Search Results (702)

This study explores immunophenotypic and angiogenic profiles in salivary gland tumors (SGTs), focusing on epithelial–mesenchymal dynamics and immune–stromal interactions. Immunohistochemical analysis of E-cadherin, Vimentin, mast cell tryptase (MCT), CD300a, CK18, CD31, and vascular endothelial growth factor (VEGF) was performed in normal salivary tissue, pleomorphic adenomas (PA), and squamous cell carcinomas (SCCs) to assess epithelial plasticity, mast cell (MC) involvement, and vascular remodeling. Normal glands showed compartmentalized E-cadherin (epithelial) and Vimentin (mesenchymal) expression, with stromal MCs positive for MCT and CD300a. PA exhibited reduced E-cadherin, increased Vimentin, and atypical co-localization of CK18 with MCT/CD300a in ductal cells, indicating immune–epithelial plasticity. SCC displayed epithelial–mesenchymal transition (EMT), architectural disruption, and reduced MCT/CD300a. Notably, diminished MCT may reflect either decreased MCs density or prior degranulation, with possible diffuse MCT in stroma. Angiogenic profiling showed maximal CD31 in PA and minimal in SCC, while VEGF peaked in normal tissue, suggesting deregulated angiogenesis. SGT progression involves immune–epithelial plasticity, vascular deregulation, and stromal reprogramming. Immune marker localization within epithelial cells challenges histogenetic models and may inform prognostic assessment and targeted therapeutic strategies. Full article

Background/Objectives: Adults with type 1 diabetes (T1D) experience disproportionately high rates of depression, anxiety, and psychological distress, yet integration of behavioral health into diabetes care remains limited. The objective of this study was to identify barriers and facilitators to mental health treatment among adults with T1D, using the Behavior Change Wheel as a framework to inform future integrated care strategies. Methods: We conducted five online focus groups with 21 adults with T1D. Discussions were guided by a semi-structured guide, with questions on lived experience, accessibility of mental health treatment, and integrated service delivery informed by the COM-B model domains. Transcripts were analyzed using qualitative content analysis, whereby meaning units were open-coded and then deductively categorized into COM-B constructs of capability, opportunity, and motivation. Results: Participants described limited psychological capability to address mental health due to the heavy self-management burden of T1D, lack of knowledge about navigating care, and uncertainty about treatment interactions. Physical opportunities were constrained by fragmented systems, high costs, and competing responsibilities. However, co-located services and telehealth were viewed as facilitators. Social opportunity was shaped by stigma, isolation, and feeling burdensome, with peer communities providing critical support. Motivation was undermined by past traumatic encounters with psychiatric care and the burden of educating providers about diabetes, contributing to mistrust and avoidance of treatment. Conclusions: Findings highlight how capability, opportunity, and motivation interact to influence engagement with mental health care among adults with T1D. Addressing these barriers through tailored, integrated models of care may strengthen access, trust, and long-term treatment engagement. Full article

Shanlan rice, a unique drought-resistant rice germplasm resource in Hainan Province, China, holds significant potential for rice genetic improvement and breeding innovation. However, its genetic diversity and significance in rice breeding remain inadequately explored. This study conducted a comprehensive analysis of phenolic acid profiles and antioxidant properties in the brown rice of 84 Shanlan rice accessions. It was revealed that colored Shanlan rice accessions exhibited significantly higher total phenolic content (249.00–2408.33 mg gallic acid equivalents per 100 g of rice flour (mg GAE/100 g)) and antioxidant capacity (DPPH: 680.39–809.63 micromoles of Trolox equivalent per 100 g (μmol TE/100 g); ABTS: 529.93–1917.77 μmol TE/100 g) compared to white-grained varieties. High-performance liquid chromatography (HPLC) analysis identified eight phenolic acids in the bound fractions, among which the sinapic acid (55.08 μg/g) and vanillic acid (11.72 μg/g) were predominant, accounting for over 60% of total bound phenolic acid content. A genome-wide association study (GWAS) identified 84 significant loci associated with these phenolic-related traits. A major quantitative trait locus (QTL) on chromosome 7 for free phenolic content, total phenolic content, flavonoids, and DPPH activity was co-located at the Rc gene locus, a key regulator of red pericarp pigmentation and proanthocyanidin biosynthesis. Haplotype analysis identified ten haplotypes in Rc, with the haplotype H002 showing the highest antioxidant capacity. Another QTL on chromosome 11 was associated with p-coumaric, vanillic, and sinapic acids, although no significant difference was observed in haplotype analysis. These results highlight Rc as a key genetic factor underlying antioxidant properties in rice, while other loci require further validation. This research provides a foundation for breeding health-benefit, drought-tolerant rice cultivars using Hainan’s unique germplasm. Full article

Background: Colorectal cancer (CRC) is significantly associated with multiple metabolic diseases, with plasma metabolites potentially mediating this relationship. This large-scale metabolomics study aims to (1) quantify the genetic correlations and causal effects between 10 metabolic disease-related phenotypes and CRC risk; (2) identify the plasma metabolites mediating these effects; and (3) explore downstream regulatory genes and druggable targets. Methods: Using linkage disequilibrium score regression and two-sample Mendelian randomization, we assessed the causal relationships between each metabolic trait and CRC. A total of 1091 plasma metabolites and 309 metabolite ratios were identified and analyzed for mediating effects by a two-step MR approach. Colocalization analyses evaluated shared genetic loci. The findings were validated in the UK Biobank for metabolite-trait associations. The expression of candidate genes was explored using data from TCGA, GTEx, and GEO. A FADS1-centered protein–protein interaction (PPI) network was constructed via STRING. Results: BMI, waist circumference, basal metabolic rate, insulin resistance and metabolic syndrome exhibited both genetic correlation and causal effects on CRC. Five plasma metabolites—mannonate, the glucose/mannose ratio, plasma free asparagine, 1-linolenoyl-2-linolenoyl-GPC (18:2/18:3), and the mannose/trans-4-hydroxyproline ratio—were identified as shared central mediators. A colocalization analysis showed rs174546 linked CRC and 1-linolenoyl-2-linoleoyl-GPC. Validation in the UK Biobank confirmed the associations between phosphatidylcholine (the lipid class of this metabolite), adiposity measures, and CRC risk. An integrative analysis of TCGA, GTEx, and GEO revealed consistent upregulation of FADS1/2/3 and FEN1 in CRC, with high FADS1 expression predicting a poorer prognosis and showing the distinct cell-type expression in adipose and colon tissue. The PPI network mapping uncovered nine FADS1 interacting proteins targeted by supplements such as α-linolenic acid and eicosapentaenoic acid. Conclusions: This study systematically reveals, for the first time, the shared intermediary plasma metabolites and their regulatory genes in the causal pathway from metabolic diseases to CRC. These findings provide candidate targets for subsequent functional validation and biomarker development. Full article

Hybrid marine energy platforms that integrate wave energy converters (WECs) and hydrokinetic turbines (HKTs) offer potential to improve energy yield and system stability in marine environments. This study identifies a compatible WEC–HKT integrated system concept through a structured concept selection framework based on multi-criteria decision analysis (MCDA). The framework follows a two-stage process: individual technology assessment using eight criteria (efficiency, TRL, self-starting capability, structural simplicity, integration feasibility, environmental adaptability, installation complexity, and indicative cost) and pairing evaluation using five integration-focused criteria (structural compatibility, PTO feasibility, mooring synergy, co-location feasibility, and control compatibility). Criterion weights were assigned through a four-level importance framework based on expert judgment from 11 specialists, with unequal weights for the individual evaluation and equal weights for the integration stage. Four WEC types (oscillating water column, point absorber, overtopping wave energy converter, and oscillating wave surge converter) and four HKT types (Darrieus, Gorlov, Savonius, and hybrid Savonius–Darrieus rotor) are assessed using literature-derived scoring and weighted ranking. The results show that the oscillating water column achieved the highest weighted score among the WECs with 4.05, slightly ahead of the point absorber, which scored 3.85. For the HKTs, the Savonius rotor led with a score of 4.05, surpassing the hybrid Savonius–Darrieus rotor, which obtained 3.50, by 0.55 points. In the pairing stage, the OWC–Savonius configuration achieved the highest integration score of 4.2, surpassing the PA–Savonius combination, which scored 3.4, by 0.8 points. This combination demonstrates favorable structural layout, PTO independence, and mooring simplicity, making it the most promising option for early-stage hybrid platform development. Full article

Background: Endothelial cells (EC), crucial components of the vascular system, are adaptable cells that maintain homeostasis and respond to pathological events through structural and functional plasticity. Hepatocyte growth factor (HGF) is a multifunctional cytokine that has been demonstrated to have protective and disruptive influence on the blood barrier function. In endothelial biology, its role is also poorly characterized. The present study explores the impact of supraphysiological concentrations of HGF on mouse brain endothelial cells (MBECs), scrutinizing how it alters their integrity and morphology. Methods: Two groups of MBECs—control (CTR) and experimental (EXP)—were analyzed at two time points: early passage (p5) and late passage (p41). The EXP-groups (p5 and p41) were treated with HGF at a concentration of 4 µL/mL. Cellular morphology was assessed with brightfield microscopy; protein expression and localization of the tight junction marker (ZO-1) and the endothelial marker (Factor VII related antigen/von Willebrand factor, vWf) were analyzed using Western blotting, immunocytochemistry, and confocal microscopy. Intercellular barrier function was estimated via Transendothelial Electric Resistance (TEER) and Transendothelial Dextran Permeability (TEDP) assays. Results: Microscopical analysis demonstrated a change in the morphology of the MBECs from a longitudinal, spindle-like shape to a rounded, more spheroid, cobblestone-like morphology under high-dose HGF treatment. Western blotting revealed a progressive decrease of ZO-1 expression in the EXP-groups. The expression of vWf did not show significant differences. Qualitative immunocytochemical staining: vWf showed consistent expression across all groups. ZO-1 displayed a punctate, well-defined membrane and cytoplasmic localization pattern in the CTR-groups at p5 and p41. In contrast, the p5 EXP-group demonstrated a shift to a more diffuse cytoplasmic pattern. At p41, the EXP-group displayed a markedly reduced ZO-1 signal with no clear-cut membrane localization. Confocal analysis: ZO-1: punctate membrane-associated localization in CTR-groups at p5 and 41. The EXP-groups at p5 and p41 confirmed the diffuse cytoplasmic ZO-1 distribution. Phalloidin: well-organized actin cytoskeleton in CTR-groups, but rearrangement and stress fiber disorganization in the EXP-groups, especially at p41. The merged images confirmed reduced co-localization of ZO-1 with actin structures. Barrier function: TEER values dropped significantly in HGF-treated cells. TEDP to small and medium molecular weight dextran increased markedly under HGF treatment. Conclusions: Our data demonstrate that supraphysiological doses of HGF in an in vitro MBEC-barrier-like model disrupt TJ organization, leading to morphological changes and functional weakening of the MBEC-barrier-like structure, as shown by uncoupling between ZO-1/F-actin cytoskeleton, reduced TEER, and increased size-selective paracellular permeability (TEDP). Full article

Dysferlin direct protein–protein interactions (PPI) previously have been elucidated with surface plasmon resonance (SPR) and predicted to underlie membrane repair in mechanotransducing myofibrils. In mechanotransducing inner ear hair cells, dysferlin is detected with Z-stack confocal immunofluorescence in the stereocilia and their inserts in the tectorial membrane (TM) co-localizing with FKBP8, consistent with the SPR determination of tight, positively Ca²⁺-dependent interaction. FKBP8, a direct binding partner of mechanotransducing TMC1, when overexpressed, evokes an elevation in anti-apoptotic BCL2, inhibition of ryanodine receptor (RYR) activity, and a consequent reduction in Ca²⁺ release. RYR3 has now been immunolocalized to the tip of the TM in close association with a third-row outer hair cell (OHC) stereociliary BCL2-positive insertion. Dysferlin, annexin A2, and Alzheimer’s proteins BACE1 and amyloid precursor protein (APP) are also accumulated in these stereociliary insertions. RYR2 and RYR1 have been immunolocalized to the TM core, in position to influence TM Ca²⁺. Dysferlin PPI pathways also intersect with AD protein pathways in the spiral ganglion (SG). Dysferlin segregates with FKBP8, BACE1, and RYR3 in the interiors of SG type I cell bodies. RYR1, RYR2, PSEN1, BCL2, and caspase 3 are primarily confined to plasma membrane sites. RYR3 pathways traverse the plasma membrane to the cell body interior. Western analysis of dysferlinopathy proteins links FKBP8 and BCL2 overexpression with RYR inhibition, indicative of dysferlin targets that are ameliorative in AD. Full article

Migraine is a complex neurological disorder that severely compromises quality of life. Current therapies remain inadequate, creating an urgent need for precision medicine approaches. To bridge this gap, we integrated genome-wide association studies (GWASs) and multi-tissue expression quantitative trait loci (eQTL) data. Using Mendelian randomization (SMR/HEIDI) to identify putatively causal genes, followed by colocalization analysis, protein–protein interaction networks, and gene enrichment, we prioritized druggable targets. Phenome-wide association studies (PheWASs) further assessed their potential safety profiles. We identified 31 migraine-associated genes in whole blood, 20 in brain tissue, and 9 genes shared by both whole blood and brain regions. Among 13 druggable genes identified from the DGIdb and supporting literature, 10 passed colocalization validation. Eight genes (TGFB3, CHRNB1, BACE2, THRA, NCOR2, NR1D1, CHD4, REV3L) showed interactions with known drug targets, enabling the computational prediction of 41 potential repurposable drugs. Based on target druggability, PPI (protein–protein interaction) and favorable PheWAS profiles, NR1D1, THRA, NCOR2, and CHD4 are prioritized for drug development. Additionally, MICU1, UFL1, LY6G5C, and PPP1CC emerged as novel pathophysiological factors. This study establishes a multi-omics framework for precision migraine therapy, translating genetic insights into clinically actionable targets. Full article

Class 1 phytoglobins (Pgbs) are known for their multifunctional roles in plant stress responses, with recent studies suggesting broader interactions involving metabolic and transcriptional regulation. Interestingly, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) moonlights in many roles in colocalized spaces during cellular stress that are strikingly suitable for supporting Pgb function. This study investigates the molecular interactions of class 1 Pgb from sugar beet (Beta vulgaris), BvPgb 1.2, and an alanine-substituted mutant (C86A), focusing on their ability to bind GAPDH and DNA. Using dual-emission isothermal spectral shift (SpS) analysis, we report strong binding interactions with GAPDH, with dissociation constants (K_D) of 260 ± 50 nM for the recombinant wild-type protein (rWT) and a significantly stronger affinity for C86A (120 ± 40 nM), suggesting that the cysteine residue limits the interaction. Remarkably strong DNA-binding affinities were also observed for both variants, displaying biphasic binding. This behavior is characteristic of hexacoordinated globins and reflects the presence of two distinct species: a fast-reacting open pentacoordinated form and a slow-reacting closed hexacoordinated form with high apparent affinity. Here, the K_D in the open configuration was 120 ± 50 nm and 50 ± 20 nM for rWT and C86A, respectively. In the closed configuration, however, the cysteine appears to support the interaction, as the K_D was measured at 100 ± 10 pM and 230 ± 60 pM for rWT and C86A, respectively. Protein–protein docking studies reinforced these findings, revealing electrostatically driven interactions between BvPgb 1.2 and GAPDH, characterized by a substantial buried surface area indicative of a stable, biologically relevant complex. Protein–DNA docking similarly confirmed energetically favorable binding near the heme pocket without obstructing ligand accessibility. Together, these findings indicate a potential regulatory role for BvPgb 1.2 through its interaction with GAPDH and DNA. Full article

This study provides an in-depth analysis of the learning dynamics of multichannel optical neurons based on spatial solitons generated in lithium niobate crystals. Single-node and multi-node configurations with different topological complexities (3 × 3, 4 × 4, and 5 × 5) were compared, assessing how the number of channels, geometry, and optical parameters affect the speed and efficiency of learning. The simulations indicate that single-node neurons achieve the desired imbalance more rapidly and with lower energy expenditure, whereas multi-node structures require higher intensities and longer timescales, yet yield a greater variety of responses, more accurately reproducing the functional diversity of biological neural tissues. The results highlight how the plasticity of these devices can be entirely modulated through optical parameters, paving the way for fully optical photonic neuromorphic networks in which memory and computation are co-localized, with potential applications in on-chip learning, adaptive routing, and distributed decision-making. Full article

Cathepsin B (CTSB), a lysosomal cysteine protease, plays pivotal roles in cellular homeostasis and pathology, including cancer progression. This study investigates the regulatory interplay between CTSB and Stefin A (STFA), an endogenous inhibitor of cysteine proteases, in renal and prostate cancer cells. Using plasmid-based overexpression and silencing systems, we demonstrated that overexpressing STFA significantly reduces CTSB activity and protein levels, while silencing STFA leads to elevated CTSB activity and expression in cancer cells but not in non-cancerous cells (embryonic kidney cells—Hek293T and endothelial cells—EA.hy926). Furthermore, STFA modulates the subcellular distribution of CTSB, with STFA overexpression reducing nuclear CTSB levels and silencing inducing cytoplasmic accumulation in cancer cells. Colocalization analysis confirms a direct interaction between STFA and CTSB, highlighting the spatial coordination necessary for effective protease inhibition. These findings underscore the critical role of the CTSB-STFA axis in maintaining proteolytic balance and suggest potential therapeutic strategies targeting this interaction in renal carcinoma and other cancers. Full article

Stalk lodging constitutes a primary constraint on achieving consistently high yields in maize. Genetic improvement of lodging resistance requires the identification of stable quantitative trait loci (QTL) to facilitate the application of genomics-assisted breeding for improving selection efficiency in breeding programs. In this study, we performed a meta-analysis to identify consensus loci and functionally characterized candidate genes associated with stalk lodging-related traits. Through meta-analysis integrating 889 reported lodging-related QTLs using the IBM2 2008 Neighbors high-density genetic map, we identified 67 meta-QTLs (MQTLs), of which 32 were determined as core MQTLs. Among them, 67% were validated by co-localized marker–trait associations from genome-wide association studies (GWAS). Comparative genomics further revealed 40 evolutionarily conserved orthologs via protein alignment with rice lodging genes, while screening of core MQTL regions detected 802 candidate genes with KEGG enrichment implicating galactose degradation II in cell wall reinforcement, supported by transcriptomic evidence of their roles in lignin biosynthesis pathways modulating mechanical strength. In conclusion, the MQTL identified and validated in our study have significant scope in marker-assisted selection (MAS) breeding and map-based cloning programs for improving maize stalk lodging. Full article

Accurate wind measurements in the mesosphere and lower thermosphere (MLT) region are essential for climate modeling, satellite drag estimation, and space weather prediction. This study presents a comprehensive comparison and correlation analysis of the zonal and meridional wind observations from co-located meteor radar and medium-frequency (MF) radar systems in Kunming (102.1°E, 24.2°N), China, in the year 2022. Both zonal and meridional wind components were analyzed within the overlapping altitude range of 70–100 km. Statistical distributions of the wind speeds from both radars followed a near-Gaussian pattern concentrated within ±100 m/s, indicating good consistency. A joint dataset was constructed for the 78–100 km range, where over 2000 h of concurrent observations were available. The strongest correlation between the wind speed measurements of the two radars was ~0.6, which occurred near 82–84 km. Seasonal analysis further indicated better consistency in the winter and spring months, while the summer months exhibited reduced correlations, especially for zonal wind measurements. Systematic biases between the two instruments were also identified, with minimal intercept offsets observed from April to October. This study is valuable in the development of high-quality, long-term MLT wind field datasets for atmospheric research and numerical model validation. Full article

Panax ginseng C. A. Meyer (P. ginseng) is a medicinal plant rich in bioactive components such as ginsenosides, polysaccharides, and volatile oils and is widely used in both the pharmaceutical and food industries. While the AP2/ERF gene family is well-documented to play crucial roles in plant growth, development, and defense responses, functional studies on this gene family in P. ginseng remain unreported. Our genome-wide analysis identified 318 PgAP2/ERF family members, which are classified into five subfamilies: AP2, DREB, ERF, RAV, and Soloist. Homology analysis revealed that segmental duplication serves as the primary evolutionary driver for the PgAP2/ERF gene family in P. ginseng. RT-qPCR analysis demonstrated that all PgAP2/ERF members in the DREB-A1 subgroup respond to cold stress. Specifically, we found that the DREB-A1 member PgAP2/ERF187 plays a pivotal role in the cold stress response, with its expression specifically induced by ABA. Overexpression of PgAP2/ERF187 in Arabidopsis significantly enhanced the expression of cold tolerance-related genes. Subcellular localization analysis confirmed the co-localization of PgABF and PgAP2/ERF187 in the nucleus. Combining transcription factor interaction predictions and yeast one-hybrid experiments, we propose that PgABF likely regulates PgAP2/ERF187 expression by directly binding to its promoter region. These findings unveil the potential mechanism of the “PgABF-PgAP2/ERF187” regulatory module within the ABA signaling pathway during P. ginseng’s cold stress adaptation, thereby providing novel theoretical insights into the molecular mechanisms underlying P. ginseng’s cold resistance. Full article

Upon activation, neutrophils perform three distinct functions: phagocytosis, degranulation of antimicrobial substances into the extracellular medium, and release of neutrophil extracellular traps. Determination of the nuclear area expansion of neutrophils activated to release neutrophil extracellular traps has become critical in demonstrating early neutrophil activation and has become standard. Here, we demonstrate an automated method for measuring nuclear area expansion in two different mammalian species: canine and bovine. For both species, neutrophils were isolated from peripheral blood and co-incubated with fresh spermatozoa for up to 120 min for canine neutrophil–spermatozoa and recently thawed cryopreserved spermatozoa up to 240 min for bovine neutrophil–spermatozoa. Fluorescence images were acquired using a TissueFAXS microscope and then analyzed using StrataQuest v.7.0 software. The images show the release of neutrophil extracellular traps upon activation with spermatozoa for both species, as evidenced by the co-localization of neutrophil elastase and DNA staining. Neutrophil nuclei were expanded as early as 15 min and were detected at up to 120 min in both species. Analysis by nuclei segmentation showed that the data sets generated for both species were reliable and consistent with previously published methods. The method was developed as an automated alternative for measuring the area expansion of neutrophil nuclei in different species. Full article