Search Results (7,645)

This study examined the effects of dietary carbohydrate levels on growth performance, immune response, and antioxidant capacity of male giant freshwater prawn Macrobrachium rosenbergii. Prawns with an initial body weight of 15.04 ± 0.08 g were fed for 9 weeks on five isonitrogenous, isolipidic diets formulated to contain 10%, 15%, 20%, 25%, and 30% carbohydrate (designated CHO10–CHO30). Weight gain rate and specific growth rate rose from CHO10 to CHO20 and then declined (peak in CHO20); broken-line regression of weight gain rate estimated the optimal dietary carbohydrate level at approximately 19.36% under the present experimental conditions. Moderate carbohydrate inclusion (15–20%) enhanced hepatopancreatic total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and catalase (CAT) activities together with the transcription of cu/znsod, cat and glutathione peroxidase (gsh-px), whereas levels ≥ 25% lowered these defenses and raised hepatopancreatic malondialdehyde (MDA). High-carbohydrate diets also increased hemolymph glucose, triglyceride, total cholesterol and low-density lipoprotein cholesterol, progressively altered the mRNA expression of genes involved in the Toll-like receptor (TLR)/myeloid differentiation primary response 88 (MyD88) signaling pathway (upregulated tlr, myd88, relish and tumor necrosis factor; downregulated inhibitor of NF-κB alpha (IκB-α)), and altered the expression of apoptosis-related genes (downregulated B-cell lymphoma 2 (bcl-2), upregulated caspase-3). These results suggest that M. rosenbergii has an estimated optimal dietary carbohydrate level of approximately 19.36% under the present experimental conditions; intakes at or above 25% are associated with compromised hepatopancreatic health and growth, likely through the induction of oxidative stress, altered transcription of TLR/MyD88 pathway-related genes, and changes in apoptosis-related gene expression. Full article

Glioblastoma multiforme (GBM) is an aggressive primary brain tumor characterized by dysregulated cellular signaling and resistance to apoptosis. Pulsed electromagnetic field (PEMF) exposure has been reported to modulate cancer-related cellular processes, while resveratrol (RES), a natural polyphenol, exhibits notable antiproliferative and pro-apoptotic actions. Here, we investigated whether 75 Hz PEMF potentiates RES-mediated apoptosis in human glioblastoma U87-MG cells by examining key molecules involved in apoptotic signaling and the transcriptional responses of PI3K/AKT/mTOR pathway-related genes. U87-MG glioblastoma cells and non-tumour human astroglial SVG-P12 cells were cultured and divided into the following six groups: (I) untreated cells; (II) RES-treated cells; (III) temozolomide (TMZ)-treated cells; (IV) PEMF-exposed cells; (V) cells treated with RES followed by PEMF exposure; and (VI) cells treated with TMZ followed by PEMF exposure. Cell viability was assessed in both cell lines by alamar blue assay, and selectivity indices were derived from the resulting IC50 values. Apoptotic responses and gene expression profiles were assessed in U87-MG cells by flow cytometry and qRT-PCR, while selected apoptosis-related proteins were evaluated by Western blotting. RES treatment induced stronger cytotoxic effects than TMZ in U87-MG cells, and this response was markedly enhanced following PEMF exposure, the IC₅₀ falling from 33.64 to 10.53 µg/mL. In SVG-P12 astroglia the IC₅₀ of RES rose from 17.95 to 98.31 µg/mL under the same exposure, so that the selectivity index of RES increased from 0.53 to 9.34, whereas that of TMZ remained essentially unchanged (1.54 versus 1.50). Combined RES and PEMF treatment significantly increased both early and late apoptosis. Molecular analyses revealed upregulation of pro-apoptotic markers accompanied by an increased Bax/BcL-2 ratio, consistent with protein-level changes. Transcripts of PI3K/AKT/mTOR pathway-related components were also elevated relative to untreated cells, but to a markedly lesser extent than the apoptotic markers. PEMF exposure significantly enhances the pro-apoptotic effects of RES in glioblastoma cells while relatively preserving SVG-P12 cell viability, supporting further investigation of this combination as a potential adjuvant approach. Full article

Background/Objectives: Meningiomas frequently involve the adjacent skull bone. The bone tumor microenvironment (TME) represents a unique niche in bone-invasive tumors and bone metastases, and can promote tumor progression through tumor–stromal interactions. We hypothesized that the bone TME may contribute to tumor cell transcriptional changes and tumor growth in meningioma. Methods: Human malignant meningioma cell lines, IOMM-Lee and HKBMM, were implanted over the calvarial bone (bone TME) and into the dorsal skin (non-bone TME) of BALB/c-nu/nu mice. Tumors from the IOMM-Lee model underwent bulk RNA sequencing with computational separation of human- and mouse-derived reads, enabling ligand–target interaction analysis of stromal cell-to-tumor cell signaling. Differential gene expression analysis, enrichment analysis, ligand–target interaction analysis, multiplex immunofluorescence, and immunohistochemistry were performed. Results: Tumor volume was significantly greater in the bone TME than in the non-bone TME in both models, whereas the Ki-67 labeling index was significantly reduced. Transcriptomic analysis revealed distinct tumor cell transcriptional states in the bone TME, characterized by upregulation of inflammation-related genes and enrichment of inflammatory signaling pathways, including interferon responses and NF-κB signaling. Ligand–target interaction analysis of stromal cell-to-tumor cell signaling identified stromal IL1B as a candidate regulator of inflammatory transcriptional programs in tumor cells. F4/80-positive macrophages expressed IL-1β, and tumor cells were positive for phospho-IKKα/β and phospho-IκBα in the bone TME. Conclusions: Tumor–stromal interactions potentially involving macrophage-derived IL-1β may be associated with inflammatory transcriptional programs in meningioma cells and with meningioma enlargement in the bone TME. These interactions may be therapeutically relevant in meningioma with bone involvement. Full article

This exploratory qualitative action research study examined the implementation and iterative refinement of mindfulness–flow–awareness–coaching (MFAC), a sensory-based mindfulness coaching approach, and explored participants’ reported experiences. Six Korean university students completed pre-MFAC and post-MFAC interviews and the six-session MFAC framework. One participant’s initial Session 4 was discontinued after an unexpected recollection resulted in emotional overwhelm, and an adjusted Session 4 was conducted one week later, resulting in 37 session deliveries. The study drew on interview and session transcripts, participant records, action records, and observational and reflexive notes. The first author conducted a chronological implementation analysis and reflexive thematic analysis, which identified four practice-based principles: prioritising sensory noticing over interpretation, establishing psychological safety before task completion, balancing structural consistency with responsive adaptation, and framing action-oriented activities as revisable attempts. Three themes characterised participants’ reported experiences: greater openness to sensory and emotional experience, contextualised self-understanding through meaning-making, and movement towards feasible action. Participants also reported discomfort, interruptions, ambiguous experiences, and incomplete actions. These findings offer a contextually grounded account of how we refined MFAC and how participants interpreted their engagement. This study positions MFAC as a practice-informed approach rather than as evidence of therapeutic efficacy or causal psychological change. Future research employing diverse methodologies should examine its applicability and transferability to broader populations and settings. Full article

Selenium-dependent antioxidant systems are critical for neuronal redox balance, but whether Parkinson’s disease (PD) involves systemic selenium deficiency or selective utilization impairment remains unclear. Using Parkinson’s Progression Markers Initiative (PPMI) proteomic data, we identified specific downregulation of glutathione peroxidase 3 (GPX3) in cerebrospinal fluid in PD, suggesting a compartment-specific alteration in GPX3-related antioxidant defense rather than a uniform systemic selenium deficit. Inorganic selenium sources suffer from low bioavailability and narrow therapeutic windows. We therefore developed a selenium-enriched peptide fraction (IPP-Se-F12) via controlled selenization of Idesia polycarpa Maxim. cake meal peptides, and characterized its selenium content, size distribution, and radical-scavenging activity. In SH-SY5Y and nematode models, IPP-Se-F12 attenuated 6-hydroxydopamine (6-OHDA)-induced cell death and rescued locomotor and dopamine-dependent behaviors more effectively than sodium selenite treatment. RNAseq further showed that IPP-Se-F12 treatment was associated with transcriptional changes in dephosphorylation, axon-guidance, and GPX3-centered antioxidant networks, including increased expression of gpx-3 and gpx-5. This study supports IPP-Se-F12 as a plant-derived selenium-associated peptide fraction with protective activity in cellular and nematode models and identifies GPX-related antioxidant regulation as a candidate mechanism for further investigation. Full article

Background: Prostate cancer (PC) is a heterogeneous disease in which the histopathological grade does not always reflect underlying biological behavior. While transcriptomic studies have provided insight into tumor biology, grade-associated molecular changes remain incompletely defined, particularly in underrepresented populations such as those from the Middle East and North Africa (MENA) region. Methods: In this study, we used a pathology-guided transcriptomic approach to examine gene expression patterns across PC grades in a MENA cohort. RNA sequencing was performed on formalin-fixed paraffin-embedded (FFPE) tissues, including benign prostatic hyperplasia (BPH, n = 7), low-grade tumors (Gleason 6–7 [3 + 4]; LG; n = 7), and high-grade tumors (Gleason 7 [4 + 3]–10; HG; n = 7). Differential expressions, pathway-level enrichment analyses and the estimation of immune cell composition were carried out, followed by comparison with publicly available datasets (TCGA-PRAD, n = 496), including LG tumors (n = 292) and HG tumors (n = 204), using the GEPIA2 and UALCAN platforms. Selected genes were further assessed using qRT-PCR in an independent set of samples (n = 21). Representative immunohistochemical images from the Human Protein Atlas were reviewed to provide descriptive protein-level context across tumor grades. Results: Transcriptomic comparisons of tumor samples with benign controls identified a set of shared transcriptional changes present in both low- and high-grade disease. Among these, SLC29A2 and IL2RA showed consistent upregulation across tumor grades and similar expression trends in external datasets. Direct comparison between HG and LG tumors revealed distinct transcriptional profiles with patterns indicative of increased proliferative activity and altered immune-related signaling in higher-grade disease. Pathway-level analyses showed the enrichment of cell-cycle and metabolic gene signatures in HG tumors, whereas inflammatory and NF-κB-associated transcriptional signatures showed a comparatively reduced expression. Additional genes, including AAMDC, ASAH2, TNFRSF1B, NFKBIL1, and NFKBIZ, were associated with these grade-dependent differences. qRT-PCR findings were generally consistent with the RNA-seq results for selected targets. Conclusions: This study describes transcriptional patterns associated with the PC grade in a MENA cohort using a pathology-guided framework. The findings highlight candidate genes associated with tumor presence and grade progression and provide a foundation for further investigation in larger, well-annotated cohorts, particularly in populations that remain underrepresented in transcriptomic studies. Full article

Our study investigated the protective effects of seed priming with 5mM polyamine spermine (Spm) on the biochemical and transcriptional responses of winter wheat during Fusarium culmorum infection. We tested the effects of the priming in two age groups of plants via two pathogen infection approaches. In the seed-inoculated plants, infection with F. culmorum induced severe cellular damage and oxidative stress, as evidenced by increase in electrolyte leakage, thiobarbituric acid reactive substances, and hydrogen peroxide levels. The pathogen also triggered metabolic changes in the plants by elevating reducing sugars, free proline, total osmotically active solutes and peroxidase activity, while at the same time suppressing the activity of catalase. On the other hand, the 5 mM Spm seed priming significantly mitigated this pathogen-induced damage. The priming effectively lowered most oxidative stress biomarkers and reduced the over-accumulation of osmolytes. Spm also restored the suppressed catalase activity, stabilized superoxide dismutase activity and altered the pathogen-mediated transcriptional response of the tested defence enzymes. Furthermore, spermine priming enhanced glutathione S-transferase activity in infected 30-day-old plants. Overall, our findings demonstrate that 5 mM spermine seed priming modulates the physiological response to F. culmorum in wheat by optimizing antioxidant enzyme activity and returning the studied metabolic parameters to near control levels. Full article

Background: Long non-coding RNAs (lncRNAs) are widely proposed as determinants of temozolomide response in glioblastoma (GBM), but many nominations rest on analyst-derived survival endpoints, screens unadjusted for O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and models evaluated with the same data used to select them. We asked which lncRNA–outcome associations remain when endpoint definition, confounder adjustment, and external validation are addressed explicitly. Methods: We analyzed 94 IDH-wildtype, temozolomide-treated primary GBM patients from The Cancer Genome Atlas (TCGA), using the rule-based progression-free interval (PFI) of the TCGA Pan-Cancer Clinical Data Resource and overall survival (OS) as separate endpoints. A joint transcriptome-wide discovery for OS was performed across TCGA and the identically processed CPTAC-3 cohort (n = 282, 209 deaths), the latter unselected for IDH status because IDH annotation is unavailable for CPTAC-3, with adjustment for MGMT promoter methylation status, cellular composition, and expression subtype. Nominated transcripts were tested for external validation in two independent CGGA cohorts, and incremental discrimination was assessed as the optimism-corrected change in C-index (ΔC-index), benchmarked against the gain expected from a transcriptome-wide search alone. Results: No lncRNA was associated with PFI at a transcriptome-wide false-discovery rate (FDR) below 0.05. The joint OS discovery nominated DIO3OS, the only transcript reaching transcriptome-wide significance (hazard ratio 1.38 per standard deviation, 95% confidence interval 1.20–1.58, FDR 0.022), and C9orf139 (FDR 0.065); both were independently significant in each discovery cohort and robust to adjustment for MGMT status, cellular composition, and expression subtype. Both, however, were null with reversed point estimates in the two CGGA cohorts, were unassociated with PFI, and added only modest optimism-corrected discrimination (ΔC-index 0.07–0.11), close to what a transcriptome-wide search alone generates. Replication was thus confined to two cohorts sharing a processing pipeline. Conclusions: We nominate DIO3OS and C9orf139 as candidate survival-associated lncRNAs in GBM, requiring prospective evaluation in cohorts with complete IDH annotation and progression endpoints, and show how endpoint definition, selection optimism, and external validation determine which lncRNA associations survive scrutiny. Full article

Cytoplasmic stress granules (SGs) form in response to diverse insults; they are dismantled when the stress subsides. SG clearance is facilitated by molecular chaperones, nuclear transport factors, and other components. The anti-parasitic drug ivermectin inhibits nuclear trafficking and has potential anti-cancer activities. However, the molecular pathways that promote ivermectin’s therapeutic actions are poorly understood. Our study defined the effects of ivermectin on stress recovery in human neuroblastoma and cervical carcinoma cells. We demonstrate that ivermectin interferes with SG disassembly in neuroblastoma cells. The delay of SG dissolution is accompanied by significant changes in the proteostasis network. Notably, ivermectin diminishes de novo protein synthesis in unstressed and stressed cells. During recovery, ivermectin reduces the abundance of hsp70 in neuroblastoma, but not in cervical carcinoma cells. Surprisingly, ivermectin has no effect on Hsf1 abundance and localization. Moreover, ivermectin does not diminish the levels of transcripts encoding hsp70. Bioorthogonal Non-Canonical Amino Acid Tagging revealed that ivermectin markedly reduces the stress-induced de novo synthesis of hsp70 in neuroblastoma cells. Taken together, ivermectin can derail stress responses by a unique mechanism that alters the translation of hsp70 mRNA and is determined by the cellular context. This information is directly relevant to ivermectin-based anti-cancer therapies. Full article

Phosphate (P_i) deficiency induces responses that enhance P_i uptake and utilization. Light may influence these responses through photosynthetic carbon supply and signaling. We examined how light affects the early root transcriptional response to P_i deficiency in hydroponically grown soybean. Plants were exposed to phosphate-sufficient (+P) or phosphate-deficient (−P) conditions for 30 h under a light/dark cycle or continuous darkness. Root transcriptomes were analyzed using Oxford Nanopore cDNA sequencing. Principal component analysis (PCA) showed that transcriptomes separated mainly by light, with weaker separation by P_i status. Under light, P_i deficiency induced a broad response involving P_i transport, signaling, transcriptional regulation, lipid remodeling, and metabolism. In darkness, relatively few genes were upregulated under P_i deficiency. This limited response was not caused by a loss of transcriptional responsiveness, because thousands of genes were upregulated by darkness itself. Comparison of fold changes revealed that darkness attenuated, rather than reversed, the −P response. Interaction-ranked gene set enrichment analysis (GSEA) showed that the weaker response in darkness extended across signaling, metabolic, and transport pathways. Light-signaling genes responded strongly to darkness but showed little phosphate-dependent regulation. Root sucrose levels were lower in darkness, consistent with reduced carbon availability as a possible contributor to the attenuated P_i-deficiency response. Full article

Auxin plays a positive role in plant responses to low-phosphorus stress. However, the molecular mechanisms underlying indole-3-acetic acid (IAA)-mediated responses to phosphorus deficiency in alfalfa remain poorly understood. Alfalfa (Medicago sativa L.) cultivar ‘Zhongmu No. 3’ was subjected to two treatments: normal phosphorus (NP, 1000 μM KH₂PO₄) and low phosphorus supplemented with 1 μM IAA (LP + IAA, 10 μM KH₂PO₄). Morphological traits, physiological parameters, transcriptomic profiles, and metabolite accumulation were analyzed at 48 h and 10 days following treatment. Compared with the NP group, plants in the LP + IAA group showed marked changes in growth-related traits. At 48 h, plant height increased by 34%, total root length was 1.24-fold that of the NP group, and lateral root number increased by 23.48%. After 10 days, root fresh weight increased by 28%, total root length was 1.25-fold that of the NP group, lateral root number increased by 36.58%, and root volume increased by 22.2%, whereas plant height, stem diameter, and shoot fresh weight remained comparable to those of the NP group. Root acid phosphatase activity was 114.8% higher than that of the NP group at 48 h. Transcriptome analysis identified 1274 and 2277 differentially expressed genes (DEGs) between the NP and LP + IAA groups at 48 h and 10 days, respectively. At 48 h, the up-regulated genes were amino phospholipid ATPase 9 and amino alcohol phosphotransferase 1, whereas phosphate transporter 1 and purple acid phosphatase 12 were up-regulated at 10 days. Metabolomic analysis identified 308 and 1296 differentially accumulated metabolites (DAMs) at 48 h and 10 days, respectively. Early responses were enriched in purine metabolism and involved (5′-phosphoribosyl)-5-formamido-4-imidazolecarboxamide (FAICAR), whereas prolonged treatment involved L-aspartic acid, adenine, and cAMP. Integrated analyses identified tryptophan metabolism, cysteine and methionine metabolism, glycerophospholipid metabolism, and plant hormone signal transduction as major regulatory pathways. CDP-choline accumulation and changes in lipid-remodeling genes further indicated enhanced membrane phospholipid remodeling. Overall, these results provide insight into the morphological, physiological, transcriptional, and metabolic responses of alfalfa to low phosphorus in the presence of exogenous IAA. Full article

Bemisia tabaci is a globally important crop pest and virus vector with widespread resistance to conventional insecticides. We evaluated the insecticidal activity of a soybean-derived lecithin preparation and associated physiological responses. Leaf-surface, dried-residue contact, artificial-diet, and egg bioassays were combined with RNA sequencing, untargeted metabolomics, RT-qPCR, histology, and transmission electron microscopy. Dried-residue exposure yielded a 4 h LC₅₀ of 1.16 mg mL⁻¹ (95% confidence interval, 0.948–1.403 mg mL⁻¹), whereas 10 mg mL⁻¹ lecithin caused 100% adult mortality within 4 h and reduced egg hatchability from 99.44% to 37.78%. No mortality was detected after adults were provided with a sucrose diet containing 10 mg mL⁻¹ lecithin for 24 h. Exposure at the 4 h LC₅₀ was associated with differential expression of 135 genes and changes in 599 metabolic features, including responses related to cuticle organization, lysosomal and autophagy pathways, and amino acid metabolism. Histology and transmission electron microscopy revealed altered abdominal tissue organization and cellular ultrastructure. These findings establish contact-associated and egg-stage activity of lecithin against B. tabaci under laboratory conditions and identify accompanying structural, transcriptional, and metabolic responses. The molecular events responsible for mortality and the contribution of ingestion-mediated exposure remain unresolved. Full article

Kazakh horses are typical seasonal breeders, and ovarian activity is markedly reduced during the non-breeding period. Hormonal stimulation can induce ovarian functional responses during seasonal anestrus; however, the early ovarian transcriptional changes associated with this response remain incompletely understood. In this study, ovarian transcriptome sequencing was performed in 12 Kazakh mares examined during the seasonal anestrous period. The mares were classified into a non-hormonally stimulated seasonal quiescent group (DB, n = 6) and a hormone-induced ovarian activation group (DY, n = 6) following cloprostenol and eCG treatment. RNA sequencing and bioinformatics analyses were conducted to identify differentially expressed genes and enriched biological pathways. Using false-discovery-rate-corrected criteria (FDR < 0.05 and |log2FC| > 1), a total of 2119 differentially expressed mRNAs and 530 differentially expressed lncRNAs were identified between the two groups. FDR-corrected GO and KEGG enrichment analyses revealed significant changes associated with immune regulation, cellular communication, metabolic processes, and reproductive functions. KEGG pathway analysis demonstrated significant enrichment of complement and coagulation cascades, cytokine–cytokine receptor interaction, chemokine signaling pathway, PI3K–Akt signaling pathway, and ovarian steroidogenesis-related pathways (q ≤ 0.05). C1QB, CREB5, and IRS1 were prioritized as transcriptomic candidate genes based on their differential expression and pathway associations, but their functional roles were not experimentally tested. RT-qPCR analysis of selected DEGs showed expression trends concordant with the RNA-seq results and was used as a technical consistency assessment. Because the DY group was pharmacologically induced during seasonal anestrus and tissues were collected shortly after ultrasound confirmation of ovarian activation, the observed transcriptional profile should be interpreted as an early hormone-responsive state rather than a stable estrous state. Furthermore, because untreated naturally cycling mares during the reproductive season were not included, endogenous seasonal effects cannot be distinguished from pharmacological effects of hormonal stimulation. Full article

Molecular mechanisms underlying the progression from compensated eccentric hypertrophy to heart failure in chronic aortic regurgitation (AR) remain poorly understood. We investigated associated transcriptional changes induced by chronic volume overload in an experimental model of severe AR. AR was induced in male Wistar rats (n = 10) by retrograde aortic valve perforation and compared with age-matched control rats (n = 8). Sixty days after surgery, cardiac remodeling was evaluated by echocardiography, invasive hemodynamics and myocardial gene-expression profiling using RT-qPCR. Chronic AR induced marked left ventricular dilatation and systolic dysfunction, consistent with decompensated eccentric hypertrophy. These functional alterations were accompanied by coordinated transcriptional changes involving pathways related to apoptosis, oxidative balance, metabolic regulation and calcium handling. AR hearts exhibited an increased BAX/BCL2 ratio, together with reduced SOD2 and increased GPX1 expression, suggesting a transcriptional profile consistent with activation of pro-apoptotic and antioxidant responses. Metabolic remodeling was characterized by decreased AMPKα1, PPARγ and GLUT4 expression, together with increased OLR1 and 15-LOX. KLK10 expression was increased. Reduced SERCA2A expression was observed, consistent with transcriptional alterations involving calcium-handling pathways. Chronic AR is associated with marked structural and functional cardiac remodeling accompanied by coordinated transcriptional alterations across multiple pathways implicated in myocardial dysfunction. This provides potential molecular pathways for further investigation. Full article

Federal Reserve press conferences convey policy path information and uncertainty beyond formal decisions. This study tests whether transcript-derived risk language predicts the magnitude of financial market responses after policy surprises and event characteristics enter the model. The dataset contains 93 official press conference transcripts from April 2011 to June 2026, with 90 scheduled events in the primary sample. A Q&A lexical risk index combines standardised frequencies of negative, uncertainty, and weak modal terms from the Loughran–McDonald dictionary. The outcome is an equal weight composite of absolute S&P 500 returns, two- and ten-year Treasury yield changes, and US dollar returns during a 70 min press conference window. OLS models use HC3 standard errors, asset-specific regressions, influence analysis, permutation testing, and leave-one-out cross-validation. Q&A lexical risk does not predict larger responses. The full-model coefficient equals −0.063 (p = 0.444), incremental R² equals 0.0034, and prediction error rises by 0.60% after adding the index. Policy surprise magnitude remains the strongest predictor. The 90-event sample limits precision for small effects, with an approximate 80% minimum detectable effect of 0.230 response index units. The estimates describe conditional association and incremental predictive content. They do not test acoustic delivery, realised intraday volatility, or a causal communication effect. Full article