Search Results (10,482)

The antioxidant properties of resveratrol (RES) against oxidative toxicity induced by testicular toxicants are well documented. The current study aimed to investigate the probable beneficial role of RES on male reproduction in adult rats following prepubertal exposure to perfluorooctanoic acid (PFOA). Healthy rats of the Wistar strain (23 days old) were allocated into four groups. Rats in group I did not receive any treatment, while rats in groups II, III, and IV received RES, PFOA, and RES + PFOA, respectively, between days 23 and 56 and were monitored for up to 90 days. Exposure to PFOA resulted in a significant reduction in spermiogram parameters, testicular 3β- and 17β-HSD activity levels, and circulatory levels of testosterone. A significant elevation in LPx, PCs, H₂O₂, and O₂⁻, associated with a concomitant reduction in SOD, CAT, GPx, GR, and GSH, was noticed in the testes, as well as region-specific changes in pro- and antioxidants in the epididymides of exposed rats compared to controls. A significant increase in serum FSH and LH, testicular cholesterol levels, and caspase-3 activity was observed in PFOA-exposed rats compared to controls. Histological analysis revealed that the integrity of the testes was deteriorated in PFOA-exposed rats. Transcriptomic profiling of the testes and epididymides revealed 98 and 611 altered genes, respectively. In the testes, apoptosis and glutathione pathways were disrupted, while in the epididymides, glutathione and bile secretion pathways were altered in PFOA-exposed rats. PFOA exposure resulted in the down-regulation in the testes of 17β-HSD, StAR, nfe2l2, ar, Lhcgr, and mRNA levels, associated with the up-regulation of casp3 mRNA, and down-regulation of alpha 1 adrenoceptor, muscarinic choline receptor 3, and androgen receptor in the epididymides of exposed rats compared to the controls. These events might lead to male infertility in PFOA-exposed rats. In contrast, restoration of selected reproductive variables was observed in RES plus PFOA-exposed rats compared to rats exposed to PFOA alone. Taken together, we postulate that prepubertal exposure to PFOA triggered oxidative damage and altered genes in the testes and epididymides, leading to suppressed male reproductive health in adult rats, while RES, with its steroidogenic, antiapoptotic, and antioxidant effects, restored PFOA-induced fertility potential in rats. Full article

Backgroub/Objectives: Exploring how early-life nutritional interventions may impact future generations, this study examines the inter- and transgenerational effects of in ovo injection of bioactive compounds on gene expression in the cecal tonsils and cecal mucosa using a chicken model. Methods: Synbiotic PoultryStar^® (Biomin) and choline were injected in ovo on the 12th day of egg incubation. Three experimental groups were established in the generation F1: (1) a control group (C) receiving 0.9% physiological saline (NaCl), (2) a synbiotic group (SYN) receiving 2 mg/embryo, and (3) a combined synbiotic and choline group (SYNCH) receiving 2 mg synbiotic and 0.25 mg choline per embryo. For the generations F2 and F3, the SYN and SYNCH groups were each divided into two subgroups: (A) those injected solely in F1 (SYNs and SYNCHs) and (B) those injected in each generation (SYNr and SYNCHr). At 21 weeks posthatching, cecal tonsil and cecal mucosa samples were collected from F1, F2, and F3 birds for transcriptomic analysis. Results: Gene expression profiling revealed distinct intergenerational and transgenerational patterns in both tissues. In cecal tonsils, a significant transgenerational impact on gene expression was noted in the generation F3, following a drop in F2. In contrast, cecal mucosa showed more gene expression changes in F2, indicating intergenerational effects. While some effects carried into F3, they were less pronounced, except in the SYNs group, which experienced an increase compared to F2. Conclusions: The study highlights that transgenerational effects of epigenetic modifications are dynamic and unpredictable, with effects potentially re-emerging in later generations under certain conditions or fading or intensifying over time. This study provides valuable insights into how epigenetic nutritional stimulation during embryonic development may regulate processes in the cecal tonsils and cecal mucosa across multiple generations. Our findings provide evidence supporting the phenomenon of epigenetic dynamics in a chicken model. Full article

Endothelial cells throughout the body sense blood flow, eliciting transcriptional and phenotypic responses. The brain endothelium, known as the blood–brain barrier (BBB), possesses unique barrier and transport properties, which are in part regulated by blood flow. We utilized RNA sequencing to analyze the transcriptome of primary cultured rat brain microvascular endothelial cells (BMECs), as well as three human induced pluripotent stem cell-derived models. We compared the transcriptional responses of these cells to either low (0.5 dyne/cm²) or high (12 dyne/cm²) shear stresses, and subsequent analyses identified genes and pathways that were influenced by shear including key BBB-associated genes (SLC2A1, LSR, PLVAP) and canonical endothelial shear-stress-response transcription factors (KLF2, KLF4). In addition, our analysis suggests that shear alone is insufficient to rescue the de-differentiation caused by in vitro primary BMEC culture. Overall, these datasets and analyses provide new insights into the influence of shear on BBB models that will aid in model selection and guide further model development. Full article

Ascorbic acid (AsA) is an important antioxidant for human health. The concept of “oil-vegetable-duel-purpose” can significantly enhance the economic benefits of the rapeseed industry. Rapeseed, when utilized as a vegetable, serves as a valuable food source of AsA. In this study, we integrated transcriptome and metabolome analyses, along with substrate feeding, to identify the L-galactose pathway as the primary source for AsA production, which is primarily regulated by light. Through seven different photoperiod treatments from 12 h/12 h (light/dark) to 24 h/0 h, we found that AsA content increased with longer photoperiods, as well as chlorophyll, carotenoids, and soluble sugars. However, an excessively long photoperiod led to photooxidative stress, which negatively affected biomass accumulation in rapeseed seedlings and subsequently impacted the total accumulation of AsA. Furthermore, different enzymes respond differently to different photoperiods. Analysis of the correlation between the expression levels of AsA biosynthesis-related genes and AsA content highlighted a dynamic balancing mechanism of AsA metabolism in response to different photoperiods. The study revealed that the 16 h/8 h photoperiod is optimal for long-term AsA accumulation in rapeseed seedlings. However, extending the photoperiod before harvest can enhance AsA content without compromising yield. These findings offer novel insights into an effective strategy for the biofortification of AsA in rapeseed. Full article

Cold tolerance in rapeseed is closely related to its growth, yield, and geographical distribution. However, the mechanisms underlying cold resistance in rapeseed remain unclear. This study aimed to explore cold resistance genes and provide new insights into the molecular mechanisms of cold resistance in rapeseed. Rapeseed M98 (cold-sensitive line) and D1 (cold-tolerant line) were used as parental lines. In their F₂ population, 30 seedlings with the lowest cold damage levels and 30 with the highest cold damage levels were selected to construct cold-tolerant and cold-sensitive pools, respectively. The two pools and parental lines were analyzed using bulk segregant sequencing (BSA-seq). The G’-value analysis indicated a single peak on Chromosome C09 as the candidate interval, which had a 2.59 Mb segment with 69 candidate genes. Combined time-course and weighted gene co-expression network analyses were performed at seven time points to reveal the genetic basis of the two-parent response to low temperatures. Twelve differentially expressed genes primarily involved in plant cold resistance were identified. Combined BSA-seq and transcriptome analysis revealed BnaC09G0354200ZS, BnaC09G0353200ZS, and BnaC09G0356600ZS as the candidate genes. Quantitative real-time PCR validation of the candidate genes was consistent with RNA-seq. This study facilitates the exploration of cold tolerance mechanisms in rapeseed. Full article

Skeletal dysplasias, characterized by bone, cartilage, and connective tissue abnormalities, often arise due to disruptions in extracellular matrix (ECM) dynamics and growth factor-dependent signaling pathways. RSPRY1, a secreted protein with RING and SPRY domains, has been implicated in bone development, yet its exact role remains to be determined. RSPRY1 gene mutations are associated with spondyloepimetaphyseal dysplasia (SEMD), a rare skeletal disorder characterized by severe epiphyseal and metaphyseal deformities. This study aimed to determine the molecular and cellular mechanisms by which RSPRY1 deficiency affects skeletal homeostasis. Transcriptome analysis of fibroblasts from patients with homozygous RSPRY1 mutations showed there was significant enrichment of transforming growth factor beta (TGF-β) signaling and ECM-related pathways. Functional wound healing assays showed that RSPRY1 knockout fibroblasts exhibited enhanced motility, a phenotype that was abrogated in RSPRY1 + SMAD3 double knockout fibroblasts, highlighting the SMAD3-dependence of RSPRY1′s effects. The observed limited response to exogenous TGF-β in RSPRY1-deficient cells indicated that there was constitutive pathway activation. These findings show that RSPRY1 is a critical regulator of TGF-β signaling in ECM dynamics and cell motility, contributing to the pathophysiology of SEMD. An improvement in our understanding of the molecular roles of RSPRY1 might yield novel therapeutic strategies that target TGF-β signaling in patients with SEMD and other skeletal dysplasias. Full article

Objective: To investigate the preclinical efficacy and identify predictive biomarkers of polo-like kinase 1 (PLK1) inhibitors in small cell lung cancer (SCLC) models. Methods: We tested the cytotoxicity of selective PLK1 inhibitors (rigosertib, volasertib, and onvansertib) in a panel of SCLC cell lines. We confirmed the therapeutic efficacy of subcutaneous xenografts of representative cell lines and in four patient-derived xenograft models generated from patients with platinum-sensitive and platinum-resistant SCLC. We employed an integrated analysis of genomic and transcriptomic sequencing data to identify potential biomarkers of the activity and mechanisms of resistance in laboratory-derived resistance models. Results: Volasertib, rigosertib, and onvansertib showed strong in vitro cytotoxicity at nanomolar concentrations in human SCLC cell lines. Rigosertib, volasertib, and onvansertib showed equivalent efficacy to that of standard care agents (irinotecan and cisplatin) in vivo with significant growth inhibition superior to cisplatin in PDX models of platinum-sensitive and platinum-resistant SCLC. There was an association between YAP1 expression and disruptive or inactivation TP53 gene mutations, with greater efficacy of PLK1 inhibitors. Comparison of lab-derived onvansertib-resistant H526 cells to parental cells revealed differential gene expression with upregulation of NAP1L3, CYP7B1, AKAP7, and FOXG1 and downregulation of RPS4Y1, KDM5D, USP9Y, and EIF1AY highlighting the potential mechanisms of resistance in the clinical setting. Conclusions: We established the efficacy of PLK1 inhibitors in vitro and in vivo using PDX models of platinum-sensitive and resistant relapsed SCLC. An ongoing phase II trial is currently testing the efficacy of onvansertib in patients with SCLC (NCT05450965). Full article

Orchids have evolved flowers with unique morphologies through coevolution with pollinators, such as insects. Among the floral organs, the lip (labellum), one of the three petals, exhibits a distinctive shape and plays a crucial role in attracting pollinators and facilitating pollination in many orchids. The lip of the terrestrial orchid Habenaria radiata is shaped like a flying white bird and is believed to attract and provide a platform for nectar-feeding pollinators, such as hawk moths. To elucidate the mechanism of lip morphogenesis, we conducted time-lapse imaging of blooming flowers to observe the extension process of the lip and analyzed the cellular morphology during the generation of serrations. We found that the wing part of the lip folds inward in the bud and fully expands in two hours after blooming. The serrations of the lip were initially formed through cell division and later deepened through polar cell elongation. Transcriptome analysis of floral buds revealed the expression of genes involved in floral organ development, cell division, and meiosis. Additionally, genes involved in serration formation are also expressed in floral buds. This study provides insights into the mechanism underlying the formation of the unique lip morphology in Habenaria radiata. Full article

Fluorene-9-bisphenol (BHPF) has been increasingly used as a bisphenol A substitute in the synthesis of various products. Previous studies have suggested that BHPF can be released from plastic bottles into drinking water, and BHPF accumulation has been reported to cause various adverse effects in humans. Nevertheless, the impact of BHPF exposure on endometrial epithelial cells remains largely unexplored. Here, we investigated the effects of exposure to different concentrations of BHPF on endometrial cells and used integrated metabolomic and transcriptomic methods to elucidate the underlying molecular mechanisms. Our results revealed significant associations between specific metabolites and genes, indicating that low-concentration exposure to BHPF affects endometrial epithelial cells by targeting pathways related to primary immunodeficiency, in which the key genes are IL7R and PTPRC. High-concentration exposure to BHPF decreased cell viability by regulating the purine metabolism pathway, as well as dysregulating the expression of PGM1, PDE3B, AK9, and ENTPD8. Our study highlights that the health risk of BHPF exposure to endometrial epithelial cells is concentration-dependent and that integrated analysis of metabolomic and transcriptomic data not only revealed the biological effects of BHPF and its underlying mechanisms, but also provided key candidate target genes for further exploration. Full article

Introduction: Prostate cancer, notably prostate adenocarcinoma (PARD), has high incidence and mortality rates. Although typically resistant to immunotherapy, recent studies have found immune targets for prostate cancer. Stratifying patients by molecular subtypes may identify those who could benefit from immunotherapy. Methods: We used single-cell and bulk RNA sequencing data from GEO and TCGA databases. We characterized the tumor microenvironment at the single-cell level, analyzing cell interactions and identifying fibroblasts linked to mitophagy. Target genes were narrowed down at the bulk transcriptome level to construct a PARD prognosis prediction nomogram. Unsupervised consensus clustering classified PARD into subtypes, analyzing differences in clinical features, immune infiltration, and immunotherapy. Furthermore, the cellular functions of the genes of interest were verified in vitro. Results: We identified ten cell types and 160 mitophagy-related single-cell differentially expressed genes (MR-scDEGs). Strong interactions were observed between fibroblasts, endothelial cells, CD8⁺ T cells, and NK cells. Fibroblasts linked to mitophagy were divided into six subtypes. Intersection of DEGs from three bulk datasets with MR-scDEGs identified 26 key genes clustered into two subgroups. COX regression analysis identified seven prognostic key genes, enabling a prognostic nomogram model. High and low-risk groups showed significant differences in clinical features, immune infiltration, immunotherapy, and drug sensitivity. In prostate cancer cell lines, CAV1, PALLD, and ITGB8 are upregulated, while CLDN7 is downregulated. Knockdown of PALLD significantly inhibits the proliferation and colony-forming ability of PC3 and DU145 cells, suggesting the important roles of this gene in prostate cancer progression. Conclusions: This study analyzed mitophagy-related genes in PARD, predicting prognosis and aiding in subtype identification and immunotherapy response analysis. This approach offers new strategies for treating prostate cancer with specific molecular subtypes and helps develop potential biomarkers for personalized medicine strategies. Full article

Clock genes regulate physiological and metabolic processes by responding to changes in environmental light and temperature, and genetic variations in these genes may facilitate environmental adaptation, offering opportunities for resilience to climate change. However, the genetic and molecular mechanisms remain unclear in marine organisms. In this study, we investigated the role of a key clock gene, the circadian locomotor output cycles kaput (Clock), in thermal adaptation using DNA affinity purification sequencing (DAP-Seq) and RNA interference (RNAi)-based transcriptome analysis. In cold-adapted Crassostrea gigas and warm-adapted Crassostrea angulata, Clock was subject to environmental selection and exhibited contrasting expression patterns. The transcriptome analysis revealed 2054 differentially expressed genes (DEGs) following the knockdown of the Clock expression, while DAP-Seq identified 150,807 genes regulated by Clock, including 5273 genes located in promoter regions. The combined analyses identified 201 overlapping genes between the two datasets, of which 98 were annotated in public databases. These 98 genes displayed distinct expression patterns in C. gigas and C. angulata under heat stress, which were potentially regulated by Clock, indicating its role in a molecular regulatory network that responds to heat stress. Notably, a heat-shock protein 70 family gene (Hsp12b) and a tripartite motif-containing protein (Trim3) were significantly upregulated in C. angulata but showed no significant changes in C. gigas, further highlighting their critical roles in thermal adaptation. This study preliminarily constructs a thermal regulatory network involving Clock, providing insights into the molecular mechanisms of clock genes in thermal adaptation. Full article

Background: N6-methyladenosine (m⁶A) modification plays a crucial role in the regulation of diverse cellular processes influenced by environmental factors. Nevertheless, the involvement of m⁶A-modified long noncoding RNAs (lncRNAs) in the pathogenesis of lung injury induced by particulate matter (PM) remains largely unexplored. Methods: Here, we establish a mouse model of PM-induced lung injury. We utilized m6A-modified RNA immunoprecipitation sequencing (MeRIP-seq) to identify differentially expressed m6A peaks on long non-coding RNAs (lncRNAs). Concurrently, we performed lncRNA sequencing (lncRNA-seq) to determine the differentially expressed lncRNAs. The candidate m6A-modified lncRNAs in the lung tissues of mice were identified through the intersection of the data obtained from these two sequencing approaches. Results: A total of 664 hypermethylated m⁶A peaks on 644 lncRNAs and 367 hypomethylated m⁶A peaks on 358 lncRNAs are confirmed. We use bioinformatic tools to analyze the potential functions and pathways of these m⁶A-modified lncRNAs, revealing their involvement in regulating inflammation, immune response, and metabolism-related pathways. Three key m⁶A-modified lncRNAs (lncRNA NR_003508, lncRNA uc008scb.1, and lncRNA ENSMUST00000159072) are identified through a joint analysis of the MeRIP-seq and lncRNA-seq data, and their validation is carried out using MeRIP-PCR and qRT-PCR. Analysis of the coding-non-coding gene co-expression network reveals that m⁶A-modified lncRNAs NR_003508 and uc008scb.1 participate in regulating pathways associated with inflammation and immune response. Conclusions: This study first provides a comprehensive transcriptome-wide analysis of m⁶A methylation profiling in lncRNAs associated with PM-induced lung injury and identifies three pivotal candidate m⁶A-modified lncRNAs. These findings shed light on a novel regulatory mechanism underlying PM-induced lung injury. Full article

Puan Panjiang black-bone chickens are renowned for their distinctive traits, deep black coloration, and high-quality protein content, making them a focus of genetic research due to their unique egg-laying abilities. In this study, 110 Puan Panjiang black-bone chickens were used to investigate the effects of natural and artificial selection influencing egg production. Whole-genome resequencing data from red junglefowl (RJF) and high-egg-production (HEP) and low-egg-production (LEP) groups of Puan Panjiang black-bone chickens revealed significant genetic variants associated with egg production traits. Additionally, transcriptome analysis of 47 samples from ovary stroma, small white follicles (SWFs), small yellow follicles (SYFs), and liver tissues from 6 HEP and 6 LEP groups identified differentially expressed genes. Notably, differences in egg production were linked to small yellow follicles rather than ovary stroma or SWFs. Key candidate genes, including TRIM7, CASR, SPTBN5, GAL1, ZP1, IL4I1, and CCL19, were identified as potential contributors to egg-laying performance. This study underscores the genetic diversity within this breed and provides valuable insights for future breeding programs to enhance egg production, supporting the sustainable development of this local resource. Full article

Sperm cytoplasmic droplets (CDs) are remnants of cytoplasm that can cause a number of problems if it not shed from the sperm after ejaculation. Exosomes can rapidly bind to sperm, but it is not clear whether exosomes can affect the migration and shedding of CDs. We first extracted and characterized seminal plasma exosomes from boar semen containing sperm with low or high rates of CDs. Then, the transcriptomic and proteomic detection of these exosomes were performed to analyze the differences between the two groups of seminal plasma exosomes. The results revealed that 486 differentially expressed genes (DEGs), 40 differentially expressed proteins (DEPs), and 503 differentially expressed lncRNAs (DElncRNAs) were identified between the low CD rate group and high CD rate group. Integrative multi-omics analysis showed that exosome components may affect migration and shedding of cytoplasmic droplets by influencing cytoskeletal regulation and insulin signaling, including regulation of the actin cytoskeleton, ECM–receptor interaction, axon guidance, insulin secretion, and the insulin signaling pathway. Overall, our study systematically revealed the DEGs, DEPs, and DElncRNAs in seminal plasma exosomes between low CD rate semen and high CD rate semen, which will help broaden our understanding of the complex molecular mechanisms involved in the shedding of CDs. Full article

The TEOSINTE-BRANCHED1/CYCLOIDEA/PROLIFERATING-CELL-FACTOR (TCP) gene family, a plant-specific transcription factor family, plays pivotal roles in various processes such as plant growth and development regulation, hormone crosstalk, and stress responses. However, a comprehensive genome-wide identification and characterization of the TCP gene family in peanut has yet to be fully elucidated. In this study, we conducted a genome-wide search and identified 51 TCP genes (designated as AhTCPs) in peanut, unevenly distributed across 17 chromosomes. These AhTCPs were phylogenetically classified into three subclasses: PCF, CIN, and CYC/TB1. Gene structure analysis of the AhTCPs revealed that most AhTCPs within the same subclade exhibited conserved motifs and domains, as well as similar gene structures. Cis-acting element analysis demonstrated that the AhTCP genes harbored numerous cis-acting elements associated with stress response, plant growth and development, plant hormone response, and light response. Intraspecific collinearity analysis unveiled significant collinear relationships among 32 pairs of these genes. Further collinear evolutionary analysis found that peanuts share 30 pairs, 24 pairs, 33 pairs, and 100 pairs of homologous genes with A. duranensis, A. ipaensis, Arabidopsis thaliana, and Glycine max, respectively. Moreover, we conducted a thorough analysis of the transcriptome expression profiles in peanuts across various tissues, under different hormone treatment conditions, in response to low- and high-calcium treatments, and under low-temperature and drought stress scenarios. The qRT-PCR results were in accordance with the transcriptome expression data. Collectively, these studies have established a solid theoretical foundation for further exploring the biological functions of the TCP gene family in peanuts, providing valuable insights into the regulatory mechanisms of plant growth, development, and stress responses. Full article