycling and enhanced lattice oxygen mobility, thus reducing the apparent activation energy and suppressing SO₂ oxidation at elevated temperatures. However, excessive Nb loading induced NH₃ oxidation and N₂O formation. This drawback was mitigated by introducing BN as a dispersion promoter, which helped secure high catalytic performance at a reduced Nb content. The VWNb/Ti-BN catalyst achieved superior NOx conversion and N₂ selectivity over a wide temperature range and benefited from notably suppressed NH₃ oxidation and SO₂-to-SO₃ oxidation. Kinetic analysis revealed that Nb primarily lowered the reaction energy barrier via redox property enhancement, whereas BN accelerated surface reaction turnover by stabilizing and dispersing active acidic sites, markedly increasing the turnover frequency without reducing the activation energy. In situ spectroscopic analysis confirmed the accelerated consumption of adsorbed NH₃ species and enhanced formation of reactive NOx intermediates, indicating SCR pathway enhancement. After aging in the presence of SO₂ and H₂O, the best-performing honeycomb-type monolithic catalyst retained and NOx conversion of >80%, demonstrating excellent long-term durability under practical conditions. A composition-aware machine learning model based on log-ratio-transformed variables quantitatively identified the synergistic balance among V, Nb, W, BN, and TiO₂ as the dominant factor governing LT SCR performance. Thus, this work provides valuable mechanistic insights and a strategy for designing wide-temperature-window SCR catalysts with improved activity, selectivity, and resistance to sulfur poisoning. Full article

Elevation is a strong proxy for the thermal environment because it causes a predictable drop in temperature and food availability. This restricts cave-dwelling bats to species with specific metabolic traits, such as torpor or migration to avoid cold stress. In this context, we aimed to reveal how thermal niche differentiation structures 25 cave-dwelling bat assemblages along elevation gradients in two of the largest Bulgarian mountains—Stara Planina and Rhodopi. Multivariate PERMANOVA showed significant differences in bat assemblages among elevation groups (F = 1.616, p = 0.046), with altitude and temperature explaining 32.4% of the variance (p = 0.001). A high degree of species turnover (91.12% dissimilarity), driven by temperature niches, was observed: mesophilic Rhinolophus species dominated warm, low-elevation caves, while cold-adapted Myotis species were more common at high elevations. SIMPER analysis identified R. euryale as an indicator in low-elevation caves (p = 0.012) and the M. myotis/blythii complex at high elevations (p = 0.003). Alpha diversity showed no variation across elevation groups (p = 0.293), indicating that species turnover occurs without overall changes to local diversity. Mid-elevation assemblages lacked specific indicator species and resembled high-elevation communities, forming an ecotone. Thermal niche partitioning, as a physiological filter, shapes cave-dwelling bat assemblages and affects climate change range-shift predictions. Full article

Digital transformation is embedding carbon metrics into construction project management through automated procurement and sustainability dashboards. Yet carbon intensity measures depend critically on how emissions are normalized, creating ambiguity in sustainability assessment. This study examines how alternative carbon intensity scaling choices affect firm rankings and portfolio outcomes within the Construction & Engineering industry. Using carbon-efficient indices for publicly traded U.S. construction firms, emissions are normalized by revenues, costs, assets, market value, enterprise value, and employment. Alternative normalization choices lead to systematic within-industry reshuffling of firm rankings driven by differences in economic fundamentals. While average financial performance does not differ systematically across metrics, portfolio turnover and financed emissions vary substantially. These results show that normalization design is a consequential element of digital sustainability systems rather than a neutral technical choice. The study provides industry-specific evidence on measurement-induced reshuffling and highlights practical implications for contractor benchmarking and digital construction governance. Full article

Circulation of pool water via a treatment plant is critical for maintaining pool water in a condition that is a safe and attractive for bathers. It is also one of the pool operations that is most costly in terms of energy used and associated carbon footprint. In this study, we compare and contrast circulation rate guidelines developed for the UK and for other northern and southern European countries and, where possible, provide an explanation of the underlying rationale. We focus on the management of turbidity-forming material and Cryptosporidium oocysts. We reveal that the parameters used to assess safe operational bathing load are relatively consistent across Europe, based on physical space requirements for bathing and other constraints such as lifeguarding. Circulation rate, on the other hand, is based on either rule-based turnover times, or a more flexible approach based on the volume of water to be treated per bather. The latter offers scope for innovation and energy savings, with the proviso that safe water is maintained for bathers. The guidance in several countries suggests reducing circulation rate when the pool is not being used by bathers. We conclude that a more progressive risk-based approach to pool management, building on these findings, offers significant opportunities for pool operators to run pools better and should be a priority for future research. Full article