Search Results (3,606)

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

The evolving legal landscape has increased marijuana accessibility across the United States, including for medical use to manage clinical symptoms among people with HIV. The effects of marijuana use remain understudied in youth with HIV (YWH), who face lifelong antiretroviral therapy (ART) and an elevated risk of developing comorbidities. This study applied a multi-modal approach, including plasma biomarker analysis, peripheral blood cell phenotyping, and transcriptome profiling, to examine the effects of recreational marijuana alone, tobacco alone, or marijuana combined with tobacco in virally suppressed YWH (≤50 RNA copies/mL) on ART compared to youth without HIV and YWH who used no substance. Marijuana use alone was associated with elevated IL-10 levels and normalization of pro-inflammatory genes and pathways, suggesting an immunomodulatory effect. Conversely, tobacco use alone or combined with marijuana was linked to increased IL-1β levels and heightened pro-inflammatory responses, including upregulation of genes involved in inflammasome activation. This study is the first to demonstrate GPR15 upregulation and potential marijuana-associated epigenetic modulation in HIV-suppressed youth. The findings identify potential markers for early detection of inflammation-related comorbidities in YWH, particularly among those exposed to tobacco and underscore the need for targeted profiling to guide personalized monitoring and early substance use intervention strategies for YWH. 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 fusion of keel petals is a defining trait of Papilionoideae flowers, contributing to floral architecture and promoting self-pollination but hindering hybridization in crops like soybean. Here, we investigated the cellular and molecular basis of keel petal fusion in Glycine max (L.) Merr. cv. Jack using anatomical and transcriptomic approaches. Microscopy revealed that keel petal fusion involves marginal cell reshaping and postgenital adhesion with defective cuticle continuity, consistent with fusion modes in other Papilionoideae species. Comparative transcriptome analysis between fused and unfused petal stages identified 23,328 differentially expressed genes, with lipid and cuticle metabolism genes showing coordinated downregulation during fusion. A set of 384 keel-enriched genes was identified, among which a previously uncharacterized gene, KPEG1 (Keel Preferential Expression Gene 1), was preferentially expressed in fused keel petals. Protein interaction network analysis revealed that KPEG1 co-expresses with epigenetics-related genes, suggesting a regulatory role in fusion through chromatin-mediated mechanisms. These findings uncover the cellular dynamics and transcriptional reprogramming underlying keel petal fusion in soybean and provide a candidate regulator for further functional studies. 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

Cerium oxide nanoparticles (CeO₂NPs) can boost crops’ salt tolerance, yet their regulatory mechanisms in rice cultivars with contrasting salt tolerance remain unclear. This study investigated the regulatory differences in poly (acrylic acid)-coated nanoceria (PNC)-primed in salt-sensitive (Huanghuazhan, H) and salt-tolerant (Xiangliangyou900, X) rice. The results showed that PNC priming improved salt tolerance in two cultivars, but the underlying mechanisms differed. In the H cultivar, the enhanced tolerance was primarily attributed to enhanced photosynthesis (net photosynthesis and transpiration rates were 53.27% and 20.52% higher than the X cultivar); increased abscisic acid (ABA) content (up by 18.80% compared to the X cultivar), and activated stress-responsive signaling. Metabolomics further revealed that the differential metabolites were enriched in galactose metabolism, ascorbate, and aldarate metabolism, synergistically maintaining intracellular redox balance. In the X cultivar, PNC boosted reactive oxygen species’ (ROS) scavenging capacity (catalase (CAT) increased 36.07%, H₂O₂ and malondialdehyde (MDA) decreased 27.31% and 48.61% compared to H); elevated endogenous indole-3-acetic acid (IAA) and gibberellic acid3 (GA3) levels by 9.55% and 9.08%; and specifically activated cellular defense response and glutathione metabolism. Transcriptome analysis further revealed that the expression of IAA/GA3 signal-responsive genes (OsARGOS/OsGASR2) and antioxidant genes (OsCatA, OsAPX1) were significantly higher in the X cultivar than the H cultivar (p < 0.05), whereas the H cultivar showed higher expression of GST and ABA-related genes. This study provides a new perspective for the mechanism of PNC-enhanced salt tolerance in rice. Full article

Hemp possesses significant healthcare value due to its rich composition of unsaturated fatty acids and a distinctive golden ratio of linoleic acid to α-linolenic acid. As a promising special-oil crop, it holds substantial potential for development and utilization. However, the regulatory mechanisms underlying its lipid metabolic pathways remain poorly understood. In this study, the independently bred hemp seed variety Longdama No. 9 was used to construct a regulatory network of the fatty-acid and lipid metabolisms through integrative transcriptomic and lipidomic analysis. Transcriptomic profiling revealed differentially expressed genes (DEGs) involved in lipid biosynthesis across various tissues. In leaves, DEGs associated with glycerolipid synthesis were generally upregulated compared to in roots and seeds. In seeds, DEGs involved in fatty-acid synthesis and triacylglycerol (TAG) assembly were predominantly upregulated. Meanwhile, root tissues showed a higher abundance of upregulated DEGs related to phospholipid biosynthesis. Lipidomic analysis further highlighted tissue-specific lipid distributions. The galactolipid monogalactosyldiacylglycerol (MGDG) was most abundant in the leaves. While phosphatidylglycerol (PG) had the highest molar percentage in the seeds, most other major phospholipids were predominantly found in the roots. The prevalence of the C36:6 molecular species in the MGDG and digalactosyldiacylglycerol (DGDG) indicates that hemp is a typical 18:3 plant. The combined transcriptomic and lipidomic analysis revealed that tissue-specific transcriptional regulation contributes to the unique lipid profile of hemp. These findings provide valuable insights into the regulation of lipid metabolism in hemp and identify key genes involved in oil biosynthesis, which can lay a theoretical foundation for the development and utilization of hemp as a special-oil crop. Full article

Background: Vitis vinifera L. exhibits diverse varietal traits influencing fruit quality and stress tolerance. The summer black grape (Xiahei), known for its superior tolerance to abiotic stress and intense pigmentation, was hypothesized to possess distinct metabolic and genetic profiles, particularly in flavonoid and anthocyanin biosynthesis. This study aimed to elucidate the metabolic and molecular basis underlying these phenotypic traits by comparing carbohydrate composition and metabolomic and transcriptomic profiles of four grape varieties (summer black, flame seedless, black grape, and red milk). Methods: Grapes were consistently sampled five days after full maturity, and metabolites were analyzed using UPLC-MS/MS and GC-MS, while transcriptome analysis employed RNA sequencing followed by qRT-PCR validation. Results: The results demonstrated that carbohydrate content was similar among all grape varieties, whereas the summer black grape showed significantly higher levels of flavonoids, particularly anthocyanins such as delphinidin-3-O-glucoside, cyanidin-3-O-glucoside, and pelargonidin-3-O-glucoside. Metabolomic analyses revealed substantial enrichment of metabolites involved in flavonoid biosynthesis pathways, in agreement with transcriptomic data showing significant upregulation of key regulatory genes (CHS, DFR, and ANS) specific to anthocyanin biosynthesis. These findings suggest that the pronounced anthocyanin accumulation in summer black grape contributes to its distinctive dark pigmentation and enhanced resistance to abiotic stresses compared to other varieties. Conclusion: This study provides novel insights into the molecular and metabolic mechanisms driving anthocyanin accumulation in summer black grapes, which could inform future breeding programs aimed at improving grape resilience. Full article

Background: Bladder cancer is a common and heterogeneous malignancy of the urinary tract. Traditional chemotherapy using bivalent platinum drugs such as cisplatin(CDDP) is often limited by severe side effects and acquired resistance. To overcome these limitations, we explored a novel Pt(IV) prodrug, DNP, designed to release both cytotoxic cisplatin and the anti-inflammatory cyclooxygenase-2 (COX-2) inhibitor naproxen(NPX). Methods: We evaluated the cytotoxic activity of DNP using both two-dimensional (2D) monolayer and three-dimensional (3D) spheroid models of bladder cancer cells. Transcriptomic analysis via RNA-seq identified apoptosis- and inflammation-related signaling pathways modulated by DNP. RNA-seq-based transcriptomic profiling revealed that DNP regulates signaling pathways associated with apoptosis and inflammation. The anti-inflammatory effects were evaluated using a lipopolysaccharide (LPS)-induced macrophage model, while the in vivo antitumor efficacy was assessed in an orthotopic MB49 bladder cancer model. Results: Compared with CDDP, DNP significantly increased intracellular platinum accumulation and exhibited superior cytotoxicity. It effectively inhibited tumor proliferation, induced apoptosis, and attenuated inflammation both in vitro and in vivo. Conclusions: These findings suggest that DNP exerts dual antitumor effects through enhanced delivery of cytotoxic and anti-inflammatory agents, offering a promising strategy for bladder cancer therapy. Full article

In a previous study, GmMYB14 overexpressing (GmMYB14-OX) transgenic soybean plants displayed a semi-dwarfism and compact phenotype, which was regulated by the brassinosteroid (BR) pathway. However, the phenotype of GmMYB14-OX plants could be partly rescued after spraying them with exogenous BR. This indicates that other hormones, in addition to BR, also play a role in regulating the architecture of GmMYB14-OX plants. We observed a significant decrease in the content of endogenous indole-3-acetic acid (IAA) in transgenic soybean lines (OX9 and OX12) compared to wild type (WT) plants. The plant height, leaf area, leaf petiole length, and leaf petiole angle of GmMYB14-OX plants could also be partly rescued after applying exogenous IAA for two weeks. Transcriptome sequencing analysis revealed that the expression of many genes within the Aux/IAA gene family underwent alterations in the GmMYB14-OX transgenic soybean plants. Among them, Glyma.02G000500 (GmIAA1) showed the highest expression in GmMYB14-OX plants. Furthermore, the results of electrophoretic mobility shift assay and dual-luciferase reporter indicate that GmMYB14 protein could bind to the promoter of GmIAA1. In summary, a decrease in endogenous IAA content may be one of the factors contributing to the compact and dwarfed architecture of GmMYB14-OX plants. GmMYB14 also acts as a transcriptional activator of GmIAA1 to potentially block IAA effects. Our findings provide a theoretical basis for further investigation of the regulatory mechanism of GmMYB14 on soybean plant architecture. Full article

Porcine epidemic diarrhea virus (PEDV) is a primary pathogen responsible for viral diarrhea in swine. The identification of host resistance genes and key regulatory elements represents a critical prerequisite for developing novel control strategies. Krüppel-like factor 4 (KLF4), a multi-functional transcription factor, is known to regulate pathogenic infections; however, its specific roles in PEDV infection remain largely undefined. In this study, we found that KLF4 expression was upregulated following PEDV infection. Next, we constructed KLF4 knockout and overexpression cells and infected them with PEDV. The results show that viral RNA and protein expression levels and infectious viral titers were significantly enhanced in PEDV-infected KLF4 knockout cells compared to infected wild-type cells. In contrast, PEDV infection levels were significantly decreased in KLF4 overexpression cells relative to control cells. Transcriptomic analysis reveals that KLF4 significantly influences the expression of genes involved in key signaling pathways, including PI3K/Akt and MAPK. Overall, our findings elucidate the functional roles and underlying mechanisms of KLF4 during PEDV infection, offering valuable molecular targets for PEDV prevention and control. Full article

Protected cultivation is a cultivation practice that plays an important role in improving crop quality. Aroma is an important flavour that assesses the quality of yuzu. In this study, C. junos cv. ‘Kitou’ grown in open fields (CJKTF) and plastic greenhouses (CJKTP) were selected as the study material. Significant differences in aroma performance between CJKTF and CJKTP were found by the olfactory senses of the members of this research group and an electronic nose, with CJKTP having a stronger aroma. Regarding VOCs, GC-MS analyses revealed 13 VOCs up-regulated and 28 VOCs down-regulated in CJKTP compared to CJKTF. Transcriptome analysis revealed that 515 genes were up-regulated and 720 genes were down-regulated in CJKTP compared to CJKTF. The differential VOCs nerolidol and γ-cadinene, and the differential genes nerolidol synthase 1 (NES1), nerolidol synthase 1-like (NES1-like), and cadinene synthase (DCS), were in the sesquiterpene synthesis pathway and showed significant correlation. NES1, NES1-like, and DCS encode terpene synthases, which may be involved in the biosynthetic pathway of nerolidol and γ-cadinene. In conclusion, the use of plastic greenhouses for cultivation may improve the quality and aroma intensity of yuzu, as well as alter the expression of related genes, compared to field cultivation. These results suggest that protected cultivation is a suitable cultivation practice to enhance the aroma of yuzu. Full article

Fibro-adipogenic progenitor cells (FAPs) support muscle tissue homeostasis, regulate muscle growth, injury repair, and fibrosis, and activate muscle progenitor cell differentiation to promote regeneration. We aimed to investigate the effects of co-culturing FAPs with muscle satellite cells (MuSCs) on myogenic differentiation. Proteomic profiling of co-culture supernatants identified significant DCX, IMP2A, NUDT16L1, SLC38A2, and IL-6 upregulation. Comparative transcriptomics of mono-cultured versus co-cultured MuSCs revealed differential expression of oxidative stress-related genes (HMOX1, ALOX5, GSTM3, TRPM2, PADI1, and CTSL). Pathway enrichment analyses highlighted cell cycle regulation, TNF signaling, and ferroptosis. Gene ontology analysis of MuSCs indicated significant gene enrichment in myosin-related components. Combined transcriptomic and proteomic analyses demonstrated HO-1 downregulation at the transcriptional and translational levels, with altered pathways being predominantly related to myosin filament, muscle system process, and muscle contraction cellular components. HO-1 knockdown reduced intracellular iron accumulation in MuSCs, suppressing iron-dependent autophagy. This alleviated oxidative stress and promoted myogenic differentiation. Exogenous IL-6 (0.1 ng/mL) downregulated HO-1 expression, initiating an identical regulatory cascade, while HO-1 overexpression reversed the IL-6-mediated reduction in the expression of the autophagy markers LC3 and ATG5, suppressing myogenic enhancement. This establishes the co-culture-induced IL-6/HO-1 axis as a core regulator of iron-dependent oxidative stress and autophagy during myogenic differentiation. Full article

Soil salinization limits the growth of agricultural crops in the world, requiring the use of methods to increase the tolerance of agricultural crops to salinity–alkali stress. Arbuscular mycorrhizal fungi (AMF) enhance plant stress adaptation through symbiosis and offer a promising strategy for remediation. However, in non-model crops such as oat (Avena sativa L.), research has mainly focused on physiological assessments, while the key genes and metabolic pathways involved in AMF-mediated growth and saline–alkali tolerance remain unclear. In this study, we employed integrated multi-omics and physiological analyses to explore the regulatory mechanisms of AMF in oats under normal and saline–alkali stress. The results indicated that AMF symbiosis significantly promoted oat growth and physiological performance under both normal and saline–alkali stress conditions. Compared to the non-inoculated group under normal conditions, AMF increased plant height and biomass by 8.5% and 15.3%, respectively. Under saline–alkali stress, AMF enhanced SPAD value and relative water content by 16.7% and 7.3%, reduced MDA content by 35.8%, increased soluble protein by 21.8%, and decreased proline by 13.3%. In addition, antioxidant enzyme activities (SOD, POD, and CAT) were elevated by 18.4%, 18.2%, and 14.8%, respectively. Transcriptomic analysis revealed that AMF colonization under saline–alkali stress induced about twice as many differentially expressed genes (DEGs) as under non-saline–alkali stressed conditions. These DEGs were primarily associated with Environmental Information Processing, Genetic Information Processing, and Metabolic Processes. According to metabolomic analysis, a total of 573 metabolites were identified across treatments, mainly comprising lipids (29.3%), organic compounds (36.8%), and secondary metabolites (21.5%). Integrated multi-omics analysis indicated that AMF optimized energy utilization and antioxidant defense by enhancing phenylpropanoid biosynthesis and amino acid metabolism pathways. This study provides new insights into how AMF may enhance oat growth and tolerance to saline–alkali stress. Full article