Specific Metabolites Research Articles

Metabolic Differences among Patients with Cirrhosis Using Q Exactive Hybrid Quadrupole Orbitrap Mass Spectrometry Technology.

The hospitalization and mortality rates of patients gradually increase following the onset and progression of liver cirrhosis (LC). We aimed to help define clinical stage and better target interventions by detecting the expression of specific metabolites in patients with different stages of LC via Q Exactive hybrid quadrupole orbitrap mass spectrometry (UPLC-Q-Exactive) technology. This noninterventional observation case-control study involved 139 patients with LC or acute-on-chronic liver failure (ACLF) in a Chinese hospital between October 2022 and April 2023. Serum specimens were analyzed for multiple metabolite levels using UPLC-Q-Exactive. Data were processed to screen for differentially accumulated metabolites (DAMs). Short time-series expression miner (STEM) analysis and enrichment analysis were performed to assess cirrhosis progression biomarkers. Following univariate and multivariate analyses, a Venn diagram indicated nine significant DAMs in common among groups. STEM analysis showed 8'-hydroxyabscisic acid, HDCA, pyruvate-3-phosphate, indospicine, eplerenone, and DEHP as significant; their levels first peaked [Child-Turcotte-Pugh (CTP) class B peaked] and then decreased with CTP grade aggravation. Significant differences among 8'-hydroxyabscisic acid, eplerenone, and DEHP were observed among LC comorbidities and between subgroups. Therefore, serum levels of six DAMs may characterize metabolomic changes, determine the severity of LC, and predict the development of ACLF.

Deciphering the role of growth regulators in enhancing plant immunity against herbivory.

Plants are central to global food production, and the pursuit of sustainability aims to enhance or preserve food quality while safeguarding the environment. Due to their immobility, plants are unable to evade unfavourable climatic setups or interactions with other living creatures. Upon their interaction with insect herbivores, plants face biotic stress, which is a constant challenge for plants, causing molecular, physiological, and biochemical changes and reducing their productivity. To combat biotic stress caused by herbivores, plants have evolved intricate defence mechanisms through growth regulators such as auxins, cytokinins, gibberellins, salicylic acid (SA), jasmonic acid (JA), ethylene (ET), abscisic acid (ABA), strigolactones and brassinosteroids. The intricate network of specific proteins, metabolites and certain phytohormones orchestrates plant defensive reactions, leading to their skilful coordination in responding to insect attacks. Comprehending the defence mechanisms holds the key to mitigating significant crop and economic losses. This review entails a comprehensive analysis of the role of growth regulators in enhancing plant immunity against herbivory, highlighting the substantial efforts by the scientific community to manage and mitigate damages from biotic stress in plants, ultimately contributing to the advancement of sustainable agriculture.

From weight loss to cancer treatment: Fasting as an adjuvant anticancer therapy

The number of studies that have been conducted on the possible benefits of different types of fasting or calorie restriction on cancer therapy, including the likelihood that these treatments lessen side effects, has been limited. However, the results are nevertheless promising. Chemotherapy’s adverse effects have led to a quest for options that reduce reliance on it. The susceptibility of tumorous cells to specific metabolites and nutrient deficiency is increasingly recognized as a key characteristic of the disease. This review delves into the data on various fasting methods and calorie restriction in rodents and humans, with a focus on biological adaptations that could potentially lower cancer risk or enhance cancer treatment results. We also emphasize recent scientific developments regarding the use of prolonged fasting and fasting-mimicking diets as a possible additional treatment for patients receiving immunotherapy or other treatments. This approach shows promise in enhancing treatment effectiveness, preventing resistance, and minimizing side effects. This study proposes that combining fasting and calorie restriction with chemotherapy, immunotherapy, or other therapies might be a potential technique to improve treatment efficacy, avoid resistance, and reduce adverse effects.

Tomato Root Exudates Infected by Meloidogyne incognita Impact the Colonization of Nematicidal Proteus vulgaris

Root exudates play a pivotal role in shaping the microbial community in the rhizosphere and can impact the efficacy of bacteria in controlling nematode populations. This study identified Proteus vulgaris BX-1 as significantly effective in controlling Meloidogyne incognita. The infection of tomato plants with this nematode induced noticeable alterations in the composition of tomato root exudates and led to an increased colonization rate of strain BX-1. Further investigation into how strain BX-1 responded to changes in tomato root exudates revealed that specific metabolites, such as caffeic acid, coumarin, salicylic acid, sebacic acid, and butyric acid, strongly attracted strain BX-1. This attraction potentially contributed to its enhanced colonization and improved efficiency in controlling nematodes. Understanding the correlation between specific metabolites in root exudates and the response of antagonistic bacteria provides valuable insights for enhancing their effectiveness as biological control agents against plant-parasitic nematodes.

Inflammatory cytokines, metabolites, and rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint destruction. Although the roles of inflammatory cytokines and metabolites in RA pathogenesis have caught a lot of attention, there is a lack of systematic studies, and their causal relationships remain unclear. We conducted a two-step mendelian randomization analysis utilizing genetic data from genome-wide association studies (GWAS) of inflammatory cytokines, metabolites, and RA. The first step assessed the causal effect of 91 inflammatory cytokines and 1400 metabolites on RA risk using inverse variance weighted method, complemented by MR-Egger, weighted median, simple mode and MR-PRESSO to ensure robustness and assess pleiotropy. The second step evaluated the mediation effects of selected metabolites on the relationship between cytokines and RA. The analysis identified 9 inflammatory cytokines, including IL-1α and IL-10, which significantly increase RA risk, while TNF-β exhibited a protective effect. Additionally, 6 metabolites were associated with increased RA risk, including 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPE and arachidonate (20:4n6). Conversely, 5 metabolites, such as docosatrienoate (22:3n3) and Cholesterol, were found to reduce RA risk. The mediation analysis revealed that TNF-β may exerts its protective effect through its influence on specific metabolites, and X-24949, which accounted for a -2.58% mediated effect in the TNF-β-RA causal pathway. This study explores the complex interplay between inflammatory cytokines, metabolites, and RA. The findings suggest potential biomarkers for early diagnosis and novel therapeutic targets, particularly those related to lipid metabolites and specific cytokines like TNF-β. Key message What is already known on this topic Inflammatory factors and metabolites are considered to be related to the onset and progression of RA. What this study adds We conducted a MR analysis to identify all inflammatory factors and metabolites associated with RA and calculated the mediation effect of inflammatory cytokines on RA through metabolites. This study contributes to a comprehensive understanding of the pathophysiological processes of RA. How this study might affect research, practice or policy This has laid the groundwork for developing early diagnosis methods and future treatments.

Prenatal exposure to neonicotinoid insecticides, fetal endocrine hormones and birth size: Findings from SMBCS

BackgroundNeonicotinoid insecticides (NNIs) were reported to be endocrine disruptors and cause adverse health effects in human. However, epidemiological evidence about the effect of prenatal NNIs exposure on birth outcome and hormones remains limited. ObjectivesThis study aimed to explore the effects of prenatal NNIs exposure on neonatal birth size and endocrine hormones, and assess the potential mediating role of hormones. MethodsThe study included 860 mother–child pairs from the Sheyang Mini Birth Cohort Study. 12 parent NNIs (p-NNIs) and 6 metabolites of NNIs (m-NNIs) were measured in maternal urine samples collected on their delivery days, and 5 thyroid hormones and 2 sex hormones were analyzed in cord serum. The concentrations of p-NNIs and its specific metabolite(s) were summed to characterize the role of each class of NNIs. Generalized linear model and weighted quantile sum regression were used to examine the impact of prenatal NNIs exposure on birth size and endocrine hormones, and potential mediating roles of hormones were further explored using mediation analysis. ResultsHigher detection frequencies of m-NNIs were observed than those in p-NNIs. A decrease in neonatal head circumference for gestation age z-score was associated with a 10-fold increase in 5-OH-IMI (β = -0.15, 95 %CI: −0.26, −0.03), ∑DIN (β = -0.22, 95 %CI: −0.40, −0.03), ∑IMI (β = -0.20, 95 %CI: −0.35, −0.06) and ∑NNIs (β = -0.23, 95 %CI: −0.42, −0.04). ∑IMI and ∑DIN were the major contributors to the significantly negative mixture effect and no sex-specific effect was observed. Negative associations were observed between ∑DIN and TT3 (β = -0.013, 95 %CI: −0.025, −0.002), ∑IMI and T (β = -0.035, 95 %CI: −0.065, −0.004), respectively. Furthermore, TT3 and T demonstrated 6.7 % and 6.1 % mediating effects on the negative association of prenatal ∑DIN and ∑IMI exposure with head circumference. ConclusionsOur findings suggested the potential endocrine disruptive properties of NNIs and their impacts on head circumference. Endocrine hormones may partly mediate these associations.

Intestinal microflora and metabolites affect the progression of acute pancreatitis (AP)

Specific intestinal metabolites are closely associated with the classification, severity, and necrosis of acute pancreatitis (AP) and provide novel insights for in-depth clinical investigations. In this study, the gut microbiota and metabolites of 49 AP patients at different treatment stages and severities were analysed via 16S rDNA sequencing and untargeted metabolomics to investigate the trends in gut microbiota composition and metabolome profiles observed in patients with severe AP. These findings revealed an imbalance in intestinal flora homeostasis among AP patients characterized by a decrease in probiotics and an increase in opportunistic pathogens, which leads to damage to the intestinal mucosal barrier through reduced short-chain fatty acid (SCFA) secretion and disruption of the intestinal epithelium. This dysbiosis influences energy metabolism, anti-inflammatory responses, and immune regulation, and these results highlight significant differences in energy metabolism pathways. These findings suggest that the differential composition of intestinal flora, along with alterations in intestinal metabolites and metabolic pathways, contribute to the compromised integrity of the intestinal mucosal barrier and disturbances in energy metabolism in patients with severe AP.

High Entropy 2D Layered Double Hydroxide Nanosheet Toward Cascaded Nanozyme-Initiated Chemodynamic and Immune Synergistic Therapy.

High-entropy nanomaterials (HEMs) are a hot topic in the fields of energy and catalysis. However, in terms of promising biomedical applications, potential therapeutic studies involving HEMs are unprecedented. Herein, we demonstrated high entropy two-dimensional layered double hydroxide (HE-LDH) nanoplatforms with versatile physicochemical advantages that reprogram the tumor microenvironment (TME) and provide antitumor treatment via cascaded nanoenzyme-initiated chemodynamic and immune synergistic therapy. In response to the TME, the multifunctional HE-LDHs sequentially release metal ions, such as Co2+, Fe3+, and Cu2+, exhibiting exquisite superoxide dismutase (SOD), peroxidase (POD), and glutathione peroxidase (GPX) activities. The multiple enzymatic activities convert specific tumor metabolites into a continuous supply of cytotoxic reactive oxygen species (ROS) to relieve hypoxia under a TME. Thus, HE-LDHs facilitate robust nanozyme-initiated chemodynamic therapy (NCDT), achieving high therapeutic efficacy without obvious side effects. In addition, the release of Zn2+ from the HE-LDH matrix triggers the cyclic GMP-AMP synthase/stimulator of interferon gene (cGAS/STING) signaling pathway, boosting the innate immunotherapeutic efficacy. The intratumoral applications of the nanocomposite in tumor-bearing mice models indicate that HE-LDH-mediated NCDT and immune synergistic therapy effectively upregulated the expression of relevant antitumor cytokines and induced cytotoxic T lymphocyte infiltration, showing superior efficacy in inhibiting tumor growth. Therefore, this work opens a new research direction toward synchronized NCDT and immunotherapy of tumors using HEMs for advanced healthcare.

Using Four Machine Learning Methods to Analyze the Association Between Polycyclic Aromatic Hydrocarbons and Visual Impairment in American Adults: Evidence from NHANES

The causes of visual impairment are complex and may be influenced by exposure to environmental pollutants. Using data from the 2003–2004 National Health and Nutrition Examination Survey (NHANES), we examined the association between exposure to ten polycyclic aromatic hydrocarbons (PAHs) and vision problems in 1149 U.S. adults. We employed various supervised learning methods, including variable selection techniques such as Lasso and elastic net, weighted quantile sum regression (WQS), and Bayesian kernel machine regression (BKMR), to assess the association between PAHs and the occurrence of visual impairments. The mediation effects between urinary 2-fluorene and inflammation were evaluated using mediation analysis. Both the lasso and elastic net models consistently identified two specific PAH congeners, 2-fluorene and 1-phenanthrene, as significant predictors. The WQS regression revealed a positive relationship between the PAH mixture and visual impairment, with notable contributions from urinary 2-fluorene (weight = 0.39) and 9-fluorene (weight = 0.21). BKMR analysis indicated that the likelihood of visual impairment increases with higher PAH exposure, showing a general upward trend. This trend also revealed a positive association between visual impairment and exposure to four specific PAH metabolites, including 2-fluorene. A significant mediation effect was observed for alkaline phosphatase (p = 0.03), with a proportion mediated of 10.48%. Our findings suggest a significant association between PAHs and visual impairment, with multiple statistical models consistently emphasizing the crucial role of 2-fluorene exposure. This study highlights the importance of considering environmental pollutants as significant contributors to visual health outcomes, providing insights for preventing visual impairment.

Fecal Microbiome Composition Correlates with Pathologic Complete Response in Patients with Operable Esophageal Cancer Treated with Combined Chemoradiotherapy and Immunotherapy

Background: Preclinical and clinical data indicate that chemoradiotherapy (CRT) in combination with checkpoint inhibitors may prime an anti-tumor immunological response in esophageal cancer. However, responses to neoadjuvant therapy can vary widely and the key biomarkers to determine response remain poorly understood. The fecal microbiome is a novel and potentially modifiable biomarker of immunotherapy response, and both fecal and tumor microbes have been found to associate with outcomes in esophageal cancer. Methods: Fecal and tumor samples were collected from patients with stage II–III resectable esophageal or gastroesophageal junction carcinoma treated with neoadjuvant immune checkpoint inhibitors (ICIs) plus CRT prior to surgical resection. Microbiome profiles were analyzed by 16S rRNA amplicon sequencing and taxonomic data were integrated with fecal metabolite analysis to assess microbial function. Results: The fecal microbiome of patients with pathological complete response (PCR) grouped in distinct clusters compared to patients with residual viable tumor (RVT) by Bray–Curtis diversity metric. Integrated taxonomic and metabolomic analysis of fecal samples identified a sphingolipid and primary bile acid as enriched in the PCR, the levels of which correlated with several bacterial species: Roseburis inulinivorans, Ruminococcus callidus, and Fusicantenibacter saccharivorans. Analysis of the tumor microbiome profiles identified several bacterial genera previously associated with esophageal tumors, including Streptococcus and Veillonella. Conclusions: These results further characterize the fecal and tumor microbiome of patients with operable esophageal cancer and identify specific microbes and metabolites that may help elucidate how microbes contribute to tumor response with neoadjuvant CRT combined with ICI.

Exploring the Prebiotic Potentials of Hydrolyzed Pectins: Mechanisms of Action and Gut Microbiota Modulation

The intestinal microbiota is a complex ecosystem where the microbial community (including bacteria) can metabolize available substrates via metabolic pathways specific to each species, often related in symbiotic relations. As a consequence of using available substrates and microbial growth, specific beneficial metabolites can be produced. When this reflects the health benefits for the host, these substrates can be categorized as prebiotics. Given that most prebiotic candidates must have a low molecular weight to be further metabolized by the microbiota, the role in the preliminary biological pretreatment is crucial. To provide proper substrates to the intestinal microbiota, a strategy could be to decrease the complexity of polysaccharides and reduce the levels of polymerization to low molecular weight for the target molecules, driving better solubilization and the consequent metabolic use by intestinal bacteria. When high molecular weight pectin is degraded (partially depolymerized), its solubility increases, thereby improving its utilization by gut microbiota. With regards to application, prebiotics have well-documented advantages when applied as food additives, as they improve gut health and can enhance drug effects, all shown by in vitro, in vivo, and clinical trials. In this review, we aim to provide systematic evidence for the mechanisms of action and the modulation of gut microbiota by the pectin-derived oligosaccharides produced by decreasing overall molecular weight after physical and/or chemical treatments and to compare with other types of prebiotics.

LC-MS metabolomics uncovers potential biomarkers of semen cryo-injury in goats.

Semen cryopreservation acts a crucial role in enhancing breed improvement and conserving genetic resources. However, it often leads to decreased sperm activity and reduced pregnancy rates. Despite significant advancements in semen freezing techniques for goats, the precise factors and mechanisms causing cryo-injury remain unclear. In this study, we examined the motility characteristics of fresh semen versus frozen-thawed semen and investigated changes in the metabolite profiles of seminal plasma using liquid chromatograph-mass spectrometry (LC-MS). A total of 364 differentially expressed metabolites (DEMs) were identified between fresh and frozen-thawed semen samples. Among these, 185 metabolites were significantly up-regulated, while 179 were down-regulated (p<0.05). The majority of these DEMs belonged to lipids and lipid-like molecules, as well as organic acids and derivatives. The Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated that these DEMs were primarily involved in pathways related to amino acid synthesis and metabolism. Additionally, metabolite set enrichment analysis (MSEA) underscored the critical role of amino acid synthesis and metabolic pathways in semen cryopreservation. Specific metabolites such as alanine, proline, phenylalanine, tryptophan, tyrosine, adenosine, citric acid, flavin adenine dinucleotide (FAD), and choline emerged as potential biomarkers for sperm cryo-injury in goats. These findings provide valuable insights into enhancing the quality of semen cryopreservation in goats, contributing to improved breeding and genetic resource conservation efforts.

Unraveling the key mechanisms of Gastrodia elata continuous cropping obstacles: soil bacteria Massilia, Burkholderia-Caballeronia-Paraburkholderia, and Dyella along with soil metabolites 4-hydroxy-benzenemethanol and N-(2-butyl)-N-octadecyl-, ethyl ester as crucial indicators

BackgroundTian-ma (Gastrodia elata) is a traditional medicinal herb found in China. It is used in healthy food and to treat various diseases, therefore cultivated extensively in southwest China. However, continuous cropping of this species has led to various obstacles, such as microbial disease and pest infestation, significantly affecting the production and development of valuable medicinal and food resources. As per the growth habit, soil is presumed to be the primary factor contributing to these obstacles, despite the known issues of continuous cropping obstacles in Gastrodia elata, such as microbial disease, there is a lack of comprehensive understanding of the specific soil bacterial communities and metabolites involved in these processes.MethodsWe analyzed soil samples collected during the year of Tian-ma cultivation (0 Year), after the Tian-ma harvest (1 Year), after two years (2 Year), and three years (3 Year) of fallowing post-cultivation using soil 16S rRNA metabarcoding sequencing by illumina platform and metabolomics (GC–MS/MS). Soil sample collected from the uncultivated field was used as the control (CK).ResultsMetabarcoding sequencing showed high bacterial alpha diversity during the cultivation of Tian-ma (0 Year) and the period of deterioration of soil bacterial community. (1 Year), with decreased anaerobic bacterial abundance and increased copiotrophic bacterial abundance. Bacteria associated with sulfur metabolism also showed increased abundance during the year of cropping obstacles. Further metabolomics approach identified 4-hydroxy-benzenemethanol as an indicator of Tian-ma continuous cropping obstacles. Besides, metabolites of the carbohydrate class were found to be the most abundant during the occurrence of continuous cropping obstacles of Gastrodia elata, suggesting that regulation of soil microbial diversity may be a critical factor in addressing these obstacles. Finally, the correlation analysis indicated a positive association between the abundance of some metabolite, e.g., carbamic acid, N-(2-butyl)-N-octadecyl-, ethyl ester detected after Tian-ma cultivation and the abundance of bacteria capable of degrading toxic metabolites, such as Massilia, Burkholderia-Caballeronia-Paraburkholderia, and Dyella.ConclusionThis study has revealed the specific soil bacteria and metabolic factors related to the continuous cropping obstacles of Gastrodia elata. These findings not only deepen our understanding of the continuous cropping issues but also pave the way for developing effective strategies to overcome them.

Preharvest salicylic acid and chitosan treatments reduce red drupelet reversion and enhance antioxidant capacity in blackberry fruit

Red drupelet reversion (RDR) is a postharvest physiological disorder affecting fresh blackberries during commercialization. The drupelets revert from fully black to red, causing detriments of the commercial value. The specific mechanism is still being investigated, some reports suggest that the occurrence of RDR is associated with pigment degradation in the fruit, and can be caused or aggravated by mechanical damage and storage conditions. Even, though studies report no significant alteration in blackberry organoleptic properties caused by RDR, the visual aspect of it affects the consumer perception of the fruit quality reducing marketability and ultimately generating economic losses. In this regard, preharvest treatments have been recently reported to have positive effects in reducing RDR in blackberries. In this study, we investigated the effects of chitosan (COS) and salicylic acid (SA) as preharvest treatments on the phenolic compound content and antioxidant capacity of blackberry fruit. The results showed that SA 3 mM and COS 0.25% treatments increased the total phenolic and flavonoid content while also enhancing the antioxidant capacity of blackberries. We also observed that the content of specialized metabolites and the activity of antioxidant enzymes have a negative correlation with the occurrence of RDR in blackberries.

Metabolomic Fingerprints: Seasonal and Farm-Specific Differences in Heterotrigona itama Bee Bread

Stingless bees’ products such as honey and bee bread are beneficial to human health. However, the metabolite composition within the products may differ according to spatial and temporal factors. This study aims to investigate the impact of spatial and temporal factors on the significant metabolite composition present in Heterotrigona itama bee bread collected from different seasons and types of bee farms. Thus, tandem mass spectrometry (LCMS/MS) based metabolomics analysis was used to achieve the said goal, focusing on H. itama bee bread samples, followed by multivariate analysis using the MetaboAnalyst platform. Our findings revealed significant metabolites that set bee bread samples apart. In terms of temporal factors, the analysis highlights specific metabolites exclusive to the wet season, such as flavones and flavonoids. However, in contrast, during the wet season, there are no significant metabolites in herbal farm samples. The results also underscore the significance of phenolic compounds in wet season samples and as vital metabolites distinguishing the groups. This study highlights a total of 24 annotated significant metabolites identified in different bee bread samples, as well as their capacity to differentiate between seasons and bee farms. Notably, these results suggest a wide variety of potential plant families as a source of bee bread. These findings shed light on the impact of seasons and diverse plant families contributing to bee bread composition, which may impact the growing meliponiculture industry greatly.

Comparative Metabolome and Transcriptome Analyses Reveal Molecular Mechanisms Involved in the Responses of Two Carex rigescens Varieties to Salt Stress

Salt stress severely inhibits crop growth and production. The native turfgrass species Carex rigescens in northern China, exhibits extraordinary tolerance to multiple abiotic stresses. However, little is known about its specific metabolites and pathways under salt stress. To explore the molecular metabolic mechanisms under salt stress, we conducted metabolome analysis combined with transcriptome analysis of two varieties of Carex rigescens with differing salt tolerances: salt-sensitive Lvping NO.1 and salt-tolerant Lvping NO.2. After 5 days of salt treatment, 114 and 131 differentially abundant metabolites (DAMs) were found in Lvping NO.1 and Lvping NO.2, respectively. Among them, six amino acids involved in the amino acid biosynthesis pathway, namely, valine, phenylalanine, isoleucine, tryptophan, threonine, and serine, were accumulated after treatment. Furthermore, most DAMs related to phenylalanine biosynthesis, metabolism, and phenylpropanoid biosynthesis increased under salt stress in both varieties. The expression profiles of metabolism-associated genes were consistent with the metabolic profiles. However, genes including HCT, β-glucosidases, and F5H, and metabolite 4-hydroxycinnamic acid, of the two varieties may account for the differences in salt tolerance. Our study provides new insights into the mechanisms underlying salt tolerance in Carex rigescens and reveals potential metabolites and genes to improve crop resilience to saline environments.

The influence of aridity on plant intraspecific chemical diversity supports adaptive differentiation and convergent evolution.

Plants synthesize a broad array of specialized chemical compounds that mediate their interactions with the surrounding environment. Some of this chemical diversity is functional and subject to natural selection, but the factors underlying chemical evolution at the intraspecific level remain largely unknown. Here, we combined chemical, environmental and genetic data to investigate the effect of aridity on the expression of chemotypes in the invasive shrub Senecio pterophorus. We studied the variation in pyrrolizidine alkaloids (PAs), a group of specialized metabolites widespread across the families Boraginaceae, Asteraceae and Fabaceae, from native populations spanning a cline of aridity and from three cross-continental introductions, under natural and common garden conditions. We examined whether the relationship between chemistry and aridity was compatible with a process of adaptive differentiation using a method that partitions the variance and covariance by controlling for the population neutral genetic structure. We found a consistent shift from retrorsine-like to seneciphylline-like compounds under increasing aridity in both natural and controlled conditions in coherence with the biosynthetic pathways. This pattern was independent of the neutral genetic structure and occurred along the environmental gradient in the native range and in a convergent manner in all nonnative regions, which suggests adaptive differentiation in response to aridity. Our findings show that the diversity of PAs in S. pterophorus has been partially shaped by aridity. Investigating how abiotic factors influence chemical evolution is key to elucidating the plant responses in future climate scenarios and the cascading effects on other trophic levels.

Study on serum metabolomics characteristics of obese patients with erectile dysfunction.

Erectile dysfunction (ED) is a common male sexual health problem that can be associated with obesity. This study aimed to identify serum metabolic differences and pathways related to ED in obese men using non-targeted metabolomics techniques. We included 54 obese male patients with (n = 27) and without (n = 27) ED. We collected 5 mL of fasting elbow vein blood and analyzed serum metabolites using ultra-high-performance liquid chromatography-mass spectrometry. Multivariate statistical methods (principal component analysis and orthogonal partial least squares discriminant analysis) were used to identify differential metabolites between the groups. Finally, pathway analysis using the Kyoto encyclopedia of genes and genomes database identified 4 differential metabolic pathways in obese men with ED compared to obese men without ED. A total of 77 differential metabolites were identified in obese men with ED compared to the control group (obese men without ED) using a threshold of variable importance in the projection > 1 and P < .05. Pathway analysis revealed 4 main differences: glycine, serine and threonine metabolism, glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis, and D-glutamine and D-glutamate metabolism. Specific metabolites associated with these pathways included betaine aldehyde, choline, L-threonine, phosphatidylcholine, L-serine, and D-glutamine. Our findings suggest abnormalities in fatty acid metabolism, phospholipid metabolism, and amino acid metabolism between obese men with and without ED. Metabolites such as betaine aldehyde, choline, L-threonine, phosphatidylcholine, L-serine, and D-glutamine may be potential biomarkers for distinguishing obese men with ED.

Reinventing gut health: leveraging dietary bioactive compounds for the prevention and treatment of diseases.

The human gut harbors a complex and diverse microbiota essential for maintaining health. Diet is the most significant modifiable factor influencing gut microbiota composition and function, particularly through bioactive compounds like polyphenols, dietary fibers, and carotenoids found in vegetables, fruits, seafood, coffee, and green tea. These compounds regulate the gut microbiota by promoting beneficial bacteria and suppressing harmful ones, leading to the production of key microbiota-derived metabolites such as short-chain fatty acids, bile acid derivatives, and tryptophan metabolites. These metabolites are crucial for gut homeostasis, influencing gut barrier function, immune responses, energy metabolism, anti-inflammatory processes, lipid digestion, and modulation of gut inflammation. This review outlines the regulatory impact of typical bioactive compounds on the gut microbiota and explores the connection between specific microbiota-derived metabolites and overall health. We discuss how dietary interventions can affect disease development and progression through mechanisms involving these metabolites. We examine the roles of bioactive compounds and their metabolites in the prevention and treatment of diseases including inflammatory bowel disease, colorectal cancer, cardiovascular diseases, obesity, and type 2 diabetes mellitus. This study provides new insights into disease prevention and underscores the potential of dietary modulation of the gut microbiota as a strategy for improving health.

Gut bacteria facilitate leaf beetles in adapting to dietary specialization by enhancing larval fitness

Dietary specialization between insect stages can reduce intraspecific food competition. The involvement of gut bacteria and the mechanisms underlying this phenomenon received limited attention. Plagiodera versicolora is a pest harming Salicaceae trees. Here, we confirmed dietary specialization in P. versicolora, wherein adults prefer new leaves, while larvae predominantly consume mature leaves when both types are available. We demonstrated the larval preference for mature leaves confers ecological advantages by promoting growth, development and immunity and this advantage is contingent upon the presence of gut bacteria. Gut microbiota in larvae revealed a significant enrichment of Pantoea when feeding new leaves, with P. anthophila exhibiting the most pronounced inhibitory effect on larval development. Further exploration identified specific metabolites, such as Tyrosyl-valine, with higher content in new leaves, which serve as substrates for the entomopathogenic gut bacterium to facilitate its proliferation. This study provides a fresh perspective on the ecological role of gut bacteria.