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Wampee (Clausena lansium (Lour.) Skeels) has natural bioactive components with diverse health benefits, but its detailed metabolism and tissue distribution are not fully understood. Here, widely targeted metabolomics analysis methods were employed to analyze the wampee fruit (peel, pulp, and seed) of 17 different varieties. A total of 1286 metabolites were annotated, including lipids, flavonoids, polyphenols, carbazole alkaloids, coumarins, and organic acids, among others. The quantitative analysis and matrix-assisted laser desorption/ionization–mass spectrometry imaging (MALDI-MSI) analysis indicated remarkable variations in metabolite categories and content in the peel, pulp, and seed of wampee fruit. Additionally, the difference analysis found that the metabolic components of peel contributed dominantly to the differences among varieties, and 7 potential biomarkers were identified. In this study, a comprehensive metabolome landscape of wampee fruit was established, which provided important information for the isolation and identification of functional components, food industry application, and nutritional improvement breeding. [ABSTRACT FROM AUTHOR]

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive disease characterized by complex metabolic rewiring that enables growth in changing nutrient availability and oxygen conditions. Transcriptome-based prognostic PDAC tumor subtypes, known as 'basal-like' and 'classical' subtypes are associated with differences in metabolic gene expression including genes involved in glycolysis. Tumor subtype-specific metabolism phenotypes may provide new targets for treatment development in PDAC, but their functional relevance has not been fully elucidated. We aimed to investigate differences in metabolic profiles and transcriptomes in tumor models derived from patients with basal-like and classical tumors. Methods: Patient-derived organoids (PDOs) were established from tumor biopsies collected from patients with metastatic PDAC, including three PDOs from basal-like and five PDOs from classical tumors. Metabolic analyses included assessment of differences in metabolic activity using Seahorse Glycolysis and Mito Stress tests and 13C-glucose metabolites tracing analysis. In order to investigate the influence of mitochondrial pyruvate transport on metabolic differences, PDOs were treated with the mitochondrial pyruvate carrier 1 (MPC1) inhibitor UK-5099. Prognostic relevance of MPC1 was determined using a tumor tissue microarray (TMA) in resectable, and proteomics profiling in metastatic PDAC datasets. Whole genome and transcriptome sequencing, differential gene expression and gene set enrichment analyses were performed in PDOs. Results: Metastatic PDAC PDOs showed subtype-specific differences in glycolysis and oxidative phosphorylation (OXPHOS). Basal-like tumor-derived PDOs had a lower baseline extracellular acidification rate, but higher glycolytic reserves and oxygen consumption rate (OCR) than classical tumor-derived PDOs. OCR difference was eliminated following treatment with UK-5099. In the 13C-glucose metabolites tracing experiment, a basal-like tumor PDO showed lower fractions of some M + 2 metabolites but higher sensitivity to UK-5099 mediated reduction in M + 2 metabolites than a classical tumor PDO. Protein level analyses revealed lower MPC1 protein levels in basal-like PDAC cases and association of low MPC1 levels with clinicopathologic parameters of tumor aggressiveness in PDAC. PDO differential gene expression analyses identified additional subtype-specific cellular pathways and potential disease outcome biomarkers. Conclusions: Our findings point to distinct metabolic profiles in PDAC subtypes with basal-like tumor PDOs showing higher OXPHOS and sensitivity to MPC1 inhibition. Subtypes-specific metabolic vulnerabilities may be exploited for selective therapeutic targeting. [ABSTRACT FROM AUTHOR]

Background: This study used metabolic phenotyping to explore the responses of highly-trained cross-country skiers to a standardized exercise test, which was part of the athletes' routine testing, and determine whether metabolic phenotyping could discriminate specific physiological, performance, and illness characteristics. Methods: Twenty-three highly-trained cross-country skiers (10 women and 13 men) participated in this study. Capillary whole-blood samples were collected before (at rest) and 2.5 min after (post-exercise) a roller-ski treadmill test consisting of 5–6 × 4-min submaximal stages followed by a self-paced time trial (~ 3 min) and analyzed using mass spectrometry. Performance level was defined by International Ski Federation distance and sprint rankings. Illness data were collected prospectively for 33 weeks using the Oslo Sports Trauma Research Center Questionnaire on Health Problems. Orthogonal partial least squares-discriminant analyses (OPLS-DA) followed by enrichment analyses were used to identify metabolic phenotypes of athlete groups with specific physiological, performance, and illness characteristics. Results: Blood metabolite phenotypes were significantly different after the standardized exercise test compared to rest for metabolites involved in energy, purine, and nucleotide metabolism (all OPLS-DA p < 0.001). Acute changes in the metabolic phenotype from rest to post-exercise could discriminate athletes with: (1) higher vs. lower peak blood lactate concentrations; (2) superior vs. inferior performance levels in sprint skiing, and (3) ≥ 2 vs. ≤ 1 self-reported illness episodes in the 33-week study period (all p < 0.05). The most important metabolites contributing to the distinction of groups according to (1) post-exercise blood lactate concentrations, (2) sprint performance, and (3) illness frequency were: (1) inosine, hypoxanthine, and deoxycholic acid, (2) sorbitol, adenosine monophosphate, and 2-hydroxyleuroylcarnitine, and (3) glucose-6-phosphate, squalene, and deoxycholic acid, respectively. Conclusion: Metabolic phenotyping discriminated between athlete groups with higher vs. lower post-exercise blood lactate concentrations, superior vs. inferior sprint skiing performance, and more vs. less self-reported illnesses. While the biological relevance of the identified biomarkers requires validation in future research, metabolic phenotyping shows promise as a tool for routine monitoring of highly-trained endurance athletes. Key Points: • The standardized exercise test led to alterations in metabolites primarily involved in carbohydrate metabolism and the tricarboxylic acid cycle, purine/pyrimidines, and nucleoside/nucleotides. • Acute changes in metabolic phenotypes could differentiate athletes with higher vs. lower [La-]peak and superior vs. inferior sprint skiers, and between athletes who were susceptible vs. non-susceptible to illness. • Metabolic phenotyping shows promise as a tool for routine monitoring of endurance athletes if cost and turnaround time is improved. [ABSTRACT FROM AUTHOR]

This study aimed to isolate and characterize a native strain of Beauveria bassiana, coded as Bv065, showcasing its potential as a biological control agent targeting the palm weevil Dynamis borassi. Originating from a naturally infected D. borassi specimen collected in southwestern Colombia, the fungus underwent molecular identification and was identified as B. bassiana, exhibiting high sequence similarity with known reference strains. The physiological characterization revealed that Bv065 thrived within a temperature range of 25 to 30 °C and a pH range of 6 to 9. Moreover, the key carbon sources that allow optimal growth of the strain were identified through metabolic profiling, including sucrose, D-mannose, and γ-amino-butyric acid. These findings offer strategic insights for scalability and formulation methodologies. Additionally, enzymatic analyses unveiled robust protease activity within Bv065, crucial for catalysing insect cuticle degradation and facilitating host penetration, thus accentuating its entomopathogenic potential. Subsequent evaluations exposed Bv065's pathogenicity against D. borassi, causing significant mortality within nine days of exposure, albeit exhibiting limited effectiveness against Rhynchophorus palmarum. This study underscores the importance of understanding optimal growth conditions and metabolic preferences of B. bassiana strains for developing effective biopesticides. The findings suggest Bv065 as a promising candidate for integrated pest management strategies in neotropical regions, particularly for controlling palm weevil infestations in coconut and peach palm cultivation. Future research avenues include refining mass production methodologies, formulating novel delivery systems, and conducting comprehensive field efficacy trials to unlock the full potential of Bv065 in fostering sustainable pest management practices. Overall, this study contributes to the growing body of knowledge on entomopathogenic fungi and their pivotal role in biological control, offering nuanced perspectives on eco-friendly alternatives to conventional insecticidal interventions. [ABSTRACT FROM AUTHOR]

Bryophyllum pinnatum (Lam.) Oken, a multipurpose medicinal herb, has drawn much interest for its therapeutic qualities from both traditional and modern medicine systems. Many active secondary metabolites, such as bufadienolides, triterpenes, phenols, alkaloids, glycosides, lipids, flavonoids, and organic acids, are responsible for the plant's curative properties. B. pinnatum exhibits a noteworthy significance in oncological research by exhibiting its ability to modify numerous pathways, which may suggest a potential anticancer impact. The herb is recommended for treating lithiasis, a common cause of renal failure, due to its effectiveness in dissolving stones and avoiding crystal formation. The plant has a major impact on diabetes, especially type II diabetes. Moreover, the versatility of B. pinnatum extends to its examination in connection to COVID-19. However, caution is warranted, as B. pinnatum has been reported to possess toxicity attributed to the presence of bufadienolides in its metabolic profile. A comprehensive investigation is essential to thoroughly understand and confirm the synthesis of potentially hazardous compounds. This is crucial for minimizing their presence and ensuring the safe consumption of B. pinnatum among diverse populations of organisms. This review highlights the various medical uses of B. pinnatum, including its ability to effectively treat kidney and liver diseases, as well as its anti-leishmanial, neuropharmacological, antibacterial, immunosuppressive, anti-tumour, and cytotoxic effects. While extensively employed in both traditional and scientific domains, the plant's complete medicinal potential, molecular mechanisms, safety profile, and pharmacodynamics remain ambiguous, rendering it an ideal candidate for pioneering research endeavours. [ABSTRACT FROM AUTHOR]

Background: Neolamarckia cadamba (Rubiaceae) is a well-recognized medicinal plant with recorded therapeutical attributes. However, a thorough assessment of active compounds in its fruits is lacking, limiting their use and valorization in pharmacological industries. Methods: Thus, this study investigated variations in the fruits' secondary metabolite (SM) profiles, as well as antioxidant activities in aqueous (WA) and ethanol (ET) extracts. Results: Liquid chromatography–electrospray ionization tandem mass spectrometry identified 541 SMs, of which 14 and 1 (di-O-glucosylquinic acid) were specifically detected in ET and WA, respectively. Phenolic acids (36.97%), flavonoids (28.10%), terpenoids (12.20%), and alkaloids (9.98%) were the dominant SMs. The SM profiles of the fruits in WA and ET were quite different. We revealed 198 differentially extracted (DE) metabolites between WA and ET, including 62 flavonoids, 57 phenolic acids, 45 terpenoids, 14 alkaloids, etc. Most DE flavones (36 out of 40), terpenoids (45 out of 45), and alkaloids (12 out of 14) had higher content in ET. Catechin and its derivatives, procyanidins, and tannins had higher content in WA. ABTS and DPPH assays showed that the antioxidant activity of ET was significantly higher than that of WA. Conclusions: Our findings will facilitate the efficient extraction and evaluation of specific active compounds in N. cadamba. [ABSTRACT FROM AUTHOR]

Liraglutide, a glucagon-like peptide-1 receptor agonist, is effective in the treatment of type 2 diabetes mellitus (T2DM) and obesity. Despite its benefits, including improved glycemic control and weight loss, the common metabolic changes induced by liraglutide and correlations between those in rodents and humans remain unknown. Here, we used advanced machine learning techniques to analyze the plasma metabolomic data in diet-induced obese (DIO) mice and patients with T2DM treated with liraglutide. Among the machine learning models, Support Vector Machine was the most suitable for DIO mice, and Gradient Boosting was the most suitable for patients with T2DM. Through the cross-evaluation of machine learning models, we found that liraglutide promotes metabolic shifts and interspecies correlations in these shifts between DIO mice and patients with T2DM. Our comparative analysis helped identify metabolic correlations influenced by liraglutide between humans and rodents and may guide future therapeutic strategies for T2DM and obesity. [ABSTRACT FROM AUTHOR]

Abstract Coronary artery disease (CAD) remains a leading cause of death worldwide and imposes a substantial socioeconomic burden on healthcare. Improving risk stratification in clinical practice could help to combat this burden. As amino acids are biologically active metabolites whose involvement in CAD remains largely unknown, this study investigated associations between circulating amino acid levels and CAD phenotypes. A high-coverage quantitative liquid chromatography-mass spectrometry approach was applied to acquire the serum amino acids profile of age- and sex-coarsened-matched patients with CAD (n = 46, 66.9 years, 74.7% male) and healthy individuals (n = 120, 67.4 years, 74.7% male) from the COmPLETE study. Multiple linear regressions were performed to investigate associations between amino acid levels and (a) the health status (CAD vs. healthy), (b) the number of affected coronary arteries, or (c) the left ventricular ejection fraction. Regressions were adjusted for age, sex, daily physical activity, sampling, and fasting time. Urea cycle amino acids (ornithine, citrulline, homocitrulline, aspartate, and arginine) were significantly and negatively associated with CAD, the number of affected coronary arteries, and the left ventricular ejection fraction. Lysine, histidine, and the glutamine/glutamate ratio were also significantly and negatively associated with the CAD phenotypes. Overall, patients with CAD displayed lower levels of urea cycle amino acids, highlighting a potential role for urea cycle amino acid profiling in cardiovascular risk stratification. Trial registration The study was registered on https://www.clinicaltrials.gov (NCT03986892) on June 5, 2019.

Abstract Background This study used metabolic phenotyping to explore the responses of highly-trained cross-country skiers to a standardized exercise test, which was part of the athletes’ routine testing, and determine whether metabolic phenotyping could discriminate specific physiological, performance, and illness characteristics. Methods Twenty-three highly-trained cross-country skiers (10 women and 13 men) participated in this study. Capillary whole-blood samples were collected before (at rest) and 2.5 min after (post-exercise) a roller-ski treadmill test consisting of 5–6 × 4-min submaximal stages followed by a self-paced time trial (~ 3 min) and analyzed using mass spectrometry. Performance level was defined by International Ski Federation distance and sprint rankings. Illness data were collected prospectively for 33 weeks using the Oslo Sports Trauma Research Center Questionnaire on Health Problems. Orthogonal partial least squares-discriminant analyses (OPLS-DA) followed by enrichment analyses were used to identify metabolic phenotypes of athlete groups with specific physiological, performance, and illness characteristics. Results Blood metabolite phenotypes were significantly different after the standardized exercise test compared to rest for metabolites involved in energy, purine, and nucleotide metabolism (all OPLS-DA p

Carissa carandas L. is a wild food plant, however, is cultivated for its fruits to be utilized to make pickles, jams, and other similar products. Fruit of this plant has been intensively investigated for its bioactive potential; however, a scanty study is reported on the leaf, which is usually wasted. In the present study, ethanolic extract of the leaf of C. carandas was analyzed for its total bioactive contents and found rich in phenolics and flavonoids (26.67 ± 0.33 mg GAE/g extract and 18.42 ± 0.05 mg RE/g extract, respectively). These findings were substantiated due to UHPLCMS/MS analysis, which disclosed the presence of about 110 secondary metabolites, mostly lignans, flavonoids, and terpenoids. In DPPH and ABTS free radical inhibition assays, the extract showed inhibitory values as 47.51 ± 0.09 and 93.09 ± 2.8 mg TE/g extract, respectively. Its further antioxidant potential was observed in CUPRAC and FRAP assays, wherein the metal reducing power was recorded as 102.05 ± 1.03 and 67.24 ± 0.9 mg TE/g extract, respectively, while in phosphomolybdenum and metal chelating assays, the extract also disclosed potential activity (0.92 ± 0.02 mmol TE/g extract and 21.42 ± 0.34 mg EDTAE/g extract). The extract was also significantly active against tyrosinase (45.69 ± 0.7 mg KAE/g extract) and showed mild activities against AChE (3.61 ± 0.16 mg GALAE/g extract), BChE (1.43 ± 0.2 mg GALAE/g extract), α-amylase (0.46 ± 0.01 mmol ACAE/g extract) and α-glucosidase (1.05 ± 0.02 mmol ACAE/g extract). In computational studies, binding affinities for AChE and BChE enzymes were from −4.21 to −12.70 and −7.58 to −12.53 kcal/mol, respectively, confirming the results of the invitro tests and ADME studies. The current finding suggested that C. carandas may be considered as a source for several nutraceutical formulations.

Abstract Background Scopoletin and umbelliferone belong to coumarins, which are plant specialized metabolites with potent and wide biological activities, the accumulation of which is induced by various environmental stresses. Coumarins have been detected in various plant species, including medicinal plants and the model organism Arabidopsis thaliana. In recent years, key role of coumarins in maintaining iron (Fe) homeostasis in plants has been demonstrated, as well as their significant impact on the rhizosphere microbiome through exudates secreted into the soil environment. Several mechanisms underlying these processes require clarification. Previously, we demonstrated that Arabidopsis is an excellent model for studying genetic variation and molecular basis of coumarin accumulation in plants. Results Here, through targeted metabolic profiling and gene expression analysis, the gene-metabolite network of scopoletin and umbelliferone accumulation was examined in more detail in selected Arabidopsis accessions (Col-0, Est-1, Tsu-1) undergoing different culture conditions and characterized by variation in coumarin content. The highest accumulation of coumarins was detected in roots grown in vitro liquid culture. The expression of 10 phenylpropanoid genes (4CL1, 4CL2, 4CL3, CCoAOMT1, C3’H, HCT, F6’H1, F6’H2,CCR1 and CCR2) was assessed by qPCR in three genetic backgrounds, cultured in vitro and in soil, and in two types of tissues (leaves and roots). We not only detected the expected variability in gene expression and coumarin accumulation among Arabidopsis accessions, but also found interesting polymorphisms in the coding sequences of the selected genes through in silico analysis and resequencing. Conclusions To the best of our knowledge, this is the first study comparing accumulation of simple coumarins and expression of phenylpropanoid-related genes in Arabidopsis accessions grown in soil and in liquid cultures. The large variations we detected in the content of coumarins and gene expression are genetically determined, but also tissue and culture dependent. It is particularly important considering that growing plants in liquid media is a widely used technology that provides a large amount of root tissue suitable for metabolomics. Research on differential accumulation of coumarins and related gene expression will be useful in future studies aimed at better understanding the physiological role of coumarins in roots and the surrounding environments.

Background: Scopoletin and umbelliferone belong to coumarins, which are plant specialized metabolites with potent and wide biological activities, the accumulation of which is induced by various environmental stresses. Coumarins have been detected in various plant species, including medicinal plants and the model organism Arabidopsis thaliana. In recent years, key role of coumarins in maintaining iron (Fe) homeostasis in plants has been demonstrated, as well as their significant impact on the rhizosphere microbiome through exudates secreted into the soil environment. Several mechanisms underlying these processes require clarification. Previously, we demonstrated that Arabidopsis is an excellent model for studying genetic variation and molecular basis of coumarin accumulation in plants. Results: Here, through targeted metabolic profiling and gene expression analysis, the gene-metabolite network of scopoletin and umbelliferone accumulation was examined in more detail in selected Arabidopsis accessions (Col-0, Est-1, Tsu-1) undergoing different culture conditions and characterized by variation in coumarin content. The highest accumulation of coumarins was detected in roots grown in vitro liquid culture. The expression of 10 phenylpropanoid genes (4CL1, 4CL2, 4CL3, CCoAOMT1, C3'H, HCT, F6'H1, F6'H2,CCR1 and CCR2) was assessed by qPCR in three genetic backgrounds, cultured in vitro and in soil, and in two types of tissues (leaves and roots). We not only detected the expected variability in gene expression and coumarin accumulation among Arabidopsis accessions, but also found interesting polymorphisms in the coding sequences of the selected genes through in silico analysis and resequencing. Conclusions: To the best of our knowledge, this is the first study comparing accumulation of simple coumarins and expression of phenylpropanoid-related genes in Arabidopsis accessions grown in soil and in liquid cultures. The large variations we detected in the content of coumarins and gene expression are genetically determined, but also tissue and culture dependent. It is particularly important considering that growing plants in liquid media is a widely used technology that provides a large amount of root tissue suitable for metabolomics. Research on differential accumulation of coumarins and related gene expression will be useful in future studies aimed at better understanding the physiological role of coumarins in roots and the surrounding environments. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer is the second leading cause of death worldwide, warranting the development of safer, more effective therapies. Liposomes and niosomes can be considered excellent drug delivery systems due to their ability to load all compounds and reduce the toxicity of the loaded drug without reducing its effectiveness. Synechocystis sp. is a unicellular, freshwater blue-green algae strain that has many bioactive compounds that qualify for use in industrial, pharmaceutical, and other fields. This study used nano-liposomes and nano-niosomes to deliver Synechocystis sp. extract against human colon, ovarian, and breast cancer cell lines. The results demonstrated potential activities against human colon, ovarian, and breast cancer cell lines. A total of 22 compounds were identified through the metabolic profiling of an extract, as it is a tool aimed at identifying biologically active compounds in the sample. Subsequently, the molecular docking of these compounds was studied, which is the most effective way to study the compound's effectiveness on a specific disease by determining the binding affinity. The results showed that compounds 21, 6, 7, 8, 12, and 19 have a high degree of correlation. Finally, these results represent a promising step toward developing effective cancer treatments. Future research should translate this approach into successful anticancer drugs through participation in clinical trials. Liposomes and niosomes can be considered excellent drug delivery systems due to their ability to load all compounds, whether hydrophobic or hydrophilic. In addition, they can reduce the toxicity of the loaded drug without reducing its effectiveness. Synechocystis sp. is a unicellular, freshwater cyanobacteria strain that contains many bioactive compounds that qualify its use in industrial, pharmaceutical, and many other fields. This study investigated the potential of nano-liposomes (L) and nano-niosomes (N) for delivering Synechocystis sp. extract against cancer cell lines. Four different types of nanoparticles were prepared using a dry powder formulation and ethanol extract of Synechocystis sp. in both nanovesicles (N1 and N2, respectively) and liposomes (L1 and L2, respectively). Analysis of the formed vesicles using zeta analysis, SEM morphological analysis, and visual examination confirmed their stability and efficiency. L1 and L2 in this investigation had effective diameters of 419 and 847 nm, respectively, with PDI values of 0.24 and 0.27. Furthermore, the zeta potentials were found to range from −31.6 mV to −43.7 mV. Regarding N1 and N2, their effective diameters were 541 nm and 1051 nm, respectively, with PDI values of 0.31 and 0.35, and zeta potentials reported from −31.6 mV to −22.2 mV, respectively. Metabolic profiling tentatively identified 22 metabolites (1–22) from the ethanolic extract. Its effect against representative human cancers was studied in vitro, specifically against colon (Caco2), ovarian (OVCAR4), and breast (MCF7) cancer cell lines. The results showed the potential activities of the prepared N1, N2, L1, and L2 against the three cell lines, where L1 had cytotoxicity IC50 values of 19.56, 33.52, and 9.24 µg/mL compared to 26.27, 56.23, and 19.61 µg/mL for L2 against Caco2, OVCAR4, and MCF7, respectively. On the other hand, N1 exhibited IC50 values of 9.09, 11.42, and 2.38 µg/mL, while N2 showed values of 15.57, 18.17, and 35.31 µg/mL against Caco2, OVCAR4, and MCF7, respectively. Meanwhile, the formulations showed little effect on normal cell lines (FHC, OCE1, and MCF10a). All of the compounds were evaluated in silico against the epidermal growth factor receptor tyrosine kinase (EGFR). The molecular docking results showed that compound 21 (1-hexadecanoyl-2-(9Z-hexadecenoyl)-3-(6′-sulfo-alpha-D-quinovosyl)-sn-glycerol), followed by compounds 6 (Sulfoquinovosyl monoacylgycerol), 7 (3-Hydroxymyristic acid), 8 (Glycolipid PF2), 12 (Palmitoleic acid), and 19 (Glyceryl monostearate), showed the highest binding affinities. These compounds formed good hydrogen bond interactions with the key amino acid Lys721 as the co-crystallized ligand. These results suggest that nano-liposomes and nano-niosomes loaded with Synechocystis sp. extract hold promise for future cancer treatment development. Further research should focus on clinical trials, stability assessments, and pharmacological profiles to translate this approach into effective anticancer drugs. [ABSTRACT FROM AUTHOR]

Introduction: Exploring metabolic changes within host E. coli through an untargeted metabolomic study of T7L variants overexpression to optimize engineered endolysins for clinical/therapeutic use. Aim and objective: This study aims to assess the impact of overexpressing T7L variants on the metabolic profiles of E. coli. The two variants considered include T7L-H37A, which has enhanced lytic activity compared to its wild-type protein, and T7L-H48K, a dead mutant with no significant activity. Methods: 1H NMR-based metabolomics was employed to compare the metabolic profiles of E. coli cells overexpressing T7L wild-type protein and its variants. Results: Overexpression of the T7L wild-type (T7L-WT) protein and its variants (T7L-H48K and T7L-H37A) was compared to RNAP overexpression in E. coli cells using 1H NMR-based metabolomics, analyzing a total of 75 annotated metabolites, including organic acids, amino acids, sugars, and nucleic acids. The results showed distinct clustering patterns for the two T7L variant groups compared with the WT, in which the dead mutant (H48K) group showed clustering close to that of RNAP. Pathway impact analysis revealed different effects of T7L variants on E. coli metabolic profiles, with T7L-H48K showing minimal alterations in energy and amino acid pathways linked to osmotic stress compared to noticeable alterations in these pathways for both T7L-H37A and T7L-WT. Conclusions: This study uncovered distinct metabolic fingerprints when comparing the overexpression of active and inactive mutants of T7L lytic enzymes in E. coli cells. These findings could contribute to the optimization and enhancement of suitable endolysins as potential alternatives to antibiotics. [ABSTRACT FROM AUTHOR]

This study investigates the growth tolerance mechanisms of Chlorella pyrenoidosa to 3-fluorophenol and its removal efficiency by algal cells. Our results indicate that C. pyrenoidosa can tolerate up to 100 mg/L of 3-fluorophenol, exhibiting a significant hormesis effect characterized by initial inhibition followed by promotion of growth. In C. pyrenoidosa cells, the activities of superoxide dismutase (SOD) and catalase (CAT), as well as the levels of malondialdehyde (MDA) and reactive oxygen species (ROS), were higher than or comparable to the control group. Metabolic analysis revealed that the 3-fluorophenol treatment activated pathways, such as glycerol phospholipid metabolism, autophagy, glycosylphosphatidylinositol (GPI)-anchored protein biosynthesis, and phenylpropanoid biosynthesis, contributed to the stabilization of cell membrane structures and enhanced cell repair capacity. After 240 h of treatment, over 50% of 3-fluorophenol was removed by algal cells, primarily through adsorption. Thus, C. pyrenoidosa shows potential as an effective biosorbent for the bioremediation of 3-fluorophenol. [ABSTRACT FROM AUTHOR]

Common wheat (Triticum aestivum L.) is one of the most valuable cereal crops worldwide. This study examined leaf extracts of 30 accessions of T. aestivum and its subspecies using 48 h maceration with methanol by GC-MS and GCxGC-MS. The plants were grown from seeds of the wheat genetics collection of the Wheat Genetics Sector of the Institute of Cytology and Genetics, SB RAS. The analysis revealed 263 components of epicuticular waxes, including linear and branched alkanes, aliphatic alcohols, aldehydes, ketones, β-diketones, carboxylic acids and their derivatives, mono- and diterpenes, phytosterols, and tocopherols. Hierarchical cluster analysis and principal component analysis were used to identify and visualize the differences between the leaf extracts of different wheat cultivars. Three clusters were identified, with the leading components being (1) octacosan-1-ol, (2) esters of saturated and unsaturated alcohols, and (3) fatty acid alkylamides, which were found for the first time in plant extracts. The results highlight the importance of metabolic studies in understanding the adaptive mechanisms and increasing wheat resistance to stress factors. These are crucial for breeding new-generation cultivars with improved traits. [ABSTRACT FROM AUTHOR]

Simple Summary: This study identified a change in metabolites by fermented blackberries using GC-MS methods in high-fat-diet-induced mice. As a result, the altered metabolites in the high-fat-diet group consisted of 29 metabolites, showing 85% identity with known components in the database. Among the 29 metabolites, essential amino acids, non-essential amino acids, conditionally essential amino acids, and other metabolites were analyzed after treatment with blackberries and fermented blackberries in high-fat-diet-induced mice. This study constitutes a valuable resource on the dietary modification of fermented blackberries for obesity treatment approaches. The aim of this study was to investigate the metabolic changes associated with the anti-obesity effects of fermented blackberry extracts in the liver tissues of high-fat-diet-fed mice using mass spectrometry-based metabolomics analysis. C57BL/6J mice were divided into eight groups: normal-diet-fed mice, high-fat-diet-fed mice, high-fat diet treated with blackberry extract, high-fat-diet mice treated with blackberry fermented by L. plantarum, and high-fat diet with blackberry fermented by L. brevis. After 12 weeks, the high-fat-diet group exhibited a greater increase in liver weight compared to the control group, and among the groups, the group administered with blackberry fermented with L. plantarum showed the most pronounced reduction in liver weight. As the primary organ responsible for amino acid metabolism, the liver is crucial for maintaining amino acid homeostasis. In our study, we observed that the levels of several essential amino acids, including isoleucine and valine, were decreased by the high-fat diet, and were recovered by administration of blackberry extract fermented with L. plantarum. Our results demonstrated the potential of blackberry extract fermented with L. plantarum as a functional material for metabolic disorders by restoring some of the amino acid metabolism disturbances induced by a high-fat diet. [ABSTRACT FROM AUTHOR]

Abstract: Interest in glutinous rice consumption has been expanding in East Asia. However, the extent of metabolite variation between common and glutinous rice has not been fully explored to identify metabolic targets for rice quality improvement. Thus, the objective of this study was to provide insights into the variation of metabolites and nutraceuticals between common and glutinous rice. Two black rice (common rice, BL-N, and glutinous rice, BL-G) and two white rice (common rice, WH-N, and glutinous rice, WH-G) types were analysed via LC-MS-based widely targeted metabolic profiling. We identified 441 and 343 types, including 160 key overlapping differentially accumulated metabolites between BL-N_vs_BL-G and WH-N_vs_WH-G, respectively. Glutinous rice showed a higher relative content of most categories of metabolites, except for quinones (in BL-N) and tannins (in WH-N). Seven vitamins, including B6, B3, B5, B13, isonicotinic acid, N-(beta-D-glucosyl)nicotinate, and 4-pyridoxic acid-O-glucoside, were significantly up-regulated in BL-G compared to BL-N. The biosynthesis of cofactors, zeatin biosynthesis, citrate cycle, amino acid metabolism, alpha-linolenic acid metabolism, and glyoxylate and dicarboxylate metabolism was the most differentially regulated pathway. Key differential metabolites in citrate cycle include citrate, isocitrate, fumarate, malate, succinate, and 2-oxoglutarate; in amino acid metabolism (L-serine, L-cysteine, L-lysine, L-glutamine, L-methionine, and L-tryptophan); and in glycolysis (UDP-glucose, D-glucose-1P, D-glucose-6P, and D-fructose-6P). The data resources in this study may contribute to a better understanding of the function and nutritional value of glutinous rice. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the metabolic changes in the livers of dairy cows from 1 wk before dry off to 1 wk after calving. Twelve high-yielding Holstein cows were included in a longitudinal study and housed in a tiestall barn. The cows were dried off at 6 wk before the expected calving date (dry period length = 42 d). During the entire lactation, the cows were milked twice daily at 0600 and 1700 h. Liver biopsies were taken from each cow at 4 different times: wk −7 (before drying off), −5 (after drying off), −1 and +1 relative to calving. A targeted metabolomics approach was performed by liquid chromatography and flow injection with electrospray ionization triple quadrupole mass spectrometry using the MxP Quant 500 kit (Biocrates Life Sciences AG). A total of 185 metabolites in the liver were used for the final data analysis. Principal component analysis revealed a clear separation by days of sampling, indicating a notable shift in metabolic phenotype from late lactation to the dry period and further changes after calving. Changes were observed in several classes of compounds, including AA and biogenic amines. In particular, the changes in acylcarnitines (AcylCN), phosphatidylcholines (PC), sphingomyelins (SM), and bile acids (BA) indicated extensive remodeling of the hepatic lipidome. The changes in AcylCN concentrations in early lactation suggest incomplete fatty acid oxidation in the liver, possibly indicating mitochondrial dysfunction or enzymatic imbalance. In addition, the changes in PC and SM species in early lactation indicate altered cell membrane composition, which may affect cell signaling and functionality. In addition, changes in BA concentrations and profiles indicate dynamic adaptations in BA synthesis, as well as lipid digestion and absorption during the observation period. In particular, principal component analysis showed an overlapping distribution of liver metabolites in primiparous and multiparous cows, indicating no significant difference between these groups. In addition, Volcano plots showed similar liver metabolism between primiparous and multiparous cows, with no significant fold changes (>1.5) in any metabolite at significant P -values (false discovery rate <0.05). These results provide valuable insight into the physiological ranges of liver metabolites during dry period and calving in healthy dairy cows and should contribute to the design and interpretation of future metabolite-based studies of the transition dairy cow. [ABSTRACT FROM AUTHOR]

Summary: Fermentation of yellow maize using different inocula yields mahewu products with varying compositions. Comprehensive analysis of the metabolites influencing distinctive characteristics of mahewu from sorghum malt (YMSM); wheat (YMW), malted millet (YMMM) and malted yellow maize (YMYM) inocula was investigated using an untargeted gas chromatography high‐resolution time‐of‐flight mass spectrometry (GC‐HRTOF‐MS)‐based metabolomics. Metabolites in mahewu from different inocula included phenols, fatty acid methyl ester (FAME), benzenes, amides, amines, cyclic compounds, fatty acid ethyl esters (FAEEs), esters, ketones and vitamins which differentiated metabolites identified in raw yellow maize (RYM). Principal component analysis (PCA) showed that the mahewu and related inocula were distinguished across PC1 and PC2. The OPLS‐DA result further intensifies the significant (P ≤ 0.05) metabolite causing variations among samples. This study serves as the first report into the metabolome of yellow maize mahewu from different inocula, serving as a foundation for the quality control of mahewu products for further research. [ABSTRACT FROM AUTHOR]

Abstract Background Geographical factors affect the nutritional, therapeutic and commercial values of fruits. Dragon fruit (Hylocereus spp) is a popular fruit in Asia and a potential functional food with diverse pharmacological attributes. Although it is produced in various localities, the information related to the altitudinal variation of dragon fruit nutrients and active compounds is scarce. Hence, this study aimed to investigate the variations in metabolite profiles of H. polyrhizus (variety Jindu1) fruit pulps from three different altitudes of China, including Wangmo (WM, 650 m), Luodian (LD, 420 m), and Zhenning (ZN, 356 m). Jindu1 is the main cultivated pitaya variety in Guizhou province, China. Results The LC-MS (liquid chromatography-mass spectroscopy)-based widely targeted metabolic profiling identified 645 metabolites, of which flavonoids (22.64%), lipids (13.80%), phenolic acids (12.40%), amino acids and derivatives (10.39%), alkaloids (8.84%), and organic acids (8.37%) were dominant. Multivariate analyses unveiled that the metabolite profiles of the fruit differed regarding the altitude. Fruits from WM (highest altitude) were prime in quality, with higher levels of flavonoids, alkaloids, nucleotides and derivatives, amino acids and derivatives, and vitamins. Fruits from LD and ZN had the highest relative content of phenolic acids and terpenoids, respectively. We identified 69 significantly differentially accumulated metabolites across the pulps of the fruits from the three locations. KEGG analysis revealed that flavone and flavonol biosynthesis and isoflavonoid biosynthesis were the most differentially regulated. It was noteworthy that most active flavonoid compounds exhibited an increasing accumulation pattern along with the increase in altitude. Vitexin and isovitexin were the major differentially accumulated flavonoids. Furthermore, we identified two potential metabolic biomarkers (vitexin and kaempferol 3-O-[2-O-β-D-galactose-6-O-a-L-rhamnose]-β-D-glucoside) to discriminate between dragon fruits from different geographical origins. Conclusion Our findings provide insights into metabolic changes in dragon fruits grown at different altitudes. Furthermore, they show that growing pitaya at high altitudes can produce fruit with higher levels of bioactive compounds, particularly flavonoids.

Abstract Background Fungal endophytes exhibit symbiotic relationships with their host plants but have recently emerged as sources for synthesizing important varieties of secondary metabolites (SMs). Many of these metabolites have shown significant importance as antibacterial, antifungal, antitumor, and anticancer drugs, leading to their exploration in medicine and pharmaceuticals. Main body of the abstract The endophytes' biosynthetic gene clusters (BGCs) are responsible for encoding enzymes that produce these SMs. The fungal endophytes' ability has been challenged due to their inability to trigger cryptic BGCs and their loss of ability to produce secondary metabolites over an extended period in an artificial culture medium. This review investigates the array of SMs produced by endophytic fungi. It identifies methods for awakening and exploiting silent BGCs to produce novel natural metabolites and explores recent advancements in metabolomics platforms used to profile SMs. Silent BGCs can be activated using various methods, including co-cultivation, one strain of many compounds, epigenetic modification, heterologous expression, and cluster-specific transcription factor methods. Short conclusion These methods reviewed effectively enhance the production of silent BGCs, leading to a significant increase in secondary metabolite production. Meanwhile, metabolomics profiling using liquid or gas chromatography coupled with mass spectrometry could provide several chances to discover bioactive compounds' complexity and chemical diversity. This review has, thus, given insight into the significance of methods used to reactivate BGCs from endophytes and the importance of varying techniques of their metabolomic profiling.

The incidence of male infertility (MI) is rising annually. According to epidemiological studies, environmental pollution (e.g., organic, inorganic, and air pollutants), occupational exposure (e.g., high temperature, organic solvents, and pesticides), and poor lifestyle (e.g., diet, sleep, smoking, alcohol consumption, and exercise) are important non‐genetic causative factors of MI. Due to multiple and complex causative factors, the dose–effect relationship, and the uncertainty of pathogenicity, the pathogenesis of MI is far from fully clarified. Recent data show that the pathogenesis of MI can be monitored by the metabolites in serum, seminal plasma, urine, testicular tissue, sperm, and other biological samples. It is considered that these metabolites are closely related to MI phenotypes and can directly reflect the individual pathological and physiological conditions. Therefore, qualitative and quantitative analysis of the metabolome, the related metabolic pathways, and the identification of biomarkers will help to explore the MI‐related metabolic problems and provide valuable insights into its pathogenic mechanisms. Here, we summarized new findings in MI metabolomics biomarkers research and their abnormal metabolic pathways triggered by the presented non‐genetic risk factors, providing a metabolic landscape of semen and seminal plasma in general MI patients. Then, we compared the similarities and differences in semen and seminal plasma biomarkers between MI patients exposed to environmental and poor lifestyle factors and MI patients in general, and summarized some common biomarkers. We provide a better understanding of the biological underpinnings of MI pathogenesis, which might offer novel diagnostic, prognostic, and precise treatment approaches to MI. [ABSTRACT FROM AUTHOR]

Background: Geographical factors affect the nutritional, therapeutic and commercial values of fruits. Dragon fruit (Hylocereus spp) is a popular fruit in Asia and a potential functional food with diverse pharmacological attributes. Although it is produced in various localities, the information related to the altitudinal variation of dragon fruit nutrients and active compounds is scarce. Hence, this study aimed to investigate the variations in metabolite profiles of H. polyrhizus (variety Jindu1) fruit pulps from three different altitudes of China, including Wangmo (WM, 650 m), Luodian (LD, 420 m), and Zhenning (ZN, 356 m). Jindu1 is the main cultivated pitaya variety in Guizhou province, China. Results: The LC-MS (liquid chromatography-mass spectroscopy)-based widely targeted metabolic profiling identified 645 metabolites, of which flavonoids (22.64%), lipids (13.80%), phenolic acids (12.40%), amino acids and derivatives (10.39%), alkaloids (8.84%), and organic acids (8.37%) were dominant. Multivariate analyses unveiled that the metabolite profiles of the fruit differed regarding the altitude. Fruits from WM (highest altitude) were prime in quality, with higher levels of flavonoids, alkaloids, nucleotides and derivatives, amino acids and derivatives, and vitamins. Fruits from LD and ZN had the highest relative content of phenolic acids and terpenoids, respectively. We identified 69 significantly differentially accumulated metabolites across the pulps of the fruits from the three locations. KEGG analysis revealed that flavone and flavonol biosynthesis and isoflavonoid biosynthesis were the most differentially regulated. It was noteworthy that most active flavonoid compounds exhibited an increasing accumulation pattern along with the increase in altitude. Vitexin and isovitexin were the major differentially accumulated flavonoids. Furthermore, we identified two potential metabolic biomarkers (vitexin and kaempferol 3-O-[2-O-β-D-galactose-6-O-a-L-rhamnose]-β-D-glucoside) to discriminate between dragon fruits from different geographical origins. Conclusion: Our findings provide insights into metabolic changes in dragon fruits grown at different altitudes. Furthermore, they show that growing pitaya at high altitudes can produce fruit with higher levels of bioactive compounds, particularly flavonoids. [ABSTRACT FROM AUTHOR]

Background: Fungal endophytes exhibit symbiotic relationships with their host plants but have recently emerged as sources for synthesizing important varieties of secondary metabolites (SMs). Many of these metabolites have shown significant importance as antibacterial, antifungal, antitumor, and anticancer drugs, leading to their exploration in medicine and pharmaceuticals. The endophytes' biosynthetic gene clusters (BGCs) are responsible for encoding enzymes that produce these SMs. The fungal endophytes' ability has been challenged due to their inability to trigger cryptic BGCs and their loss of ability to produce secondary metabolites over an extended period in an artificial culture medium. This review investigates the array of SMs produced by endophytic fungi. It identifies methods for awakening and exploiting silent BGCs to produce novel natural metabolites and explores recent advancements in metabolomics platforms used to profile SMs. Silent BGCs can be activated using various methods, including co-cultivation, one strain of many compounds, epigenetic modification, heterologous expression, and cluster-specific transcription factor methods. Short conclusion: These methods reviewed effectively enhance the production of silent BGCs, leading to a significant increase in secondary metabolite production. Meanwhile, metabolomics profiling using liquid or gas chromatography coupled with mass spectrometry could provide several chances to discover bioactive compounds' complexity and chemical diversity. This review has, thus, given insight into the significance of methods used to reactivate BGCs from endophytes and the importance of varying techniques of their metabolomic profiling. [ABSTRACT FROM AUTHOR]

In traditional Chinese medicine, Aurantii Fructus Immatures (AFIs) have been utilized for more than 2000 years. The proportions of different fruit parts are crucial for evaluating AFI quality in China. However, the basis for this statement's substance is unclear. Differences in quality are intimately correlated with a plant's metabolite composition. On the basis of a widely targeted metabolome, this study intended to investigate the metabolite composition and evaluate the antioxidant capacity of the peel and pulp of an AFI. Metabolites were identified and quantified by UHPLC-QqQ-MS. To assess their antioxidant ability, DPPH and ABTS assays were carried out. There were 1327 chemical compounds identified by UHPLC-QqQ-MS. After screening the differential metabolites using a multivariate statistical analysis, it was found that there were 695 significant differences in the metabolites between the peel and the pulp. Among them, it was discovered that the content of active ingredients in the peel group was higher than that in the pulp group. Furthermore, the aqueous extracts from the peel showed stronger antioxidant capacities than those from the pulp. The metabolites and antioxidant capacities were significantly different between the peel and the pulp. This study of different fruit parts might provide a guide for AFI quality assessments. [ABSTRACT FROM AUTHOR]

Owing to its high nutritional content of protein, oil, fatty acids, and sugars, soybean (Glycine max L.), one of the most significant legume crops, is utilized worldwide as food, feed, and fuel for daily life applications. The seeds, leaves, branches, roots, and pods of soybean contain essential bioactive compounds, including flavonoids, isoflavonoids, and other specialized metabolites, that play important roles in plant growth, development, and stress responses. In recent years, significant progress has been made in increasing soybean production. Therefore, here, we summarize the most recent breakthroughs in metabolite profiling and bioactive compound identification in soybeans to inform future digital breeding approaches. In addition to classical metabolite investigations, the discovery of metabolites involved in the dehydration response was made through a recent study that examined the regulatory network of metabolites and plant hormone genes. This review aimed to provide a metabolic perspective on soybeans that will benefit soybean production. The findings of this review will facilitate the development of novel soybean cultivars containing highly valuable metabolites for digital breeding. [ABSTRACT FROM AUTHOR]

FLH 13-11 is an F1 interspecific hybrid muscadine grape genotype that was developed to produce new anthocyanins for pigment color stability. This hybrid resulted from a cross between 'Marsh' (Vitis munsoniana) and 'Magoon' (V. rotundifolia) and has been cultivated for the wine and juice industry. This report characterizes anthocyanins produced in fully ripe berries and reveals a significant difference in total anthocyanin contents from two continuous cropping seasons. High-performance liquid chromatography with a diode array detector (HPLC-DAD) and HPLC–quadrupole time-of-flight tandem mass spectrometry (HPLC-qTOF-MS/MS) were used to profile anthocyanins in berries. The resulting data showed that fourteen anthocyanins were detected, six from 2011 and nine from 2012, with only one produced in both seasons. However, the anthocyanidin profiles of the berries were the same. Five anthocyanins were annotated as diglucosides of anthocyanidins based on MS/MS features, including delphinidin 3,5-diglucoside produced in both seasons, cyanidin 3,5-diglucoside mainly formed in 2011, petunidin 3,5-diglucoside, malvidin 3,5-diglucoside, and peonidin 3,5-glucoside only detected in 2012. Also, three anthocyanidin-diglucoside-like anthocyanins and three monoglucosides, including peonidin 3-glucoside, delphinidin 3-glucoside like, and pelargonidin 3-glucoside-like anthocyanins, were detected in 2011 and 2012, respectively. These results indicate that FLH 13-11 can produce both anthocyanidin-diglucosides and -monoglucosides, and their biosynthesis is closely dependent on cropping years. [ABSTRACT FROM AUTHOR]

Objective: Tumor cells can acquire a large amount of energy and structural components by reprogramming energy metabolism; moreover, metabolic profiles slightly differ according to cancer type. This study compared and assessed the metabolic profile of head and neck squamous cell carcinoma (HNSCC) and normal tissues, which were collected from patients without cancer. Subjects and Methods: Overall, 23 patients with HNSCC and 6 patients without cancer were included in the analysis. Metabolomic profiles were analyzed using capillary electrophoresis‐mass spectrometry. Gene expression was evaluated using real‐time reverse transcription‐polymerase chain reaction. Results: Glycolysis, the pentose phosphate pathway, tricarboxylic acid cycle, and glutamine metabolism were upregulated in HNSCC tissues based on gene expression analysis. HNSCC could then have enhanced energy production and structural component. The levels of lactate, succinate, glutathione, 2‐hydroxyglutarate, and S‐adenosylmethionine, considered as oncometabolites, increased and these had accumulated in HNSCC tissues. Conclusions: The level of metabolites and the expression of enzymes differ between HNSCC and normal tissues. Reprogramming metabolism in HNSCC provides an energy source as well as structural components, creating a system that offers rapid proliferation, progression, and is less likely to be eliminated. [ABSTRACT FROM AUTHOR]

Background: Ilexsaponin A1 (IA1) is a bioactive triterpene saponin derived from natural medicinal plants. IA1 exhibits anti-inflammatory and proangiogenic activities and improves intestinal barrier function. It has been reported that IA1 could be metabolized into a dominant metabolite, ilexgenin A (IA) by β-glucosidase enzymes in intestinal microflora. Materials and Methods: Herein, an accurate, sensitive, and selective method based on ultra-performance liquid chromatography coupled with mass spectrometry was established to simultaneously profile the metabolism and pharmacokinetic behaviors of IA1 in normal and antibiotic-treated rat plasma after intragastric administration of IA1. The precursor-to-product ion pairs of IA and IA1 were m / z 501.32↓439.32 and m / z 663.38↓501.32, respectively. For method validation, the specificity, matrix effect, accuracy, precision, and stability of the pharmacokinetic study were measured, and a calibration curve was created. The collaborative pharmacological target pathways of IA1 and its metabolite IA were investigated using network pharmacology tools. Results: The validated analytical method was successfully utilized to investigate the pharmacokinetics of IA1 in normal and antibiotic-treated rats. The bioavailability of IA1 and conversion from IA1 to IA were significantly inhibited by antibiotic-treated rats after oral administration of IA1. Fragment ions at m/z 483.3155, 455.3159, 439.3233, 421.3136, 395.3362, 152.9952, 113.0256, and 71.0531 were characteristic of the IA1 moiety. IA1 was metabolized in rat plasma by biotransformation routes involving deglycosylation, decarboxylation, isomerization, hydrogenation, dehydrogenation, and oxidation. Considering database analysis, IA and IA1 play synergistic role in common pharmacological pathways, such as hypertrophic cardiomyopathy and dilated cardiomyopathy. Conclusion: The experiments illustrated that β-glucosidase activity inhibited by antibiotics suppressed the hydrolysis reaction of IA1 in the intestinal tract. IA1 and IA play a synergistic role in exerting effects. [ABSTRACT FROM AUTHOR]

This study used two types of analyses and statistical calculations on powdered samples of Polygala root (PR) and Senega root (SR): (1) determination of saponin content by an independently developed quantitative analysis of tenuifolin content using a flow reactor, and (2) near-infrared spectroscopy (NIR) using crude drug powders as direct samples for metabolic profiling. Furthermore, a prediction model for tenuifolin content was developed and validated using multivariate analysis based on the results of (1) and (2). The goal of this study was to develop a rapid analytical method utilizing the saponin content and explore the possibility of quality control through a wide-area survey of crude drugs using NIR spectroscopy. Consequently, various parameters and appropriate wavelengths were examined in the regression analysis, and a model with a reasonable contribution rate and prediction accuracy was successfully developed. In this case, the wavenumber contributing to the model was consistent with that of tenuifolin, confirming that this model was based on saponin content. In this series of analyses, we have succeeded in developing a model that can quickly estimate saponin content without post-processing and have demonstrated a brief way to perform quality control of crude drugs in the clinical field and on the market. [ABSTRACT FROM AUTHOR]

The genus Rosa is globally popular with well-established applications since it has a high edible and medicinal value. However, relatively limited research has been conducted on the composition and quality of wild Rosa fruits. The present study aimed to compare the properties and chemical components of five wild edible Rosa fruits, Rosa roxburghii, Rosa sterilis, Rosa laevigata, Rosa davurica, and Rosa sericea. The UPLC-ESI-MS/MS approach identified the key metabolites among the five Rosa fruits as flavonoids, phenolic acids, and organic acids. The main differential metabolites among the five fruits are flavonoids (22.29–45.13%), phenolic acids (17–22.27%), and terpenoids (7.7–24%), respectively. In total, 125 compounds served as potential markers for the five Rosa species. Differential metabolic pathways of five Rosa fruits were analyzed using the KEGG approach. Rosa laevigata fruits showed the highest total polysaccharide (TPS) content of 64.48 g/100 g. All the five Rosa extracts effectively decreased the levels of malondialdehyde while increasing the activities of superoxide dismutase and glutathione peroxidase in the H2O2-induced HaCaT cell model, demonstrating high potential for antioxidant development. Our findings suggest that the five studied Rosa fruits exhibit biological activity and edible value worth further exploration. [ABSTRACT FROM AUTHOR]

Objective: This study set out to examine the phenylpropanoid pathway gene expression and phenolic compound accumulation in different organs of Chelidonium majus (C. majus). Methods: Total RNA was extracted and expression of phenylpropanoid biosynthesis genes was assessed using quantitative real-time polymerase chain reaction in different organs of C. majus. In addition, the phenylpropanoid compounds were analyzed from different organs of C. majus by using high-performance liquid chromatography. Results: The results demonstrate the variance in the expression levels of phenylpropanoid pathway genes in the flowers, leaves, stems, and roots of C. majus. CmPAL and CmC4H were expressed at their greatest levels in the stem, while CmCHS and CmCHI were strongly expressed in the leaf, and CmF3H, CmFLS, Cm4CL, and CmDFR were more abundant in the flower. The total phenolic contents in the different organs also varied significantly. The highest value was recorded in the flowers (2152.89 ± 78.71 µg/g dry wt.), which was 54.26 times higher than the lowest values obtained from roots (39.68 ± 0.05 µg/g dry wt.). Except for roots, rutin showed the highest level in all other organs. According to a heat map, the majority of the phenolic compounds were highest in the flower. By using variable importance in projection analysis, the most significant metabolite was found to be chlorogenic acid, which had a positive association with all phenolic chemicals, but it showed a negative correlation with trans-cinnamic acid. Except for trans-cinnamic acid, all other phenolic compounds likewise showed positive correlation with other phenolic compounds. Conclusions: This work offers pertinent data on the expression analysis of genes involved in the phenylpropanoid biosynthetic pathway and the presence of phenolic compounds in C. majus. These findings will be helpful for the researcher to understand the relationship between the expression level of phenylpropanoid pathway genes and phenylpropanoid compound accumulation in C. majus. [ABSTRACT FROM AUTHOR]

With 64,050 new diagnoses and 50,550 deaths in the US in 2023, pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of all human malignancies. Early detection and improved prognostication remain critical unmet needs. We applied next-generation metabolomics, using quantitative tandem mass spectrometry on plasma, to develop biochemical signatures that identify PDAC. We first compared plasma from 10 PDAC patients to 169 samples from healthy controls. Using metabolomic algorithms and machine learning, we identified ratios that incorporate amino acids, biogenic amines, lysophosphatidylcholines, phosphatidylcholines and acylcarnitines that distinguished PDAC from normal controls. A confirmatory analysis then applied the algorithms to 30 PDACs compared with 60 age- and sex-matched controls. Metabolic signatures were then analyzed to compare survival, measured in months, from date of diagnosis to date of death that identified metabolite ratios that stratified PDACs into distinct survival groups. The results suggest that metabolic signatures could provide PDAC diagnoses earlier than tumor markers or radiographic measures and offer insights into disease severity that could allow more judicious use of therapy by stratifying patients into metabolic-risk subgroups. [ABSTRACT FROM AUTHOR]

Glyphosate is the most widely used herbicide and works by inhibiting the enzyme 5-enolpyruvylshikimate 3-phosphate synthase (EPSPS) of the shikimate pathway, preventing the aromatic amino acid biosynthesis. When applied to plants, it provokes the accumulation of quinate, a metabolite synthesized through a side branch of the shikimate pathway. The joint application of glyphosate and quinate enhanced glyphosate efficacy on Amaranthus palmeri, requiring one-quarter of the recommended dose of glyphosate for complete control. Expression of the genes of the shikimate pathway and non-targeted GC-MS metabolic profiling were conducted to compare the physiological response after glyphosate, quinate or the combination of both. A perturbed gene expression of the shikimate pathway was detected after quinate applied alone, while no relevant changes in the metabolome were detected. The sub-lethal glyphosate treatment induced gene expression in the shikimate pathway, accumulation of the metabolites located upstream EPSPS and disturbances in the amino acid content. The exacerbation of the phytotoxicity in the lethal combined treatment was not related to any specific change in the expression level of the shikimate pathway. Metabolic profiling indicated that the accumulation of quinate and quinate derivatives detected after quinate applied alone was severely enhanced after the combined treatment of quinate and glyphosate.

Nutraceuticals have gained increasing interest, prompting the need to investigate plant extracts for their beneficial properties and potential side effects. This study aimed to assess the nutraceutical effects of environmentally clean extracts from Rosmarinus officinalis and Gongolaria abies-marina (formerly Cystoseira abies-marina (Phaeophyceae)) on the metabolic profile of streptozotocin-induced diabetic rats. We conducted untargeted LC-QTOF-MS metabolic profiling on six groups of rats: three diabetic groups receiving either a placebo, R. officinalis, or G. abies-marina extracts, and three corresponding control groups. The metabolic analysis revealed significant alterations in the levels of various glycerophospholipids, sterol lipids, and fatty acyls. Both extracts influenced the metabolic profile, partially mitigating diabetes-induced changes. Notably, G. abies-marina extract had a more pronounced impact on the animals' metabolic profiles compared to R. officinalis. In conclusion, our findings suggest that environmentally clean extracts from R. officinalis and G. abies-marina possess nutraceutical potential, as they were able to modulate the metabolic profile in streptozotocin-induced diabetic rats. G. abies-marina extract exhibited a more substantial effect on metabolic alterations induced by diabetes compared to R. officinalis. These results warrant further exploration of these plant extracts for their potential in managing diabetes-related metabolic disturbances.

Mitochondrial malate dehydrogenase 2 (MDH2) is crucial to cellular energy generation through direct participation in the tricarboxylic acid (TCA) cycle and the malate aspartate shuttle (MAS). Inherited MDH2 deficiency is an ultra-rare metabolic disease caused by bi-allelic pathogenic variants in the MDH2 gene, resulting in early-onset encephalopathy, psychomotor delay, muscular hypotonia and frequent seizures. Currently, there is no cure for this devastating disease. We recently reported symptomatic improvement of a three-year-old girl with MDH2 deficiency following treatment with the triglyceride triheptanoin. Here, we aimed to better characterize this disease and improve our understanding of the potential utility of triheptanoin treatment. Using fibroblasts derived from this patient, we generated induced pluripotent stem cells (hiPSCs) and differentiated them into hepatocytes (hiPSC-Heps). Characterization of patient-derived hiPSCs and hiPSC-Heps revealed significantly reduced MDH2 protein expression. Untargeted proteotyping of hiPSC-Heps revealed global dysregulation of mitochondrial proteins, including upregulation of TCA cycle and fatty acid oxidation enzymes. Metabolomic profiling confirmed TCA cycle and MAS dysregulation, and demonstrated normalization of malate, fumarate and aspartate following treatment with the triheptanoin components glycerol and heptanoate. Taken together, our results provide the first patient-derived hiPSC-Hep-based model of MDH2 deficiency, confirm altered TCA cycle function, and provide further evidence for the implementation of triheptanoin therapy for this ultra-rare disease. Synopsis: This study reveals altered expression of mitochondrial pathways including the tricarboxylic acid cycle and changes in metabolite profiles in malate dehydrogenase 2 deficiency and provides the molecular basis for triheptanoin treatment in this ultra-rare disease.

Abstract Background With the increasing consumer awareness of the strong relationship between food and health, flax became a promising functional food due to its bioactive nutraceutical composition. Intra-specific crosses of eight contrasting flax genotypes were performed previously, and within segregating F6 progeny families, we investigated a close-up composition of phytochemicals derived from whole seeds. Results The considerable genetic variation among the flax F6 families suggested that intra-specific hybridization is essential in flax breeding to obtain and broaden genetic variability and largely affirmed the opportunity for selecting promising lines. Also, significant variations in the targeted metabolite contents and antioxidant properties were observed among brown and yellow-seeded families. Notably, brown-seeded families expressed the highest average values of saturated fatty acids, protein, fiber, tocopherol, phenolics, SDG, and SECO lignans. Yellow-seeded families represented the highest average content of unsaturated fatty acids and mucilage. The cultivation year significantly affects flaxseed’s composition and functional properties, presumably due to temperature, humidity, and sunshine time differences. Interestingly, the seeds obtained in warmer conditions were more potent and had more chemical constituents. The favorable genetic correlations among all evaluated traits suggest the possibility of joint genetic selection for several nutritional and phytochemical characteristics in flax. The current study highlights the importance and utilization of 19 top families as their seeds and oil play imperative roles in the pharmaceuticals and food industries. The antioxidant capacity of the seeds showed that families 84B, 23B, 35Y, 95Y, 30B, 88B, and 78B serve as a natural source of dietary antioxidants beneficial to human health. To increase the oxidative stability of the flaxseed oil, the quality evaluation identified some families with low levels of linolenic acid. Conclusions These findings are essential to improving flaxseed’s nutritional quality and therapeutic properties through a bulk breeding program.

Abstract Background Genome streamlining, the process by which genomes become smaller and encode fewer genes over time, is a common phenomenon among pathogenic bacteria. This reduction is driven by selection for minimized energy expenditure in a nutrient-rich environment. As pathogens evolve to become more reliant on the host, metabolic genes and resulting capabilities are lost in favor of siphoning metabolites from the host. Characterizing genome streamlining, gene loss, and metabolic pathway degradation can be useful in assessing pathogen dependency on host metabolism and identifying potential targets for host-directed therapeutics. Results PoMeLo (Predictor of M etabolic L oss) is a novel evolutionary genomics-guided computational approach for identifying metabolic gaps in the genomes of pathogenic bacteria. PoMeLo leverages a centralized public database of high-quality genomes and annotations and allows the user to compare an unlimited number of genomes across individual genes and pathways. PoMeLo runs locally using user-friendly prompts in a matter of minutes and generates tabular and visual outputs for users to compare predicted metabolic capacity between groups of bacteria and individual species. Each pathway is assigned a Predicted Metabolic Loss (PML) score to assess the magnitude of genome streamlining. Optionally, PoMeLo places the results in an evolutionary context by including phylogenetic relationships in visual outputs. It can also initially compute phylogenetically-weighted mean genome sizes to identify genome streamlining events. Here, we describe PoMeLo and demonstrate its use in identifying metabolic gaps in genomes of pathogenic Treponema species. Conclusions PoMeLo represents an advance over existing methods for identifying metabolic gaps in genomic data, allowing comparison across large numbers of genomes and placing the resulting data in a phylogenetic context. PoMeLo is freely available for academic and non-academic use at https://github.com/czbiohub-sf/pomelo .

Abstract Background Metabolites play critical roles in regulating nutritional qualities of plants, thereby influencing their consumption and human health. However, the genetic basis underlying the metabolite-based nutrient quality and domestication of root and tuber crops remain largely unknown. Results We report a comprehensive study combining metabolic and phenotypic genome-wide association studies to dissect the genetic basis of metabolites in the storage root (SR) of cassava. We quantify 2,980 metabolic features in 299 cultivated cassava accessions. We detect 18,218 significant marker-metabolite associations via metabolic genome-wide association mapping and identify 12 candidate genes responsible for the levels of metabolites that are of potential nutritional importance. Me3GT, MeMYB4, and UGT85K4/UGT85K5, which are involved in flavone, anthocyanin, and cyanogenic glucoside metabolism, respectively, are functionally validated through in vitro enzyme assays and in vivo gene silencing analyses. We identify a cluster of cyanogenic glucoside biosynthesis genes, among which CYP79D1, CYP71E7b, and UGT85K5 are highly co-expressed and their allelic combination contributes to low linamarin content. We find MeMYB4 is responsible for variations in cyanidin 3-O-glucoside and delphinidin 3-O-rutinoside contents, thus controlling SR endothelium color. We find human selection affects quercetin 3-O-glucoside content and SR weight per plant. The candidate gene MeFLS1 is subject to selection during cassava domestication, leading to decreased quercetin 3-O-glucoside content and thus increased SR weight per plant. Conclusions These findings reveal the genetic basis of cassava SR metabolome variation, establish a linkage between metabolites and agronomic traits, and offer useful resources for genetically improving the nutrition of cassava and other root crops.

Abstract This work compared the metabolic profile of a parental MDA-MB-231 cisplatin-sensitive triple negative breast cancer (TNBC) cell line with that of a derived cisplatin-resistant line, to characterize inherent metabolic adaptations to resistance, as a means for marker and new TNBC therapies discovery. Supported by cytotoxic, microscopic and biochemical characterization of both lines, Nuclear Magnetic Resonance (NMR) metabolomics was employed to characterize cell polar extracts for the two cell lines, as a function of time (0, 24 and 48 h), and identify statistically relevant differences both between sensitive and resistant cells and their time course behavior. Biochemical results revealed a slight increase in activation of the NF-κB pathway and a marked decrease of the ERK signaling pathway in resistant cells. This was accompanied by lower glycolytic and glutaminolytic activities, possibly linked to glutamine being required to increase stemness capacity and, hence, higher survival to cisplatin. The TCA cycle dynamics seemed to be time-dependent, with an apparent activation at 48 h preferentially supported by anaplerotic aromatic amino acids, leucine and lysine. A distinct behavior of leucine, compared to the other branched-chain-amino-acids, suggested the importance of the recognized relationship between leucine and in mTOR-mediated autophagy to increase resistance. Suggested markers of MDA-MB-231 TNBC cisplatin-resistance included higher phosphocreatine/creatine ratios, hypotaurine/taurine–mediated antioxidant protective mechanisms, a generalized marked depletion in nucleotides/nucleosides, and a distinctive pattern of choline compounds. Although the putative hypotheses generated here require biological demonstration, they pave the way to the use of metabolites as markers of cisplatin-resistance in TNBC and as guidance to develop therapies.

Wampee (Clausena lansium (Lour.) Skeels) has natural bioactive components with diverse health benefits, but its detailed metabolism and tissue distribution are not fully understood. Here, widely targeted metabolomics analysis methods were employed to analyze the wampee fruit (peel, pulp, and seed) of 17 different varieties. A total of 1286 metabolites were annotated, including lipids, flavonoids, polyphenols, carbazole alkaloids, coumarins, and organic acids, among others. The quantitative analysis and matrix-assisted laser desorption/ionization–mass spectrometry imaging (MALDI-MSI) analysis indicated remarkable variations in metabolite categories and content in the peel, pulp, and seed of wampee fruit. Additionally, the difference analysis found that the metabolic components of peel contributed dominantly to the differences among varieties, and 7 potential biomarkers were identified. In this study, a comprehensive metabolome landscape of wampee fruit was established, which provided important information for the isolation and identification of functional components, food industry application, and nutritional improvement breeding.

Liraglutide, a glucagon-like peptide-1 receptor agonist, is effective in the treatment of type 2 diabetes mellitus (T2DM) and obesity. Despite its benefits, including improved glycemic control and weight loss, the common metabolic changes induced by liraglutide and correlations between those in rodents and humans remain unknown. Here, we used advanced machine learning techniques to analyze the plasma metabolomic data in diet-induced obese (DIO) mice and patients with T2DM treated with liraglutide. Among the machine learning models, Support Vector Machine was the most suitable for DIO mice, and Gradient Boosting was the most suitable for patients with T2DM. Through the cross-evaluation of machine learning models, we found that liraglutide promotes metabolic shifts and interspecies correlations in these shifts between DIO mice and patients with T2DM. Our comparative analysis helped identify metabolic correlations influenced by liraglutide between humans and rodents and may guide future therapeutic strategies for T2DM and obesity.

Background: Neolamarckia cadamba (Rubiaceae) is a well-recognized medicinal plant with recorded therapeutical attributes. However, a thorough assessment of active compounds in its fruits is lacking, limiting their use and valorization in pharmacological industries. Methods: Thus, this study investigated variations in the fruits’ secondary metabolite (SM) profiles, as well as antioxidant activities in aqueous (WA) and ethanol (ET) extracts. Results: Liquid chromatography–electrospray ionization tandem mass spectrometry identified 541 SMs, of which 14 and 1 (di-O-glucosylquinic acid) were specifically detected in ET and WA, respectively. Phenolic acids (36.97%), flavonoids (28.10%), terpenoids (12.20%), and alkaloids (9.98%) were the dominant SMs. The SM profiles of the fruits in WA and ET were quite different. We revealed 198 differentially extracted (DE) metabolites between WA and ET, including 62 flavonoids, 57 phenolic acids, 45 terpenoids, 14 alkaloids, etc. Most DE flavones (36 out of 40), terpenoids (45 out of 45), and alkaloids (12 out of 14) had higher content in ET. Catechin and its derivatives, procyanidins, and tannins had higher content in WA. ABTS and DPPH assays showed that the antioxidant activity of ET was significantly higher than that of WA. Conclusions: Our findings will facilitate the efficient extraction and evaluation of specific active compounds in N. cadamba.

Due to their immediate exhalation after generation at the cellular/microbiome levels, exhaled volatile organic compounds (VOCs) may provide real-time information on pathophysiological mechanisms and the host response to infection. In recent years, the metabolic profiling of the most frequent respiratory infections has gained interest as it holds potential for the early, non-invasive detection of pathogens and the monitoring of disease progression and the response to therapy. Using previously unpublished data, randomly selected individuals from a COVID-19 test center were included in the study. Based on multiplex PCR results (non-SARS-CoV-2 respiratory pathogens), the breath profiles of 479 subjects with the presence or absence of flu-like symptoms were obtained using proton-transfer-reaction time-of-flight mass spectrometry. Among 223 individuals, one respiratory pathogen was detected in 171 cases, and more than one pathogen in 52 cases. A total of 256 subjects had negative PCR test results and had no symptoms. The exhaled VOC profiles were affected by the presence of Haemophilus influenzae, Streptococcus pneumoniae, and Rhinovirus. The endogenous ketone, short-chain fatty acid, organosulfur, aldehyde, and terpene concentrations changed, but only a few compounds exhibited concentration changes above inter-individual physiological variations. Based on the VOC origins, the observed concentration changes may be attributed to oxidative stress and antioxidative defense, energy metabolism, systemic microbial immune homeostasis, and inflammation. In contrast to previous studies with pre-selected patient groups, the results of this study demonstrate the broad inter-individual variations in VOC profiles in real-life screening conditions. As no unique infection markers exist, only concentration changes clearly above the mentioned variations can be regarded as indicative of infection or colonization. [ABSTRACT FROM AUTHOR]

Background: Genome streamlining, the process by which genomes become smaller and encode fewer genes over time, is a common phenomenon among pathogenic bacteria. This reduction is driven by selection for minimized energy expenditure in a nutrient-rich environment. As pathogens evolve to become more reliant on the host, metabolic genes and resulting capabilities are lost in favor of siphoning metabolites from the host. Characterizing genome streamlining, gene loss, and metabolic pathway degradation can be useful in assessing pathogen dependency on host metabolism and identifying potential targets for host-directed therapeutics. Results: PoMeLo (Predictor of Metabolic Loss) is a novel evolutionary genomics-guided computational approach for identifying metabolic gaps in the genomes of pathogenic bacteria. PoMeLo leverages a centralized public database of high-quality genomes and annotations and allows the user to compare an unlimited number of genomes across individual genes and pathways. PoMeLo runs locally using user-friendly prompts in a matter of minutes and generates tabular and visual outputs for users to compare predicted metabolic capacity between groups of bacteria and individual species. Each pathway is assigned a Predicted Metabolic Loss (PML) score to assess the magnitude of genome streamlining. Optionally, PoMeLo places the results in an evolutionary context by including phylogenetic relationships in visual outputs. It can also initially compute phylogenetically-weighted mean genome sizes to identify genome streamlining events. Here, we describe PoMeLo and demonstrate its use in identifying metabolic gaps in genomes of pathogenic Treponema species. Conclusions: PoMeLo represents an advance over existing methods for identifying metabolic gaps in genomic data, allowing comparison across large numbers of genomes and placing the resulting data in a phylogenetic context. PoMeLo is freely available for academic and non-academic use at https://github.com/czbiohub-sf/pomelo. [ABSTRACT FROM AUTHOR]

Background: With the increasing consumer awareness of the strong relationship between food and health, flax became a promising functional food due to its bioactive nutraceutical composition. Intra-specific crosses of eight contrasting flax genotypes were performed previously, and within segregating F6 progeny families, we investigated a close-up composition of phytochemicals derived from whole seeds. Results: The considerable genetic variation among the flax F6 families suggested that intra-specific hybridization is essential in flax breeding to obtain and broaden genetic variability and largely affirmed the opportunity for selecting promising lines. Also, significant variations in the targeted metabolite contents and antioxidant properties were observed among brown and yellow-seeded families. Notably, brown-seeded families expressed the highest average values of saturated fatty acids, protein, fiber, tocopherol, phenolics, SDG, and SECO lignans. Yellow-seeded families represented the highest average content of unsaturated fatty acids and mucilage. The cultivation year significantly affects flaxseed's composition and functional properties, presumably due to temperature, humidity, and sunshine time differences. Interestingly, the seeds obtained in warmer conditions were more potent and had more chemical constituents. The favorable genetic correlations among all evaluated traits suggest the possibility of joint genetic selection for several nutritional and phytochemical characteristics in flax. The current study highlights the importance and utilization of 19 top families as their seeds and oil play imperative roles in the pharmaceuticals and food industries. The antioxidant capacity of the seeds showed that families 84B, 23B, 35Y, 95Y, 30B, 88B, and 78B serve as a natural source of dietary antioxidants beneficial to human health. To increase the oxidative stability of the flaxseed oil, the quality evaluation identified some families with low levels of linolenic acid. Conclusions: These findings are essential to improving flaxseed's nutritional quality and therapeutic properties through a bulk breeding program. [ABSTRACT FROM AUTHOR]

Piriformospora indica is an important endophytic fungus with broad potential for alleviating biotic and abiotic stress on host plants. This study monitored the growth dynamics of P. indica on five commonly used artificial media for microorganisms and analyzed its metabolic characteristics using Biolog Phenotype Microarray (PM) technology. The results showed that P. indica grew fastest on Potato Dextrose Agar (PDA), followed by Kidney Bean Agar (KBA), Alkyl Ester Agar (AEA), Oatmeal Agar (OA), and Luria-Bertani Agar (LB), and the most suitable medium for spore production was OA. Using Biolog PM1-10, 950 metabolic phenotypes of P. indica were obtained. P. indica could metabolize 87.89% of the tested carbon sources, 87.63% of the tested nitrogen sources, 96.61% of the tested phosphorus sources, and 100% of the tested sulfur sources. P. indica displayed 92 kinds of tested biosynthetic pathways, and it could grow under 92 kinds of tested osmotic pressures and 88 kinds of tested pH conditions. PM plates 1-2 revealed 43 efficient carbon sources, including M-Hydroxyphenyl acid, N-Acetyl-D-Glucosamine, Tyramine, Maltotrios, α-D-Glucosine, I-Erythritol, L-Valine, D-Melezitose, D-Tagatose, and Turanose. PM plates 3,6-8 indicated 170 efficient nitrogen sources, including Adenosine, Inosine Allantoin, D, L-Lactamide, Arg-Met, lle-Trp, Ala-Arg, Thr-Arg, Trp-Tyr, Val-Asn, Gly-Gly-D-Leu, Gly-Gly-Phe, and Leu-Leu-Leu. This study demonstrates that P. indica can metabolize a variety of substrates, such as carbon and nitrogen sources, and has a wide range of environmental adaptability. The growth dynamics on artificial culturemedia andmetabolic phenotypes of P. indica can be used to investigate its biological characteristics, screen for more suitable growth and sporulation conditions, and elucidate the physiological mechanisms that enhance the stress resistance of host plants. This study provides a theoretical basis for its better application in agriculture. [ABSTRACT FROM AUTHOR]

The ability of bacteria to efficiently remove phenolic pollutants depends on their genetic makeup and environmental conditions. This study examined a novel strain, Pseudomonas aeruginosa STV1713, for degrading higher concentrations of phenol and 2,4-dichlorophenol. After optimization, a combination of degradation parameters, such as pH (7.0), temperature (32.5 °C), and ammonium nitrate concentration (0.7 g/L), was found to reduce degradation time while promoting cell growth. Under these optimal conditions, the bacterium effectively degraded up to 2000 mg/L of phenol and 1400 mg/L of 2,4-dichlorophenol, while maximum tolerance was observed till 2100 mg/L and 1500 mg/L, respectively. Metabolic profiling identified crucial metabolites in the ortho-degradation pathway during pollutant removal. Additionally, transcriptome analysis revealed that P. aeruginosa STV1713 utilizes different branches of the beta ketoadipate pathway for phenol and 2,4-DCP removal. Moreover, under high pollutant stress, the bacterium survived through differential gene expression in ribosome biogenesis, chemotaxis, membrane transport, and other pathways. [ABSTRACT FROM AUTHOR]