Search Results (965)

Background/Objectives: Phenylketonuria (PKU) is a rare autosomal recessive disorder caused by phenylalanine hydroxylase (PAH) deficiency, impairing the conversion of phenylalanine (Phe) to tyrosine. Although early diagnosis and intervention yield excellent outcomes, dietary adherence often declines in adulthood, potentially leading to poor metabolic control and adverse nutritional consequences. This study aimed to evaluate physical activity levels, nutritional status, metabolic control, and anthropometric outcomes in adults with classic PKU, which have not been sufficiently researched in the current literature. Methods: This cross-sectional study included 100 adults with classical PKU (cPKU; baseline phenylalanine levels ≥ 1200 µmol/L) under regular follow-up at the Division of Metabolism, Hacettepe İhsan Doğramacı Childrens’ Hospital. Sociodemographic traits and dietary behaviors were evaluated through structured interviews carried out by a dietitian. Dietary intake was assessed by using a 24 h dietary recall method, and nutrient analyses were performed with the Bebis 7.2 software program. Using the short version of the International Physical Activity Questionnaire (IPAQ), physical activity levels were specified, and participants were categorized according to established scoring criteria. Results: A hundred adults with classical PKU took part in the study, including 47 males and 53 females, with a mean age of 23.84 ± 5.41 years; 5% of participants were underweight, 40% had normal weight, 39% were overweight, and 16% were listed as obese. The intake of mean daily energy is 2443.8 ± 384.6 kcal for men and 1822.5 ± 312.7 kcal for women. Carbohydrates contributed approximately 61% of total daily energy intake in both genders, whereas protein accounted for 12–13% and fat for approximately 26–27% of total energy intake; 17% of participants were physically inactive, 40% were minimally active, and 43% met criteria for sufficient physical activity according to IPAQ-based classification. Energy intake, the use of Phe-free protein substitutes, and BMI were significantly higher in the sufficiently active group compared to the low-active group in men, while no significant differences were observed between physical activity groups among women. Conclusions: Adults with classical PKU showed a high prevalence of overweight and obesity, together with differences in dietary intake and physical activity patterns. Physical activity levels were associated with several nutritional and metabolic characteristics; however, further long-term research is required to fully understand these connections. Full article

Plant quality is strongly influenced by environmental conditions, including the presence of micronutrients and potentially toxic elements in the soil. This study aimed to evaluate the effect of soil-applied fluorine on the content of exogenous (essential) and endogenous (non-essential) amino acids in black radish roots and the aerial biomass of narrow-leaved lupine. The following essential amino acids were identified: histidine, threonine, arginine, lysine, tyrosine, leucine, phenylalanine, isoleucine, methionine, and valine. The group of endogenous amino acids comprised cysteine, proline, serine, glutamic acid, aspartic acid, glycine, and alanine. Increasing fluorine application generally enhanced the accumulation of both essential and endogenous amino acids in lupine shoots and radish roots. The strongest stimulatory effect on the synthesis of most amino acids was observed at the lowest fluorine doses, i.e., 20 mg F kg⁻¹ soil for narrow-leaved lupine and 100 mg F kg⁻¹ soil for black radish. By contrast, the concentrations of certain endogenous amino acids, such as aspartic acid, glutamic acid and proline in radish roots and aspartic acid in lupine shoots, were highest at intermediate fluorine contamination levels. Moreover, the maximum contents of tyrosine and cysteine in lupine aerial parts were recorded under the highest fluorine dose. Overall, protein derived from black radish exhibited a higher nutritional value than that of narrow-leaved lupine. The results obtained show that simulated soil contamination with fluoride stimulates amino acid synthesis in both plants. The research enables a better assessment of the quality and nutritional value of crops grown under conditions of environmental contamination, and helps to explain the mechanisms by which plants defend themselves against chemical stress. The research suggests that moderate fluoride contamination causes changes in nitrogen metabolism, increasing amino acid production, which may be a defence mechanism in plants against stress. Full article

Background: Root rot caused by Fusarium solani is a devastating disease in Angelica sinensis (danggui), leading to severe yield and quality losses. Sustainable control strategies are urgently needed. According to the plant “cry for help” theory, plants under pathogen attack may recruit beneficial microbes via root exudates. However, whether A. sinensis employs this strategy against F. solani remains unknown. This study aimed to identify potential “cry for help” metabolites and evaluate their biocontrol potential. Methods: LC-MS analysis revealed that F. solani infection significantly altered the metabolic profiles of both A. sinensis roots and rhizosphere soil. Results: Comparative analysis identified seven metabolites specifically upregulated in infected plants but not detected in the pathogen, including taurine, oxoadipic acid, quinolinic acid, 6-phosphogluconic acid, methyl cinnamate, 2-phenylethanol, and (R)-3-hydroxybutyric acid. Exogenous application of these seven metabolites revealed that taurine and methyl cinnamate significantly alleviated disease symptoms, improved plant growth (root length, biomass), and enhanced the activities of key defense enzymes (peroxidase, POD, phenylalanine ammonia-lyase, PAL, lipoxygenase, LOX, polyphenol oxidase, PPO). Furthermore, taurine and methyl cinnamate reshaped the rhizosphere microbiome. The incidence of root rot was reduced by 51.3% and 50.8%, respectively. Taurine enriched actinobacteria (e.g., Paeniglutamicibacter) and reduced the relative abundance of pathogenic Ascomycota fungi, while methyl cinnamate markedly enriched the nitrogen-fixing bacterium Azotobacter and the saprophytic fungus Schizothecium. Crucially, both treatments significantly suppressed the proliferation of F. solani in the rhizosphere. Conclusions: Our findings demonstrate for the first time that A. sinensis activates a “cry for help” response upon attack by F. solani, with taurine and methyl cinnamate preliminarily identified as key signaling metabolites that can directly or indirectly inhibit the development of A. sinensis root rot. These compounds enhance plant resistance and recruit beneficial microorganisms, offering a novel and promising ecological strategy for the green control of A. sinensis root rot. Full article

Background: Phenylketonuria (PKU) is a metabolic disorder requiring a strict low-phenylalanine diet. Oral health impairment, including bacteriome dysbiosis, is common in PKU, yet the mycobiome remains poorly defined. This pilot study aimed to characterise the salivary oral mycobiome of children with PKU compared with controls and to explore associations with dietary intake. Methods: Saliva samples from 18 children, including 8 patients with PKU and 10 age-matched controls, were profiled using internal transcribed spacer (ITS) amplicon sequencing. Alpha/beta diversity, taxonomic composition, diet–fungi correlations, discriminative taxa and LEfSe were analysed. Results: Alpha diversity did not differ significantly between groups after correction for multiple comparisons, although exploratory subgroup analyses suggested lower evenness in PKU children aged <10 years compared with older controls. Beta diversity differed by diagnosis (PERMANOVA: F = 1.7251, p = 0.0062) and in the age–diagnosis model (F = 1.8502, p = 0.0004). Taxonomic analyses identified nominal differences in several fungal taxa, including Candida (p = 0.011), Saccharomycetales_fam_Incertae_sedis (p = 0.011), Naganishia (p = 0.020), and Aspergillaceae (p = 0.036) in PKU samples; however, these findings should be interpreted as exploratory because many did not remain significant after FDR correction. Diet–mycobiome analyses identified selected FDR-supported associations, including an inverse relationship between phenylalanine intake and Naganishia in PKU. Conclusions: This pilot study suggests preliminary compositional differences in the oral mycobiome of children with PKU that may be related to dietary therapy and metabolic context. These exploratory findings require validation in larger cohorts with detailed oral health assessment and control of confounders. Full article

2-Phenylethanol (2-PE) is a key aromatic alcohol contributing to the rose-like odor in brewed wines, primarily synthesized by yeast metabolism with a typical yield of less than 100 mg/L. To enhance the 2-PE content in brewed wines, this study used CRISPR-Cas9 gene editing technology to delete the ARO8 gene (encoding aromatic transaminase I) in Saccharomyces cerevisiae SY. The single-factor experiments were performed to optimize the fermentation process, and the 2-PE content in the brewed wine was measured by high-performance liquid chromatography. The results demonstrated that the 2-PE content in whisky fermented by the SY-A8 was 0.73 g/L, increasing 23.73% compared to SY. The fermentation conditions of SY-A8 were optimized through single-factor experiments and the Box–Behnken design. The optimal conditions were a sugar concentration of 46.30 g/L, a fermentation time of 6 days, and an L-phenylalanine concentration of 1.43 g/L. The high 2-phenylethanol aroma whisky was brewed with a higher 2-phenylethanol content of 3.68 g/L in a 1 L fermenter at the optimal conditions. In conclusion, the modification of Saccharomyces cerevisiae by CRISPR-Cas9 gene editing combined with fermentation process optimization provides an effective technical strategy for improving the 2-PE content in whisky, thereby providing a research perspective for the flavor enhancement of whisky and other brewed wines. Full article

Lilium lancifolium Thunb. is an important economic crop widely cultivated and traded across Asia and has significant pharmacological activity. Despite decades of research on their chemical composition, the spatial distribution patterns of characteristic secondary metabolites within the bulbs remain poorly understood. In this study, we used matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) technology to characterize and spatially visualize multiple metabolites within the bulb for the first time. Additionally, ultra-high-performance liquid chromatography-Orbitrap Exploris mass spectrometry (UHPLC-OE-MS) was used to obtain comprehensive metabolite information from the bulbs. Using spatial metabolomics, we successfully identified nine steroidal saponins, three phenolic acid glycerides, and six other metabolites. Subsequently, we analyzed the spatial distribution of steroidal saponins and phenolic acid glycerides, which are key bioactive components. The analysis revealed that most of the steroidal saponins and phenolic acid glycerides, such as deacylbrownioside and regaloside A, exhibited a similar distribution pattern, mainly being enriched in the outer regions (A2, B2) and basal regions (B1, B2) on an individual scale. Further metabolomic and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that 11 substances detected in the bulbs, including diosgenin, phenylalanine, and acetyl-CoA, were jointly associated with 39 metabolic pathways, including “phenylpropanoid biosynthesis” and “terpenoid backbone biosynthesis”. Based on the above findings, we propose biosynthetic pathways and accumulation patterns of steroidal saponins and phenolic acid glycerides in bulbs. This study provides a basis for precise resource utilization of L. lancifolium bulbs and a methodology to elucidate the biosynthesis of plant metabolites. Full article

Elicitation is a powerful strategy for increasing bioactive metabolites in plant systems. This study is among the first to integrate growth responses, antioxidant enzyme activities, and metabolite profiling in G. paniculata adventitious roots (ARs). The study aims to evaluate the effects of yeast extract (YE) and salicylic acid (SA) on biomass traits, antioxidant enzymes (peroxidase, polyphenol oxidase, and phenylalanine ammonia-lyase), and phenolic metabolite profiles. ARs were exposed to YE (0.25–2 g L⁻¹) and SA (50–400 µM) for 28 days. Yeast extract significantly enhanced antioxidant capacity by promoting enzyme activities, phenolics, and flavonoids. In contrast, SA exhibited concentration-dependent effects. Moderate concentrations improved antioxidant activity, while higher concentrations promoted the accumulation of specific flavonoids. Maximum biomass production was achieved with 1 g L⁻¹ YE, which also resulted in the highest metabolite productivity. Conversely, SA treatments caused a progressive reduction in biomass with increasing concentration, although they enhanced the accumulation of selected bioactive compounds. Notably, 100 µM SA resulted in the highest phenolic content and antioxidant activity, whereas 400 µM SA markedly increased flavonoids such as rutin and quercetin. HPLC analysis identified seventeen phenolic compounds, demonstrating that YE acts as a broad-spectrum elicitor, whereas SA functions as a selective metabolic modulator. The differential enzymatic responses further highlight elicitor-specific regulatory patterns in antioxidant defense and secondary metabolism. Overall, these findings demonstrate that elicitor type and concentration differentially influence the balance between growth and secondary metabolism, providing a framework for optimizing metabolite production in controlled in-vitro systems. Full article

Anthracnose, caused by Colletotrichum spp., is a major foliar disease limiting rubber tree (Hevea brasiliensis) productivity. To uncover resistance mechanisms, we compared resistant and susceptible germplasm using an integrated framework combining leaf structural analysis, physiological defense profiling, and transcriptome sequencing. Resistant germplasm exhibited lower stomatal density and more compact mesophyll, likely restricting pathogen entry and within-leaf spread. Following inoculation, resistant accessions showed stronger antioxidant responses, with higher activities of superoxide dismutase (SOD) and peroxidase (POD), and elevated phenylpropanoid-related enzymes, including polyphenol oxidase (PPO) and phenylalanine ammonia-lyase (PAL), peaking at 24–48 h post inoculation. These responses were accompanied by enhanced reactive oxygen species (ROS) accumulation (H₂O₂) but reduced lipid peroxidation (malondialdehyde), indicating efficient oxidative stress regulation. Microscopic observation revealed delayed infection progression and postponed differentiation of infection structures in resistant germplasm. Transcriptomic analysis further demonstrated that differentially expressed genes were mainly enriched in pathways related to signal transduction and secondary metabolism, particularly phenylpropanoid metabolism and related secondary metabolic pathways. Together, these results suggest that anthracnose resistance is mediated by coordinated structural barriers, redox homeostasis, and transcriptional regulation of defense networks. This study provides a mechanistic framework for resistance-oriented breeding and the utilization of resistant germplasm in rubber tree. Full article

The hybrid approach remains a compelling strategy for designing molecules that combine enhanced biological activity with a favorable safety profile. Marine peptides, in particular, have attracted significant attention due to their well-documented broad spectrum of biological activities. Peptides derived from rays have been recognized for their diverse biological activities. Notably, physicochemical properties of these peptides support practical application without requiring further refinement of the mature molecule or specialized formulations. In this study, we present two new chimeric peptides, PK01# and PK02#, which incorporate an opioid pharmacophore linked to a short amino acid sequence derived from the skate Raja porosa. Those compounds interact with the opioidergic system, specifically targeting the mu-opioid receptor (MOR). Furthermore, the compounds were evaluated for their effects on cancer cell viability through in vitro MTT assays (as an exploratory endpoint) and for their binding compatibility with EGFR via in silico docking. Both compounds showed limited effects on cell viability in HeLa, SAS, and PANC-1 cells, while PK02# induced a minor reduction in metabolic activity in glioblastoma cells without reaching IC50 values or significant cytotoxic thresholds. Interestingly, the structures of these hybrid compounds offer valuable insights into the role of phenylalanine residues within their sequences, which appear to be critical for both biological activity and receptor interaction. Moreover, these findings may support future structural optimization of peptide hybrids focused on receptor modulation and biological profiling. Full article

Enhancing egg production in geese without antibiotics remains a challenge in poultry science. This study compared the effects of Lactobacillus (LAB) and Bacillus (BAC) probiotics on laying performance, gut microbiota, and serum metabolism in Zhedong White geese. Birds were fed a control diet or diets supplemented with LAB or BAC. Egg production and quality were monitored throughout the trial. Serum metabolomics and fecal 16S rRNA sequencing were integrated with KEGG enrichment and correlation analyses to uncover functional mechanisms. Both probiotics improved laying performance and egg quality. Total egg production of the LAB group was 8.5% higher than that of the BAC group (p < 0.05). The LAB group’s advantage in egg production was consistent with its stronger activation of the steroid hormone biosynthesis pathway (elevated serum corticosterone and tetrahydrocorticosterone indicated an overall enhancement of steroidogenic flux). Simultaneously, the LAB group exhibited a more efficient conversion of L-phenylalanine to catecholamine precursors, which drove activation of the neuroendocrine reproductive axis. The BAC group showed more significant changes in nitrogen and energy metabolism pathways and a more pronounced expansion of energy-harvesting Firmicutes. These findings reveal two strain-specific regulatory pathways: LAB functions through the “aromatic amino acid–neuroendocrine–steroid hormone axis,” while BAC relies on the “gut microbiota–energy metabolism” pathway, with direct implications for the precise application of probiotics under antibiotic-free farming conditions. Full article

Epimedium is a traditional Chinese tonic used to tonify the kidneys, enhance sexual function, and strengthen muscles and bones. However, the potential effects of Epimedium on the semen quality of Bama boars remain incompletely elucidated. The objective of this study was to evaluate the effects of dietary Epimedium ultrafine powder (EP) supplementation on the semen quality of Bama boars and to explore the underlying mechanisms. The objective of this study was to evaluate the effects of dietary EP supplementation on the semen quality of Bama boars and to explore the underlying mechanisms. Eighteen healthy, sexually mature adult male Bama boars were randomly divided into three groups (n = 6) and fed either a basal diet (CON) or the basal diet supplemented with 0.3% (EP3) or 0.5% (EP5) Epimedium ultrafine powder for five weeks. This study employed enzyme-linked immunosorbent assay (ELISA), 16S RNA gene sequencing, non-targeted metabolomics (CON and EP5), and Spearman correlation analysis, among other methods. The results indicated that dietary Epimedium (0.3% and 0.5%) increased the levels of serum TP, FSH, and SOD and decreased the abnormal sperm rate and the levels of serum TBA, TNF-α, and IL-6. Among them, adding 0.5% Epimedium in the diet increased sperm motility and the levels of serum T, LH, and IgG. 16S rRNA gene sequencing analysis revealed that both 0.3% and 0.5% Epimedium supplementation reduced the abundance of Streptococcus. Specifically, the 0.3% dose decreased Prevotella abundance, while the 0.5% dose reduced Escherichia-Shigella abundance. PICRUSt2 analysis revealed that the pathways of phenylalanine, butanoate, biotin, and arachidonic acid metabolism were significantly enriched in the Epimedium group. A non-targeted metabolomics analysis identified that indole-3-acrylic acid, DL-tryptophan, 2-hydroxyphenylalanine, and propionylcarnitine showed significant upregulation after Epimedium supplementation. Spearman correlation analysis indicated that Streptococcus was negatively correlated with sperm motility and serum-related parameters (TP, T, LH, IgM, and IgG). Streptococcus and Escherichia-Shigella were negatively correlated with indole-3-acrylic acid, DL-tryptophan, and biotin. In conclusion, Epimedium has a positive impact on the seminal quality, reproductive hormones, and immune–antioxidant levels of Bama boars by regulating the composition and metabolites of the intestinal microbiota. Full article

This study investigated the effects of different cultivation environments on melon quality development and the underlying metabolic regulatory mechanisms. Using ‘Yangjiaocui’ and ‘Boyang 9’ melons, we systematically compared their physicochemical properties, nutritional components, volatile compounds, and metabolites under saline–alkali versus normal conditions, employing an integrated multi-omics analytical model. The results showed that saline–alkali cultivation significantly increased several nutritional components (e.g., soluble solids, vitamin C, flavonoids, and polyphenols) compared to normal conditions. Gas chromatography–ion mobility spectrometry (GC-IMS) detected 36 volatiles, predominantly esters and ketones, with 13 key markers such as isovaleric acid isovaleryl ester and ethyl butyrate, effectively discriminating cultivars and growth origins. Liquid chromatography–mass spectrometry (LC-MS) detected 702 metabolites, chiefly organic acids and lipids. KEGG pathway enrichment analysis revealed that flavonoid biosynthesis was the most significantly enriched pathway (enrichment factor ~1, extreme significance), with coordinated regulation of tyrosine and phenylalanine metabolism redirecting metabolic flux toward defensive secondary metabolites. In conclusion, our results suggest that saline–alkali cultivation may contribute to improved nutritional profiles, and multi-omics analysis effectively differentiates melon varieties and origins. This study provides a theoretical basis for understanding the quality, flavor, and metabolite profiles of melon under saline–alkali stress, employing a multi-omics approach. Full article

Background: Nitrous oxide (N₂O) is increasingly used as a recreational drug, leading to neurological and systemic toxicities. However, due to the rapid elimination and minimal alteration of nitrogen oxides, the short direct detection window complicates the assessment of N₂O exposure. Method: In this study, we investigated the effects of chronic N₂O exposure on plasma metabolites using an untargeted metabolomics approach in a mouse model. C57BL/6 mice were exposed to 90,000 ppm N₂O (1 h, twice daily for 28 days) or room air. Plasma samples were analyzed via UHPLC -Triple TOF -MS. Orthogonal partial least squares discriminant analysis (OPLS-DA) and receiver operating characteristic (ROC) curves were used to identify differential metabolites. Result: A total of 35 differential metabolites were identified. Eight metabolites with an area under the curve (AUC) > 0.90 were selected as candidate biomarkers, including up-regulated SOPC and PC(16:0/16:0) (suggesting disrupted phospholipid remodeling and membrane integrity), and down-regulated DL-tryptophan, creatine, ectoine, indole, His-Ser, and Ile-Pro. Pathway enrichment analysis revealed significant alterations in glycine, serine and threonine metabolism; phenylalanine, tyrosine and tryptophan biosynthesis; protein digestion and absorption; and tryptophan metabolism. Conclusions: Our data indicate that chronic N₂O exposure disrupts multiple amino acid-related metabolic pathways (e.g., tryptophan-kynurenine pathway) and phospholipid homeostasis. The identified metabolite changes, along with vitamin B₁₂, homocysteine, and methylmalonic acid, may constitute a specific metabolic fingerprint for N₂O exposure. These findings help reveal the intrinsic mechanistic links underlying metabolic disorders induced by N₂O exposure. Full article

Dark septate endophytes (DSE) and ericoid mycorrhizal fungi (ERMF) are employed to augment the abiotic stress resistance of fruits. However, their potential functions in enhancing the drought resistance of blueberry, an economically important fruit, remain unclear. Thus, this study aims to identify optimal inoculation combinations to enhance the drought resistance of blueberry seedlings. Specifically, the effects of single and dual inoculations with DSE (Cladosporium cladosporioides, D79) and ERMF (Oidiodendron citrinum, N12) on seedling physiology and metabolism were explored under varying drought conditions. The results showed that dual inoculation significantly improved leaf physiological characteristics. Under severe drought stress, the 1:2 DSE:ERMF ratio (D1N2) notably increased leaf relative water content (RWC) and reduced electrolyte leakage by up to 42.1% compared with the non-inoculated control. Dual inoculation also significantly decreased malondialdehyde (MDA) content, with the smallest increase observed in D1N2. Regarding antioxidant enzymes, dual inoculation sustained higher superoxide dismutase (SOD) activity under moderate drought and minimized the decline in SOD activity under severe drought (the lowest decrease was 36.4% in D1N2 versus 56.7% in CK). Moreover, the antioxidant losses under drought stress were reduced by upregulating various metabolic processes, especially the biosynthesis of phenylalanine, tyrosine, and tryptophan. A comprehensive evaluation suggested that inoculation with a 1:2 mixture of DSE and ERMF most effectively improved blueberry drought resistance, primarily by enhancing water and metabolite supply and stimulating the antioxidant defenses. Full article

Aromatic compounds derived from the shikimate (SHK) pathway constitute a diverse class of high-value molecules with applications in the pharmaceutical, food, cosmetic, and chemical industries. In microbial systems, particularly Escherichia coli, this pathway links central carbon metabolism (CCM) to the biosynthesis of L-tyrosine (L-Tyr), L-phenylalanine (L-Phe), and L-tryptophan (L-Trp), which serve as key precursors for structurally diverse metabolites. Over the past decades, metabolic engineering strategies have focused on increasing precursor availability, relieving feedback inhibition, and eliminating competing pathways. More recently, advances in synthetic biology have enabled dynamic control of metabolic flux through pathway modularization, genome-scale interventions, and regulatory circuit design. In this review, we provide a comprehensive overview of the engineering of E. coli for aromatic compound biosynthesis, highlighting key developments in the optimization of the SHK pathway and its major metabolic nodes chorismate, L-Tyr, L-Phe, and L-Trp. We examine emerging approaches, including CRISPR-based regulation, biosensor-driven dynamic control, membrane engineering, and synthetic microbial consortia. Despite significant progress, challenges related to pathway regulation, cofactor balance, metabolic burden, and product toxicity remain critical bottlenecks. Integrating metabolic engineering with synthetic biology is driving the development of programmable, scalable microbial platforms for the efficient bioproduction of aromatic compounds. Full article