Search Results (19,445)

Alpine meadow ecosystems are highly sensitive to global change, yet the response mechanisms of soil respiration (Rs) to nitrogen deposition remain unclear. This research employed a gradient nitrogen addition experiment (0, 5, 10, 15, 20 g·m⁻²·a⁻¹) in an alpine meadow ecosystem in Northwest China to determine the major factors regulating soil respiration responses. High nitrogen inputs (N15 and N20) significantly elevated Rs by 31.96% and 29.21% relative to the control (p < 0.05). Nitrogen addition significantly increased soil ammonium nitrogen (NH₄⁺-N) content, as well as the activities of cellobiohydrolase (CBH) and peroxidase (POD). Microbial community structure shifted with nitrogen addition, showing increased relative abundance of Actinobacteriota (14–25%) and Basidiomycota (13–26%). Functional prediction analysis revealed that high nitrogen treatments enhanced bacterial carbon metabolism functions such as fermentation and ureolysis, while enriching fungal functional guilds like Wood Saprotroph and Arbuscular Mycorrhizal fungi. Partial Least Squares Path Modeling (PLS-PM) indicated that nitrogen addition indirectly drives changes in Rs by regulating physicochemical factors (e.g., NH₄⁺-N), which subsequently influence microbial community composition, functional potential, and key enzyme activities. These findings elucidate the factors influencing soil respiration under varying nitrogen addition levels, providing a theoretical basis for assessing soil carbon cycling in alpine meadows under global change scenarios. Full article

The industrial potential of Clostridium beijerinckii for acetone–butanol–ethanol (ABE) fermentation is limited by oxygen sensitivity and suboptimal solvent productivity. Peroxide repressor (PerR), a key negative regulator protein, is reported to suppress the oxidative stress defense system in anaerobic clostridia, leading to poor survival of bacteria under aerobic conditions. However, the regulatory mechanism underlying this phenomenon remains unclear. This study demonstrates that targeted deletion of perR (Cbei_1336) in the solvent-deficient strain C. beijerinckii DS confers robust oxygen tolerance and enhances ABE fermentation performance. The engineered perR mutant exhibited unprecedented aerobic growth under atmospheric oxygen (21% O₂), achieving a (3.79 ± 0.09)-fold increase in biomass accumulation, a (2.84 ± 0.12)-fold improvement in glucose utilization efficiency, a (57.23 ± 0.01)-fold elevation in butanol production, and a (32.78 ± 0.02)-fold amplification in acetone output compared to the parental strain. Transcriptomic analysis revealed that perR knockout simultaneously upregulated oxidative defense systems and activated ABE pathway-related genes. This genetic rewiring redirected carbon flux from acidogenesis to solventogenesis, yielding a (9.64 ± 0.90)-fold increase in total solvent titer (15.61 ± 0.89 vs. 1.62 ± 0.12 g/L) and a (2.71 ± 0.04)-fold rise in volumetric productivity (0.19 ± 0.01 vs. 0.07 ± 0.01 g/L/h). Our findings establish PerR as a master regulator of both oxygen resilience and metabolic reprogramming, providing a scalable engineering strategy for industrial oxygen-tolerant ABE bioprocessing toward low-cost biobutanol production. Full article

The increasing interest in the presence of contaminants of emerging concern (CEC) in aquatic environments has driven research into biological mechanisms capable of eliminating pharmaceutical compounds like paracetamol, considering different plant species as model systems. Thus, the use of hairy roots (HRs) has become an interesting tool. This study explores the ability of tobacco HRs to remove paracetamol, with an emphasis on elucidating the main metabolism steps and key enzymes involved in the green liver detoxification process, as well as the antioxidant response. The deepening of these aspects has been carried out through gene expression and biochemical analysis under circadian regulation. Our results reveal that HRs efficiently removed paracetamol (100 mg L⁻¹) from the culture medium, achieving around 99% removal at ZT16 h (Zeitgeber Time 16). The early activation of antioxidant defense mechanisms, demonstrated by enhanced peroxidase (POD) activity and total antioxidant capacity (TAA) during the light phase, has been observed. Furthermore, glutathione S-transferase (GSTs) activity and glutathione (GSH) levels, potentially linked to paracetamol conjugation, were also assessed. Gene expression analyses confirmed GST gene upregulation in response to paracetamol treatment, with GSTF6-like and GSTF8-like maintaining circadian rhythms as in the control, and GSTZ1-like only displayed rhythmic expression upon treatment. Additionally, the modulation of core circadian clock genes (NtLHY1 and NtTOC1) suggests that the plant response to paracetamol is tightly regulated by the circadian system. Together, these findings shed light on the complex molecular and biochemical mechanisms underlying paracetamol detoxification in tobacco HRs and underscore the significant role of circadian regulation in orchestrating these responses. Full article

The impact of maternal dietary restriction and hydroxytyrosol (HT) supplementation during the last third of gestation on plasma malondialdehyde (MDA) concentration, total antioxidant capacity (ABTS assay), and peripheral blood gene expression related to antioxidant defence, immune response, and energy metabolism was evaluated in beef cows and calves. Two feeding treatments in late gestation (T100% vs. T60% of nutrient requirements) and two HT levels (Control vs. HT at 180 mg/kg of diet) were evaluated during gestation (n = 46 cows) and lactation (n = 37 cows and calves). In pregnant cows, undernutrition led to inhibition of glucose oxidation (PDK4), decreased lipid synthesis (HMGCS1 and SCD) and TLR signalling; T60% cows showed higher plasma MDA (p < 0.05) with no positive effect of HT on antioxidant capacity. Contrarily, during lactation, earlier HT supplementation upregulated antioxidant capacity and modulated antioxidant gene expression (p < 0.05). In calves, there was an increase in SOD1, CAT, and GPX1, especially in the T60%-HT group (p < 0.05). Interestingly, HT supplementation increased glucose transport (SCLA2A1/GLUT1) during pregnancy and lactation (p < 0.05). However, it caused different effects on immunometabolic regulation in both dams and calves, depending on maternal diet. Overall, maternal HT supplementation under restricted nutritional conditions promoted postpartum antioxidant capacity and modulated immune and metabolic gene expression in cows and calves. Full article

Depressive disorder is the most prevalent mental illness, and increasing evidence suggests its potential bidirectional relationship with metabolic disorders. Given the limited efficacy of conventional antidepressants (including Selective Serotonin Reuptake Inhibitors; SSRIs) and the growing prevalence of treatment-resistant depression, there is a significant need to identify alternative molecular pathways underlying the pathophysiology of depressive disorder, which may represent novel therapeutic targets for other agents. Emerging evidence indicates that metabolic dysfunction and depressive disorder share a common pathophysiological molecular mechanism and increase each other’s risk. Targeting peripheral metabolic pathways and their interactions with the central nervous system may alleviate depressive symptoms. Glucagon-Like Peptide-1 agonists (GLP-1 RAs) and Sodium–Glucose Cotransporter-2 (SGLT2) inhibitors, widely used in the treatment of type 2 diabetes and obesity, exhibit neurotrophic and anti-inflammatory effects, ameliorate oxidative stress, and enhance mitochondrial function, collectively contributing to the antidepressant-like effects observed in preclinical studies. Peroxisome Proliferator-Activated Receptor (PPAR) α agonists primarily regulate lipid and glucose metabolism, which may potentially improve neuronal plasticity and mood regulation. Moreover, agents such as Angiotensin Receptor Blockers (ARBs) and Angiotensin Receptor-Neprilysin Inhibitors (ARNIs), used in hypertension treatment, exert central anti-inflammatory and neuroprotective effects via the modulation of the renin–angiotensin–aldosterone system (RAAS), implicated in affective disorders. Nevertheless, long-term, head-to-head trials are required to establish their efficacy, safety, and therapeutic positioning within current treatment paradigms. The aim of this review is to summarize current evidence on metabolic modulators as potential antidepressant strategies, focusing on their molecular mechanisms, preclinical and clinical findings, and prospects for integration into future therapies for depression. Full article

Monoterpenoids serve as essential components of plant essential oils and play significant roles in plant growth, development, and insect resistance. Artemisia annua, an important medicinal plant, produces abundant terpenoids. While previous research on A. annua has predominantly focused on artemisinin biosynthesis and its regulation, studies on other terpenoids in this plant have significantly lagged behind. To comprehensively investigate monoterpene biosynthesis in A. annua, we analyzed monoterpenes across its different tissues using optimized extraction and chromatographic conditions developed to enhance sensitivity and resolution in our GC-MS-based analytical method. In A. annua, 31 monoterpenoid compounds were identified. Subsequently, eight candidate monoterpene synthases (mTPS) were characterized in Escherichia coli, confirming their catalytic activity in converting geranyl pyrophosphate (GPP) into distinct monoterpene products. Subcellular localization revealed these TPSs in chloroplasts, consistent with the widely reported chloroplast localization of TPS enzymes. These enzymes were functionally defined as monoterpenoid synthases, collectively responsible for synthesizing 18 monoterpenoid metabolites. Notably, AaTPS13, AaTPS19, and AaTPS20 exhibited substantial product promiscuity. Critically, the AaTPS19 was identified as the first known terpene synthase producing 2-pinanol. These findings systematically elucidate the biosynthesis of monoterpenoids in A. annua and provide key enzymatic elements for metabolic engineering and synthetic biology applications in monoterpenoid production. Full article

This review article focuses on the role of choline in ovarian follicular development, regulated by nutrient–epigenetic interactions. Choline, a key feed additive, participates in DNA methylation and steroid hormone synthesis via its methyl donor function. However, its role in follicular hierarchy and maturation is unclear. Research lacks an understanding of species-specific choline metabolism, follicular fluid methylation dynamics, and toxicity thresholds. This study combines animal nutrition, epigenetics, and reproductive endocrinology. Using in vitro follicle culture models, metabolomics analysis, and cytochrome P450 family 19 subfamily A member 1 (CYP19a1) methylation site screening, it reveals that choline regulates follicle hierarchy through the betaine-S-adenosylmethionine (SAM) pathway. Proper dietary choline reduces homocysteine (HCY) and boosts CYP19a1 demethylation, enhancing theca cell estradiol (E₂) production and accelerating follicle maturation. In contrast, inadequate or excessive choline causes mesoderm-specific transcript (MEST) gene methylation abnormalities or trimethylamine N-oxide (TMAO)-mediated β-oxidation inhibition, increasing follicle atresia. A phenomenon of steroidogenic factor 1 (SF-1) methylation has been observed in poultry, showing that choline affects offspring egg-laying persistence by altering the adrenal–ovarian axis DNA methylation imprint. Future research should establish a precise choline supply system based on the HCY/TMAO ratio in follicular fluid and the CYP19a1 methylation map to improve animal reproduction. Full article

Despite advances in early detection and targeted therapies, breast cancer (BC) remains a leading cause of cancer-related mortality among women worldwide. Resistance develops through the interplay of tumor-intrinsic heterogeneity and tumor-extrinsic influences, including the tumor microenvironment and immune–metabolic interactions. This complexity drives therapeutic evasion, metastatic progression, and poor outcomes. Resistance mechanisms include drug efflux, genetic mutations, and altered signaling pathways. Additional contributors are cancer stem cell plasticity, exosomal RNA transfer, stromal remodeling, epigenetic alterations, and metabolic reprogramming. Microbial influences and immune evasion further reduce treatment effectiveness. Collectively, these processes converge on regulated cell death (RCD) pathways—apoptosis, ferroptosis, and pyroptosis—where metabolic shifts and immune suppression recalibrate cell death thresholds. Nutrient competition, hypoxia-driven signaling, and lactate accumulation weaken antitumor immunity and reinforce resistance niches. In this review, we synthesize the genetic, metabolic, epigenetic, immunological, and microenvironmental drivers of BC resistance within a unified framework. We highlight the convergence of these mechanisms on RCD and immune–metabolic signaling as central principles. Artificial intelligence (AI) is emphasized as a cross-cutting connector that links major domains of resistance biology. AI supports early detection through ctDNA and imaging, predicts efflux- and mutation-driven resistance, models apoptotic and ferroptotic vulnerabilities, and stratifies high-risk patients such as TNBC patients. Full article

Background and Methods: To address the need for dietary interventions in sub-healthy populations and promote sustainable utilization of agricultural by-products, we isolated Pinus pumila hypoglycemic peptide (PHP) from nut oil meal through enzymatic extraction, ion exchange and gel chromatography purification, and simulated gastric digestion. Results: PHP exhibited significant inhibitory activity against α-amylase and α-glucosidase. In type 2 diabetic mice, PHP significantly ameliorated the “three-more-one-less” syndrome, reduced glycosylated hemoglobin and insulin levels, mitigated liver and kidney tissue lesions, and improved glucose and lipid metabolic disorders—effects partly supported by its enhancement of intestinal barrier function via restoring gut microbiota diversity. Gut microbiota analysis revealed that PHP exerts hypoglycemic effects by regulating gut microbial composition: increasing SCFA-producing taxa, reducing pro-inflammatory/metabolic disorder-associated taxa, and normalizing the Firmicutes/Bacteroidetes ratio. KEGG pathway analysis demonstrated that PHP mediates synergistic hypoglycemic effects by regulating carbohydrate metabolism, amino acid metabolism, and cofactor/vitamin metabolism. Conclusions: This work provides a theoretical foundation for developing natural functional foods from agricultural by-products, supporting PHP’s potential as a dietary supplement for metabolic regulation. Full article

Background/Objectives: Population aging and its associated chronic conditions have become an unprecedented challenge in the United States and worldwide. Many aged individuals experience certain forms of cognitive decline, which increases their risk of developing a pre-dementia condition called mild cognitive impairment and even dementia. No effective pharmacological treatments are available to treat normal age-associated cognitive decline or mild cognitive impairment. Our previous study has shown the potent anti-inflammatory effects of shiitake mushroom-derived vesicle-like nanoparticles (S-VLNs) in vitro and in an acute inflammatory disease model. In this study, we aimed to investigate the potential benefits of orally administered S-VLNs in aged mice. Methods: S-VLNs were extracted from fresh shiitake mushrooms. S-VLNs in phosphate-buffered saline (PBS) or vehicle only was orally administered to 13-month-old male C57BL/6J mice weekly for 9 months. These mice were subjected to a series of physiological tests, followed by euthanasia at 22 months of age. Their fecal samples were subjected to 16S rRNA and untargeted metabolomics analyses, followed by comprehensive bioinformatics analyses. Results: The long-term oral administration of S-VLNs significantly improved the cognitive function of aged mice. Orally administered S-VLNs did not travel to the brain. Instead, they impacted the composition of the gut microbiota and reshaped the fecal metabolome. Functional predictions of the gut microbiota and fecal metabolome suggested that S-VLNs regulated tryptophan metabolism. Specifically, S-VLNs markedly decreased the tryptophan-related metabolite kynurenic acid (KYNA). The integrative analyses of omics data identified a strong correlation between 18 gut bacterial genera and 66 fecal metabolites. KYNA was found to highly correlate with five genera positively and twelve genera negatively. Conclusions: The oral intake of S-VLNs represents a new and superior dietary approach with the ability to modulate the gut microbiota and fecal metabolome and to improve cognitive function during aging. Full article

Eukaryotes use diverse nutrient acquisition strategies, including autotrophy, heterotrophy, mixotrophy, and symbiosis, which shape the evolution of cell regulatory networks. The Target of Rapamycin (TOR) kinase is a conserved growth regulator that in most species functions within two complexes, TORC1 and TORC2. TORC1 is broadly conserved and uniquely sensitive to rapamycin, whereas the evolutionary distribution of TORC2 is less well-defined. We built a sensitive hidden Markov model (HMM)-based pipeline to survey core TORC1 and TORC2 components across more than 800 sequenced eukaryotic genomes spanning multiple major supergroups. Both complexes are present in early-branching lineages, consistent with their presence in the last eukaryotic common ancestor, followed by multiple lineage-specific losses of TORC2 and, more rarely, TORC1. A striking pattern emerges in which TORC2 is uniformly absent from photosynthetic autotrophs derived from primary endosymbiosis and frequently lost in those derived from secondary or tertiary events. In contrast, TORC2 is consistently retained in mixotrophs, which obtain carbon from both photosynthesis and environmental uptake, and in free-living obligate heterotrophs. These findings suggest that TORC2 supports heterotrophic metabolism and is often dispensable under strict autotrophy. Our results provide a framework for the evolutionary divergence of TOR signaling and highlight metabolic and ecological pressures that shape TOR complex retention across eukaryotes. Full article

Background: The dysregulation of both glucose and lipid metabolism is the main clinical features of type 2 diabetes. Qihua Tongtiao Formula (QHTTF) is our team’s current clinical empirical formula, and the related patent has been granted. It is composed of Astragalus membranaceus, Atractylodes macrocephala koidz, Aurantii Fructus Immaturus, Radix Bupleuri, Ligusticum chuanxiong hort, Angelicae sinensis radix, Raphanus sativus, and Polyporus umbellatus. It can alleviate tissue pathological damage in type 2 diabetic rats by improving glycolipid metabolism disorders. Nevertheless, the specific mechanisms of QHTTF in the treatment of type 2 diabetes remain unclear. Purpose: This research aims to explore the fundamental effect and underlying mechanism of the QHTTF formula in ZDF rats via network pharmacology, biological validation, and metabolomics technology. Methods: The chemical compounds of QHTTF were initially identified via UHPLC-MS/MS analysis. Meanwhile, drug targets, genes, related diseases, and differential metabolites of QHTTF in the treatment of T2DM were obtained through network pharmacology, molecular docking, and metabolomics. Then, we conducted animal experiments to further explore the therapeutic molecular mechanism of QHTTF in ZDF rats. Results: A total of 39 main chemical components were recognized through LC-MS/MS technology, and 22 remained after the second screening. Network pharmacology and molecular docking results revealed that 59 intersection targets were involved in the treatment of glycolipid metabolic disorders, and the PPARα, PPARγ, and TNF proteins were identified as crucial targets through PPI network analysis. Additionally, serum metabolomics analysis of ZDF rats showed that QHTTF could regulate linoleic acid metabolism, fructose and mannose metabolism, galactose metabolism, fatty acid biosynthesis, and other related signaling pathways. The results of biological experiments proved that QHTTF effectively lowered blood glucose and lipid levels, alleviated hepatic and pancreatic pathological damage, increased the expression of IRS-1 and GLUT4 in the pancreas, and improved insulin resistance, while inhibiting the inflammatory response and oxidative stress, as well as enhancing the expression of liver PPARα, PPARγ, and AMPK proteins in ZDF rats. Conclusions: In summary, QHTTF exerted a significant effect in improving glycolipid metabolism disorders of ZDF rats, which might show therapeutic effects by relieving insulin resistance, mitigating inflammation and oxidative damage, regulating related glucose, fatty acid, and amino acid metabolism, and increasing the expression of PPARα, PPARγ, and AMPK proteins by combining network analysis, metabolomics, and biological research. Full article

It is of great significance to analyze the molecular mechanism of rice response to heavy ion irradiation and to mine its key response genes for food security. In this study, the regression equation for the dose survival rate was constructed using heavy ion irradiation on rice pollen. Through an immunofluorescence experiment, it was found that DSBs induced by irradiation could be repaired quickly, but the repair of complex damage required more time. RNA-seq of irradiated pollen showed that the gene expression patterns at different time points were significantly different. A total of 5,556 differentially expressed genes (DEGs) were screened out, and the number of DEGs decreased with time. DEGs were mainly involved in stress response, protein folding, DNA repair, and other damage response processes at 0–1 h. At 6 h, the cells turned to normal metabolism functions, such as organic synthesis and protein activity. Combined with weighted gene co-expression network analysis (WGCNA) and trend analysis, the key transcription factor OsERF110 was identified in response to heavy ion irradiation, which acts on the nucleus and cell membrane. A total of 45,680 OsERF110 binding peaks were identified by DNA affinity purification sequencing (DAP-seq) in the whole genome. When this method was combined with RNA sequencing (RNA-seq), 62 OsERF110 target genes were further screened. These target genes were involved in DNA repair, stress response, redox, metabolic regulation, and other processes, forming the OsERF110 mediated radiation response regulatory network. The results of this study provide a new target for rice mutation breeding and lay a theoretical foundation for radiation biology research. Full article

The circadian rhythm controls the sleep/wake cycle and a wide variety of metabolic and physiological functions. Clock genes regulate it in response to both external and endogenous stimuli, and their expression may change because of aging, leading to an increased risk of health problems. Despite the well-described benefits of physical exercise as a circadian synchronizer, there is a lack of literature regarding the role of chronic exercise intensity in clock gene expression during aging. This article aims to analyze the differential expression of genes that regulate the biological clock under the effects of variable-intensity aerobic swimming training in aging mice, determining whether these exercise regimens interfere with the genomic regulation of the circadian rhythm. For this purpose, the mice were exposed to low- and high-intensity exercise and had their heart and gastrocnemius tissues molecularly analyzed by cDNA synthesis and qPCR to determine the expression levels of the selected genes: Clock, Arntl, Per1, Per2, Cry1, Cry2, and Nr1d1. The results showed that low-intensity exercise, performed at workloads below the anaerobic threshold, significantly changed their expression in the gastrocnemius muscle (p < 0.05), while high-intensity exercise had no statistically significant effects (p > 0.05), with the heart being immune to exercise influence except when it comes to the Per1 gene, for which expression was increased (p = 0.031) by low-intensity exercise. Additionally, both body weight and lactate thresholds had no change during the experiment (p > 0.05), while the maximum supported workload was maintained for high-intensity exercise (p > 0.05) and increased for low-intensity exercise (p < 0.01), with the control group experiencing a decay instead (p < 0.05). Thus, the present study highlights the importance of chronic exercise in modulating clock genes and opens exciting possibilities for circadian medicine, such as improvements in exercise capacity, heart condition, and lipid metabolism for subjects of low-intensity regimens. Full article

Background: Hereditary hemochromatosis (HH) is a genetic disorder of iron metabolism, characterized by progressive iron accumulation. Neurological involvement, which can manifest with various symptoms, including movement disorders, is uncommon. Methods: We describe a case of a 50-year-old male patient homozygous for the H63D variant of the HFE gene (encoding the human homeostatic iron regulator protein), who also carried the c.340+4T>C polymorphism in the same gene and has been affected since the age of 13 years by hemidystonia involving primarily his right upper extremity. His brain MRI, obtained approximately 35 years after initial symptoms, revealed iron deposition predominantly in the contralateral pallidum. The patient has shown no progression of his neurologic syndrome and no systemic manifestations over the 35 years of follow-up. Moreover, we conducted a comprehensive literature search in Pubmed and Web of Science in English of all previously reported cases of movement disorders due to HH. Results: We found 19 studies including 69 patients with movement disorders. Movement disorders associated with HH were, in most cases, hypokinetic and less commonly hyperkinetic. The most common movement disorders were tremor, parkinsonism, ataxia, and less frequent dystonia, chorea, and myoclonus. Movement disorders could either precede the diagnosis of HH, or they could occur with a variable latency ranging from a few months up to 12 years after disease onset. Iron deposition on brain MRI in the basal ganglia or cerebellum was found in few of those cases. Conclusions: The association between hemochromatosis and movement disorders is rare. Blood analysis, including serum iron, ferritin, and transferrin saturation levels, should be investigated in patients with movement disorders of unknown etiology or with iron deposition on neuroimaging. A better understanding of genotype-phenotype correlations would facilitate the early diagnosis of HH. Full article