Search Results (15,733)

This study examines the extent to which smart cities are expressions of nationally homogeneous development trends by way of an analysis of their structural characteristics from a multivariate viewpoint. Drawing on data from the International Institute for Management Development IMD Smart City Index 2024, we find a sample of 102 cities across the world clustering along six key dimensions of smartness: mobility, environment, government, economy, people, and living. The aim is to examine if cities within a country have similar profiles and, if so, to what degree such similarity translates to other macro-level institutional, political, and cultural conditions. Our results verify a tight correspondence between city profiles and national contexts, implying that macro-level governance arrangements, policy coordination, and institutional capacity are pivotal in influencing local smart city development. Planned centralised countries possess more uniform city characteristics, while decentralised nations possess more variant urban policies. This study contributes to international debate regarding smart cities by empirically identifying national directions of urban innovation. It offers pragmatic inputs for policymakers that aim to align local efforts with overall sustainable development agendas. Moreover, this study introduces a novel application of Linear Discriminant Analysis (LDA) to classify smart city profiles based on national models. While the analysis yields high classification accuracy, it is important to note that the sample is skewed toward cities from the Global North, potentially limiting the generalisability of the results. Full article

Ankylosing spondylitis (AS) displays wide inter-patient variability that is not accounted for by HLA-B27 alone, suggesting that additional immune and metabolic modifiers contribute to disease severity. Using a genetically matched design, we profiled peripheral blood mononuclear cells from two brother pairs discordant for AS severity and one healthy brother pair. Strand-specific RNA-seq was analyzed with a family-blocked DESeq2 model, while untargeted metabolites were quantified using gas chromatography–mass spectrometry (GC-MS) and liquid chromatography–mass spectrometry (LC-MS). Differential features were defined as follows: differentially expressed genes (DEGs) (|log₂FC| ≥ 1 and FDR < 0.05) and metabolites (VIP > 1, FC ≥ 1.2, and BH-adjusted p < 0.05). Pathway enrichment was performed with KEGG and Gene Ontology (GO). A total of 325 genes were differentially expressed. Type I interferon and neutrophil granule transcripts (e.g., IFI44L, ISG15, S100A8/A9) were markedly up-regulated, whereas mitochondrial β-oxidation genes (ACADM, CPT1A, ACOT12) were repressed. Metabolomics revealed 110 discriminant features, including 25 MS/MS-annotated metabolites. Primary bile acid intermediates were depleted, whereas oxidized fatty acid derivatives such as 12-Z-octadecadienal and palmitic amide accumulated. Spearman correlation identified two antagonistic modules (i) interferon/neutrophil genes linked to pro-oxidative lipids and (ii) lipid catabolism genes linked to bile acid species that persisted when severe and mild siblings were compared directly. Enrichment mapping associated these modules with viral defense, neutrophil degranulation, fatty acid β-oxidation, and bile acid biosynthesis pathways. This sibling-paired peripheral blood mononuclear cell (PBMC) dual-omics study delineates an interferon-driven lipid–bile acid axis that tracks AS severity, supporting composite PBMC-based biomarkers for future prospective validation and highlighting mitochondrial lipid clearance and bile acid homeostasis as potential therapeutic targets. Full article

The TIFY gene family participates in crucial processes including plant development, stress adaptation, and hormonal signaling cascades. While the TIFY gene family has been extensively characterized in model plant systems and agricultural crops, its functional role in Eucalyptus grandis, a commercially valuable tree species of significant ecological and economic importance, remains largely unexplored. In the present investigation, systematic identification and characterization of the TIFY gene family were performed in E. grandis using a combination of genome-wide bioinformatics approaches and RNA-seq-based expression profiling. Nineteen EgTIFY genes were identified in total and further grouped into four distinct subfamilies, TIFY, JAZ (subdivided into JAZ I and JAZ II), PPD, and ZML, based on phylogenetic relationships. These genes exhibited considerable variation in gene structure, chromosomal localization, and evolutionary divergence. Promoter analysis identified a multitude of cis-acting motifs involved in mediating hormone responsiveness and regulating abiotic stress responses. Transcriptomic profiling indicated that EgJAZ9 was strongly upregulated under methyl jasmonate (JA) treatment, suggesting its involvement in JA signaling pathways. Taken together, these results offer valuable perspectives on the evolutionary traits and putative functional roles of EgTIFY genes. Full article

Understanding the genetic basis of high-performance animals is vital for biological insight and breeding. This study aimed to identify genetic factors distinguishing champion gamecocks (Gallus gallus domesticus) from less successful ones, representing the first study to link transcriptomic profiles directly to competitive outcomes. Using RNA sequencing on non-invasive feather samples, we compared gene expression between high-performing (≥80% win rate) and low-performing (≤20% win rate) cohorts. Our analysis identified 441 differentially expressed genes. Notably, the high-performing cocks exhibited the significant upregulation of genes integral to muscle development and repair (e.g., SYNPO2, POPDC2) and enhanced neural function (NRN1). Conversely, several genes involved in neural development pathways, including CNTNAP2 and GFRA4, were significantly downregulated in the high-performing group. These findings suggest that a rooster’s competitive success is not determined by a single factor, but by a complex interplay of superior muscular capabilities and uniquely regulated neurological pathways. The identified genes provide a set of potential biomarkers that could inform selective breeding strategies aimed at enhancing performance traits in gamecocks. Full article

The impact of burdock tea (BT) made from burdock (Arctium lappa) roots in normal individuals and animal models remains largely unknown, particularly on lung protection. This study examined responses of oxidative stress, inflammation, and the microbiota within the cecum and the lung to BT treatment in healthy Wistar rats. A middle-dose BT reduced the Chao1 and Shannon indices, and both low and middle doses induced structural alterations in the cecal microbiota. Additionally, low doses increased the abundances of Phascolarctobacterium, Alloprevotella, Desulfovibrio, and the NK4A214 group. In the lung, middle and high doses increased Corynebacterium, with high doses also boosting Megasphaera and Lactobacillus. Functionally, low doses downregulated the biosynthesis of antibiotics in the cecal microbiota, while middle doses reduced the Epstein–Barr virus and Escherichia coli pathogenic infection pathways; additionally, middle and high doses modulated chromosomal proteins and bile acid biosynthesis in the pulmonary microbiota. BT treatment enhanced the content of short-chain fatty acids (SCFAs), upregulated the expression of GPR43, and suppressed NLRP3 expression in both the colon and lung tissues, while concurrently promoting the expression of ZO-1 and Occludin. Furthermore, serum levels of IL-1β and IL-6, as well as tissue levels of MDA, were significantly reduced. Notably, propionate exhibited an inverse correlation with MDA, IL-6, and NLRP3, while showing a positive correlation with ZO-1. Similarly, acetate was negatively correlated with MDA and NLRP3 and positively correlated with ZO-1. Overall, BT exhibits a nontoxic profile and may protect lung tissue through its antioxidant nature and gut–lung axis mediated by SCFAs. Full article

The peach landrace ‘Liuyefeitao’ exhibits the unique reproductive trait of self-compatibility combined with cross-incompatibility, contrasting with typical Prunus species in this way. In preliminary studies involving controlled pollination assays, we showed complete pollen tube arrest in cross-pollinated styles, whereas self-pollination enabled full tube elongation. S-genotyping identified a homozygous S₂S₂ genotype with intact S₂-RNase but a truncated PpSFB2 due to a frameshift mutation. Transcriptome profiling of the styles revealed 7937 differentially expressed genes (DEGs) between self- and cross-pollination treatments, with significant enrichment in plant MAPK signaling, plant–pathogen interactions, and plant hormone signaling transduction pathways (|Fold Change| ≥ 2, FDR < 0.01). Notably, PpSLFL3 (a pollen F-box gene) showed down-regulation in cross-pollinated styles, as validated by means of qRT-PCR. Protein interaction assays revealed direct binding between PpSLFL3 and S₂-RNase via Y2H and BiFC analysis, suggesting its role in mediating SCF complex-dependent degradation. We propose that insufficient PpSLFL3 expression during cross-pollination disrupts SCF ubiquitin ligase complex-mediated degradation of non-self S₂-RNase, leading to the toxic degradation of RNA in pollen tubes by S₂-RNase. This mechanism is mechanistically similar to unilateral reproductive barriers in Solanaceae but represents a novel regulatory module in Rosaceae. Our findings provide critical insights into the evolution of cross-incompatibility systems and molecular breeding strategies for Prunus species. Full article

Background/Objectives: Dyslipidemia is a prevalent metabolic disorder closely linked to cardiovascular complications and muscular pathologies, often managed using statins such as simvastatin. However, statin-induced myopathy remains a significant treatment-limiting side effect, necessitating the exploration of safe, natural alternatives. Spirulina platensis, a phytochemical-rich marine-derived cyanobacterium, has emerged as a promising bioactive nutraceutical with potent antioxidant and anti-inflammatory properties. This study evaluated the comparative effects of Spirulina platensis and simvastatin in attenuating dyslipidemia-induced skeletal muscle injury in adult male albino rats. Methods: Forty animals were allocated to the control and high-fat diet (HFD) groups. After 4 weeks, the dyslipidemic rats were subdivided into untreated, simvastatin-treated, and Spirulina platensis-treated subgroups. Serum lipid profile, creatine kinase (CK), and malondialdehyde (MDA) levels were assessed. Histological, ultrastructural, and immunohistochemical analyses were conducted to assess muscle fiber integrity and expression of TGF-β1 and Bcl2. Results: Spirulina platensis significantly improved lipid parameters, reduced CK and MDA levels, preserved muscle histoarchitecture, and downregulated fibrotic (↓TGF-β1) and apoptotic (↑Bcl2) responses compared to the dyslipidemic and simvastatin-treated groups. Our results proved that Spirulina platensis ameliorates the effects of statin-associated myopathy while exerting lipid-lowering, cytoprotective, and antifibrotic effects. Conclusion: These molecular and ultrastructural benefits position Spirulina platensis as a promising, natural alternative to statins for managing dyslipidemia and preventing statin-induced myopathy. Future translational and clinical studies are warranted to further validate its efficacy and safety, supporting its broader application in metabolic and muscle-related disorders. Full article

Background: Magnetically controlled capsule endoscopy (MCCE) has shown promise in upper gastrointestinal evaluation and is a potentially less invasive alternative to esophagogastroduodenoscopy (EGD). We performed a systematic review and meta-analysis aiming to measure its diagnostic performance compared to EGD for esophageal varices. Methods: Our protocol was registered on PROSPERO (CRD420251081967). A systematic search of multiple databases was conducted through July 2025 for studies assessing the diagnostic performance of MCCE compared to EGD for EV. The primary outcomes were sensitivity and specificity. Secondary outcomes included the area under the curve (AUC), likelihood ratios, diagnostic odds ratio, and safety. Pooled effect estimates were calculated using a random effects model and expressed as proportions with 95% confidence intervals (CI). Heterogeneity was assessed using the I² statistic. Results: Five prospective studies with 795 patients (68.8% male, mean age of 55.1) were included. The pooled sensitivity and specificity were 87.1% (95% CI: 68.5–95.4) and 95.2% (95% CI: 88.4–98.1), respectively, with an AUC of 0.97. Following subgroup analysis of cirrhotic patients, pooled sensitivity and specificity were 96.0% (95% CI: 93.6–97.5; I² = 43%) and 95.2% (95% CI: 84.2–98.6; I² = 88.4%), respectively. Furthermore, MCCE use with detachable strings increased sensitivity to 96% (95% CI: 93.7–97.5; I² = 0%) and specificity to 96.3% (95% CI: 87.2–99.0; I² = 76.8%). Only four adverse events occurred across the five studies. Conclusions: Our meta-analysis demonstrated the high sensitivity, specificity, and diagnostic accuracy of MCCE, along with a favorable safety profile. Further large-scale trials are needed to validate our findings. Full article

Proinflammatory cytokines such as IL-1β, IL-6, and TNF-α are key mediators of inflammatory bone loss and are commonly described as inhibitors of osteoblast function. However, their effects on osteogenesis remain controversial, likely due to the differences in the cell models and experimental settings in in vitro studies. We recently showed that these cytokines significantly enhanced the mineralization of primary human osteoblast-like cells (OBs). Here, we provide the first analysis of cytokine effects on the osteogenesis of the widely used human osteoblastic cell line hFOB 1.19 and compare them to primary OBs. Unexpectedly, all three cytokines significantly inhibited mineralization in hFOB 1.19 cells without affecting the proliferation. IL-1β and TNF-α also suppressed ALP activity, whereas IL-6 acted ALP-independent but increased the osteogenic marker expression despite the reduced mineralization, indicating a possible uncoupled differentiation and mineralization. Morphological and transcriptional analyses indicated that hFOB 1.19 cells represent an earlier osteogenic differentiation stage, while primary OBs show phenotypic heterogeneity and donor-dependent expression profiles. These data demonstrate that proinflammatory cytokines can have severely different effects on the osteogenesis of different cell models, supported by the highly contradictory findings reported in the literature. Nevertheless, elucidating the mechanisms underlying the inhibition of osteogenesis in hFOB 1.19 cells may provide important insights into the cell model and differentiation-stage-specific cytokine effects. Full article

Steroid hormones play critical roles in the development and progression of NSCLC through both genomic and non-genomic pathways. This review summarizes the expression profiles and molecular functions of estrogen, progesterone, androgen, and glucocorticoid receptors in NSCLC. Estrogen and progesterone receptors exhibit gender-specific prognostic significance, while glucocorticoid receptors influence tumor growth and immune responses. Emerging evidence supports the use of anti-estrogen therapies and glucocorticoids as adjuncts to existing treatment strategies, including immunotherapy. The crosstalk between hormone signaling and oncogenic pathways such as EGFR or immune checkpoints offers opportunities for novel combination therapies. However, challenges remain in biomarker development, drug resistance, and managing the dual effects of glucocorticoids. A deeper understanding of hormone–tumor–immune interactions is essential to optimize hormone-targeted interventions in NSCLC. Full article

Previous studies have demonstrated that Helianthus tuberosus L. polysaccharide (HTLP) exhibits potent immunomodulating activity. The aim of this study was to investigate the molecular mechanisms underlying this activity and explore its potential applications in various anti-inflammatory models. We examined the anti-inflammatory potential of HTLP using in vitro and in vivo models. In vitro, we assessed the impact of HTLP on the expression of key inflammatory genes (TNFA, IL1B, IL6, IL12B, IL23, CD40, CD80, CD274, CSF1, and NAMPT) in lipopolysaccharide (LPS)-stimulated THP-1 cells. In vivo, we employed rat pocket granuloma and formalin- and carrageenan-induced oedema models. HTLP significantly reduced oedema volume in the in vivo models. In the carrageenan-induced oedema model, HTLP exhibited efficacy significantly higher than that of ibuprofen, reducing oedema by 76% at 8 h (p < 0.01). In the air pouch granuloma model, HTLP showed comparable anti-inflammatory activity to ibuprofen. In the formalin-induced oedema model, HTLP reduced oedema, demonstrating less efficacy than ibuprofen, with a reduction of 58% versus ibuprofen’s 65% (p < 0.001). The anti-inflammatory mechanism of HTLP involves not only the suppression of pro-inflammatory cytokine expression (TNFA, IL1B, IL6, IL12B, IL23, CD40, CD80, CD274, and CSF1) but also the activation of cell survival and cellular defence mechanisms (NAMPT) and the upregulation of the anti-inflammatory cytokine (IL10). The observed biological activity of HTLP suggests its potential as a valuable therapeutic agent for inflammatory conditions. The combination of functional and molecular evidence demonstrates HTLP’s potent anti-inflammatory properties across multiple models, with efficacy approaching or exceeding that of ibuprofen in certain models. However, further studies are necessary to fully elucidate its mechanism of action and to evaluate its long-term efficacy and safety. Full article

The colonization of Fusobacterium nucleatum (F. nucleatum) in the microenvironment of gastric cancer (GC) is closely associated with tumor progression, but its impact on host metabolic remodeling remains unclear. This study aims to elucidate the mechanistic link between F. nucleatum infection and metabolic changes in GC tissue. By integrating 16S rRNA microbiome sequencing and LC-MS/MS metabolomics, the differences in microbial composition and metabolic profiles between Fusobacterium sp.-positive and -negative GC tissues were systematically compared, and the correlation of differential microbes and differential metabolites was analyzed. The impact of F. nucleatum on the glutathione (GSH) metabolic pathway was validated through in vitro tissue testing and the use of the infection model of GC cell lines (such as AGS and HGC27). Integrative omics analysis showed a strong negative correlation between Fusobacterium sp. infection and antioxidant metabolite GSH levels in GCs (p < 0.001). Metabolic reprogramming features: Eleven differentially expressed metabolites were identified using LC-MS/MS metabolomics screening (p < 0.05). GSH was significantly depleted in the Fusobacterium sp.-positive group. Experimental validation: At the histological level, the abundance of F. nucleatum in GC tissues was higher than that in the paired adjacent non-cancerous (NC) tissues; at the cellular level, after F. nucleatum infection of GC cells, the intracellular GSH level decreased (p < 0.01), accompanied by a decrease in glutathione synthetase (GSS) mRNA expression and reactive oxygen species (ROS). This study is the first to demonstrate that F. nucleatum suppresses the GSH synthesis pathway, leading to the breakdown of antioxidant capacity and the formation of an oxidative stress microenvironment in GC cells. These findings provide new insights into the metabolic mechanism of F. nucleatum in promoting GC progression and suggest that targeting the F. nucleatum-GSH axis could offer a novel strategy for GC therapeutic intervention. Full article

RNA-directed DNA methylation (RdDM) is an epigenetic mechanism involved in several biological processes in plants, requiring complex machinery including the chromatin remodeling protein CLASSY (CLSY). The CLSY family regulates global and locus-specific DNA methylation and was initially identified in Arabidopsis thaliana. Despite reports in other plants, detailed knowledge about CLSY proteins in soybean is scarce. In this work, we used profile hidden Markov models (profile HMMs) specifically constructed for CLSY detection to identify new members in soybean and to analyze their phylogenetic relationships across bryophyte, basal angiosperm, basal eudicot, monocots, and eudicots. We identified two new candidates for CLSY1-2 and one for DRD1 in soybean and, for the first time, detected CLSY and DRD1 genes in Aquilegia coerulea. Phylogenetic analysis indicated two main CLSY groups: one similar to Arabidopsis CLSY1-2 and another to CLSY3-4. Gene duplication analysis demonstrated that whole-genome duplication/segmental duplication events contributed to CLSY family expansion in soybean. RT-qPCR analysis showed that CLSY and five other epigenetic regulator genes had stress-modulated expression during soybean germination under salt and osmotic stress, with variation among cultivars. Our findings enhance comprehension of the evolutionary dynamics of the CLSY family and furnish insights into their response to abiotic stress in soybean. Full article

2-Amino-14,16-dimethyloctadecan-3-ol (AOD) is commonly found in foods contaminated with Fusarium avenaceum, particularly cereals or fruits, and is structurally related to Fusarium mycotoxins (fumonisins) and mammalian sphingoid bases, especially 1-deoxysphinganine (m18:0); therefore, it might enter systemic circulation and tissues upon dietary intake. Knowledge about what happens when cells are exposed to AOD is limited, but it has been reported to be cytotoxic and to induce vacuolization in HepG2 cells. We also found that AOD is cytotoxic for HepG2 cells, but even at a concentration where cell viability remained above 85% (5 μM), it altered 24 differentially expressed genes based on RNA sequencing-based transcriptomic profiling. Among these genes, 13 were shared with cells treated with m18:0. These overlapping differentially expressed genes were primarily enriched in activated stress response pathways of cells, including the upregulation of specific genes in the hypoxia-inducible factor 1α (HIF-1α) signaling pathway, such as hexokinase 1 (HK1) and egl-9 family hypoxia-inducible factor 3 (EGLN3), the activation of key components in the p53 signaling pathway, and the induction of cellular senescence-associated transcriptional programs involving serpin family E member 1 (SERPINE1). Transcriptional analysis of genes related to sphingolipid metabolism showed that treatment with AOD increased the mRNA expression of ceramide synthase 4 (CerS4), sphingosine-1-phosphate phosphatase 1 (SGPP1), and UDP-glucosylceramide glucosyltransferase (UGCG), while decreasing the expression of dihydroceramide desaturase 1 (DEGS1) and fatty acid desaturase 3 (FADS3), a pattern of gene expression changes that mirrored the alterations observed with m18:0 treatment. Lipidomic analyses revealed that AOD significantly perturbed the sphingolipid composition of HepG2 cells, specifically increasing hexosylceramide content while decreasing ceramide and sphingomyelin levels. Moreover, AOD was found to undergo intracellular metabolism to N-acyl-AODs, perhaps by ceramide synthase(s), since this acylation was inhibited by fumonisin B1 (FB1). These findings demonstrate that AOD or possibly its N-acyl metabolites can alter cellular sphingolipid metabolism and affect the expression of genes involved in cell stress. These new insights call for more studies of the impact of this food contaminant on cells and the implications for human health. Full article

Abscisic acid (ABA) is a key phytohormone involved in regulating plant growth and responses to environmental stress. As receptors of ABA, pyrabactin resistance 1 (PYR)/PYR1-like (PYL) proteins play a central role in initiating ABA signal transduction. In this study, a total of 30 PopPYL genes were identified and classified into three sub-families (PYL I–III) in the pan-genome of 17 Populus species, through phylogenetic analysis. Among these subfamilies, the PYL I subfamily was the largest, comprising 21 members, whereas PYL III was the smallest, with only four members. To elucidate the evolutionary dynamics of these genes, we conducted synteny and Ka/Ks analyses. Results indicated that most PopPYL genes had undergone purifying selection (Ka/Ks < 1), while a few were subject to positive selection (Ka/Ks > 1). Promoter analysis revealed 258 cis-regulatory elements in the PYL genes of Populus euphratica (EUP) and Populus pruinosa (PRU), including 127 elements responsive to abiotic stress and 33 ABA-related elements. Furthermore, six structural variations (SVs) were detected in PYL_EUP genes and significantly influenced gene expression levels (p < 0.05). To further explore the functional roles of PYL genes, we analyzed tissue-specific expression profiles of 17 PYL_EUP genes under drought stress conditions. PYL6_EUP was predominantly expressed in roots, PYL17_EUP exhibited leaf-specific expression, and PYL1_EUP showed elevated expression in stems. These findings suggest that the drought response of PYL_EUP genes is tissue-specific. Overall, this study highlights the utility of pan-genomics in elucidating gene family evolution and suggests that PYL_EUP genes contribute to the regulation of drought stress responses in EUP, offering valuable genetic resources for functional characterization of PYL genes. Full article