Search Results (5,826)

A new trinor-sesterterpenoid penitalarin D (1), with a 3,6-dioxabicyclo[3.1.0]hexane moiety, as well as two known compounds, penitalarin C (2) and nafuredin A (3), were obtained from the mangrove sediment-derived Talaromyces sp. SCSIO 41412. Their structures were determined by detailed NMR, MS spectroscopic analyses, and ECD calculations. Penitalarin D (1) and nafuredin A (3) showed toxicity or no toxicity against HepG2 cells at a concentration of 200 μM. The transcriptome sequencing and bioinformatics analysis revealed that 3 could be effective by regulating ferroptosis pathways in HepG2 cells, which was subsequently validated by RT-qPCR, demonstrating significant upregulation of ferroptosis-related genes. Pre-treatment with 3 could mitigate hypoxia-reoxygenation-induced damage in the oxygen glucose deprivation/reperfusion (OGD/R) cell model. Given the structural similarity of compounds 1, 2, and 3, we also screened compounds 1 and 2 in an AML12 OGD/R model. As no significant activity was observed, compound 3 was selected for subsequent in vivo studies. Subsequently, in vivo experiments demonstrated that 3 could significantly decrease pro-inflammatory cytokines and display the hepatoprotective effects against hepatic ischemia-reperfusion injury (HIRI). These findings identified nafuredin A (3) as a promising hepatoprotective agent for new drug development. Full article

BRAF inhibitors have a 50–70% response rate in melanoma but are less effective for thyroid cancer. Differential response may be from activation or expression of downstream mitogen-activated protein kinase (MAPK) pathway genes. Retrospective analysis compared whole exome and transcriptome sequencing in melanoma and thyroid cancers from April 2019 to October 2023. The MAPK Activation Score (MPAS) was calculated using Z-score normalized/log-transformed values indicating expression across 10 MAPK-associated genes. Our tumor registry provided outcome data. BRAF V600E mutations were identified in 33 of 200 (17%) melanomas and 14 (7%) had other BRAF mutations (V600K/R). Of 49 thyroid tumor samples, BRAF V600E mutations were found in 19 (39%). RNA expression of BRAF and the 10 MAPK-associated genes were increased in melanomas with V600E compared to wild-type BRAF (p = 0.02). Conversely, BRAF V600E mutation in thyroid cancer was not associated with increased expression nor MAPK pathway activation. No significant difference in overall survival based on BRAF mutation was observed in the subset of patients where data was available. The MAPK pathway is differentially affected by the different cancers, with increased MAPK activation observed in melanoma and not in thyroid cancer. This may account in part for the observed differential response to BRAF inhibitors. Full article

Understanding the genetic basis of high-performance animals is vital for biological insight and breeding. This study aimed to identify genetic factors distinguishing champion gamecocks (Gallus gallus domesticus) from less successful ones, representing the first study to link transcriptomic profiles directly to competitive outcomes. Using RNA sequencing on non-invasive feather samples, we compared gene expression between high-performing (≥80% win rate) and low-performing (≤20% win rate) cohorts. Our analysis identified 441 differentially expressed genes. Notably, the high-performing cocks exhibited the significant upregulation of genes integral to muscle development and repair (e.g., SYNPO2, POPDC2) and enhanced neural function (NRN1). Conversely, several genes involved in neural development pathways, including CNTNAP2 and GFRA4, were significantly downregulated in the high-performing group. These findings suggest that a rooster’s competitive success is not determined by a single factor, but by a complex interplay of superior muscular capabilities and uniquely regulated neurological pathways. The identified genes provide a set of potential biomarkers that could inform selective breeding strategies aimed at enhancing performance traits in gamecocks. Full article

Thesium chinense Turcz. (T. chinense), a perennial herb in the Santalaceae family, exhibits potent antibacterial and anti-inflammatory properties. Transcriptome sequencing was performed on one- and two-year-old T. chinense plants across seedling, flowering, and fruiting stages (all sampled from the same location) using the illumina NovaSeq 6000 platform. A total of 58,706 unigenes were identified, including 1656 transcription factors (TFs). Further analysis classified these TFs into seven functional categories, enabling the reconstruction of a representative TF regulatory network. Differential expression analysis revealed that the number of differentially expressed genes (DEGs) ranged from 2000 to 5000 during different developmental stages in first-year plants, while varying between 1000 and 2000 in second-year plants. Comparative analysis of DEGs between one- and two-year-old plants showed that they were primarily associated with sesquiterpene, triterpene, and terpene skeleton biosynthesis, as well as other metabolic pathways. Additionally, analysis of key genes involved in flavonoid biosynthesis—the major bioactive compounds in T. chinense—revealed their predominant accumulation during the first year of growth. This study provides valuable insights into the developmental biology of T. chinense and establishes a foundation for future research on flavonoid biosynthesis pathway genes and their therapeutic applications. Full article

The peach landrace ‘Liuyefeitao’ exhibits the unique reproductive trait of self-compatibility combined with cross-incompatibility, contrasting with typical Prunus species in this way. In preliminary studies involving controlled pollination assays, we showed complete pollen tube arrest in cross-pollinated styles, whereas self-pollination enabled full tube elongation. S-genotyping identified a homozygous S₂S₂ genotype with intact S₂-RNase but a truncated PpSFB2 due to a frameshift mutation. Transcriptome profiling of the styles revealed 7937 differentially expressed genes (DEGs) between self- and cross-pollination treatments, with significant enrichment in plant MAPK signaling, plant–pathogen interactions, and plant hormone signaling transduction pathways (|Fold Change| ≥ 2, FDR < 0.01). Notably, PpSLFL3 (a pollen F-box gene) showed down-regulation in cross-pollinated styles, as validated by means of qRT-PCR. Protein interaction assays revealed direct binding between PpSLFL3 and S₂-RNase via Y2H and BiFC analysis, suggesting its role in mediating SCF complex-dependent degradation. We propose that insufficient PpSLFL3 expression during cross-pollination disrupts SCF ubiquitin ligase complex-mediated degradation of non-self S₂-RNase, leading to the toxic degradation of RNA in pollen tubes by S₂-RNase. This mechanism is mechanistically similar to unilateral reproductive barriers in Solanaceae but represents a novel regulatory module in Rosaceae. Our findings provide critical insights into the evolution of cross-incompatibility systems and molecular breeding strategies for Prunus species. Full article

In chickens, meat yield is a crucial trait in breeding programs. Identifying key molecular markers associated with increased muscle yield is essential for breeding strategies. This study applied transcriptome sequencing and machine learning methods to examine gene expression and alternative splicing (AS) events in muscle tissues of commercial broilers and local chickens. On the basis of differentially expressed genes (DEGs) and differentially spliced transcripts (DSTs) significantly related to breast muscle weight percentage (BrP), high-accuracy prediction models were developed by evaluating 10 machine learning models (e.g., eXtreme Gradient Boosting (XGBoost), Generalized Linear Model Network (Glmnet)). Feature importance was assessed using the Shapley Additive exPlanations (SHAP) method. The results revealed that 50 DEGs and 95 DSTs contributed significantly to BrP prediction. The XGBoost model achieved over 90% accuracy when using DEGs, and the Glmnet model reached 95% accuracy when using DSTs. Through Shapley evaluation, genes and AS events (e.g., ENSGALG00010012060, HINTW, and VIPR2-201) were identified as having the highest contributions to BrP prediction. Additionally, the breed effect was effectively mitigated. This study introduces new candidate genes and AS targets for the molecular breeding of poultry breast muscle traits, offering a paradigm shift from traditional gene mining approaches to artificial intelligence-driven predictive methods. Full article

Meat quality is influenced by genetic, nutritional, and microbial factors, with increasing attention on the role of gut-derived metabolites. In this study, we conducted untargeted metabolomics of 10 gut tract sites and RNA sequencing (RNA-seq) of longissimus dorsi muscles in Meigu goats and Liangshan black sheep raised under standardized conditions. Results showed that goat muscle contained significantly higher levels of essential amino acids (e.g., methionine) and specific fatty acids (e.g., C18:3_N6, C20:4_N6), suggesting improved nutritional quality. Transcriptomic analysis identified 3133 differentially expressed genes (DEGs), among which ADCY1 and SLC38A4 were upregulated in goats and strongly associated with meat traits. Using integrative correlation analysis, we uncovered 17 genes and 19 gut metabolites that were significantly correlated with more than eight meat quality parameters across multiple gut sites. Notably, these metabolites included bioactive compounds such as L-tyrosine ethyl ester and pelargonidin 3-O-glucoside, while genes were enriched in pathways related to amino acid transport, cAMP signaling, and muscle development. Together, these findings highlight a potential gut–muscle axis involving metabolite-mediated modulation of muscle gene expression, contributing to breed-specific differences in meat composition and quality. This study provides a valuable framework for improving ruminant meat quality through integrative multi-omics analysis. Full article

2-Amino-14,16-dimethyloctadecan-3-ol (AOD) is commonly found in foods contaminated with Fusarium avenaceum, particularly cereals or fruits, and is structurally related to Fusarium mycotoxins (fumonisins) and mammalian sphingoid bases, especially 1-deoxysphinganine (m18:0); therefore, it might enter systemic circulation and tissues upon dietary intake. Knowledge about what happens when cells are exposed to AOD is limited, but it has been reported to be cytotoxic and to induce vacuolization in HepG2 cells. We also found that AOD is cytotoxic for HepG2 cells, but even at a concentration where cell viability remained above 85% (5 μM), it altered 24 differentially expressed genes based on RNA sequencing-based transcriptomic profiling. Among these genes, 13 were shared with cells treated with m18:0. These overlapping differentially expressed genes were primarily enriched in activated stress response pathways of cells, including the upregulation of specific genes in the hypoxia-inducible factor 1α (HIF-1α) signaling pathway, such as hexokinase 1 (HK1) and egl-9 family hypoxia-inducible factor 3 (EGLN3), the activation of key components in the p53 signaling pathway, and the induction of cellular senescence-associated transcriptional programs involving serpin family E member 1 (SERPINE1). Transcriptional analysis of genes related to sphingolipid metabolism showed that treatment with AOD increased the mRNA expression of ceramide synthase 4 (CerS4), sphingosine-1-phosphate phosphatase 1 (SGPP1), and UDP-glucosylceramide glucosyltransferase (UGCG), while decreasing the expression of dihydroceramide desaturase 1 (DEGS1) and fatty acid desaturase 3 (FADS3), a pattern of gene expression changes that mirrored the alterations observed with m18:0 treatment. Lipidomic analyses revealed that AOD significantly perturbed the sphingolipid composition of HepG2 cells, specifically increasing hexosylceramide content while decreasing ceramide and sphingomyelin levels. Moreover, AOD was found to undergo intracellular metabolism to N-acyl-AODs, perhaps by ceramide synthase(s), since this acylation was inhibited by fumonisin B1 (FB1). These findings demonstrate that AOD or possibly its N-acyl metabolites can alter cellular sphingolipid metabolism and affect the expression of genes involved in cell stress. These new insights call for more studies of the impact of this food contaminant on cells and the implications for human health. Full article

Background: Transcription factors have been linked to changes in various physiological processes, such as attractive and rewarding phenotypes during plant–pollinator interactions. In the genus Petunia, most species are pollinated by bees, but hawkmoth- and bird pollination are also observed. Here, we aimed to test the hypothesis that species with the same pollination syndrome evolved through convergence, while differences in pollinators indicate divergence. We selected six genes (MYB-FL, DFR, EOBII, ODO1, BPBT, and NEC1) involved in establishing pollination syndromes to explore the potential role of cis-regulatory elements in shifts among pollination syndromes, attracting and rewarding pollinators. Methods: We retrieved the genomic sequences of genes from the genomes of four Petunia species, which exhibit distinct pollination syndromes. We analyzed the cis-regulatory elements, focusing on the structure and composition of motifs, and inferred the functions of these transcription factors using Gene Ontology analysis. Results: All sequences were highly conserved among species, with variations in promoter motif structure and TF binding sites. The evolutionary relationships among the genes closely reflected the species’ phylogeny. Likewise, regulatory elements and gene structure mostly followed the species’ evolutionary history. However, different pollination syndromes are present, and there is an unexpected lack of convergence between the two bee-pollinated species. Conclusions: Our findings showed that the most recent common ancestor of these species better predicts relationships among gene regulatory elements than does the pollination syndrome. To fully understand the evolution of pollination syndromes in Petunia, additional studies are needed to analyze entire pathways and compare genomes and transcriptomes. Full article

As the laying cycle is prolonged, the egg albumen quality exhibits a declining trend. A Haugh unit (HU) is a standard measure of the albumen quality, which reflects viscosity and freshness. During the late laying period, the HU not only decreased significantly, but also exhibited greater variability among individuals. The magnum, as the primary site of albumen synthesis, plays a central role in this process; however, the mechanisms by which it regulates the albumen quality remain unclear. To address this, we obtained genomic and transcriptomic data from 254 individuals, along with single-cell RNA sequencing (scRNA-seq) data of the magnum tissue. Genome-wide association studies (GWAS) across five laying stages (66, 72, 80, 90, and 100 weeks of age) identified 77 HU-associated SNPs. Expression quantitative trait locus (eQTL) mapping linked these variants to the expression of 12 genes in magnum tissue. In addition, transcriptomic analysis using linear regression and random forest models identified 259 genes that significantly correlated with the HU. Single-cell RNA sequencing further revealed two key cell types, plasma cells and a subset of epithelial cells, marked by ADAMTSL1 and OVAL, which are functionally relevant to the HU. Through integrated Transcriptome-Wide Association Study (TWAS) and Summary-data-based Mendelian Randomization (SMR) analyses, we identified four robust regulators of the albumen quality: CISD, NQO2, SLC22A23, and CMTM6. These genes are functionally involved in mitochondrial function, antioxidant defense, and membrane transport. Overall, our findings uncovered the genetic and cellular mechanisms underlying age-related decline in the albumen quality and identified potential targets for improving the egg quality in aging flocks. Full article

Honeybees are vital pollinators with functional differentiation as a key survival strategy. The Chinese honeybee (Apis cerana cerana) exhibits exceptional nectar foraging in complex terrains, yet how alternative splicing (AS) and polyadenylation (APA) regulate its labor division remains unclear. Here, we applied PacBio full-length transcriptome sequencing to annotate worker bee transcriptomes across three developmental stages (Ac3d, Ac10d, Ac21d), calibrating the third-generation sequencing data with second-generation sequencing to enhance transcriptome annotation accuracy. We identified 17,961 isoforms and 1922 APA genes, finding that alternative first exon was the major type of AS, while APA enhances transcriptomic diversity via dual polyadenylation sites in most genes. Functional analyses revealed AS enrichment in growth signaling (Vg6, CYP15A1) and immune pathways (PTPRR), whereas APA regulated growth signaling (Vg6), energy metabolism (Acsl1, AcceFE), and oxidative stress (PTPRR, PPO2). Validation by PCR and 3′RACE confirmed stage-specific AS/APA events in key genes. These findings significantly enhance the A. cerana cerana reference genome annotation and provide valuable insights into the mechanisms of AS and APA regulation underlying honeybee development and functional transitions. Full article

Lycium barbarum is a traditional medicinal and edible plant species in China, exhibiting notable salt tolerance that enables cultivation in salt-affected soils. However, intensifying soil salinization has rendered severe salt stress a critical limiting factor for its fruit yield and quality. Universal stress proteins (USPs) serve as crucial regulators for plant abiotic stress responses through developmental process modulation. Nevertheless, the characteristics and functional divergence of USP gene family members remain unexplored in L. barbarum. Here, we performed genome-wide identification and characterization of the USP gene family in L. barbarum, revealing 52 members unevenly distributed across all 12 chromosomes. Phylogenetic analysis classified these LbUSP members into four distinct groups, demonstrating the integration of the conserved USP domain and diverse motifs within each group. Collinearity analysis indicated a stronger synteny of LbUSPs with orthologs in Solanum lycopersicum than with other species (Arabidopsis thaliana, Vitis vinifera, and Oryza sativa), demonstrating that gene duplication coupled with functional conservation represented the primary mechanism underlying USP family expansion in L. barbarum. In silico promoter screening detected abundant cis-acting elements associated with abiotic/biotic stress responses (MYB and MYC binding sites), phytohormone regulation (ABRE motif), and growth/development processes (Box-4 and G-box). Transcriptome sequencing and RT-qPCR validation revealed tissue-specific differential expression patterns of LbUSP8, LbUSP11, LbUSP12, LbUSP23, and LbUSP25 in roots and stems under salt stress, identifying them as prime candidates for mediating salt resistance in L. barbarum. Our findings establish a foundation for the functional characterization of LbUSPs and molecular breeding of salt-tolerant L. barbarum cultivars. Full article

Tumor-initiating cells (TICs) constitute a subpopulation of cancer cells with stem-like properties contributing to tumorigenesis, progression, recurrence, and therapeutic resistance. Despite their biological importance, their molecular signatures that distinguish them from non-TICs remain incompletely characterized. This study aimed to comprehensively analyze transcriptomic differences between TICs and non-TICs, identify TIC-specific gene expression patterns, and construct a machine learning-based classifier that could accurately predict TIC status. RNA sequencing data were obtained from four human cell lines representing TIC (TS10 and TS32) and non-TIC (32A and Epi). Transcriptomic profiles were analyzed via principal component, hierarchical clustering, and differential expression analysis. Gene-Ontology and Kyoto-Encyclopedia of Genes and Genomes pathway enrichment analyses were conducted for functional interpretation. A logistic-regression model was trained on differentially expressed genes to predict TIC status. Model performance was validated using synthetic data and external projection. TICs exhibited distinct transcriptomic signatures, including enrichment of non-coding RNAs (e.g., MIR4737 and SNORD19) and selective upregulation of metabolic transporters (e.g., SLC25A1, SLC16A1, and FASN). Functional pathway analysis revealed TIC-specific activation of oxidative phosphorylation, PI3K-Akt signaling, and ribosome-related processes. The logistic-regression model achieved perfect classification (area under the curve of 1.00), and its key features indicated metabolic and translational reprogramming unique to TICs. Transcriptomic state-space embedding analysis suggested reversible transitions between TIC and non-TIC states driven by transcriptional and epigenetic regulators. This study reveals a unique transcriptomic landscape defining TICs and establishes a highly accurate machine learning-based TIC classifier. These findings enhance our understanding of TIC biology and show promising strategies for TIC-targeted diagnostics and therapeutic interventions. Full article

Background and Objectives: Most of the research on the role of the BRCA1 gene in breast cancer is focused on monoallelic germline alterations and loss of heterozygosity in tumors. The aim of this study was to identify the characteristic transcriptomic pattern of monoallelic somatic BRCA1 inactivation and estimate its correlation with event-free breast cancer survival. Materials and Methods: We conducted global transcriptome sequencing of breast cancer tissue samples to identify differentially expressed genes and signaling pathways associated with monoallelic somatic BRCA1 inactivation. The study group involved 36 patient samples categorized based on BRCA1 inactivation status. Subsequently, the differential gene expression and Kaplan-Meier analyses in the groups with and without monoallelic somatic BRCA1 inactivation were performed. Results: Kaplan-Meier analysis showed a tendency for longer event-free survival in patients with monoallelic somatic BRCA1 inactivation, suggesting somatic BRCA1 inactivation to be a favorable prognostic. Differential gene expression analysis followed by the STRING tool enrichment analysis showed significant enrichment of proteins in the extracellular region and extracellular space. Conclusions: In this study, we identified transcriptomic profiles of differentially expressed genes TPSD1, FABP4, CARTPT, and MMP9 as indicative of homologous recombination-impaired tumors with a tendency for better therapy results. Full article

Rafiq syndrome (RAFQS) is a rare autosomal recessive disorder that is classified as a type II congenital disorder of glycosylation (CDG-II), and caused by MAN1B1 gene mutation. To date, 24 pathogenic MAN1B1 mutations have been reported in association with MAN1B1-CDG. However, the underlying pathogenic mechanisms remain poorly understood. In this study, we recruited a consanguineous family from Pakistan with multiple affected individuals exhibiting mild facial dysmorphism, developmental delay, and intellectual disability. Utilizing exome sequencing and homozygosity mapping, we identified a novel MAN1B1 mutation (c.772_775del) that co-segregated with RAFQS in this family. Analysis of public single-cell transcriptomic data revealed that MAN1B1 is predominantly expressed in dorsal progenitors and intermediate excitatory neurons during human brain development. Knockdown of Man1b1 in primarily cultured mouse excitatory neurons disrupted axon growth, dendrite formation, and spine maturation, and could not be rescued by truncated variants identified in the family. Furthermore, in utero, electroporation experiments revealed that Man1b1 knockdown in the murine cortex impaired neural stem cells’ proliferation and differentiation, as well as cortical neuron migration. Collectively, these findings elucidate a critical role for MAN1B1 in the etiology of RAFQS and demonstrate that loss-of-function mutation in MAN1B1 disrupt neuro-developmental processes, providing mechanistic insights into the pathogenesis of this disorder. Full article