Search Results (912)

The ecological rice–eel co-culture system is not only beneficial for enhancing productivity and sustainability in agriculture but also plays a crucial role in promoting environmental health. In the present study, based on the long-term positioning trial of the rice–eel co-culture system that began in 2016 and was sampled in 2023, the effects of reduced nitrogen fertilizer application on soil physico-chemical properties and the bacterial community were investigated. Treatments included a conventional regular fertilization treatment (RT), rice–eel co-culture system regular fertilization (IT), and nitrogen-reduction 10%, 30%, and 50% fertilization treatments (IT90, IT70, and IT50). Our research demonstrated the following: (1) Compared to RT, IT significantly increased soil water-stable macroaggregates (R0.25), mean weight diameter (MWD), geometric mean diameter (GMD), and available phosphorus content, with the increases of 15.66%, 25.49%, 36.00%, and 18.42%, respectively. Among the nitrogen-reduction fertilization treatments, IT90 showed the most significant effect. Compared to IT, IT90 significantly increased R0.25, MWD, GMD, and available nitrogen content, with increases of 4.4%, 7.81%, 8.82%, and 28.89%, respectively. (2) Compared to RT, at the phylum level, the diversity of Chloroflexi was significantly increased under IT and IT50, and the diversity of Gemmatimonadota was significantly increased under IT90, IT70, and IT50. The diversity of Acidobacteriota was significantly higher in IT90 and IT70 compared to IT. It was shown that the rice–eel co-culture system and nitrogen fertilizer reduction could effectively improve the degradation capacity of organic matter and promote soil nitrogen cycling. In addition, redundancy analysis (RDA) identified total phosphorus, total nitrogen, and available nitrogen (p = 0.007) as the three most important environmental factors driving changes in the bacterial community. (3) The functional prediction analysis of soil microbiota showed that, compared to RT, the diversity of pathways related to biosynthesis (carbohydrate biosynthesis and cell structure biosynthesis) and metabolism (L-glutamate and L-glutamine biosynthesis) was significantly higher under IT70, IT90, IT, and IT50 (in descending order). However, the diversity of pathways associated with degradation/utilization/assimilation (secondary metabolite degradation and amine and polyamine degradation) was significantly lower under all the rice–eel co-culture treatments. In conclusion, the rice–eel co-culture system improved soil physicochemical properties and the soil microbial environment compared with conventional planting, and the best soil improvement was achieved with 10% less N fertilizer application. Full article

Ericoid mycorrhizal fungi (EMF) enhance plant fitness and metabolic regulations in nutrient-poor soils, though the mechanisms diving these interactions require further elucidation. This study investigated the physiological and metabolic responses of blueberry seedlings following 2- and 3-weeks inoculation with Oidiodendron maius H14. The results indicated that EMF could significantly increases plant biomass, improve the accumulation of osmoregulatory substances in leaves. Additionally, the colonization rate of EMF are 26.18% and 30.22% after 2- and 3-weeks, respectively. The Metabolomics analysis identified 758 (593 up- and 165 down-regulated) and 805 (577 up- and 228 down-regulated) differential metabolites in roots at 2- and 3-weeks inoculation with O. maius H14, respectively. KEGG pathway annotation revealed that O. maius H14 triggered various amino acid metabolism pathways, including tryptophan metabolism and arginine and proline metabolism. These findings suggested that O. maius H14 stimulated root-specific biosynthesis of growth-promoting compounds and antimicrobial compounds. Concomitant downregulation of stress-associated genes and upregulation of glutamine synthetase suggest EMF modulates host defense responses to facilitate symbiosis. Thus, our results demonstrated that O. maius H14 orchestrates a metabolic reprogramming in blueberry roots, enhancing growth and stress tolerance through coordinated changes in primary and specialized metabolism, which could inform strategies for improving symbiosis and metabolic engineering in horticultural practices. Full article

Background/Objectives: Gut microbiota research has gained momentum in recent years broadening knowledge of microbial components and their potential effects on health and well-being. Strong association between explicit microbes and metabolic diseases associated with obesity and type 2 diabetes mellitus, gastrointestinal disorders, neurodegenerative diseases, and even cancers have been established. Akkermansia muciniphila is a budding next-generation probiotic that plays an important role in systemic metabolism, intestinal health, and immune regulation, establishing strong implications for its use as a potent therapeutic intervention in diverse diseases. This project aimed at evaluating whether bacterial cell extracts of VH Akkermansia muciniphila (Vidya Strain; VS) can stimulate insulin secretion in INS-1 pancreatic beta cells and GLP-1 secretion in NCI-H716 human L-cells, both established in vitro models for studying metabolic regulation. Methods: Cultured VH Akkermansia muciniphila extracts were administered in a dose-dependent manner on INS-1 cells, and glucose-stimulated insulin secretion (GSIS) was measured via ELISA. Treated Human L-cell lines (NCI-H716) were analyzed for GLP-1 secretion. Results: Our study demonstrated that VH Akkermansia muciniphila extracts modestly increase insulin secretion from INS-1 beta cells and, more notably, induce a robust, dose-dependent rise in GLP-1 secretion from NCI-H716 L-cells, with the highest dose achieving over a 2000% increase comparable to glutamine. Conclusions: These findings suggest that VH A. muciniphila extracts may offer metabolic benefits by enhancing GLP-1 release, highlighting their potential for managing type 2 diabetes and obesity. Full article

Background: Salmonella infections pose a serious threat to both animal and human health worldwide. Notably, there is an increasing trend in the resistance of Salmonella to fluoroquinolones, the first-line drugs for clinical treatment. Methods: Utilizing Salmonella Typhimurium CICC 10420 as the test strain, ciprofloxacin was used for in vitro induction to develop the drug-resistant strain H1. Changes in the minimum inhibitory concentrations (MICs) of various antimicrobial agents were determined using the broth microdilution method. Transcriptomic and metabolomic analyses were conducted to investigate alterations in gene and metabolite expression. A combined drug susceptibility test was performed to evaluate the potential of exogenous metabolites to restore antibiotic susceptibility. Results: The MICs of strain H1 for ofloxacin and enrofloxacin increased by 128- and 256-fold, respectively, and the strain also exhibited resistance to ceftriaxone, ampicillin, and tetracycline. A single-point mutation of Glu469Asp in the GyrB was detected in strain H1. Integrated multi-omics analysis showed significant differences in gene and metabolite expression across multiple pathways, including two-component systems, ABC transporters, pentose phosphate pathway, purine metabolism, glyoxylate and dicarboxylate metabolism, amino sugar and nucleotide sugar metabolism, pantothenate and coenzyme A biosynthesis, pyrimidine metabolism, arginine and proline biosynthesis, and glutathione metabolism. Notably, the addition of exogenous glutamine, in combination with tetracycline, significantly reduced the resistance of strain H1 to tetracycline. Conclusion: Ciprofloxacin-induced Salmonella resistance involves both target site mutations and extensive reprogramming of the metabolic network. Exogenous metabolite supplementation presents a promising strategy for reversing resistance and enhancing antibiotic efficacy. Full article

Colorectal cancer (CRC) remains a leading cause of cancer morbidity and mortality worldwide, especially in older adults where frailty complicates treatment outcomes. Multimodal prehabilitation—comprising nutritional support, physical exercise, and psychological interventions—has emerged as a promising strategy to enhance patients’ resilience before CRC surgery. Clinical studies demonstrate that prehabilitation significantly reduces postoperative complications, shortens hospital stays, and improves functional recovery. Nutritional interventions focus on counteracting malnutrition and sarcopenia through tailored dietary counseling, protein supplementation, and immunonutrients like arginine and glutamine. Physical exercise enhances cardiorespiratory fitness and muscle strength while modulating immune and metabolic pathways critical for surgical recovery. Psychological support reduces anxiety and depression, promoting mental resilience that correlates with better postoperative outcomes. Despite clear clinical benefits, the molecular mechanisms underlying prehabilitation’s effects—such as inflammation modulation, immune activation, and metabolic rewiring—remain poorly understood. This review addresses this knowledge gap by exploring potential biological pathways influenced by prehabilitation, aiming to guide more targeted, personalized approaches in CRC patient management. Advancing molecular insights may optimize prehabilitation protocols and improve survival and quality of life for CRC patients undergoing surgery. Full article

Pancreatic cancer, specifically pancreatic ductal adenocarcinoma (PDAC), ranks among the most lethal malignancies, with a 5-year survival rate of under 10%. The most prevalent KRAS mutations occur in three hotspot residues: glycine-12 (G12), glycine-13 (G13), and glutamine-61 (Q61), leading to the constant activation of the Ras pathway, making them the primary focus in oncologic drug development. Selective KRAS G12C inhibitors (e.g., sotorasib, adagrasib) have demonstrated moderate efficacy in clinical trials; however, this mutation is infrequent in PDAC. Emerging therapies targeting KRAS G12D and G12V mutations, such as MRTX1133, PROTACs, and active-state inhibitors, show promise in preclinical studies. Pan-RAS inhibitors like ADT-007, RMC-9805, and RMC-6236 compounds provide broader coverage of mutations. Their efficacy and safety are currently being investigated in several clinical trials. A major challenge is the development of resistance mechanisms, including secondary mutations and pathway reactivation. Combination therapies targeting the RAS/MAPK axis, SHP2, mTOR, or SOS1 are under clinical investigation. Immunotherapy alone has demonstrated limited effectiveness, attributed to an immunosuppressive tumor microenvironment, although synergistic effects are noted when paired with KRAS-targeted agents. Furthermore, KRAS mutations reprogram cancer metabolism, enhancing glycolysis, macropinocytosis, and autophagy, which are being explored therapeutically. RNA interference technologies have also shown potential in silencing mutant KRAS and reducing tumorigenicity. Future strategies should emphasize the combination of targeted therapies with metabolic or immunomodulatory agents to overcome resistance and enhance survival in KRAS-mutated PDAC. Full article

Qingke (Hordeum vulgare L. var. nudum Hook. f.), a staple crop in the Tibetan Plateau, suffers from severe yield reduction under continuous cropping (by 38.67%), yet the underlying mechanisms remain unclear. This study systematically investigated the effects of 23-year continuous cropping (23y-CC) on the nutrient dynamics, carbohydrate metabolism, and enzymatic activities in Qingke leaves across five developmental stages (T1: seedling; T2: tillering; T3: jointing; T4: flowering; T5: filling). Compared to the control (first-year planting), 23y-CC significantly reduced leaf nitrogen (N), phosphorus (P), and potassium (K) contents by 60.94%, 47.96%, and 60.82%, respectively, at early growth stages. Key nitrogen-metabolizing enzymes, including glutamate synthase (GOGAT), glutamine synthase (GS), and nitrate reductase (NR), exhibited reduced activities under 23y-CC, indicating impaired nitrogen assimilation. Carbohydrate profiling revealed lower starch and glucose contents but higher sucrose accumulation in later stages (T4–T5) under 23y-CC, accompanied by the dysregulation of sucrose synthase (SS) and invertase activities. These findings elucidate how continuous cropping disrupts nutrient homeostasis and carbon allocation, ultimately compromising Qingke productivity. This study provides novel insights into agronomic strategies for mitigating continuous cropping obstacles in Qingke. Full article

The insect resistance expression of Bacillus thuringiensis (Bt) cotton (Gossypium hirsutum L.) is unstable due to temporal and spatial variations in the Bt protein content in different organs and growth stages. The aim of this study was to improve the Bt protein content in cotton flowers and investigate the underlying physiological mechanism using biochemical analytical methods. In this study, a split-plot design with three replications was used. The main plots included two Bt cotton cultivars (a conventional cultivar, Sikang1 (S1), and a hybrid cultivar, Sikang3 (S3)), while five soil nitrogen application levels (CK (control check): normal level; N1: 125% of the CK; N2: 150% of the CK; N3: 175% of the CK; N4: 200% of the CK) constituted the subplots. The Bt protein content and related nitrogen metabolism parameters were measured. We found that the Bt protein content increased and then decreased with increasing nitrogen rates. It reached its maximum at N3, with significant increases of 71.86% in 2021 and 39.36% in 2022 compared to the CK. Correlation analysis indicated that the Bt protein content was significantly positively related to the soluble protein and free amino acid contents, as well as the GPT (glutamic pyruvic transaminase), GOT (glutamic oxaloacetic transaminase), GS (glutamine synthetase) and GOGAT (glutamate synthetase) activities. On the other hand, negative correlations were found between the Bt protein content and protease and peptidase activities. In addition, stepwise regression and path analysis indicated that the increased Bt protein content was mainly due to the enhanced GS and GOGAT activities. In summary, appropriately increasing nitrogen fertilizer application is a practical way to increase flower Bt protein content and insecticidal efficacy of Bt cotton. These findings provide an actionable agronomic strategy for sustaining Bt expression during the critical flowering period. Full article

Background: Huang Qin Decoction (HQD) is a well-established Traditional Chinese Medicine (TCM) formulation recognized for its application in the treatment of colorectal cancer (CRC). However, the precise therapeutic mechanisms remain inadequately defined. Methods: This study integrates metabolomics from a mouse model and network pharmacology to screen potential targets and bio-active ingredients of HQD. The pharmacological activity of HQD for CRC was evidenced via single-cell RNA sequencing (scRNA-seq), molecular docking, and molecular dynamics simulations. Atomic force microscopy (AFM) assays and cellular experimental validation were used to confirm the relative mechanisms. Results: The metabolite profile undergoes significant alterations, with metabolic reprogramming evident during the malignant progression of CRC liver metastasis. Network pharmacology analysis identified that HQD regulates several metabolic pathways, including arginine biosynthesis, alanine, aspartate, and glutamate metabolism, nitrogen metabolism, phenylalanine metabolism, and linoleic acid metabolism, by targeting key proteins such as aspartate aminotransferase (GOT1), cytochrome P450 1A2 (CYP1A2), and carbonic anhydrase 2 (CA2). ScRNA-seq analysis indicated that HQD may enhance the functionality of cytotoxic T cells, thereby reversing the immunosuppressive microenvironment. Virtual verification revealed a strong binding affinity between the identified hub targets and active constituents of HQD, a finding subsequently corroborated by AFM assays. Cellular experiments confirmed that naringenin treatment inhibits the proliferation, migration, and invasion of CRC cells by downregulating GOT1 expression and disrupting glutamine metabolism. Conclusions: Computational prediction and in vitro validation reveal the active ingredients, potential targets, and molecular mechanisms of HQD against CRC liver metastasis, thereby providing a scientific foundation for the application of TCM in CRC treatment. Full article

Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy with rising incidence and poor prognosis. TP53, previously identified as the most frequently mutated gene in EAC in our studies, plays a central role in tumor suppression and regulation. However, the metabolic consequences of TP53 mutations in EAC remain largely uncharacterized. We metabolically profiled three TP53-mutant EAC cell models (OE33, OE19, and FLO1) representing progressive stages of tumor differentiation and harboring distinct TP53 alterations. Our analyses revealed different metabolic phenotypes associated with TP53 status. OE33 cells predominantly use glycolytic metabolism but display limited adaptability to environmental changes, possibly due to a higher differentiation state. FLO1 cells exhibit a strong glycolytic dependence, elevated lactate production, and robust proliferation under acidic conditions, consistent with an aggressive and metastatic phenotype. OE19 cells preferentially utilize oxidative phosphorylation, demonstrated by resilience to glucose and glutamine deprivation, and ROS accumulation. These findings highlight the metabolic plasticity of EAC and suggest that TP53 mutation type might influence bioenergetic dependencies. Targeting these metabolic vulnerabilities may offer novel therapeutic avenues for personalized treatment in EAC. Full article

As tumor research has deepened, the deregulation of cellular metabolism has emerged as yet another recognized hallmark of cancer. Tumor cells adapt different biochemical pathways to support their rapid growth, proliferation, and invasion, resulting in distinct anabolic and catabolic activities compared with healthy tissues. Certain metabolic shifts, such as altered glucose and glutamine utilization and increased de novo fatty acid synthesis, are critical early on, while others may become essential only during metastasis. These metabolic adaptations are closely shaped by, and in turn remodel, the tumor microenvironment, creating favorable conditions for their spread. Anticancer metabolic strategies should integrate pharmacological approaches aimed at inhibiting specific biochemical pathways with well-defined dietary interventions as adjunctive therapies, considering also the role of gut microbiota in modulating diet and treatment responses. Given the established link between the consumption of foods rich in saturated fatty acids and sugars and an increased cancer risk, the effects of diet cannot be ignored. However, current evidence from controlled and multicenter clinical trials remains insufficient to provide definitive clinical recommendations. Further research using modern omics methods, such as metabolomics, proteomics, and lipidomics, is necessary to understand the changes in the metabolic profiles of various cancers at different stages of their development and to determine the potential for modifying these profiles through pharmacological agents and dietary modifications. Therefore, clinical trials should combine standard treatments with novel approaches targeting metabolic reprogramming, such as inhibition of specific enzymes and transporters or binding proteins, alongside the implementation of dietary restrictions that limit nutrient availability for tumor growth. However, to optimize therapeutic efficacy, a precision medicine approach should be adopted that balances the destruction of cancer cells with the protection of healthy ones. This approach, among others, should be based on cell type-specific metabolic profiling, which is crucial for personalizing oncology treatment. Full article

In addition to their well-known role in ATP production, mitochondria are vital to cancer cell metabolism due to their involvement in redox regulation, apoptosis, calcium signaling, and biosynthesis. This review explores how cancer cells drive the extensive reprogramming of mitochondrial structure and function, enabling malignant cells to survive hostile microenvironments, evade therapy, and proliferate rapidly. While glycolysis (the Warburg effect) was once thought to be the dominant force behind cancer metabolism, recent updates underscore the pivotal contribution of mitochondrial oxidative phosphorylation (OXPHOS) to tumor development. Cancer cells often exhibit enhanced mitochondrial ATP production, metabolic flexibility, and the ability to switch between energy sources such as glucose, glutamine, and pyruvate. Equally important are changes in mitochondrial morphology and dynamics. Due to disruptions in fusion and fission processes, regulated by proteins like Drp1 and MFN1/2, cancer cells often display fragmented mitochondria, which are linked to increased motility, metastasis, and tumor progression. Moreover, structural mitochondrial alterations not only contribute to drug resistance but may also serve as biomarkers for therapeutic response. Emerging evidence also points to the influence of oncometabolites and retrograde signaling in reshaping mitochondrial behavior under oncogenic stress. Collectively, these insights position mitochondria as central regulators of cancer biology and attractive targets for therapy. By unraveling the molecular mechanisms underlying mitochondrial reprogramming—from energy production to structural remodeling—researchers can identify new approaches to disrupt cancer metabolism and enhance treatment efficacy. Full article

Nitrogen (N) critically regulates wheat growth and grain quality, yet the molecular mechanisms underlying foliar nitrogen application remain unclear. This study evaluated the effects of foliar nitrogen application (12.25 kg ha⁻¹) on the growth, grain yield, and quality of spring wheat, as well as its molecular mechanisms. The results indicated that N was absorbed within 3 h post-application, with leaf nitrogen concentration peaking at 12 h. The N treatment increased whole-plant dry matter accumulation and grain protein content by 11.34% and 6.8%, respectively. Amino acid content peaked 24 h post-application, increasing by 25.3% compared to the control. RNA-sequencing analysis identified 4559 and 3455 differentially expressed genes at 3 h and 24 h after urea treatment, respectively, these DEGs being primarily involved in nitrogen metabolism, photosynthetic carbon fixation, amino acid biosynthesis, antioxidant systems, and nucleotide biosynthesis. Notably, the plastidic glutamine synthetase gene (GS2) is crucial in the initial phase of urea application (3 h post-treatment). The pronounced downregulation of GS2 initiates a reconfiguration of nitrogen assimilation pathways. This downregulation impedes glutamine synthesis, resulting in a transient accumulation of free ammonia. In response to ammonia toxicity, the leaves promptly activate the GDH (glutamate dehydrogenase) pathway to facilitate the temporary translocation of ammonium. This compensatory mechanism suggests that GS2 downregulation may be a key switch that redirects nitrogen metabolism from the GS/GOGAT cycle to the GDH bypass. Additionally, the upregulation of the purine and pyrimidine metabolic routes channels nitrogen resources towards nucleic acid synthesis, and thereby supporting growth. Amino acids are then transported to the seeds, culminating in enhanced seed protein content. This research elucidates the molecular mechanisms underlying the foliar response to urea application, offering significant insights for further investigation. Full article

Adenosine holds significant application value in the fields of food additives and pharmaceutical intermediate synthesis. Engineering strains to enhance their efficiency in utilizing fermentation substrates is considered an effective strategy for improving production yield. However, modifications to adenosine-producing strains remain challenging due to the complex physiological and metabolic regulation governing adenosine biosynthesis. In this study, the molecular regulatory mechanisms of adenosine biosynthesis in a high-yielding Bacillus subtilis strain were analyzed through transcriptome sequencing. Under conditions in which an additional 10 g/L glutamine and 6 g/L hypoxanthine were supplemented at 48 h of cultivation to promote adenosine synthesis, a total of 105 significantly differentially expressed genes (69 downregulated and 36 upregulated) were identified, with key genes related to adenosine biosynthesis primarily concentrated in the downstream purine metabolic pathway. Notably, core biosynthetic genes including purD, guaC, purH, and purN showed significant downregulation in the high-yielding strain, suggesting that adenosine accumulation might inhibit related gene expression through negative feedback mechanisms. Fermentation kinetic analysis revealed that biomass reached its peak at 48 h (OD₆₀₀ = 0.82), with a glucose consumption rate of 73.28% at this stage. Gene expression pattern analysis demonstrated that purD, guaC, purH, and purN maintained relatively stable expression levels during fermentation. However, the exogenous supplementation of inosine (6 g/L) and glutamine (10 g/L) induced significant inhibition of their expression—a trend paralleling that observed with exogenous adenosine addition. This research elucidates key regulatory nodes in the adenosine biosynthesis of Bacillus subtilis and provides theoretical support and candidate targets for the targeted modification of industrial strains through metabolic engineering strategies. Full article

Background: Obesity-associated metabolic disorders represent a critical global health challenge, which necessitates innovative strategies targeting lipid metabolism. Peanut skin procyanidins (PSPs), abundant bioactive compounds derived from agricultural by-products, show potential in lipid regulation, but molecular mechanisms remain unclear. Methods: This study integrated hepatic metabolomics, network pharmacology, and gut microbiota analysis to systematically decipher the mechanisms for PSP to ameliorate high-fat diet (HFD)-induced lipid metabolism disorders. Results: PSP intervention significantly attenuated HFD-induced increases in LDL-C, TG, and TC levels and effectively mitigated hepatic lipid accumulation. Metabolomics revealed that PSP reshaped hepatic lipid dynamics by modulating glycerophospholipid, linoleic acid, arachidonic acid, tryptophan, and nitrogen metabolism. Subsequent network pharmacology identified PLA2G10, PLA2G5, PLA2G2A, and CYP1B1 as the core targets, and PSP could markedly suppress their HFD-induced overexpression. Furthermore, PSP selectively reshaped the gut microbiota, enriching beneficial genera such as Akkermansia and Bacteroides while reducing the abundance of harmful bacteria within Firmicutes. PICRUSt-based functional prediction indicated that PSP alters gut microbial glutamine synthetase activity. Conclusions: Mechanistically, PSP regulates lipid metabolism by downregulating PLA2G10, PLA2G5, PLA2G2A, and CYP1B1 expression, remodeling gut microbiota structure, and increasing hepatic glutamine level. These findings provide novel insights into value-added utilization of agricultural byproducts and development of targeted intervention strategies for metabolic diseases. Full article