Search Results (1,293)

Metabolic resistance is commonly attributed to the overexpression of detoxification enzymes, whereas the metabolic systems that sustain detoxification remain less well resolved. Here, we integrated widely targeted metabolomics and transcriptomics to compare the clothianidin-resistant brown planthopper strain CLR with the susceptible strain CLS and validated candidate genes in an independent nitenpyram-resistant background. CLR and CLS exhibited distinct metabolomic profiles. Differential genes and metabolites converged on carbon metabolism, glycolysis/gluconeogenesis, the tricarboxylic acid cycle, glutathione metabolism, pentose and glucuronate interconversions, cytochrome P450-mediated xenobiotic metabolism, and ABC transporters. These changes were summarized into four interconnected modules involving glycolytic energy supply, protective sugar-derived metabolites, pyruvate–TCA–malate metabolism, and UGT-mediated glycosylation. Expression analysis identified a mitochondrial NADP-dependent isocitrate dehydrogenase gene and UDP-glucosyltransferase 2 (UGT2) as consistently upregulated in both resistant backgrounds. Silencing NADP reduced the LC₅₀ of nitenpyram and clothianidin by 1.84- and approximately 1.81-fold, respectively, whereas UGT2 silencing produced corresponding reductions of 1.89- and 1.83-fold. These findings indicate that neonicotinoid resistance in Nilaparvata lugens is supported by coordinated remodelling of central metabolism and detoxification and identify two candidate metabolic nodes for further resistance management research. Full article

Herpetospermum pedunculosum is an endangered cucurbitaceous medicinal plant whose functional genomic and metabolic studies are constrained by the lack of efficient aseptic seedling and genetic transformation systems. Here, we established a rapid aseptic seedling production method and a RUBY-assisted hairy root transformation platform integrated with metabolomic evaluation. The cotton-supported liquid culture method provided a favorable balance between germination performance and experimental operability. Microsyringe-mediated stem-base inoculation with Rhizobium rhizogenes K599 carrying 35S::RUBY enabled rapid visual screening of RUBY-positive hairy roots, with a maximum transformation efficiency of 93.33%. Widely targeted metabolomics identified 242 metabolites and revealed major differences in amino acid/nitrogen and sugar metabolism, lipid-related metabolism, specialized metabolite biosynthesis, hormone-related pathways, and ABC transporters among wild-type, vector-free K599-induced, and RUBY-expressing roots. In addition, 80 HpRHL-like bHLH genes were identified. As a proof of concept, RT-qPCR confirmed HpRHL76 overexpression, which was associated with an increase in mean root hair length from approximately 0.4 to 1.1 mm. Together, this integrated framework provides a practical basis for preliminary candidate gene assessment, functional genomic studies, and future metabolic engineering of medicinally relevant compounds in H. pedunculosum, and may serve as a methodological reference for other difficult-to-transform medicinal plants. Full article

Obesity-related complications have long been significant risk factors threatening human health. Sanhua tea is an instant tea composed of Rosa rugosa Thunb., Jasminum sambac (L.) Ait., Citrus aurantium L. var. amara Engl., Nelumbo nucifera Gaertn., and Ligusticum chuanxiong Hort. This study aimed to investigate the protective effects and underlying mechanisms of Sanhua tea in obese mice. An obesity model was established by feeding C57BL/6J mice a high-fat diet. Mice received intragastric Sanhua tea at doses (500, 1500, and 2500 mg/kg/day) for three weeks. Biochemical analyses indicated that Sanhua tea significantly reduced total cholesterol, triglyceride, low-density lipoprotein cholesterol, and pro-inflammatory cytokine levels in serum. Sanhua tea also alleviated liver oxidative stress by reducing malondialdehyde levels and regulating the activities of related enzymes. Additionally, Sanhua tea maintained gut microbiota diversity and reshaped microbial composition, reducing the Firmicutes/Bacteroidota ratio, increasing beneficial bacterial communities, and significantly decreasing harmful bacterial communities. Metabolomics analysis revealed that Sanhua tea altered liver metabolites, which were significantly associated with specific gut microbes. These metabolites influenced pathways such as ABC transporters, general metabolic pathways, and central carbon metabolism in cancer, contributing to obesity alleviation. In conclusion, Sanhua tea alleviated obesity symptoms in mice by modulating blood lipid levels, liver metabolism, and gut microbiota. Full article

Background/Objectives: Antimicrobial resistance in microbial communities is a global health concern that leads to millions of deaths each year. Many bacterial pathogens have resistance to multiple antibiotics. Domestic wastewater treatment facilities are reservoirs for antibiotic-resistant bacteria and resistance genes. Wastewater-based epidemiology surveillance is crucial for monitoring antibiotic resistance genes (ARGs). Türkiye has one of the highest levels of antibiotic resistance with a lack of research on resistomes. This study is a focused reanalysis of publicly available wastewater metagenomes from Türkiye, comparing them to global and other country’s results. Methods: Ten metagenomic data of wastewater treatment from Türkiye were downloaded from NCBI-SRA database. Metagenome assemblies were performed and high-quality metagenome-assembled genomes (HQ-MAGs) were included in the study. Taxonomic annotations and antibiotic resistance profiles were identified in both the metagenome assemblies and HQ-MAGs. Results: A total of 401 different ARGs in 25 antibiotic classes have been identified, including Mcr (including mcr-1, mcr-2, mcr-3 and mcr-5 variants) and optrA. The vanR two-component regulatory system genes for controlling vancomycin antibiotic resistance were one of the most dominant along with other vancomycin resistance genes such as vanA and vanB. A total of 115 HQ-MAGs were obtained with at least eight ARGs. The HQ-MAG with the highest number of resistance genes (58) was found to belong to E. coli. The most frequently encountered resistance genes in HQ-MAGs were the multidrug ABC transporter, vanR, bacA and patA which confer resistance to multidrug, glycopeptide, bacitracin and fluoroquinolone antibiotic groups, respectively. Conclusions: To effectively address the problems of antibiotic resistance outbreaks, comparable AMR surveillance at national and global levels is required for the identification and prioritization of ARGs and resistance genes. This is the first report conducted in Türkiye. Full article

To investigate the differences in pulp metabolites among four varieties of Pouteria caimito fruit (JZL1, JZL3, JZL5, and JZL6), ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was employed for the separation and identification of metabolites. A total of 1285 metabolites were identified, including 648 in positive ion mode and 637 in negative ion mode. At the class level, carboxylic acids and derivatives (14.32%) and organooxygen compounds (11.83%) accounted for the highest proportions; at the subclass level, amino acids, peptides, and analogues (12.53%) as well as carbohydrates and carbohydrate conjugates (9.49%) were the main categories. PLS-DA analysis revealed significant differences in metabolite profiles among the four varieties, with numerous up-regulated and down-regulated metabolites in each comparison group, and some metabolites showed fold changes > 10 or <0.1. KEGG pathway enrichment analysis further indicated that differential metabolites were primarily enriched in pathways such as ABC transporters, citrate cycle (TCA cycle), starch and sucrose metabolism, and linoleic acid metabolism. This study provides an important metabolomic basis for variety identification, nutritional quality evaluation, and functional component development of Pouteria caimito fruit. Full article

Bergapten is a plant-derived linear furanocoumarin widely distributed in Rutaceae and Apiaceae species and increasingly recognized for its multifunctional anticancer potential. This review critically synthesizes current evidence on bergapten’s biosynthesis, physicochemical and pharmacokinetic properties, anti-inflammatory and antioxidant pharmacodynamics, and mechanistic antitumor activity, highlighting its translational relevance within pharmaceutical development. Preclinical studies across diverse malignancies demonstrate pleiotropic anticancer effects. Mechanistically, bergapten activates mitochondrial apoptosis via Bax/Bcl-2 modulation and caspase cascades, induces cell cycle arrest through p53–p21 signaling, and suppresses PI3K/Akt/mTOR and NF-κB pathways. Additional effects include PTEN-mediated autophagy induction, interference with metabolic reprogramming, reversal of multidrug resistance through ABC transporter modulation, and context-dependent photoactivated cytotoxicity. Beyond direct tumor cell targeting, bergapten attenuates pro-inflammatory mediators and regulates redox homeostasis through downregulation of NOX4-derived ROS and activation of Nrf2-driven antioxidant defenses, addressing the redox–inflammatory axis implicated in carcinogenesis. Despite promising mechanistic depth, clinical translation is limited by incomplete human pharmacokinetic data and poor aqueous solubility. Nanotechnology-enabled delivery systems and structural derivatives offer strategies to enhance bioavailability and therapeutic index. Overall, bergapten emerges as a systems-level phytochemical candidate warranting further translational investigation in oncology. Full article

Crop straw is an abundant lignocellulosic resource, but its efficient bioconversion is hindered by the recalcitrant structure of plant cell walls. This study integrated degradation phenotyping, enzyme activity assays, whole-genome analysis, and comparative transcriptomics to link the wheat-straw degradation performance of strain XH2 with its enzymatic and molecular responses. Strain XH2 was isolated from fully decomposed compost collected in Anhui Province, China, selected based on the formation of a distinct hydrolysis halo on CMC-Congo red agar, and deposited in the China Center for Type Culture Collection (CCTCC) under accession number CCTCC M 2025519. Morphological, cultural, phylogenetic, and genomic analyses identified strain XH2 as Streptomyces thermocarboxydus. Its degradation capacity was evaluated during 28 days of cultivation by measuring straw degradation, lignocellulosic components, scanning electron microscopy (SEM), and extracellular enzyme activities. S. thermocarboxydus XH2 caused marked disruption of the wheat-straw surface and achieved a degradation rate of 31.45%. Cellulose and hemicellulose contents decreased from 41.10% to 28.87% and from 30.72% to 16.85%, respectively, whereas lignin decreased from 8.28% to 6.30%. Endoglucanase activity, filter paper activity (FPase, an indicator of total cellulase activity), and xylanase activity peaked on day 7, reaching 35.99, 17.68, and 37.01 U/mL, respectively. Genome analysis revealed multiple genes encoding cellulases and hemicellulases. Comparative transcriptomic analysis after 72 h of cultivation in wheat-straw medium identified 1614 differentially expressed genes relative to Gause No. 1 medium, with major enrichment in ABC transporters and fructose and mannose metabolism. Most genes associated with polysaccharide degradation were upregulated. These findings link the degradation phenotype of S. thermocarboxydus XH2 to its enzymatic and molecular responses and support its further evaluation as a candidate for wheat-straw bioconversion under greenhouse and field conditions. Full article

Although Alternaria gansuense causes yellow stunt and root rot (YSRR)—a destructive disease of the leguminous forage Astragalus adsurgens in northern China—systematic investigations of this pathogen at the protein level remain scarce. In this study, we establish an optimized proteomic workflow for A. gansuense by comparing two protein extraction methods. Using data-independent acquisition (DIA) mass spectrometry with a DIA-NN search against the Alternaria protein database, we construct the first comprehensive proteome reference map of A. gansuense, then perform functional annotation via Gene Ontology, KOG, KEGG, InterPro domain, and subcellular localization analyses. A total of 5052 proteins were identified from vegetative mycelia, and the proteome was found to be predominantly composed of proteins involved in primary metabolism, signal transduction, secondary metabolism, and stress responses. Notably, a set of putative pathogenicity-associated proteins, including two-component regulators (SSK1p), protein kinases, cytochrome P450 enzymes, and ABC transporters, was identified. These proteins are homologs of well-characterized virulence factors in other pathogenic fungi, suggesting a potential coordinated signaling—metabolism—defense network that may contribute to fungal virulence. Subcellular localization further shows that cytoplasmic and nuclear proteins together account for over 50% of the annotated proteome. This study presents the first comprehensive proteomic reference map for A. gansuense, providing a valuable resource for functional genomics. Subsequent experimental validation of the bioinformatically predicted candidate molecular targets presented here may help to dissect the pathogenic mechanisms of YSRR and enable the development of novel disease management strategies. Full article

Yeast hydrolysate (YH) is a yeast-derived functional feed ingredient containing bioactive peptides, amino acids, nucleotides, β-glucans, and mannan oligosaccharides, which may exert prebiotic-like effects by regulating nutrient metabolism, host health, and intestinal microbial homeostasis. However, its effects on lactating Dezhou jennies remain largely unclear. This study investigated the effects of dietary YH supplementation on body weight change, serum biochemical parameters, serum metabolomic profiles, and fecal microbiota composition in lactating Dezhou jennies. Sixteen healthy lactating Dezhou jennies were randomly assigned to a control group fed a basal diet (MCON, n = 8) or a YH supplementation group fed the basal diet supplemented with YH (MYE, n = 8) for 60 days. Compared with the MCON group, the MYE group showed numerically higher final body weight and body weight change. Serum biochemical analysis showed that YH supplementation significantly decreased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and increased triglyceride (TG) concentrations, while all measured biochemical parameters remained within physiological reference ranges. Serum metabolomic profiling identified 193 differential metabolites between the two groups, including 55 upregulated and 138 downregulated metabolites in the MYE group. These metabolites were mainly associated with amino acid metabolism, lipid metabolism, bile acid metabolism, steroid hormone biosynthesis, mineral absorption, ABC transporters, and protein digestion and absorption, indicating that YH supplementation reshaped nutrient-related metabolic pathways in lactating Dezhou jennies. Fecal microbiota analysis showed no significant changes in α-diversity or overall community structure; however, the MYE group displayed numerically higher microbial richness indices, more unique ASVs and genera, a lower relative abundance of Bacteroidota, and a higher relative abundance of Bacillota. LEfSe analysis further revealed enrichment of specific bacterial taxa in the MYE group, including Christensenellaceae_R-7_group, Anaerovorax, and UCG-related taxa. Collectively, these preliminary findings suggest that dietary YH supplementation may alter selected serum biochemical indices and circulating metabolites and may selectively affect the relative abundance of certain fecal bacterial taxa in lactating Dezhou jennies. However, given the limited sample size, these results should be interpreted cautiously, and larger-scale studies are needed to confirm their reproducibility and practical significance. Full article

Buchwaldoboletus xylophilus is a rare saprotrophic edible mushroom in the Boletaceae and is the second bolete species to have been successfully cultivated artificially, yet its developmental molecular regulation remains unexplored. We integrated RNA-seq transcriptomics and untargeted LC-MS/MS metabolomics across five developmental stages (A–E), applying differential expression, alternative splicing, ceRNA network construction, WGCNA, machine learning, consensus clustering, and O2PLS joint modelling. Transcriptomic analysis revealed that the mycelium-to-primordium transition (stage A to C) showed the most drastic reprogramming, with 2233 differentially expressed genes, while metabolomic comparison between stage A and E revealed overwhelmingly upregulated metabolites (184 up vs. 10 down), indicating asymmetric regulation between the two omics layers. Notably, mutually exclusive exon splicing events exhibited high functional significance, and all top ceRNA hubs were lncRNAs. Unsupervised consensus clustering validated the molecular distinctness of the sampled stages. Metabolite enrichment highlighted antioxidant functions and ABC transporter pathways, and O2PLS integrative modelling confirmed a strong shared developmental signal between transcriptome and metabolome. This study provides the first multidimensional molecular atlas for B. xylophilus, revealing a non-linear developmental programme, transcriptome–metabolome decoupling, and a central role of antioxidant defence throughout development. Our findings offer mechanistic clues regarding the evolutionary transition from ectomycorrhizal to saprotrophic lifestyles in the Boletaceae and establish a multi-omics foundation for the molecular breeding of this emerging edible and medicinal mushroom. Full article

Wheat stripe rust (yellow rust), a devastating disease caused by the phytopathogen Puccinia striiformis f. sp. tritici (Pst), poses a major threat to global wheat (Triticum aestivum L.) production. Under ongoing climate warming, the highly virulent Pst race CYR34 has become predominant in China and exhibits increased tolerance to elevated temperatures. Although temperature is known to influence Pst urediniospore germination, the molecular mechanisms underlying temperature sensitivity during this process remain poorly understood. In this study, we combined histological examinations with transcriptome sequencing across multiple temperature regimes to identify temperature-responsive genes and characterize the predicted protein association networks in Pst. Urediniospore germination of three Pst races was tested; stronger heat tolerance was observed in CYR34-8 with 67.40–77.40% germination at 9–16 °C. RNA-Seq analysis identified 89 differentially expressed genes (DEGs) associated with temperature sensitivity, and their expression patterns were validated by qRT-PCR. The DEGs were significantly enriched in ubiquinone and other terpenoid-quinone biosynthesis, glycan degradation, and longevity-regulating pathways. Among these DEGs, genes annotated as encoding an ABC transporter, malate dehydrogenase, Hsp70, and a class 3 lipase were identified as putative hub genes in the predicted protein association network and may be associated with the coordination of temperature responses and metabolic processes. Full article

PBU (N-phenyl-N′-thiazolylurea) promotes callus induction and adventitious bud differentiation in eucalyptus, but the miRNA-mediated regulatory mechanisms underlying these effects remain unclear. In this study, calli of Eucalyptus urophylla × E. grandis clone DH32-29 with distinct phenotypes were cultured at four PBU concentrations (0, 0.1, 1 and 5 mg L⁻¹) and analyzed by small-RNA sequencing, targeted metabolomics, and qRT-PCR validation. A total of 114 common differentially expressed miRNAs were identified, targeting 610 mRNAs. Functional enrichment analysis revealed that these targets were predominantly associated with lignin metabolism, phenylpropanoid metabolism, biotin metabolism, tryptophan metabolism, protein processing in the endoplasmic reticulum, and galactose metabolism. Metabolomic profiling detected 3029 metabolites, with differential metabolites enriched in the ABC transporter pathway, galloyl sugar biosynthesis, and cofactor biosynthesis. Key miRNA families, including miR164, miR165/166, and miR396, exhibited PBU concentration-dependent expression patterns and were predicted, based on in silico target prediction and qRT-PCR co-expression, to be potentially associated with target genes involved in lignin biosynthesis, ROS-related metabolism, and cytokinin homeostasis; these regulatory relationships remain to be experimentally validated. Among the tested concentrations, 1 mg L⁻¹ PBU was the dosage associated with the strongest reprogramming of secondary metabolism and with metabolic signatures suggestive of better preserved redox homeostasis; future work will build on this reference dataset with quantitative regeneration phenotyping and direct redox measurements to confirm this candidate optimum. These findings provide new insights into PBU-mediated in vitro regeneration in eucalyptus and offer a molecular basis for optimizing regeneration systems in E. urophylla × E. grandis. These findings provide new insights into the miRNA-metabolite regulatory network underlying phenylurea-mediated callus differentiation in woody plants. Full article

Cancer pain affects more than half of all oncology patients and represents one of the most challenging therapeutic problems in modern medicine. Despite the central role of opioids in cancer pain management—codified by the WHO analgesic ladder—the clinical response to these agents is highly variable between individuals. Pharmacogenomics promises to explain this heterogeneity by identifying functionally relevant genetic polymorphisms in genes encoding opioid receptors, metabolizing enzymes, and membrane transport proteins. However, after two decades of intensive research, clinical translation of genetic data into actionable prescribing strategies remains elusive. A narrative-critical review of the literature was conducted by searching PubMed, Scopus, and Web of Science databases from inception to March 2026, using the search terms “opioid,” “pharmacogenomics,” “pharmacogenetics,” “cancer pain,” “polymorphism,” and individual gene names (OPRM1, CYP2D6, COMT, ABCB1, SLC22A1, UGT2B7, and others). Reference lists of included articles were hand-searched for additional relevant studies. Inclusion was restricted to English-language articles reporting original data or systematic reviews on genetic polymorphisms and opioid response, with priority given to studies conducted in cancer pain populations. Clinical practice guidelines from CPIC, NCCN, ESMO, EAPC, and ASCO were consulted for current recommendations. This narrative-critical review examines the evidence on genetic polymorphisms relevant to opioid response in cancer pain, covering three functional categories: (1) pharmacodynamic genes, including opioid receptors (OPRM1, OPRD1, OPRK1) and neuromodulatory targets (COMT, KCNJ6, MC1R); (2) pharmacokinetic enzymes (CYP2D6, CYP3A4/5, UGT2B7); and (3) membrane transporters, including ABC efflux pumps (ABCB1, ABCG2, ABCC2) and SLC uptake carriers (SLC22A1, SLCO1B1, SLC6A4, SLC6A2). A dedicated section addresses the direct and indirect interference of the tumour itself—through the tumour microenvironment, neuroimmune signalling, epigenetic reprogramming, and cancer-induced organ dysfunction—on opioid pharmacogenomics. The overall evidence is poor and fragmented, a finding intrinsic to the extraordinary diversity, large number, and context-dependent biological activity of the polymorphisms identified. The tumour itself acts as a pervasive confounder that systematically distorts genotype–phenotype relationships. The path forward requires a paradigm shift from candidate-gene association studies to system pharmacogenomics and multi-omic integration. Full article

Sorghum (Sorghum bicolor (L.) Moench) is an important crop with remarkable tolerance to adverse environments, including nitrogen deficiency. To investigate the mechanisms underlying sorghum tolerance to low-nitrogen (LN) stress, we integrated phenotypic evaluation, transcriptome profiling, weighted gene co-expression network analysis (WGCNA), and haplotype analysis. Two accessions, the LN-tolerant ‘Liaonian B-1’ and the LN-sensitive ‘Yikeerli’, were examined under hydroponic and field conditions. Under LN conditions, Liaonian B-1 showed increases of 32% in root length, 4.3-fold in root fresh weight, and 91% in root dry weight, whereas the LN-sensitive accession showed severe reductions in shoot biomass and a decrease in root fresh weight, with root dry weight remaining relatively stable. Transcriptomic analysis revealed more shared differentially expressed genes and stronger enrichment of N metabolism pathways in shoots, whereas roots showed enrichment of ATP-binding cassette (ABC) transporter and fatty acid elongation pathways. WGCNA identified 500 hub genes in roots and shoots. Five genes in the glutamine synthetase/glutamate synthase (GS-GOGAT) pathway were significantly associated with nitrogen-related traits. SORBI_3001G116400, which encodes glutamate synthase, showed the strongest haplotype effect in 232 sorghum accessions. The A allele (Hap1) was significantly associated with increased plant height, SPAD value, grain number, nitrogen accumulation, and biomass under LN stress, suggesting that SORBI_3001G116400 as a candidate gene requiring functional validation and testing in additional genetic backgrounds. Full article

Cadmium (Cd) is a toxic metal that poses a significant threat to crop production and global food security. Transporters play a critical role in mediating the uptake of metal ions, including Cd. However, a substantial number of Cd transporters in rice remain uncharacterized. In this study, we identify OsMDR4, a member of the multidrug resistance protein family, as a mediator of Cd uptake in rice. Heterologous overexpression of OsMDR4 in yeast increased both Cd sensitivity and intracellular Cd accumulation. Consistent with this, the Cd concentrations in both roots and shoots of the mdr4 mutants were significantly lower than those in wild type. Kinetic analysis further revealed that the maximum Cd uptake rate in mdr4 mutants was markedly reduced compared with wild type. Expression analysis showed that OsMDR4 is primarily expressed in the epidermis and root hairs of rice seedlings and in floral organs during the flowering stage. Notably, OsMDR4 expression in seedling roots was upregulated in response to Cd exposure. Subcellular localization analysis revealed that OsMDR4–EGFP was predominantly localized to the plasma membrane in a heterologous Arabidopsis protoplast system. In summary, we have identified and characterized OsMDR4 as a previously uncharacterized protein that contributes to cadmium accumulation in rice. Full article