Perfluorooctane sulfonate (PFOS), a persistent organic pollutant widely present in daily life, accumulates in the human body through contaminated drinking water and poses significant risks to the reproductive system. However, the specific mechanisms underlying its toxicity to mammalian oocytes remain poorly understood. To address this research gap, this study employed an invitro maturation (IVM) model to systematically investigate the effects of PFOS on porcine oocyte maturation and embryonic development by supplementing with varying concentrations of PFOS and taurine, combined with morphological observations, gene expression analysis, and metabolomic profiling. The results demonstrated that PFOS exposure significantly impaired oocyte quality, as evidenced by inhibited polar body extrusion, reduced blastocyst formation rates, abnormal spindle assembly, and disrupted actin cytoskeleton and cortical granule distribution. Metabolomic analysis further revealed that taurine effectively ameliorated mitochondrial dysfunction by regulating PFOS-induced disturbances in lipid, amino acid, and energy metabolism. Immunofluorescence staining and RT-qPCR confirmed that PFOS exposure led to mitochondrial damage, triggering ROS generation and apoptosis, whereas taurine supplementation markedly mitigated these adverse effects. In conclusion, this study elucidates the molecular mechanisms by which PFOS impairs porcine oocyte quality and provides novel insights into intervention strategies for persistent organic pollutants, holding significant implications for improving female reproductive health.

Overexpression of PbWRKY66 negatively regulate phosphate uptake and root-to-shoot distribution in Arabidopsis.

Single-cell combined transcriptome explores the molecular mechanism of purine metabolism in keloids.

Most medications administered during pregnancy will enter the fetal circulation through the placenta. The activity of placental drug-metabolizing cytochrome P450 (CYP) enzymes modulates the extent of this transfer. However, many gaps exist in understanding how CYP expression and activity vary across gestation and how placental sex influences these changes. Therefore, we aimed to characterize the expression and activity of placental CYPs throughout gestation stratified by sex. Placentas were collected from participants who provided informed consent and received care at the University of Pennsylvania hospital between 18-23.5 weeks gestational age (GA; Tri2, n=27), 20-366/7 weeks GA for preterm delivery (preterm, n=40), or 37 to 41 weeks GA for uncomplicated delivery (term, n=40). The DESeq2 R package was used to perform differential expression analysis of CYP gene expression. CYP2C8 and 2D6 activity was measured in vitro using established mass spectrometry assays and analyzed using Kruskal Wallis-ANOVA. Placental expression of CYP1A2, CYP2C8, CYP3A5, and CYP3A7 decreased towards the end of pregnancy, whereasCYP2C9 and CYP2D6 expression increased toward the end of pregnancy. When considering placental sex, CYP2D6 expression was lower in Tri2 vs term in males (log2 fold change (logFC)=-1.1123) and females (logFC=-1.3750), whereas CYP2C8 was higher in the same comparisons (male logFC=1.4940, female logFC=1.2659). In females only, CYP2D6 and CYP2C8 activity increased in term vs Tri2 placentae (P=0.0004 and P=0.0281, respectively). Consistent with this, female placental CYP2D6 and CYP2C8 activity was positively associated with gestational age (P=0.0020 and P=0.0009, respectively). Placental activity of two CYPs responsible for metabolizing 25% of drugs increases from Tri2 to term in a sex-specific manner, which may affect fetal exposure to maternally administered medications metabolized by these isoforms.

Altered gene expression associated with postoperative delirium in patients undergoing surgery and anesthesia.

Synthesis of Tridax procumbens mediated TiO2 nanoparticles, investigation of antibacterial and anti-cancer activity against selected oral pathogens.

Defense priming enables plants to adopt a heightened state of alert without directly triggering defense responses, enabling faster and stronger activation upon subsequent stress. In this study evaluated zinc oxide nanoparticles (ZnO NPs) as a priming in wheat against spot blotch caused by Bipolaris sorokiniana . ZnO NPs priming alone did not induce visible defense responses; however, upon pathogen challenge, primed plants exhibited a significant increase in resistance. Among the tested concentrations, 15 mg L⁻¹ concentration was most effective, significantly enhancing shoot and root growth, biomass, and leaf area, while reducing disease severity by ⁓ 66.67% compared to unprimed infected plants. Primed plants also showed elevated chlorophyll and carotenoid contents, increased total ROS scavenging activity (77.01%), and reduced lipid peroxidation (37.37%). Antioxidant enzyme activities (SOD, CAT, APX) and levels of total phenolics (111.11%), ascorbic acid, proline (41.44%), PAL (59.86%), and POX (37.91%) were markedly enhanced, contributing to improved biochemical defense. Yield traits, including spike number, spike length, spikelet fertility and density, as well as thousand grain weight were positively affected. Notably, these benefits persisted in the F1 generation, indicating intergenerational effects. Epigenetic analysis revealed altered cytosine methylation in the promoter regions of PR1 and PR3 , correlating with elevated PR3 expression and suggesting heritable epigenetic reprogramming. Overall, this work provides the first evidence of ZnO NPs functioning as a defense priming agent and its intergenerational effect in wheat, offering a sustainable and heritable approach against spot blotch, with potential implications for crop protection and yield improvement. Graphical representation of the experimental workflow depicting the green synthesis, characterization, and application of ZnO NPs for intergenerational priming in wheat ( Triticum aestivum HUW 510) against spot blotch disease. ZnO NPs were synthesized using potato extract and 0.2 M zinc nitrate [Zn(NO₃)₂] at pH 6.5–7.5 and characterized by SEM, TEM, FTIR, and UV-Vis spectroscopy. Wheat seeds were treated with water (negative control), 0.2 M zinc nitrate (positive control), or ZnO NPs at concentrations of 5, 10, 15, and 20 mg/L, and grown under controlled conditions. In the F0 generation, plants were assessed for morphological traits and disease phenotypes. Based on disease response, 15 mg/L ZnO NPs was identified as the most effective concentration and was selected for further analysis of biochemical parameters, epigenetic modifications, gene expression, and yield attributes. Seeds from the F0 generation were then used to raise the F1 generation, which was similarly evaluated to investigate the persistence of priming-induced effects across generations.

Glioblastoma (GBM) is the most aggressive primary brain tumor with currently no treatment with long-term efficacy. Systematic relapses and therapeutic resistance are partly associated with the presence of glioblastoma stem cells (GSC) within the tumor. Existing options to overcome GSC protection are limited. Characterizing GSC resistance mechanisms appears crucial to identify efficient targeted inhibitors. A GSC model obtained by dedifferentiation of GBM cell lines (dGSC) was previously validated for GSC characteristics. In this study, viability of dGSC after treatment with diversified cytotoxic drugs was compared to parental cell lines. GSC phenotype acquisition is associated with a greatly decreased sensitivity to most cytotoxic drugs. Proteins expression, cell cycle and iron dosage analyses demonstrated that dGSC resistance acquisition is accompanied by decreased proliferation, STAT3 and Akt activation, increased iron storage and protection against oxidative stress. BMI1 and EZH2 epigenetic regulators are associated with resistance in GBM and were expressed in both dGSC and GBM cells. Akt activation in dGSC could redirect EZH2 toward histone methylation independent functions, through S21 phosphorylation. BMI1 and EZH2 inhibition decreased viability in both GBM cells and dGSC. Notably, EZH2 inhibition through GSK343 decreased proliferation and Akt activation, without impacting EZH2-associated epigenetic modification (H3K27me3), but with the induction of a ferroptosis signature. GSK343 effects on viability, proliferation and ferroptosis were confirmed in two lines of patient-derived GSC. GSK343 overcame resistant dGSC protection to trigger cell death by a mechanism involving oxidative stress. To conclude, GSK343-mediated EZH2 inhibition efficiently eliminated resistant GSC through ferroptosis, in a H3K27me3-independent manner.

Identification and validation of a pyroptosis-relevant model for the prognosis of cutaneous melanoma

Differential gene expression (DGE) analysis enables researchers to investigate the link between gene expression and the phenotypic responses observed in organisms across time, experimental, or field conditions. Accurate quantification of gene expression is essential when performing DGE experiments, with a range of methods having been developed to enable the study of gene expression within a species. Quantifying differences in expression not just within but across multiple species can also be used to reveal the genetic mechanisms underlying phenotypic differences observed between species. Accurate quantification of gene expression across multiple species requires a suitable reference; it should include each species' own expressed transcripts to mitigate reference bias, with the orthology relationships of transcripts being used to facilitate comparison of expression at the gene level. Production of such a reference remains a challenge, despite its necessity for minimising bias during multispecies DGE analysis. Our software BINge specifically aims to address this need through use of a novel approach to modelling orthology which results in multispecies transcript clusters that accurately reflect their locus orthology. Evaluation experiments demonstrate the effectiveness of this approach over existing clustering methods which have not been designed for producing a reference suitable for multispecies DGE analysis. Source code and documentation for BINge are available from the GitHub repository at https://github.com/zkstewart/BINge.

Cerebellar focused ultrasound stimulation modulates neural response at hippocampus and suppresses epileptiform activity.

Cellular responses of human Muller glia exposed to test dust pollution.

Gut-brain axis-mediated mechanisms and immune regulatory pathways in vascular dementia: Insights into microbiota-derived metabolites and novel therapeutic strategies.

Osteoarthritis (OA) is a degenerative joint disorder characterized by progressive articular cartilage destruction and chronic inflammation. However, the dynamic changes in immune cell subpopulations during OA progression and their specific regulatory interactions with chondrocyte subsets remain poorly understood. We aim to comprehensively characterize disease-specific subpopulations of chondrocytes and their distinct molecular signatures, as well as to decode the compositional diversity of infiltrating immune cells by a secondary observational analysis of public GEO database. We integrated four single-cell RNA sequencing datasets of 20 knee OA patients and 6 healthy donors. Cellular subpopulations were identified using t-SNE-based clustering. Differential gene expression analysis was performed, followed by pathway enrichment analysis to elucidate key biological processes. Chondrocyte differentiation trajectories were reconstructed using pseudotime analysis. Intercellular communication networks were deciphered using CellChat. Chondrocytes were subdivided into eight distinct subpopulations. GO enrichment analysis highlighted extracellular matrix deposition, mineralization, and chondrocyte differentiation as central biological events. Trajectory analysis indicated that fibrotic chondrocytes occupy terminal positions. Among lymphocytes, effector T cells and NK cells appeared to mediate cytotoxic effects, with complement pathway activation playing a key role in regulating their functions. Macrophages constituted the majority of myeloid cells and were categorized into four subpopulations, among C1Q+macrophages were strongly associated with complement activation. CellChat analysis suggested that MIF signaling may promote inflammatory microenvironment formation in OA. We propose a model wherein chondrocyte-derived MIF recruits immune cells during progression of OA. Attached immune cells collectively sustain a chronic inflammatory milieu. Additionally, C1Q+macrophages produce complement components that activate the complement cascade, stimulating C5AR1+macrophages and enhancing lymphocyte-mediated cytotoxicity. These findings provide novel insights into the cellular mechanisms and intercellular crosstalk underlying OA progression. Key Points • The fibrotic chondrocytes occupy terminal differentiation stages of chondrocytes in OA. • Complement-activated effector T cells and NK cells mediate cytotoxic effects within the OA microenvironment. • C1Q⁺macrophages were closely linked to complement activation. • MIF signaling may promote inflammatory microenvironment formation in OA.

Atherosclerosis, a leading cause of cardiovascular disease, is driven by the accumulation of oxidized low-density lipoproteins (oxLDL) in arterial walls. 7-Ketocholesterol (7KC), a major oxysterol found in oxLDL and atherosclerotic plaques, triggers multiple cell injuries including loss of lysosomal integrity, oxidative stress, apoptosis, and impaired autophagy in vascular cells. Bis(monoacylglycero)phosphate (BMP), also known as lysobisphosphatidic acid, is a unique phospholipid concentrated in the endolysosomal compartment, known to regulate vesicle dynamics, lysosomal enzyme activities, intracellular cholesterol trafficking and its oxidative metabolism. Using a validated model of BMP enrichment in murine RAW 264.7 macrophages, we investigated whether BMP could exert protective activity against 7KC-induced damage. Our findings revealed that BMP enrichment provides comprehensive protection against 7KC at the cellular level by preserving cell viability, morphology, and neutral lipid balance. Mechanistically, BMP enrichment prevented apoptosis by maintaining mitochondrial integrity and blocking caspase activation. This was demonstrated by normalized BAX/BCL2 ratios, preserved pro-Caspase-3 levels, and reduced PARP cleavage. Remarkably, BMP enrichment also restored autophagic flux, thereby preventing the pathological accumulation of LC3-II and p62 that characterizes autophagy dysfunction. Enhanced colocalization between LC3 and BMP suggests direct functional interactions in the stress response. Gene expression analysis confirmed that BMP enrichment normalized the transcriptional dysregulation of key autophagy regulators, including Sqstm1, Becn1, and Pink1. Taken together, these results suggest that BMP is an endogenous protective factor that counteracts 7KC-induced cellular damage at multiple steps by regulating cell death and autophagy pathways in a coordinated manner.

Phytotherapeutic potential of Bauhinia purpurea Linn. in hyperoxic lung injury: Insights from in vivo, network pharmacology and in silico analyses.

Childhood obesity is a growing global health crisis associated with an increased risk of metabolic and cardiovascular diseases in adulthood. While accumulating evidence implicates immune dysregulation in obesity pathogenesis, the specific transcriptional alterations of immune cells, particularly NK cells and T cells in the context of childhood obesity, and their potential as non-invasive diagnostic biomarkers, remain largely unexplored. Here, we investigated the transcriptional alterations of NK cells and T cells in childhood obesity and evaluated their potential as non-invasive diagnostic biomarkers. To this end, we integrated bulk RNA-seq datasets (GSE205668 and GSE87493), adipose single-cell RNA-seq data (GSE159960), and blood qPCR validation to identify NK- and T-cell-related diagnostic biomarkers for childhood obesity. Differential expression analysis and WGCNA were applied to the bulk datasets to derive obesity-associated candidates, and single-cell RNA-seq was used to define immune-cell composition, infer NK-cell pseudotemporal dynamics, and quantify cell-cell communication. Genes shared between the bulk and single-cell analyses were prioritized using an ensemble machine-learning workflow comprising 110 model configurations and five feature-selection methods. TBC1D10C expression was validated by qPCR in an independent cohort of 29 children. Transcriptome-based analyses indicated reduced relative representation of NK cells and T cells in childhood obesity, with altered transcriptional programs and inferred impairment of NK-CD4 + T-cell communication. A 13-gene NK- and T-cell-based diagnostic signature was derived, and TBC1D10C was consistently prioritized by all feature-selection methods. The signature showed good discrimination between childhood obesity and controls across datasets (AUC 0.753-0.808), and comparable performance was observed for TBC1D10C alone. Enrichment analyses associated higher TBC1D10C expression with immune pathways, including Th1/Th2 differentiation, IL-17 signaling, and NK cell-mediated cytotoxicity. qPCR confirmed significant upregulation of TBC1D10C in peripheral blood from children with obesity. Across independent cohorts and platforms, TBC1D10C was identified as a reproducible NK- and T-cell-associated biomarker for childhood obesity, and immune dysregulation relevant to obesity pathophysiology may be reflected by its expression. Therefore, we propose TBC1D10C as a promising diagnostic biomarker and highlight its potential role in the immunopathology of childhood obesity.

Single-cell transcriptomics and metabolomics demonstrate that Taohe Chengqi decoction alleviates sepsis-associated acute lung injury by modulating immunometabolism.

Cell migration and adhesion in autophagy-induced damage of human trophoblast cells.

Microbiota-responsive BmMBF2-11 limits dysbiosis and promotes intestinal immune homeostasis in the silkworm.