Search Results (13,276)

Background: Intuitive inquiry meditation (Can-Hua-Tou) is a unique mental practice which differs from relaxation-based practices by continuously demanding intuitive inquiry. It emphasizes the doubt-driven self-interrogation, also referred to as Chan/Zen meditation. Nonetheless, its electrophysiological signature remains poorly characterized. Methods: We recorded 128-channel EEG from 20 male Buddhist monks (5–28 years Can-Hua-Tou experience) and 18 male novice lay practitioners (<0.5 year) during three counter-balanced eyes-closed blocks: Zen inquiry meditation (ZEN), a phonological control task silently murmuring “A-B-C-D” (ABCD), and passive resting state (REST). Power spectral density was computed for alpha (8–12 Hz), beta (12–30 Hz) and gamma (30–45 Hz) bands and mapped across the scalp. Mixed-design ANOVAs and electrode-wise tests were corrected with false discovery rate (p < 0.05). Results: Alpha power increased globally with eyes closed, but condition- or group-specific effects did not survive FDR correction, indicating comparable relaxation in both cohorts. In contrast, monks displayed a robust beta augmentation, showing significantly higher beta over parietal-occipital leads than novices across all conditions. The most pronounced difference lay in the gamma band: monks exhibited trait-like fronto-parietal gamma elevations in all three conditions, with additional, though sub-threshold, increases during ZEN. Novices showed negligible beta or gamma modulation across tasks. No significant group × condition interaction emerged after correction, yet only experts expressed concurrent beta/gamma amplification during meditative inquiry. Conclusions: Long-term Can-Hua-Tou practice is associated with frequency-specific neural adaptations—stable high-frequency synchrony and state-dependent beta enhancement—consistent with Buddhist constructs of citta-ekāgratā (one-pointed concentration) and vigilance during self-inquiry. Unlike mindfulness styles that accentuate alpha/theta, Chan inquiry manifests an oscillatory profile dominated by beta–gamma dynamics, underscoring that different contemplative strategies sculpt distinct neurophysiological phenotypes. These findings advance contemplative neuroscience by linking intensive cognitive meditation to enduring high-frequency cortical synchrony. Future research integrating cross-frequency coupling analyses, source localization, and behavioral correlates of insight will further fully delineate the mechanisms underpinning this advanced contemplative expertise. Full article

Lacticaseibacillus rhamnosus (Lbs. rhamnosus) is renowned for its tolerance to gastric acid and adaptability to bile and alkaline conditions, and is crucial for intestinal health and immune regulation. In this study, integrated transcriptomic and proteomic analyses were employed to elucidate the response mechanisms of Lbs. rhamnosus under osmotic stress, induced by exposure to 0.6 M sodium lactate, which elevates environmental osmotic pressure. It was shown that 792 differentially expressed genes and 138 differentially expressed proteins were detected in Lbs. rhamnosus ATCC 53103 treated with osmotic stress. The differential regulation of these genes/proteins mainly includes the inhibition of fatty acid metabolism with membrane structural remodeling (downregulation of the acetyl coenzyme A carboxylase family and fatty acid binding protein family expression), dynamic homeostasis of amino acid metabolism (restriction of the synthesis of histidine, cysteine, leucine, etc., and enhancement of the catabolism of lysine, tryptophan, etc.), and survival-oriented reconfiguration of carbohydrate metabolism (gene expression related to the glycolytic pathway increases, while gene expression related to the pentose phosphate pathway decreases). These synergistic alterations in metabolic regulation may facilitate the adaptive response of Lbs. rhamnosus ATCC 53103 to osmotic stress. Overall, our findings deepen the current understanding of the stress response mechanisms in lactic acid bacteria and offer novel insights into the survival strategies employed by Lbs. rhamnosus ATCC 53103 under hyperosmotic conditions. Full article

The pituitary adenylate cyclase-activating polypeptide receptor 1 (PAC1) plays a pivotal role in central nervous system development and homeostasis. Comparisons of PAC1 knockout (PAC1^−/−), heterozygous (PAC1^+/−) and wild-type (PAC1^+/+) mice demonstrate that PAC1 deficiency severely impairs pre-weaning survival and results in marked developmental deficits, including reduced postnatal weight and altered locomotor behavior. PAC1^−/− mice exhibited hyperlocomotion, reduced anxiety-like behavior, and transient deficits in motor coordination. Gene expression analyses revealed widespread dysregulation of oligodendrocyte-associated markers, with significant myelin reduction and decreased mature oligodendrocyte density in the corpus callosum. ER stress was evidenced in both white matter and motor cortex, as indicated by altered expression of UPR-related genes and increased phosphorylated (p)IRE1⁺ neurons. Retinal morphology was compromised in PAC1^−/− animals, with reduced overall retinal and ganglion cell layer thickness. Notably, no gross morphological or molecular abnormalities were detected in the spinal cord regarding myelin content or MBP expression; however, synaptic marker expression was selectively reduced in the ventral horn of PAC1-deficient mice. Together, these findings highlight a critical role for PAC1 in oligodendrocyte maturation, retinal development, and synaptogenesis, providing new insights with relevance in multiple sclerosis and other neurodevelopmental and neurodegenerative conditions. Full article

Understanding genetic variation in commercially valuable tree species is essential for improving breeding and conservation efforts. This study investigates genetic variation, heritability, and trait relationships in Pterocarpus macrocarpus, a vital hardwood species for Thailand’s reforestation initiatives. We evaluated growth (height and diameter), morphology (biomass dry weight and specific leaf weight), and physiological traits (net photosynthesis [A], transpiration rate [E], and water-use efficiency [WUE]) across 112 open-pollinated families from six natural populations under controlled nursery conditions over 30 weeks. Using a randomised complete block design, variance and covariance analyses were conducted to estimate genetic parameters. Seedling survival reached 95%, confirming favourable conditions for genetic expression. There were significant differences among populations and families within populations in growth and biomass. In contrast, physiological traits showed notable family-level variation (A, E, WUE) and only population effects for WUE. Residual variance was predominant across traits, indicating considerable within-family variation. Growth and biomass exhibited moderate to high heritability (individual: 0.39–1.00; family: 0.61–0.90), while specific leaf weight and shoot-to-root ratio had lower heritability at the individual level. Physiological traits showed low to moderate heritabilities (individual: 0.26–0.43; family: 0.47–0.62), with maternal effects via seed weight significantly influencing early growth. The heritability of height decreased over time, whereas the heritability of diameter remained stable. Strong genetic correlations among growth and biomass suggest the potential for combined selection gains. However, physiological traits show weak or no correlations with growth, highlighting their independent genetic control. Variation at the population level in growth and WUE may reflect adaptive responses to seed-source environments. Our findings support the use of nursery-based screening as a cost-effective method for the early identification of high-quality families. WUE is a promising focus for breeding programs targeting drought-prone regions. This study provides key insights for advancing the genetic improvement and conservation of P. macrocarpus, emphasizing the importance of incorporating physiological traits into breeding and conservation strategies. Full article

Background: Ischemic stroke (IS) is a significant cause of global mortality and disability. Yiqi Huoxue Jieyu granules (YHJGs) show therapeutic potential for IS, but their mechanisms remain unclear. This study investigated YHJGs’ effects through network pharmacology, molecular docking, and experimental validation. Methods: Active YHJG components and IS targets were identified from TCMSP, GeneCards, and DisGeNET databases. Network analysis and molecular docking (AutoDock Vina) were performed. In vivo studies used 72 male Sprague-Dawley rats (MCAO model) divided into sham, model, nimodipine (10.8 mg/kg), and three YHJG dose groups (0.72, 1.44, 2.88 g/kg). Assessments included neurological scores, TTC staining, histopathology, and molecular analyses (qPCR/Western blot). Results: Network analysis identified 256 shared targets between YHJG and IS, with PI3K-AKT and MAPK as key pathways. Molecular docking showed strong binding between YHJG compounds (e.g., quercetin) and core targets (AKT1, ERK1/2). YHJG treatment significantly improved neurological function (p < 0.01), reduced infarct volume (p < 0.01), and attenuated neuronal damage. The expression of IL-1β, TNF-α, IL-6, AKT1, and pERK1/2/ERK1/2 significantly increased in the MCAO group (p < 0.01), while YHJG treatment significantly reduced their expression (p < 0.01). PPAR-γ expression significantly increased in the YHJG-H group (p < 0.01). Conclusions: The expression of IL-1β, TNF-α, IL-6, AKT1, and pERK1/2/ERK1/2 significantly increased in the MCAO group, while YHJG treatment significantly reduced their expression. PPAR-γ expression significantly increased in the YHJG-H group. YHJGs could treat IS through diverse ingredients, targets, and pathways by inhibiting inflammatory indices and AKT1 expression, and reducing ERK1/2 phosphorylation. Full article

Alkaline stress, driven by high pH and carbonate accumulation, results in severe physiological damage in plants. While the molecular mechanisms underlying alkaline tolerance have been partially elucidated in many crops, they remain largely unexplored in wheat. We hypothesize that alkaline stress tolerance in wheat is genotype-dependent. This study employed an integrated multi-omics approach to assess alkaline stress responses, combining genome-wide association study (GWAS) and RNA-seq analyses. Systematic phenotyping revealed severe alkaline stress-induced root architecture remodeling—with 57% and 73% length reductions after 1- and 3-day treatments, respectively—across 258 accessions. Analysis of the GWAS results identified nine significant alkaline tolerance QTLs on chromosomes 1A, 3B, 3D, 4A, and 5B, along with 285 associated candidate genes. Using contrasting genotypes—Dingxi 38 (tolerant) and TDP.D-27 (sensitive)—as experimental materials, physiological analyses demonstrated that root elongation was less inhibited in Dingxi 38 under alkaline stress compared to TDP.D-27, with superior root integrity observed in the tolerant genotype. Concurrently, Dingxi 38 exhibited enhanced reactive oxygen species (ROS) scavenging capacity. Subsequent RNA-seq analysis identified differentially expressed genes (DEGs) involved in ion homeostasis, oxidative defense, and cell wall remodeling. Integrated GWAS and RNA-seq analyses allowed for the identification of seven high-confidence candidate genes, including transcription factors (MYB38, bHLH148), metabolic regulators (ATP-PFK3), and transporters (OCT7), elucidating a mechanistic basis for adaptation to alkaline conditions. These findings advance our understanding of alkaline tolerance in wheat and provide candidate targets for molecular breeding of saline- and alkaline-tolerant crops. Full article

This study examines patterns of artificial intelligence (AI) adoption in Ecuadorian micro and small enterprises (MSEs), with an emphasis on functional diversity across value chain activities. Based on a cross-sectional dataset of 781 enterprises and an entropy-based model, it assesses internal variability in AI use and explores its relationship with strategic perception and dynamic capabilities. The findings reveal predominant partial adoption, alongside high functional entropy in sectors such as mining and services, suggesting an ongoing phase of technological experimentation. However, a significant gap emerges between perceived strategic use and actual functional configurations—especially among microenterprises—indicating a misalignment between intent and organizational capacity. Barriers to adoption include limited technical skills, high costs, infrastructure constraints, and cultural resistance, yet over 70% of non-adopters express future adoption intentions. Regional analysis identifies both the Andean Highlands and Coastal regions as “innovative,” although with distinct profiles of digital maturity. While microenterprises focus on accessible tools (e.g., chatbots), small enterprises engage in data analytics and automation. Correlation analyses reveal no significant relationship between functional diversity and strategic value or capability development, underscoring the importance of qualitative organizational factors. While primarily descriptive, the entropy-based approach provides a robust diagnostic baseline that can be complemented by multivariate or qualitative methods to uncover causal mechanisms and strengthen policy implications. The proposed framework offers a replicable and adaptable tool for characterizing AI integration and informing differentiated support policies, with relevance for Ecuador and other emerging economies facing fragmented digital transformation. Full article

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly heterogeneous malignancy, characterized by low tumor cellularity, a dense stromal response, and intricate cellular and molecular interactions within the tumor microenvironment (TME). Although bulk omics technologies have enhanced our understanding of the molecular landscape of PDAC, the specific contributions of non-malignant immune and stromal components to tumor progression and therapeutic response remain poorly understood. Methods: We explored genome-wide DNA methylation and transcriptomic data from the Cancer Genome Atlas Pancreatic Adenocarcinoma cohort (TCGA-PAAD) to profile the immune composition of the TME and uncover gene co-expression networks. Bioinformatic analyses included DNA methylation profiling followed by hierarchical deconvolution, epigenetic age estimation, and a weighted gene co-expression network analysis (WGCNA). Results: The unsupervised clustering of methylation profiles identified two major tumor groups, with Group 2 (n = 98) exhibiting higher tumor purity and a greater frequency of KRAS mutations compared to Group 1 (n = 87) (p < 0.0001). The hierarchical deconvolution of DNA methylation data revealed three distinct TME subtypes, termed hypo-inflamed (immune-deserted), myeloid-enriched, and lymphoid-enriched (notably T-cell predominant). These immune clusters were further supported by co-expression modules identified via WGCNA, which were enriched in immune regulatory and signaling pathways. Conclusions: This integrative epigenomic–transcriptomic analysis offers a robust framework for stratifying PDAC patients based on the tumor immune microenvironment (TIME), providing valuable insights for biomarker discovery and the development of precision immunotherapies. Full article

Prenatal exposure to air pollution is a major public health concern due to its potential to impair fetal brain development. This study examined whether maternal inflammatory and oxidative stress biomarkers mediate the association between trimester-specific air pollutant exposure during pregnancy and infant neurodevelopment at one year. We analyzed 87 mother–infant pairs from the OBESO perinatal cohort in Mexico City. Trimester-specific exposure to CO, PM₁₀, PM_2.5, SO₂, and O₃ was estimated using residential geolocation. Biomarkers were measured in the first and third trimesters by protocol, and intra-pregnancy change was calculated as Δ(3T–1T) for cytokines (IL-1β, IL-6, TNFα) and oxidative stress markers (malondialdehyde (MDA), protein carbonyls (PC), and total antioxidant capacity (TAC). Infant neurodevelopment at 12 months was assessed using Bayley-III. Exploratory mediation analyses were conducted, adjusting for gestational age at birth, pre-eclampsia, gestational diabetes, fetal growth restriction, marital status, mode of delivery, and infant sex; bootstrapping was applied to obtain robust estimates. Third-trimester CO exposure was associated with poorer receptive language (coef = 0.754, p = 0.02). PM_2.5 exposure showed direct effects on expressive language in the first (coef = 0.01, p = 0.04) and third trimesters (coef = 0.007, p = 0.015) in models including IL-1β. Third-trimester O₃ and SO₂ exposures were linked to lower expressive scores in models including TNFα (coef = 0.007, p = 0.02), MDA (coef = 0.008, p = 0.04), and PC (coef = 0.007, 95% p = 0.04). Meanwhile PM₁₀ exposure was associated with socio-emotional outcomes in models with IL-6 and TAC (coef = 0.003, p = 0.04). These findings indicate that maternal inflammation and oxidative stress biomarkers did not mediate the associations between prenatal air pollution exposure and infant neurodevelopment, and this study cannot elucidate their specific biological role in neurodevelopment. Full article

Background/Objectives: Breast cancer (BrCA) is among the deadliest cancers for women in the world. The disease has four distinct molecular subtypes which can be determined by gene expression profiling. Understanding these subtypes has enabled the development of targeted therapeutics. Additionally, following initial successful treatment, some patients experience disease recurrence events. Methods: In this study, we used radiomics coupled with machine learning techniques to predict molecular subtypes and disease recurrence events from a dataset of MRI features deriving from a single-institutional, retrospective collection of 922 biopsy-confirmed invasive BrCA patients. The feature-rich and comprehensive dataset consists of radiomic as well as demographic, clinical, and molecular subtype information. We focused our analyses on Black and White patients who were 50 years or younger at diagnosis (n = 346) to identify racial disparities that exist between molecular subtypes and disease recurrence events. Random Forest and AdaBoostM1 were applied to over 500 radiomics features. Results: Radiomics alone or combined with gene expression data can accurately predict molecular subtype and disease recurrence events for both racial groups. In total, we found over 40 radiomics features that have significant associations with race. The radiomic features that are most predictive in the Breast and Fibroglandular Tissue Volume imaging category for Black patients was breast volume (Breast_Vol) and for White patients was post contrast tissue volume (TissueVol_PostCon). Conclusions: These results suggest that radiomics can be used to predict differences in BrCA recurrence and molecular subtype between racial groups and can have an impact on clinical outcomes. Full article

Objectives: Oocyte quality is crucial for female fertility, but the underlying molecular mechanisms remain unclear. This study investigates the non-canonical role of the telomerase RNA protein (TERP), whose function in oogenesis is unknown, in safeguarding female gamete quality. Methods: We used gain-of-function (AT) and loss-of-function (D7) mutant mouse lines to assess oocyte quality via morphological and molecular analyses. Key methods included immunofluorescence of meiotic spindles, Western blotting for the autophagy marker LC3B, and qRT-PCR to quantify the perinatal ovarian reserve. Results: Both AT and D7 mutations caused severe meiotic spindle abnormalities, including aberrant morphology and increased size. The D7 mutation, in particular, led to impaired cytoplasmic maturation and reduced autophagy levels in oocytes. Furthermore, loss of TERP function resulted in an abnormally large ovarian reserve in newborn females, which correlated with decreased expression of autophagy and lysosomal markers in the newborn ovary. Conclusions: This study establishes a novel, non-canonical function for TERP as a crucial regulator of oocyte quality. TERP dysregulation compromises meiotic integrity and oocyte maturation by disrupting lysosome-dependent autophagy. Full article

The aim of the study described in this article is to analyse and compare the opinions of high school graduates and this year’s leavers of the schools run by the Polish sisters. The Congregation was founded by Marcelina Darowska, who also created a deeply personalistic pedagogical system, which is, however, unknown and not well described in the scientific literature. The participants had the opportunity to express their opinion on the contemporary relevance of Darowska’s educational system. The main research question was: How do the participants assess the consistency between the approach to students in the sisters’ schools and Darowska’s concept? The data were analysed using mixed methods. Most of the participants (who were researched using the survey method) confirmed that the role of the teacher and the student at the sisters’ school corresponds to Marcelina Darowska’s views in this area. Full article

Renal cancer is among the deadliest human malignancies. MCM7, a cell cycle-regulating protein, is frequently overexpressed in cancers and is associated with hyperproliferation and cancer progression. miR-25-3p, miR-93-5p, and miR-106b-5p form the miR-106b-25 cluster, located within the MCM7 gene, and have previously been reported as upregulated in RCC. This study investigates whether miRNAs from the miR-106b-25 cluster regulate common target genes, enhance one another’s effect, and act synergistically with MCM7 to promote tumor progression. Tissue samples from clear cell RCC (ccRCC) and paired controls were analysed to assess MCM7 expression and genes targeted by the miR-106b-25 cluster. Findings were further validated using the TCGA-KIRC dataset. Functional studies in RCC-derived cell lines were conducted to evaluate the effects of miRNAs on target gene expression, as well as MCM7, and the combined contributions of MCM7 and the miR-106b-25 cluster to renal cancer progression. We demonstrate that MCM7 is upregulated at both transcript and protein levels in RCC, contributing to cancer progression by regulating cell proliferation and caspase-3/7 activity. Furthermore, we identified cancer-related genes aberrantly expressed in ccRCC (BRMS1L, CPEB3, DNAJB9, KIF3B, NFIB, PTPRJ, RBL2) and targeted by members of the miR-106b-25 cluster, suggesting that their dysregulation may be driven by these miRNAs. Inhibition of the miR-106b-25 cluster increases caspase-3/7 activity. These findings demonstrate that both MCM7 and the miR-106b-25 cluster contribute to renal cancer progression. Full article

Background and Objectives: Endometrial adenocarcinoma is among the most prevalent malignancies of the female reproductive system, and therapeutic options remain limited, particularly in advanced stages. In recent years, natural agents, especially flavonoids, have gained considerable interest for their capacity to enhance the effectiveness of chemotherapeutic drugs and modulate tumor-related molecular mechanisms. Hesperidin, a citrus-derived flavonoid, is recognized for its antioxidant and anti-inflammatory effects, while Gemcitabine, a nucleoside analog, is widely used in cancer treatment. Investigating their combined effects on endometrial carcinoma cells could yield novel insights into multimodal therapeutic development. This current study aimed to assess the impact of Hesperidin (Hes) and Gemcitabine (Gem) on ISHIKAWA cells, a human endometrial adenocarcinoma model, with particular attention to pathways associated with hypoxia, angiogenesis, apoptosis, and oxidative stress. Materials and Methods: ISHIKAWA cells were treated with varying concentrations of Hes (50–200 µM) and Gem (10–50 nM), either individually or together, for 24 and 48 h. Cell viability was determined using the MTT assay, while apoptosis was measured by Caspase-3/7 activity and NucBlue nuclear staining. Intracellular reactive oxygen species (ROS) generation was quantified via DCFH-DA fluorescence. Expression levels of HIF-1α, VEGF, Bax, Bcl-2, and Caspase-3 were examined by RT-qPCR. Synergistic interactions were analyzed with the Chou–Talalay combination index. Biological enrichment was further explored using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results: Both Hes and Gem significantly decreased ISHIKAWA cell viability in a concentration- and time-dependent manner (p < 0.001). The combined treatment induced stronger apoptotic effects, as reflected by increased Caspase-3/7 activity and nuclear morphological changes. RT-qPCR demonstrated upregulation of Bax and Caspase-3, together with downregulation of Bcl-2, HIF-1α, and VEGF. While Hes reduced intracellular ROS, Gem elevated it; their combination produced a balanced oxidative response. All dose combinations displayed strong synergism (CI < 1). GO and KEGG enrichment confirmed the involvement of apoptosis-, angiogenesis-, and hypoxia-related pathways. Conclusions: Co-treatment with Hes and Gem exhibits synergistic anticancer activity in endometrial cancer cells by promoting apoptosis, suppressing angiogenesis- and hypoxia-related gene expression, and modulating oxidative stress. This combined therapeutic approach highlights its potential as a promising adjuvant option, warranting further evaluation in in vivo and translational studies. Full article

Sand pear is a fruit tree crop with high economic value, widely cultivated in East Asia. However, ripening fruits often suffer from high-temperature stress, which has adverse effects on the quality and yield of the fruit. In this study, we perform high-temperature treatment on mature stage ‘Housui’ pear fruits. The results showed that heat stress decreased fruit firmness and mineral elements, as well as lead to the flesh appearance of watercore. High temperature induces H₂O₂, MDA, and the antioxidant enzyme activity including SOD, APX, POD, and CAT were significantly increased. Transcriptome and metabolomic analyses revealed that heat stress up-regulated genes related to sucrose synthesis (SPS) while down-regulating those involved in sucrose degradation (SS and NI), resulting in sucrose accumulation. Moreover, the expression of sorbitol dehydrogenase (SDH) and sorbitol transporter (SOT) genes was markedly suppressed, leading to sorbitol accumulation and impaired transport, which promoted watercore development. High temperature also stimulated the expression of ethylene synthesis genes, accelerating abnormal ripening of fruits. In addition, high temperature decreased the accumulation of organic acid and bioactive compounds. Additionally, several antioxidant enzymes genes, five heat shock transcription factors (HSFs) and 34 heat shock protein (HSP) genes were significantly up-regulated. Together, these findings provided new insights into the transcriptional response and metabolomic reprogramming of sand pear response to high-temperature stress. Full article