Class Of Metabolites Research Articles

Differential in vitro cytotoxic effects and metabolomic insights into raw and powdered Manuka honey through UPLC-Q-TOF-MS

Manuka honey (MH) has garnered much attention due to its remarkable antimicrobial, anticancer, immunomodulatory and wound-healing properties. This study compared the antiproliferative effects of raw and powdered MH (pMH) on various human and murine cancer cell lines. A detailed metabolomics analysis was also carried out using untargeted ultrahigh-performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry (UPLC-Q-TOF-MS) to compare the constituents in raw MH and pMH. The results of the viability studies showed that both raw MH and pMH caused a dose-dependent inhibition of tumor cell growth at concentrations of > 1% w/v (equivalent to ~ 10 mg/ml). A differential susceptibility to MH was observed among the cell lines with the human MDA-MB-231 and A549 cells and murine B16.F10 cells being relatively resistant to MH while the murine MC38 colorectal adeno-carcinoma cells showing the most sensitivity. The effect of raw MH and pMH on cell viability was validated using 2 indepndent assays. Metabolomics analysis detected 2440 compounds, out of which 833 were successfully identified. Among these, 90 phytochemical compounds, predominantly comprising terpenoids, flavonoids, coumarins and derivatives, and phenylpropanoic acids, and 79 lipids were identifiable. Significant differences in 5 metabolite classes, including flavonoids, phenols, terpenoids, carbohydrates, and organic acids were observed between the raw and pMH. Moreover, several altered metabolic pathways were identified in pMH compared to raw MH, such as energy metabolism, amino acid metabolism, and various other pathways that collectively influence biological functions associated with cellular growth, signaling, and stress response.

Diversity of African fungi, chemical constituents and biological activities

Besides plants and animals, the fungal kingdom consists of several species characterized by various forms and applications. Fungi are amazing producers of bioactive natural products with applications in medicine and agriculture. Though this kingdom has been extensively investigated worldwide, it remains relatively underexplored in Africa. To address the knowledge gaps, encourage research interest, and suggest opportunities for the discovery of more bioactive substances from African fungi, we considered it appropriate to extensively review the research work carried out on African fungi since 1988. This review summarizes the diversity and distribution of fungi throughout Africa, the secondary metabolites yet reported from studied fungi, their biological activities and, the countries where they were collected. The studied fungi originated from eleven African countries and were mainly endophytic fungi and higher fungi (macrofungi). Their investigation led to the isolation of five hundred and three (503) compounds with polyketides representing the main class of secondary metabolites. The compounds exhibited varied biological activities with antibacterial and antiproliferative properties being the most prominent.

The Production of Useful Phenol Compounds with Antioxidant Potential in Gametophytes and Sporophytes from In Vitro Cultures in Four Ornamental Ferns Species

Ferns are vascular plants with significant ornamental value, and in recent years, they have also been considered for the potential application in different economic sectors like nutrition, medicine and cosmetics. This study aimed to obtain in vitro fern gametophytes and sporophytes and evaluate their potential as secondary metabolites sources. For this study four fern species were used: Polypodium vulgare L. (PV), Asplenium trichomanes L. (AT), Athyrium filix-femina L. Roth (AF), and Osmunda regalis L. (OR). The polyphenols, flavonoids, tannins and terpenoids content and antioxidant activity were estimated by different colorimetric methods. For metabolite identification and their antioxidant activity, HP-TLC separations were used. Also, quantitative HPLC–DAD analysis was performed to estimate the content of certain metabolites. The results showed that in vitro generation of gametophytes registered higher growth rates in OR, PV, and AF, while the regeneration of sporophytes was better for PV, AT, and AF. The OR gametophyte produced the highest quantities in all analyzed metabolite classes and also had the highest antioxidant values. We report for the first time the presence of metabolites such as catechin, caffeic acid, gallic acid, ferulic acid, cinnamic acid, or rutin in OR. In this study, we demonstrated the possibility of producing potent antioxidant metabolites by in vitro cultures in ferns.

Metabolic profiling and biomarkers identification in cluster bean under drought stress using GC-MS technique.

The Cluster bean is an economically significant annual legume, widely known as guar. Plant productivity is frequently constrained by drought conditions. In this work, we have identified the untargeted drought stress-responsive metabolites in mature leaves of cluster beans under drought and control condition. To analyse the untargeted metabolites, gas chromatography-mass spectrometry (GC-MS) technique was used. Supervised partial least-squares discriminate analysis and heat map were used to identify the most significant metabolites for drought tolerance. The mature leaves of drought-treated C. tetragonoloba cv. 'HG-365' which is a drought-tolerant cultivar, showed various types of amino acids, fatty acids, sugar alcohols and sugars as the major classes of metabolites recognized by GC-MS metabolome analysis. Metabolite profiling of guar leaves showed 23 altered metabolites. Eight metabolites (proline, valine, D-pinitol, palmitic acid, dodecanoic acid, threonine, glucose, and glycerol monostearate) with VIP score greater than one were considered as biomarkers and three metabolite biomarkers (D-pinitol, valine, and glycerol monostearate) were found for the first time in guar under drought stress. In this work, four amino acids (alanine, valine, serine and aspartic acid) were also studied, which played a significant role in drought-tolerant pathway in guar. This study provides information on the first-ever GC-MS metabolic profiling of guar. This work gives in-depth details on guar's untargeted drought-responsive metabolites and biomarkers, which can plausibly be used for further identification of biochemical pathways, enzymes, and the location of various genes under drought stress.

Unraveling the metabolomic architecture of autism in a large Danish population-based cohort

BackgroundThe prevalence of autism in Denmark has been increasing, reaching 1.65% among 10-year-old children, and similar trends are seen elsewhere. Although there are several factors associated with autism, including genetic, environmental, and prenatal factors, the molecular etiology of autism is largely unknown. Here, we use untargeted metabolomics to characterize the neonatal metabolome from dried blood spots collected shortly after birth.MethodsWe analyze the metabolomic profiles of a subset of a large Danish population-based cohort (iPSYCH2015) consisting of over 1400 newborns, who later are diagnosed with autism and matching controls and in two Swedish population-based cohorts comprising over 7000 adult participants. Mass spectrometry analysis was performed by a timsTOF Pro operated in QTOF mode, using data-dependent acquisition. By applying an untargeted metabolomics approach, we could reproducibly measure over 800 metabolite features.ResultsWe detected underlying molecular perturbations across several metabolite classes that precede autism. In particular, the cyclic dipeptide cyclo-leucine-proline (FDR-adjusted p = 0.003) and the carnitine-related 5-aminovaleric acid betaine (5-AVAB) (FDR-adjusted p = 0.03), were associated with an increased probability for autism, independently of known prenatal and genetic risk factors. Analysis of genetic and dietary data in adults revealed that 5-AVAB was associated with increased habitual dietary intake of dairy (FDR-adjusted p < 0.05) and with variants near SLC22A4 and SLC22A5 (p < 5.0e − 8), coding for a transmembrane carnitine transporter protein involved in controlling intracellular carnitine levels.ConclusionsCyclo-leucine-proline and 5-AVAB are associated with future diagnosis of autism in Danish neonates, both representing novel early biomarkers for autism. 5-AVAB is potentially modifiable and may influence carnitine homeostasis.

Identification of tomato F-box proteins functioning in phenylpropanoid metabolism.

Phenylpropanoids, a class of specialized metabolites, play crucial roles in plant growth and stress adaptation and include diverse phenolic compounds such as flavonoids. Phenylalanine ammonia-lyase (PAL) and chalcone synthase (CHS) are essential enzymes functioning at the entry points of general phenylpropanoid biosynthesis and flavonoid biosynthesis, respectively. In Arabidopsis, PAL and CHS are turned over through ubiquitination-dependent proteasomal degradation. Specific kelch domain-containing F-Box (KFB) proteins as components of ubiquitin E3 ligase directly interact with PAL or CHS, leading to polyubiquitinated PAL and CHS, which in turn influences phenylpropanoid and flavonoid production. Although phenylpropanoids are vital for tomato nutritional value and stress responses, the post-translational regulation of PAL and CHS in tomato remains unknown. We identified 31 putative KFB-encoding genes in the tomato genome. Our homology analysis and phylogenetic study predicted four PAL-interacting SlKFBs, while SlKFB18 was identified as the sole candidate for the CHS-interacting KFB. Consistent with their homolog function, the predicted four PAL-interacting SlKFBs function in PAL degradation. Surprisingly, SlKFB18 did not interact with tomato CHS and the overexpression or knocking out of SlKFB18 did not affect phenylpropanoid contents in tomato transgenic lines, suggesting its irreverence with flavonoid metabolism. Our study successfully discovered the post-translational regulatory machinery of PALs in tomato while highlighting the limitation of relying solely on a homology-based approach to predict interacting partners of F-box proteins.

Metabolomic and Proteomic Analysis of ApoE4-Carrying H4 Neuroglioma Cells in Alzheimer's Disease Using OrbiSIMS and LC-MS/MS.

Growing clinical evidence reveals that systematic molecular alterations in the brain occur 20 years before the onset of AD pathological features. Apolipoprotein E4 (ApoE4) is one of the most significant genetic risk factors for Alzheimer's disease (AD), which is not only associated with the AD pathological features such as amyloid-β deposition, phosphorylation of tau proteins, and neuroinflammation but is also involved in metabolism, neuron growth, and synaptic plasticity. Multiomics, such as metabolomics and proteomics, are applied widely in identifying key disease-related molecular alterations and disease-progression-related changes. Despite recent advances in the development of analytical technologies, screening the entire profile of metabolites remains challenging due to the numerous classes of compounds with diverse chemical properties that require different extraction processes for mass spectrometry. In this study, we utilized Orbitrap Secondary Ion Mass Spectrometry (OrbiSIMS) as a chemical filtering screening tool to examine molecular alterations in ApoE4-carried neuroglioma cells compared to wild-type H4 cells. The findings were compared using liquid chromatography (LC)-MS/MS targeted metabolomics analysis for the confirmation of specific metabolite classes. Detected alterations in peptide fragments by OrbiSIMS provided preliminary indications of protein changes. These were extensively analyzed through proteomics to explore ApoE4's impact on proteins. Our metabolomics approach, combining OrbiSIMS and LC-MS/MS, revealed disruptions in lipid metabolism, including glycerophospholipids and sphingolipids, as well as amino acid metabolism, encompassing alanine, aspartate, and glutamate metabolism; aminoacyl-tRNA biosynthesis; glutamine metabolism; and taurine and hypotaurine metabolism. Further LC-MS/MS proteomics studies confirmed the dysfunction in amino acid and tRNA aminoacylation metabolic processes, and highlighted RNA splicing alterations influenced by ApoE4.

Can lichens be indicators for air pollution monitoring in Kandy City, Sri Lanka?

The quality of the surrounding environment significantly impacts lichen diversity and composition, but crustose lichens, particularly those in disturbed environments, can persist. Although the effects of habitat disturbances on the morphology, anatomy, chemical composition, and fertility of lichen species have not been extensively researched, understanding their mechanisms is crucial for understanding their persistence in their environment. The study aimed to identify common lichen species in polluted and semi-polluted environments and compare their morphology, anatomy, chemical composition, and fertility. A two-kilometer stretch along the road that passes through the University of Peradeniya was selected as the semi-disturbed site based on previous records, while the area around Kandy Lake was designated as the polluted site. Using conventional keys, lichen species were identified, and using a hand lens, dissecting microscope, and compound microscope, the morphological traits of the thallus, apothecia, soredia, and isidia, as well as the anatomical features of the thallus, apothecia, and ascospores, were compared between the two sites. Thin-layer chromatography was used to separate and elucidate the secondary metabolites of lichen. Thirty-nine species were discovered on the university site, 15 in the area around Kandy Lake, and species gathered from both locations shared commonalities, including Physcia sp., Parmotrema sp., Lecanora sp., Graphis sp., and Lepraria sp. The color difference between all species, as measured by mean dE, is visible to the naked eye and changes from a pale to a dark hue from a semi-disturbed site to a polluted one. In comparison to disturbed sites, the majority of species displayed an increased mean area in semi-polluted sites. Layer thickness increases or decreases depending on how well each layer can withstand disruptions. Depsinose has been recognized as a potential class of metabolites generated by lichens present in both locations. Only lake sites exhibit toxic metal compounds, as opposed to semi-disturbed sites. Every pH value was acidic, and most species at the lake site had more acidic pH than those at the university site. There is no specific trend in apothecial number and ascospore numbers in common lichen species in both sites. The current study showed that changes in certain morphological and anatomical biochemical characteristics can be triggered by the environment, suggesting that the quality of the environment significantly affects the growth and reproductive success of lichens, thereby survival or extinction, and proposed that bioindicator and bioaccumulator species concerning the changes occurred.

Broadcasters, receivers, functional groups of metabolites, and the link to heart failure by revealing metabolomic network connectivity.

Blood-based small molecule metabolites offer easy accessibility and hold significant potential for insights into health processes, the impact of lifestyle, and genetic variation on disease, enabling precise risk prevention. In a prospective study with records of heart failure (HF) incidence, we present metabolite profiling data from individuals without HF at baseline. We uncovered the interconnectivity of metabolites using data-driven and causal networks augmented with polygenic factors. Exploring the networks, we identified metabolite broadcasters, receivers, mediators, and subnetworks corresponding to functional classes of metabolites, and provided insights into the link between metabolomic architecture and regulation in health. We incorporated the network structure into the identification of metabolites associated with HF to control the effect of confounding metabolites. We identified metabolites associated with higher and lower risk of HF incidence, such as glycine, ureidopropionic and glycocholic acids, and LPC 18:2. These associations were not confounded by the other metabolites due to uncovering the connectivity among metabolites and adjusting each association for the confounding metabolites. Examples of our findings include the direct influence of asparagine on glycine, both of which were inversely associated with HF. These two metabolites were influenced by polygenic factors and only essential amino acids, which are not synthesized in the human body and are obtained directly from the diet. Metabolites may play a critical role in linking genetic background and lifestyle factors to HF incidence. Revealing the underlying connectivity of metabolites associated with HF strengthens the findings and facilitates studying complex conditions like HF.

Phytochemical drivers of insect herbivory: a functional toolbox to support agroecological diversification.

Plant metabolism is a key feature of biodiversity that remains underexploited in functional frameworks used in agroecology. Here, we study how phytochemical diversity considered at three organizational levels can promote pest control. In a factorial field experiment, we manipulated plant diversity in three monocultures and three mixed crops of oilseed rape to explore how intra- and interspecific phytochemical diversity affects pest infestation. We combined recent progress in metabolomics with classic metrics used in ecology to test a box of hypotheses grounded in plant defence theory. According to the hypothesis of 'phytochemically mediated coevolution', our study stresses the relationships between herbivore infestation and particular classes of specialized metabolites like glucosinolates. Among 178 significant relationships between metabolites and herbivory rates, only 20% were negative. At the plant level, phytochemical abundance and richness had poor predictive power on pest regulation. This challenges the hypothesis of 'synergistic effects'. At the crop cover level, in line with the hypothesis of 'associational resistance', the phytochemical dissimilarity between neighbouring plants limited pest infestation. We discuss the intricate links between associational resistance and bottom-up pest control. Bridging different levels of organization in agroecosystems helps to dissect the multi-scale relationships between phytochemistry and insect herbivory.

Compounds from Natural Products Candidates to Drug for Chikungunya Virus Infection: A Systematic Review

Introduction: Chikungunya fever is a disease caused by infection with the Chikungunya virus, transmitted by Aedes aegypti and Aedes albopictus mosquitoes. Despite its self-limited character, more than 60% of patients have chronic recurrent arthralgia with debilitating pain that lasts for years. Aim: The objective of this review was to gather and analyze evidence from the literature on potential therapeutic strategies with molecules from natural products for the treatment of Chikungunya fever. Methods: A search was performed for clinical trials, observational studies, in vitro or in vivo, without restriction of the year of publication or language in electronic databases (Medline/PubMed, EMBASE, Google Scholar, The Cochrane Library, LILACS (BVS), clinical trial registries (Clinical Trials.gov), digital libraries from CAPES theses and dissertations (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil) and conference abstracts. A quality assessment of the selected studies was performed using the SYRCLE, RoB2 and SciRAP tools. Results: 42 studies were included, which showed molecules with potential antiviral pharmacological activity or with activity in reducing the joint complications caused by CHIKV infection. Conclusions: Among the molecules found in the survey of references, regarding the class of secondary metabolites, flavonoids stood out and for this reason, the molecules may be promising candidates for future clinical trials. Overall, evidence from in vitro studies was of acceptable quality; in vivo and intervention studies showed a high risk of bias, which is a limitation of these studies.

Green synthesized extracts/Au complex of Phyllospongia lamellosa: Unrevealing the anti-cancer and anti-bacterial potentialities, supported by metabolomics and molecular modeling

The anti-cancer and anti-bacterial potential of the Red Sea sponge Phyllospongia lamellosa in its bulk (crude extracts) and gold nanostructure (loaded on gold nanaoparticles) were investigated. Metabolomics analysis was conducted, and subsequently, molecular modeling studies were conducted to explore and anticipate the P. lamellosa secondary metabolites and their potential target for their various bioactivities. The chloroformic extract (CE) and ethyl acetate extract (EE) of the P. lamellosa predicted to include bioactive lipophilic and moderately polar metabolites, respectively, were used to synthesize gold nanoparticles (AuNPs). The prepared AuNPs were characterized through transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and UV–vis spectrophotometric analyses. The cytotoxic activities were tested against MCF-7, MDB-231, and MCF-10A. Moreover, the anti-bacterial, antifungal, and anti-biofilm activity were assessed. Definite classes of metabolites were identified in CE (terpenoids) and EE (brominated phenyl ethers and sulfated fatty amides). Molecular modeling involving docking and molecular dynamics identified Protein-tyrosine phosphatase 1B (PTP1B) as a potential target for the anti-cancer activities of terpenoids. Moreover, CE exhibited the most powerful activity against breast cancer cell lines, matching our molecular modeling study. On the other hand, only EE was demonstrated to possess powerful anti-bacterial and anti-biofilm activity against Escherichia coli. In conclusion, depending on their bioactive metabolites, P. lamellosa-derived extracts, after being loaded on AuNPs, could be considered anti-cancer, anti-bacterial, and anti-biofilm bioactive products. Future work should be completed to produce drug leads.

Solid Lipid Nanoparticles Encapsulating a Benzoxanthene Derivative in a Model of the Human Blood-Brain Barrier: Modulation of Angiogenic Parameters and Inflammation in Vascular Endothelial Growth Factor-Stimulated Angiogenesis.

Lignans, a class of secondary metabolites found in plants, along with their derivatives, exhibit diverse pharmacological activities, including antioxidant, antimicrobial, anti-inflammatory, and antiangiogenic ones. Angiogenesis, the formation of new blood vessels from pre-existing ones, is a crucial process for cancer growth and development. Several studies have elucidated the synergistic relationship between angiogenesis and inflammation in various inflammatory diseases, highlighting a correlation between inflammation and vascular endothelial growth factor (VEGF)-induced angiogenesis. Thus, the identification of novel molecules capable of modulating VEGF effects presents promising prospects for developing therapies aimed at stabilizing, reversing, or even arresting disease progression. Lignans often suffer from low aqueous solubility and, for their use, encapsulation in a delivery system is needed. In this research, a bioinspired benzoxantene has been encapsulated in solid lipid nanoparticles that have been characterized for their pharmacotechnical properties and their thermotropic behavior. The effects of these encapsulated nanoparticles on angiogenic parameters and inflammation in VEGF-induced angiogenesis were evaluated using human brain microvascular endothelial cells (HBMECs) as a human blood-brain barrier model.

Evaluation of antiulcer potential of tambulin and ombuin isolated from Zanthoxylum armatum

ObjectivesZanthoxulym armatum fruit is traditionally used as carminative, anthelmintic, stomachic, and to relieve gastritis. It is commonly found in Nepal, Uttarakhand, and the Himalayan region of India. Tribal peoples used this fruit for various purposes and also as a spice ingredient. The present study aims to investigate the antiulcer potential of the fruit extract, and its isolated compounds. Materials and methodsFruits were extracted with successive extraction methods with hexane, ethyl acetate, and butanol. All the fractions were evaluated for phytochemical investigations. Further, the ethyl acetate fraction, tambulin, and ombuin were tested for antiulcer activity induced by ethanol and pylorus ligation-induced methods. The IL-1β, TNF-α, and IL-6 cytokines were also studied followed by histopathology. ResultsIt has been demonstrated that the ethyl acetate fraction possesses a major class of secondary metabolites. No acute toxicity was observed, as all the organs (heart, kidney, lung, stomach, and liver) were found in normal range and no significant weight variation was found. The antiulcer activity was performed at two different doses of all samples. Tambulin possesses the most significant activity at the dose of 50 mg/kg. Ulcer index and percent ulcer inhibition of tambulin were found to be 2.8 ± 0.6 mm2 and 69.5 ± 0.18 % in pylorus –ligated model whereas 5.2 ± 0.7 mm2 and 70.2 ± 0.15 in the ethanol-induced model. Histopathology results also support the above-mentioned data. ConclusionTambulin, a flavonoidal compound isolated from fruits of Z. armatum was found to be useful in the management of ulcers. Ethylacetate extract and ombuin also possess dose-dependent activity.

Natural sanitizers pre- and post-milking in the prevention of bovine mastitis

Approaches focused on improving animal health are essential strategies to increase the quality and productivity of the livestock sector. Bovine mastitis is a prevalent disease in dairy farming worldwide. There are various ways to prevent infections and mammary inflammation in cows, such as using sanitizers or disinfectants before and after milking to clean the cow's udder surface and reduce contamination. Chlorine-based disinfectants are commonly used, and in some cases, antibiotics are used to prevent mastitis. This review aimed to analyze scientific articles that used plants as a sanitizer for a cow's udder in the last 5 years. There were few records of experiments with plants for disinfecting cows' udders; a total of 10 articles and 12 plant species were mentioned, including twice Piper betle and Acacia nilotica. Among the classes of metabolites indicated as active are terpenoids, flavonoids, and tannins. Studies indicate that plant extracts exhibit antimicrobial properties. Plant-based disinfectants promote sustainable and environmentally friendly sanitation in the livestock production sector, as these products are biodegradable and renewable.

Sequential Blood Collection from Inferior Vena Cava Followed by Portal Vein to Evaluate Gut Microbial Metabolites in Mice.

Gut microbial products are known to act both locally within the intestine and get absorbed into circulation, where their effects can extend to numerous distant organ systems. Short-chain fatty acids (SCFA) are one class of metabolites produced by gut microbes during the fermentation of indigestible dietary fiber. They are now recognizedas important contributors to how the gut microbiome influences extra-intestinal organ systems via the gut-lung, gut-brain, and other gut-organ axes throughout the host. SCFAs are absorbed from the colon, through intestinal tissue,into the portal vein (PV). They then pass through the liver, and are consumed in various organs such as the brain, muscle, adipose tissue, and lungs. SCFAs are most easily measured in the expelled fecal material however, more accurate measurements have been obtained from intra-colonic fecal contents. Here we propose that sampling PV and systemic circulating plasma of a single subject may be preferable for studying theabsorption, transport, and systemic levels of SCFAs in mice. We present a new technique for efficient blood sampling from the PV and inferior vena cava (IVC) that allows for the collection of relatively large volumes of blood from the portal and systemic circulations. This is accomplished by ligating the PV, thereby allowingfor the dilation or enlargement of the PV as it backfills from the mesenteric veins that drain into it. Using this method, we were able to improve the rate of successful collection as well as the total amount of blood collected (up to 0.3 mL from IVC and 0.5 mL from PV).

The metabolic landscape of the bacteria Rhodococcus erythropolis used in the biodesulfurization of petroleum products: an emphasis on 2-hydroxybiphenyl.

Microorganisms produce diverse classes of metabolites under various physiological conditions. Many bacterial strains have been reported to carry out the process of desulfurization in a cost-effective manner by converting dibenzothiophene (DBT) into 2-hydroxybiphenyl (2-HBP) and then using the 2-HBP as a carbon source for growth and development. Key rate-limiting factors and an increased concentration of 2HBP (400µM) affect the biodesulfurization activity of bacteria through the produced metabolites. Thus, this study was designed to explore the nature of the metabolites produced by Rhodococcus erythropolis in the presence of DBT and 2HBP supplemented with a culture medium. A total of 330 metabolites were detected, and the key metabolites identified were 11Z-eicosaenoyl-EA, 1-carboxyethylisoleucine, 1(3)-glyceryl-PGF2alpha, taurine, 2-hydroxynicotinic acid, 4,4-dimethyl-14alpha-hydroxymethyl-5alpha-cholest-8-en-3beta-ol, and 10-nitrooleic acid. The supplementation of DBT and DBT-2HBP resulted in the differential regulation of these metabolites, either through downregulation or overexpression. Furthermore, at high concentrations of 2-HBP, 1-carboxyethylisoleucine, taurine, 2-hydroxynicotinic acid, and nicotinic acid were upregulated. This work proposes that the identified metabolites may play a role in bacteria-mediated desulphurization and could be beneficial in developing a cost-effective method of desulphurization for refining petroleum.

AI-driven discovery of blood xenobiotic biomarkers in neovascular age-related macular degeneration using iterative random forests

PurposeTo investigate the xenobiotic profiles of patients with neovascular age-related macular degeneration (nAMD) undergoing anti-vascular endothelial growth factor (anti-VEGF) intravitreal therapy (IVT) to identify biomarkers indicative of clinical phenotypes through advanced AI methodologies.MethodsIn this cross-sectional observational study, we analyzed 156 peripheral blood xenobiotic features in a cohort of 46 nAMD patients stratified by choroidal neovascularization (CNV) control under anti-VEGF IVT. We employed Liquid Chromatography—Tandem Mass Spectrometry (LC–MS/MS) for measurement and leveraged an AI-driven iterative Random Forests (iRF) approach for robust pattern recognition and feature selection, aligning molecular profiles with clinical phenotypes.ResultsAI-augmented iRF models effectively refined the metabolite spectrum by discarding non-predictive elements. Perfluorooctanesulfonate (PFOS) and Ethyl β-glucopyranoside were identified as significant biomarkers through this process, associated with various clinically relevant phenotypes. Unlike single metabolite classes, drug metabolites were distinctly correlated with subretinal fluid presence.ConclusionsThis study underscores the enhanced capability of AI, particularly iRF, in dissecting complex metabolomic data to elucidate the xenobiotic landscape of nAMD and environmental impact on the disease. The preliminary biomarkers discovered offer promising directions for personalized treatment strategies, although further validation in broader cohorts is essential for clinical application.

Terpene synthases GhTPS6 and GhTPS47 participate in resistance to Verticillium dahliae in upland cotton

Terpene synthases (TPSs) are enzymes responsible for catalyzing the production of diverse terpenes, the largest class of secondary metabolites in plants. Here, we identified 107 TPS gene loci encompassing 92 full-length TPS genes in upland cotton (Gossypium hirsutum L.). Phylogenetic analysis showed they were divided into six subfamilies. Segmental duplication and tandem duplication events contributed greatly to the expansion of TPS gene family, particularly the TPS-a and TPS-b subfamilies. Expression profile analysis screened out that GhTPSs may mediate the interaction between cotton and Verticillium dahliae. Three-dimensional structures and subcellular localizations of the two selected GhTPSs, GhTPS6 and GhTPS47, which belong to the TPS-a subfamily, demonstrated similarity in protein structures and nucleus and cytoplasm localization. Virus-induced gene silencing (VIGS) of the two GhTPSs yielded plants characterized by increased wilting and chlorosis, more severe vascular browning, and higher disease index than control plants. Additionally, knockdown of GhTPS6 and GhTPS47 led to the down-regulation of cotton terpene synthesis following V. dahliae infection, indicating that these two genes may positively regulate resistance to V. dahliae through the modulation of disease-resistant terpene biosynthesis. Overall, our study represents a comprehensive analysis of the G. hirsutum TPS gene family, revealing their potential roles in defense responses against Verticillium wilt.

Comprehensive analysis of the metabolic nutritional components and exploration of health‐promoting small molecules in japonica rice and indica rice seeds

AbstractThe comprehensive detection of primary metabolites and secondary metabolites in japonica rice (Nipponbare) and indica rice seeds (93‐11) were clarified by using a combination of targeted and untargeted metabolomics approaches we created. A total of 246 metabolites were identified, encompassing 4 primary metabolite classes (3 sugars, 6 organic acids, 21 amino acids, 5 lipids) and 3 secondary flavonoid metabolite classes (17 flavones, 2 flavonones, 4 flavonols), as well as various other secondary metabolites. We found that japonica rice contains higher levels of sugars (especially fructose), alanine, flavonols, and luteolin complexes, while indica rice contains higher levels of organic acids, amino acids (excluding alanine), flavanones, and apigenin and its complexes. Exploring and comparing the comprehensive nutritional composition of the two types of rice not only enabled individuals to choose their staple food according to their own physical condition but also provided new insights for the development of health‐promoting rice.