Search Results (9,781)

Sulfur metabolism and stress responses are fundamental to plant growth and seed development. ETHE1 encodes a mitochondrial sulfur dioxygenase that plays important roles in these processes; however, its function in Jatropha curcas remains unknown. In this study, we report the cloning and in silico characterization of a putative JcETHE1 gene from J. curcas. Bioinformatic analysis revealed that JcETHE1 has an open reading frame of 726 bp encoding a 241-amino-acid protein, which is predicted to localize in mitochondria and possesses a typical sulfur dioxygenase conserved domain. Because the transcript ends were not experimentally confirmed and the predicted protein is shorter than related plant homologues, the possibility that the cloned sequence is partial cannot be excluded. Phylogenetic analysis showed that JcETHE1 clusters within the Euphorbiaceae clade, showing high similarity to ETHE1 from Manihot esculenta and Hevea brasiliensis. In silico promoter analysis suggested that, in addition to core elements, the JcETHE1 promoter contains multiple putative regulatory elements associated with light response, hormone responses (ABA, ethylene, gibberellin), floral development (CArG-box, AAGAA-motif), stress responses, and endosperm development. These findings provide a molecular basis for future functional studies of JcETHE1 and suggest that it may serve as a potential candidate gene for further investigation into reproductive development and stress responses in J. curcas. However, these hypotheses require experimental validation. Full article

Obesity is a multifactorial metabolic disorder characterized by dysregulated energy homeostasis, impaired lipid metabolism, and altered hypothalamic appetite signaling. This study aimed to evaluate the anti-obesity effects and underlying mechanisms of a 95% ethanol extract of Artocarpus integer stem bark in a high-fat diet (HFD)-induced obese rat model. Obesity was induced in male Wistar rats using HFD feeding, followed by treatment with the extract (200–800 mg/kg/day, oral). Semaglutide and resveratrol were used as reference compounds. Body weight, food intake, adiposity, serum lipid profile, adipokines, histological changes, and gene expression related to lipid metabolism (Fas, Pparγ, Cpt-1, AdipoR1) and hypothalamic appetite regulation (Pomc, Mc4r, Npy) were evaluated. Phytochemical profiling was performed using LC–HRMS. The extract markedly reduced body weight gain, visceral adiposity, and food intake compared with the HFD control (p < 0.05), with the high-dose extract demonstrating a substantial weight-reducing effect that approached the magnitude of semaglutide. Treatment improved dyslipidemia by decreasing total cholesterol and triglycerides while increasing HDL levels. Adipokine imbalance was restored, as evidenced by reduced leptin and amylin and increased adiponectin levels. At the molecular level, the extract downregulated lipogenic genes (Fas, Pparγ), partially restored Cpt-1 expression, and normalized AdipoR1. In the hypothalamus, Pomc and Mc4r were upregulated, whereas Npy was suppressed. LC–HRMS analysis revealed the presence of stilbene, chalcone, and flavonoid derivatives. In conclusion, A. integer stem bark extract exerts anti-obesity effects through coordinated modulation of appetite signaling and lipid metabolism, supporting its potential as a multi-target phytotherapeutic agent for obesity management. Full article

Colorectal cancer (CRC) exhibits substantial metabolic heterogeneity, but the organization of sphingolipid remodeling remains incompletely understood. In this exploratory single-center study, we integrated patient-matched tissue lipidomics, systemic oxidative stress profiling, and independent transcriptomic analyses. Tumor tissue, adjacent non-neoplastic mucosa, and preoperative serum were collected from 40 patients with CRC, with serum obtained from 23 hospitalized non-cancer controls. Sphingolipids were quantified by UHPLC–MS/MS, while total antioxidant capacity, total oxidant status, and oxidative stress index characterized systemic redox status. Paired lipidomics revealed coordinated remodeling with increased S1P-associated measures, selective ceramide depletion, and elevated S1P-to-ceramide ratios. Multivariate analyses did not identify stable discrete lipidomic subgroups and revealed variation consistent with a continuum-like organization within the measured sphingolipid feature space. In separate principal component analyses, ratio-derived variables showed a more concentrated low-dimensional covariance structure than absolute lipid concentrations. Circulating sphingolipids showed limited correspondence with tumor-local remodeling, whereas oxidative stress markers showed strong apparent discrimination between CRC and hospitalized non-cancer controls, although this finding may be affected by residual confounding. TCGA–GTEx analyses provided complementary pathway-level transcriptomic context, while anatomically resolved analysis of 374 TCGA tumors identified 3376 genes significantly associated with colorectal anatomical position, including six sphingolipid-related genes. Overall, these exploratory findings support a conceptual CRC Metabolic Continuum while requiring validation in larger, independent cohorts. Full article

Algae biomass and cellular exudated compounds have several biotechnological applications in various areas, such as agriculture, pharmaceutical, human and animal feed, and bioenergy, among others. However, many of these applications have not been developed to their full capability, in part due to the need to better understand the underlying principles of their cellular regulation of growth and metabolism. Recently, synthetic biology has been implemented as a new option to not only build new biological devices and systems but also comprehend the natural biochemical pathways present in living organisms. The use of this technology is still underdeveloped in algae research when compared to yeast and bacterial applications. Part of this effect is due to restraints on building multi-gene circuits, which are associated with the lack of controllable promoters and transcription factors in algae. This scenario could be improved by the development of orthogonal gene promoters, supported by the understanding of global biological responses related to their function in the host metabolism. With the integrative analysis of genomics, transcriptomics and proteomics, we may be able to find patterns of optimal orthogonality and address the rational design of optimal gene promoters that enhance algae biotechnological applications. In this paper, we will review the existing approaches and discuss future perspectives on the creation of orthogonal gene promoters in algae. Full article

Ecological speciation via divergent selection despite gene flow remains poorly documented in fungi. We integrated niche modeling and comparative genomics to examine ecological and genomic divergence among three ectomycorrhizal Thelephora species. T. ganbajun is restricted to mid-elevation Yunnan with climatically stable environments; T. aurantiotincta occupies lower elevations with pronounced temperature seasonality; and T. terrestris displays the broadest distribution, tolerating extreme temperature fluctuations and low precipitation. Phylogenomic analysis recovered the three species as distinct lineages, with T. terrestris diverging at 21.16 Mya and T. ganbajun and T. aurantiotincta splitting at 14.97 Mya. Gene flow analysis revealed unidirectional introgression: T. terrestris donated to both other species, and T. aurantiotincta donated to T. ganbajun, with negligible reverse migration. T. terrestris possesses the largest genome (40.73 Mb) with recent LTR retrotransposon expansion and amplified cytochrome P450 and lignocellulose-active CAZymes. T. ganbajun shows expanded copper transport and cell wall remodeling genes, while T. aurantiotincta exhibits expansion of fatty acid metabolism genes. These results document pronounced niche differentiation, genomic divergence, and directional historical gene flow among closely related species, providing an ecological and genomic basis for examining ecological speciation in fungi. Full article

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

Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder characterized by chronic inflammation, insulin resistance, and reproductive dysfunction. Although empagliflozin, a sodium-glucose cotransporter-2 inhibitor, has demonstrated anti-inflammatory and metabolic benefits, its molecular mechanisms in PCOS remain poorly understood. This study investigated the anti-inflammatory mechanisms of empagliflozin in PCOS using network pharmacology, molecular docking, and molecular dynamics simulations. Potential drug targets were identified using SwissTargetPrediction and SuperPred, while PCOS- and inflammation-related genes were obtained from GeneCards. Overlapping targets were subjected to Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, protein–protein interaction network, and hub gene analyses. Molecular docking and 50 ns molecular dynamics simulations were performed to evaluate binding affinity and complex stability. Key inflammatory targets identified included TNF, IL6, IL1B, TLR4, STAT3, and PTGS2, with significant enrichment in cytokine-mediated signaling, TNF signaling, and NF-κB pathways. Empagliflozin showed strong binding affinities for PTGS2 (−9.0 kcal/mol) and TLR4 (−8.8 kcal/mol), while molecular dynamics simulations demonstrated stable protein–ligand complexes throughout the simulation. These findings suggest that empagliflozin may alleviate PCOS-associated inflammation by modulating the TLR4/NF-κB/PTGS2 signaling axis, supporting its potential as a repurposed therapeutic agent for PCOS and providing a foundation for future experimental validation. Full article

Hepatic ischemia–reperfusion injury (HIRI) is not only a common complication of liver transplantation and major hepatic surgery but also a critical determinant of postoperative prognosis. Lactate metabolic reprogramming has been observed in HIRI, yet the role of lactate and its related lactylation in the pathogenesis of HIRI remains unclear. To address this, we integrated single-cell and bulk RNA-seq data with multiple bioinformatic approaches. Five single-cell gene set activity scoring methods (AUCell, UCell, singscore, ssGSEA, and AddModuleScore) were applied to evaluate lactylation activity across cell types, followed by differentially expressed gene (DEG) analysis and high-dimensional Weighted Correlation Network Analysis (hdWGCNA) to identify lactylation-associated genes. Five machine learning algorithms (Random Forest, Boruta, LASSO, GBM, and Decision Tree) were used to screen optimal feature genes, with SHAP analysis further explaining their importance. Bulk RNA sequencing data from the Gene Expression Omnibus (GEO) database were used for validation. Furthermore, NR4A3-related inhibitors were screened using the ChEMBL online tool and assessed by docking and molecular dynamic simulation. We observed significant heterogeneity in lactate metabolism activity across cell types in hepatic ischemia–reperfusion injury (HIRI), with higher activity levels observed for hepatocytes and mononuclear phagocytes. The integration of SHAP and machine learning identified PFKFB3, ZYX, and NR4A3 as closely associated with high lactylation after HIRI, and cross-analysis with bulk RNA data confirmed their consistent upregulation. Candidate gene expression was experimentally validated in a murine liver IRI model through Western blotting and RT-qPCR. Although lactylation has been previously reported in HIRI, this study’s unique contribution is to reveal the cell-type heterogeneity of lactylation-related gene expression at the single-cell level through multi-omics integration and machine learning. The identification of NR4A3, PFKFB3, and ZYX as lactylation-associated regulators proposes novel therapeutic targets for improving graft survival in liver transplantation. Full article

Glyphodes pyloalis Walker is a devastating phytophagous pest of mulberry (Morus spp.) that severely compromises leaf yield and quality, thereby threatening sericultural productivity. Although jasmonic acid (JA) and salicylic acid (SA) are well-established regulators of plant antiherbivore defenses, their specific roles in modulating mulberry responses to G. pyloalis herbivory remain poorly understood. Here, we employed an integrative approach combining herbivory bioassays, exogenous hormone treatment, physiological analysis, and RNA-sequencing (RNA-seq) to dissect JA- and SA-mediated defense networks in mulberry. Exogenous application of both hormones enhanced chlorophyll content, with JA exerting the strongest effect. However, they differentially modulated antioxidant enzyme activities, with SA primarily elevating superoxide dismutase (SOD) and JA enhancing peroxidase (POD) and catalase (CAT). Transcriptomic and functional-enrichment analyses showed that JA-responsive DEGs were predominantly associated with photoprotection, carbohydrate metabolism, phenylpropanoid and flavonoid biosynthesis, MAPK signaling, ABC transporters, and defense-related enzyme functions. By comparison, SA-responsive DEGs were strongly associated with photosynthesis-related gene expression, chloroplast organization, carbon metabolism, glutathione metabolism, and systemic immune-related processes. Notably, several key transcription factors, including MaHDZIP1, MaLBD28, MaGATA5, MaTALE2, MaARF4, MaSBP1 and MaSBP12, were upregulated under both hormone treatments. Collectively, these findings indicate that exogenous JA and SA treatments elicited overlapping yet distinct defense-related responses in mulberry. This work provides an integrated physiological and transcriptomic framework for the future development of hormone-mediated strategies against G. pyloalis in sericulture. Full article

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

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

Sacred lotus (Nelumbo nucifera) is an important aquatic crop whose growth and productivity are severely constrained by environmental stresses. Salicylic Acid (SA), Jasmonic Acid (JA), and Abscisic Acid (ABA) are key plant growth regulators (PGRs) involved in stress responses, but their regulatory mechanisms in lotus remain unclear. In this study, transcriptome sequencing was performed in lotus seedlings treated with exogenous SA, JA, and ABA to characterize hormone-responsive regulatory networks. SA predominantly resulted in transcriptional repression, with responsive genes mainly associated with photosynthesis and ribosome-related pathways, whereas JA and ABA showed similar regulatory patterns with enrichment of hormone signaling and Mitogen-activated protein kinase (MAPK) pathways, but distinct roles in defense regulation and stress adaptation. A total of 607 genes were identified as commonly responsive to the three PGRs and were significantly enriched in cold response, defense response, secondary metabolism, and photosynthesis-related pathways. Protein–protein interaction analysis identified two hub genes encoding light-harvesting chlorophyll a/b-binding proteins, suggesting that the photosynthesis–antenna proteins pathway may represent a convergent regulatory node in hormone-mediated stress responses. This study provides new insights into SA-, JA-, and ABA-mediated stress responses and identifies potential candidate genes for improving stress tolerance in lotus. Full article

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

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

Background: Periodontitis is a chronic inflammatory disease characterized by dysregulated host immune responses that drive connective tissue destruction and alveolar bone loss. Human gingival fibroblasts (HGFs) are central regulators of periodontal inflammation through their production of cytokines, chemokines, matrix-remodeling enzymes, and other inflammatory mediators. Although cannabinoid receptor 2 (CB2) activation has demonstrated anti-inflammatory properties, its coordinated effects on multiple inflammatory pathways in gingival fibroblasts remain poorly understood. This study investigated the transcriptomic effects of the selective CB2 agonist HU-308 on IL-1β-induced inflammatory responses in HGFs. Methods: Primary HGFs were divided into untreated controls, IL-1β-stimulated cells (10 ng/mL), and IL-1β-stimulated cells treated with HU-308 (10 μM). Twenty-four hours after stimulation, transcriptome-wide expression profiling was performed using Affymetrix Human Clariom S microarrays, followed by targeted analysis of selected inflammation-related transcriptional domains. Selected transcripts were evaluated within predefined biological domains including cytokines, chemokines, extracellular matrix-associated genes, NO/cGMP-related genes, transporter-associated genes, and GPCR-related transcripts. Gene expression was analyzed using one-way ANOVA with Tukey’s post hoc test. Results: IL-1β induced a coordinated inflammatory transcriptional program characterized by increased expression of pro-inflammatory cytokines, chemokines, matrix metalloproteinases, glucose transporter genes, and multiple GPCR-related transcripts, while suppressing collagen-associated genes, NOS3, GPR4, and GPR78. HU-308 broadly attenuated these inflammatory responses by reducing the expression of cytokines, chemokines, matrix metalloproteinases, and several GPCR-related genes while restoring collagen-associated transcripts, nitric oxide signaling components, anti-inflammatory mediators, and selected glucose transporters toward basal levels. Schematic multidimensional visualizations were used to illustrate relative expression patterns among selected transcripts within each functional domain; these visualizations do not represent statistically derived gene networks or molecular interactions. Conclusions: Pharmacological modulation of CB2 by HU-308 exerts broad immunomodulatory effects in IL-1β-stimulated human gingival fibroblasts by coordinately regulating multiple transcriptional networks involved in periodontal inflammation. These findings demonstrate that HU-308 treatment is associated with coordinated modulation of inflammatory, extracellular matrix, nitric oxide, metabolic, and GPCR-associated transcriptional pathways in IL-1β-stimulated HGFs. The results support the hypothesis that CB2 signaling may participate in the broader regulation of these interconnected responses; however, receptor-specific studies using CB2 antagonism or CNR2 knockdown are required to establish causality. Full article