Search Results (1,202)

New psychoactive substances (NPSs) have emerged as a significant global public health challenge due to their ability to mimic traditional drugs. Among these, mephedrone has gained attention because of its widespread use and associated toxicities. This review provides a comprehensive analysis of the structure, pharmacokinetic properties, and metabolic pathways of mephedrone, highlighting its phase I and phase II metabolites as potential biomarkers for detection and forensic applications. A comprehensive literature search was performed without date restrictions. The search employed key terms such as “mephedrone metabolites”, “pharmacokinetics of mephedrone”, “phase I metabolites of mephedrone”, and “phase II metabolites of mephedrone”. Additionally, the reference lists of selected studies were screened to ensure a thorough review of the literature. Mephedrone is a chiral compound existing in two enantiomeric forms, exhibiting different affinities for monoamine transporters and distinct pharmacological profiles. In vivo animal studies indicate rapid absorption, significant tissue distribution, and the formation of multiple phase I metabolites (e.g., normephedrone, dihydromephedrone, 4-carboxymephedrone) that influence its neurochemical effects. Phase II metabolism involves conjugation reactions leading to metabolites such as N-succinyl-normephedrone and N-glutaryl-normephedrone, further complicating its metabolic profile. These findings underscore the importance of elucidating mephedrone’s metabolic pathways to improve detection methods, enhance our understanding of its toxicological risks, and inform future therapeutic strategies. Full article

Early weaning of piglets elicits weaning stress, which in turn induces oxidative stress and consequently impairs growth and development. Hydrogen-rich water (HRW), characterized by selective antioxidant properties, mitigates oxidative stress damage and serves as an ideal intervention. This study aimed to evaluate the effects of HRW on weaned piglets, specifically investigating its impact on growth performance, diarrhea incidence, antioxidant function, intestinal morphology, gut microbiota, and hepatic metabolites. The results demonstrate that HRW significantly increased the average daily feed intake and significantly reduced the diarrhea rate in weaned piglets. Analysis of serum oxidative stress indicators revealed that HRW significantly elevated the activities of total antioxidant capacity and total superoxide dismutase while significantly decreasing malondialdehyde concentration. Assessment of intestinal morphology showed that HRW significantly increased the villus height to crypt depth ratio in the duodenum, jejunum, and ileum. Microbial analysis indicated that HRW significantly increased the abundance of Prevotella in the colon. Furthermore, HRW increased the abundance of beneficial bacteria, such as Akkermansia, in the jejunum and cecum, while concurrently reducing the abundance of harmful bacteria like Escherichia. Hepatic metabolite profiling revealed that HRW significantly altered the metabolite composition in the liver of weaned piglets. Differentially abundant metabolites were enriched in oxidative stress-related KEGG pathways, including ABC transporters; pyruvate metabolism; autophagy; FoxO signaling pathway; glutathione metabolism; ferroptosis; and AMPK signaling pathways. In conclusion, HRW alleviates diarrhea and promotes growth in weaned piglets by enhancing antioxidant capacity. These findings provide a scientific foundation for the application of HRW in swine production and serve as a reference for further exploration into the mechanisms underlying HRW’s effects on animal health and productivity. Full article

The apicoplast is a highly specialized organelle in the biosynthesis of essential metabolites in most of the apicomplexan protozoa. This organelle is surrounded by four layers of membranes. However, the molecular mechanisms mediating transmembrane transport are not yet fully understood. In this study, we conducted a phenotypic analysis to investigate the role of a major facilitator superfamily transporter (TgApMFS1) in the survival of the parasite. The results indicated that TgApMFS1 is critical for the survival of Toxoplasma gondii in cell culture conditions. Further analysis indicated that these transporters are crucial for the biogenesis of organelles and the metabolic processes of parasite. Full article

Vibrio parahaemolyticus is a major foodborne pathogen worldwide, responsible for seafood-associated poisoning. Among its toxin genes, tdh2 is the most critical. To investigate the role of tdh2 in V. parahaemolyticus under gastrointestinal conditions, we constructed tdh2 deletion and complementation strains and compared their survival under acid (pH 3 and 4) and bile stress (2%). The results showed that tdh2 expression was significantly upregulated under cold (4 °C) and bile stress (0.9%). Survival assays and PI staining revealed that the tdh2 mutant strain (VP: △tdh2) was more sensitive to acid and bile stress than the wild-type (WT), and this sensitivity was rescued by tdh2 complementation. These findings suggest that tdh2 plays a protective role in enhancing V. parahaemolyticus tolerance to acid and bile stress. In the VP: △tdh2 strain, seven genes were significantly upregulated and six were downregulated as a result of tdh2 deletion. These genes included VPA1332 (vtrA), VPA1348 (vtrB), VP2467 (ompU), VP0301 and VP1995 (ABC transporters), VP0527 (nhaR), and VP2553 (rpoS), among others. Additionally, LC-MS/MS analysis identified 12 differential metabolites between the WT and VP: △tdh2 strains, including phosphatidylserine (PS) (17:2 (9Z,12Z) /0:0 and 20:1 (11Z) /0:0), phosphatidylglycerol (PG) (17:0/0:0), flavin mononucleotide (FMN), and various nucleotides. The protective mechanism of tdh2 may involve preserving cell membrane permeability through regulation of ompU and ABC transporters and enhancing electron transfer efficiency via regulation of nhaR. The resulting reduction in ATP, DNA, and RNA synthesis—along with changes in membrane permeability and electron transfer due to decreased FMN—likely contributed to the reduced survival of the VP: △tdh2 strain. Meanwhile, the cells actively synthesized phospholipids to repair membrane damage, leading to increased levels of PS and PG. This study provides important insights into strategies for preventing and controlling food poisoning caused by tdh⁺ V. parahaemolyticus. 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

Mung bean (Vigna radiate) sprouts are a popular choice among sprouted vegetables in Asia. Currently, the impact of nitrogen sources on the growth of mung bean sprouts remains poorly understood, and the underlying biological mechanisms responsible for the observed nonlinear growth patterns at different nitrogen levels have yet to be elucidated. In this research, in addition to conventional growth monitoring and quality evaluation, a comparative proteomics method was applied to investigate the molecular mechanisms of mung bean in response to 0, 0.025, 0.05, 0.075, and 0.1% urea concentrations. Our results indicated that mung bean sprout height and yield increased with rising urea concentrations but were suppressed beyond the L3 level (0.075% urea). Nitrate nitrogen and free amino acid content rose steadily with urea levels, whereas protein content, nitrate reductase activity, and nitrite levels followed a peak-then-decline trend, peaking at intermediate concentrations. Differential expression protein analysis was conducted on mung bean sprouts treated with different concentrations of urea, and more differentially expressed proteins participated in the L3 urea concentration. Analysis of common differential proteins among comparison groups showed that the mung bean sprouts enhanced their adaptability to urea stress environments by upregulating chlorophyll a-b binding protein and cationic amino acid transporter and downregulating the levels of glycosyltransferase, L-ascorbic acid, and cytochrome P450. The proteomic analysis uncovered the regulatory mechanisms governing these metabolic pathways, identifying 47 differentially expressed proteins (DEPs) involved in the biosynthesis of proteins, free amino acids, and nitrogen-related metabolites. Full article

Cordyceps takaomontana is a medicinal fungus with significant pharmacological value, but how soil microbes promote its growth remains unclear. We established a solid-state co-culture system involving C. takaomontana synnemata and its native soil fungi of Fusarium paeoniae and Bjerkandera minispora. Both F. paeoniae and B. minispora significantly promoted synnematal growth and enhanced antioxidant enzyme activities. Total triterpenoid content increased substantially. F. paeoniae markedly elevated levels of ergosterol peroxide, whereas B. minispora boosted accumulation of L-arabinose, ergotamine, and euphol. Metabolomics revealed that both fungi activated key metabolic pathways (including ABC transporters, mineral absorption, and protein digestion/absorption). F. paeoniae uniquely upregulated phenylalanine metabolism. This work elucidates the metabolic mechanisms underlying growth promotion of C. takaomontana mediated by F. paeoniae and B. minispora as well as deciphers potential pharmacologically active metabolites. These findings provide a foundation for strategically improving artificial cultivation and developing functional microbial inoculants. Full article

Background/Objectives: Sweet potato is a tropical and subtropical crop and its growth and yield are susceptible to low-temperature stress. However, the molecular mechanisms underlying the low temperature stress of sweetpotato are unknown. Methods: In this work, combined transcriptome and metabolism analysis was employed to investigate the low-temperature responses of two sweet potato cultivars, namely, the low-temperature-resistant cultivar “X33” and the low-temperature-sensitive cultivar “W7”. Results: The differentially expressed metabolites (DEMs) of X33 at different time stages clustered in five profiles, while they clustered in four profiles of W7 with significant differences. Differentially expressed genes (DEGs) in X33 and W7 at different time points clustered in five profiles. More DEGs exhibited continuous or persistent positive responses to low-temperature stress in X33 than in W7. There were 1918 continuously upregulated genes and 6410 persistent upregulated genes in X33, whereas 1781 and 5804 were found in W7, respectively. Core genes involved in Ca²⁺ signaling, MAPK cascades, the reactive oxygen species (ROS) signaling pathway, and transcription factor families (including bHLH, NAC, and WRKY) may play significant roles in response to low temperature in sweet potato. Thirty-one common differentially expressed metabolites (DEMs) were identified in the two cultivars in response to low temperature. The KEGG analysis of these common DEMs mainly belonged to isoquinoline alkaloid biosynthesis, phosphonate and phosphinate metabolism, flavonoid biosynthesis, cysteine and methionine metabolism, glycine, serine, and threonine metabolism, ABC transporters, and glycerophospholipid metabolism. Five DEMs with identified Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were selected for correlation analysis. KEGG enrichment analysis showed that the carbohydrate metabolism, phenylpropanoid metabolism, and glutathione metabolism pathways were significantly enriched and played vital roles in low-temperature resistance in sweet potato. Conclusions: These findings contribute to a deeper understanding of the molecular mechanisms underlying plant cold tolerance and offer targets for molecular breeding efforts to enhance low-temperature resistance. Full article

Photosynthesis in plants and the electron transport chain in mitochondria are examples of life-sustaining electron transfer processes. The benzoquinones plastoquinone and ubiquinone are key components of these pathways that cycle through their oxidized and reduced forms. Previously, we reported direct photoreduction of biologically relevant quinones mediated by photosensitizers, red light and electron donors. Herein we examined direct photoreduction of the quinone imine 2,6-dichlorophenolindophenol (DCPIP) using red light, methylene blue as the photosensitizer and ethylenediaminetetraacetic acid (EDTA) as the electron donor. Photoreduction of DCPIP by methylene blue and EDTA was very pH-dependent, with three-fold enhanced rates at pH 6.9 vs. pH 7.4. Photochemical redox cycling of DCPIP produced hydrogen peroxide via singlet oxygen-dependent reoxidation of reduced DCPIP. Histidine enhanced photoreduction by scavenging singlet oxygen, whereas increased molecular oxygen exposure slowed DCPIP photoreduction. Attempts to photoreduce DCPIP with pheophorbide A, a chlorophyll metabolite, and triethanolamine as the electron donor in 20% dimethylformamide were unsuccessful. Photoreduced benzoquinones including 2,3-dimethoxy-5-methyl-p-benzoquinone (CoQ₀), methoxy-benzoquinone and methyl-benzoquinone were used to examine electron transfer to DCPIP. For photoreduced CoQ₀ and methoxy-benzoquinone, electron transfer to DCPIP was rapid and complete, whereas for reduced methyl benzoquinone, it was incomplete due to differences in reduction potential. Nonetheless, electron transfer from photoreduced quinols to DCPIP is a rapid and sensitive method to investigate quinone photoreduction by chlorophyll metabolites. Full article

Anthocyanins are important phenolic compounds in grape skins, affecting the color, oxidation resistance, and aging ability of red wine. In recent years, global warming has had a negative effect on anthocyanin biosynthesis in grape berries. Ethylene serves as a crucial phytohormone regulating the development and ripening processes of fruit; however, the specific molecular mechanism and the regulatory network between ethylene signaling and the anthocyanin biosynthesis pathway remain incompletely understood. In this study, 400 mg/L ethephon (ETH) solution was sprayed onto the surface of grape berries at the lag phase (EL-34), and the changes in anthocyanin-related genes and metabolites were explored through transcriptomic and metabolomic analysis. The results showed that ETH treatment increased Brix and pH in mature berries. In total, 35 individual anthocyanins were detected, in which 21 individual anthocyanins were enhanced by ETH treatment. However, the anthocyanin profile was not affected by exogenous ethylene. Transcriptomics analysis showed that there were a total of 825 and 1399 differentially expressed genes (DEGs) 12 h and 24 h after treatment. Moreover, key structural genes in the anthocyanin synthesis pathway were strongly induced, including VvPAL, VvCHS, VvF3H, VvF3′5′H, VvDFR and VvUFGT. At the maturity stage (EL-38), the expression levels of these genes were still higher in EHT-treated berries than in the control. ETH treatment also influenced the expression of genes related to hormone biosynthesis and signal transduction. The ethylene biosynthesis gene (VvACO), ethylene receptor genes (VvETR2, VvERS1 and VvEIN4), ABA biosynthesis gene (VvNCED2), and ABA receptor gene (VvPYL4) were up-regulated by ETH treatment, while the auxin biosynthesis gene (VvTAA3) and seven genes of the auxin-responsive protein were inhibited by exogenous ethylene. Meanwhile, ETH treatment promoted the expression of the sugar transporter gene (VvEDL16) and two sucrose synthase genes (VvSUS2 and VvSUS6). In EHT-treated berries, 19 MYB and 23 ERF genes were expressed differently compared with the control (p < 0.05). This study provides the theoretical foundation and technical support for the regulation of anthocyanin synthesis in non-climacteric fruit. Full article

This study integrated non-targeted metabolomics and transcriptomics to investigate dynamic changes in Antheraea pernyi pupae across five developmental stages. Metabolomic analysis identified 1246 metabolites, primarily organic acids, lipids, heterocyclic compounds, and oxygen-containing organics. Principal component analysis revealed stage-specific metabolic profiles: amino acid derivatives (pyruvate, proline, lysine) declined, while pyrimidines (cytidine, uridine, β-alanine) and monosaccharides (glucose, mannose) increased. 18β-glycyrrhetinic and ursolic acids accumulated significantly in the middle and late stages. Transcriptomic analysis identified 7230 differentially expressed genes (DEGs), with 366, 1705, and 5159 significantly differentially expressed genes in the T1, T3, and T5 comparison groups, respectively. KEGG enrichment highlighted ABC transporters, amino acid/pyrimidine metabolism, and tyrosine pathways as developmentally critical, with aminoacyl-tRNA biosynthesis upregulated in later phases. Integrated multi-omics analysis revealed coordinated shifts in metabolites and genes across developmental phases, reflecting dynamic nutrient remodeling during pupal maturation. This study systematically delineates the molecular transitions driving pupal development in Antheraea pernyi pupae, uncovering conserved pathway interactions and mechanistic insights into nutrient metabolism. These findings provide a scientific foundation for leveraging pupal resources in functional food innovation and bioactive compound discovery for pharmaceutical applications. Full article

Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, comprises embryonal (ERMS) and alveolar (ARMS) subtypes with distinct histopathological features, clinical outcomes, and therapeutic responses. To better characterize their molecular distinctions, we performed untargeted plasma proteomics and metabolomics profiling in children with ERMS (n = 18), ARMS (n = 17), and matched healthy controls (n = 18). Differential expression, functional enrichment (GO, KEGG, RaMP-DB), co-expression network analysis (WGCNA/WMCNA), and multi-omics integration (DIABLO, MOFA) revealed distinct molecular signatures for each subtype. ARMS displayed elevated oncogenic and stemness-associated proteins (e.g., cyclin E1, FAP, myotrophin) and metabolites involved in lipid transport, fatty acid metabolism, and polyamine biosynthesis. In contrast, ERMS was enriched in immune-related and myogenic proteins (e.g., myosin-9, SAA2, S100A11) and metabolites linked to glutamate/glycine metabolism and redox homeostasis. Pathway analyses highlighted subtype-specific activation of PI3K-Akt and Hippo signaling in ARMS and immune and coagulation pathways in ERMS. Additionally, the proteomics and metabolomics datasets showed association with clinical parameters, including disease stage, lymph node involvement, and age, demonstrating clear molecular discrimination consistent with clinical observation. Co-expression networks and integrative analyses further reinforced these distinctions, uncovering coordinated protein–metabolite modules. Our findings reveal novel, subtype-specific molecular programs in RMS and propose candidate biomarkers and pathways that may guide precision diagnostics and therapeutic targeting in pediatric sarcomas. Full article

Background/Objectives: Chronic manganese (Mn) exposure is a recognized environmental contributor to Parkinsonian syndromes, including Mn-induced Parkinsonism (MnIP). This study aimed to evaluate whole-blood Mn levels and investigate disease/exposure-status-related alterations in metabolomic and lipidomic profiles. Methods: A case–control study (N = 97) was conducted in Brescia, Italy, stratifying participants by Parkinsonism diagnosis and residential Mn exposure. Whole-blood Mn was quantified using ICP-MS. Untargeted metabolomic and lipidomic profiling was conducted using LC-MS. Statistical analyses included Mann–Whitney U tests, conditional logistic regression, ANCOVA, and pathway analysis. Results: Whole-blood Mn levels were significantly elevated in Parkinsonism cases vs. controls (median: 1.55 µg/dL [IQR: 0.75] vs. 1.02 µg/dL [IQR: 0.37]; p = 0.001), with Mn associated with increased odds of Parkinsonism (OR = 2.42, 95% CI: 1.13–5.17; p = 0.022). The disease effect metabolites included 3-sulfoxy-L-tyrosine (β = 1.12), formiminoglutamic acid (β = 0.99), and glyoxylic acid (β = 0.83); all FDR p < 0.001. The exposure effect was associated with elevated glycocholic acid (β = 0.51; FDR p = 0.006) and disrupted butanoate (Impact = 0.03; p = 0.004) and glutamate metabolism (p = 0.03). Additionally, SLC-mediated transmembrane transport was enriched (p = 0.003). The interaction effect identified palmitelaidic acid (β = 0.30; FDR p < 0.001), vitamin B6 metabolism (Impact = 0.08; p = 0.03), and glucose homeostasis pathways. In lipidomics, triacylglycerols and phosphatidylethanolamines were associated with the disease effect (e.g., TG(16:0_10:0_18:1), β = 0.79; FDR p < 0.01). Ferroptosis and endocannabinoid signaling were enriched in both disease and interaction effects, while sphingolipid metabolism was specific to the interaction effect. Conclusions: Mn exposure and Parkinsonism are associated with distinct metabolic and lipidomic perturbations. These findings support the utility of omics in identifying environmentally linked Parkinsonism biomarkers and mechanisms. Full article

Background/Objectives: Hypertension is a pathological condition characterized by elevated systolic and/or diastolic blood pressure. A range of pharmacotherapeutic agents are available to treat this condition and prevent complications, including the angiotensin II AT1-receptor blocker losartan. Following oral administration, losartan is exposed to a variety of enzymes that facilitate its metabolism or transportation. The structural characteristics of the genes that encode the enzymes may potentially impact the pharmacokinetics and pharmacodynamics of losartan, thereby modulating its effects on the treatment process. Methods: In this study, a computational model of losartan pharmacokinetics was developed, taking into account the influence of different alleles of the CYP2C9 gene, which plays a pivotal role in losartan metabolism, and the ABCB1 gene, which is responsible for losartan transport. Results: Alterations in the modeled activities of the enzymes encoded by CYP2C9 and ABCB1 result in changes in the losartan and its metabolite profiles that are consistent with known experimental data in real patients with different CYP2C9 and ABCB1 genotypes. Conclusions: The findings of the modeling can potentially be used to personalize drug therapy for arterial hypertension. Full article

Copper pyrithione (CuPT), an emerging biocide used in ship antifouling coatings, may accumulate in marine sediments and pose risks to non-target organisms. However, current research on CuPT toxicity remains limited. Litopenaeus vannamei, one of the world’s most important aquaculture shrimp species, relies heavily on its hepatopancreas for energy metabolism, detoxification, and immune responses. Due to their benthic habitat, these shrimps are highly vulnerable to contamination in sediment environments. This study investigated the toxicological response in the hepatopancreas of L. vannamei exposed to CuPT (128 μg/L) for 3 and 48 h. Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) fluorescence staining revealed increased apoptosis, deformation of hepatic tubule lumens, and the loss of stellate structures in the hepatopancreas after CuPT 48 h exposure. A large number of differentially expressed genes (DEGs) were identified by transcriptomics analysis at 3 and 48 h, respectively. Most of these DEGs were related to detoxification, glucose transport, and immunity. Metabolomic analysis identified numerous significantly different metabolites (SDMs) at both 3 and 48 h post-exposure, with most SDMs associated with energy metabolism, fatty acid metabolism, and related pathways. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of metabolomics and transcriptome revealed that both DEGs and SDMs were enriched in arachidonic acid metabolism, fatty acid biosynthesis, and glycolysis/gluconeogenesis pathways at 3 h, while at 48 h they were enriched in the starch and sucrose metabolism, amino sugar and nucleotide sugar metabolism, and galactose metabolism pathways. These results suggested that CuPT disrupts the energy and lipid homeostasis of L. vannamei. This disruption compelled L. vannamei to allocate additional energy toward sustaining basal physiological functions and consequently caused the accumulation of large amounts of reactive oxygen species (ROS) in the body, leading to apoptosis and subsequent tissue damage, and ultimately suppressed the immune system and impaired the health of L. vannamei. Our study elucidates the molecular mechanisms of CuPT-induced metabolic disruption and immunotoxicity in L. vannamei through integrated multi-omics analyses, providing new insights for ecological risk assessment of this emerging antifoulant. Full article