Search Results (2,707)

The toxicity of glucosinolate, isothiocyanate and sinapin limits canola meal’s use as non-ruminant animal feed. While monoculture microbial biorefining has been explored, the potential and capability of insect-associated microbiomes in this context remain underexplored. Herein, we extracted the gut and frass extracts from canola feeding larvae of Heliothis moth (HP), cabbage white (WCF) and cabbage looper (CL). Canola meal was fermented for one week with these extracts, followed by liquid chromatography–mass spectrometry (LC-MS)-assisted metabolomics analysis. Elevated branched-SCFAs 2-hydroxy butyrate and 3-hydroxy butyrate and propionate were observed in HP and WCF ferments, respectively. Aliphatic glucosinolates and sinapins showed ≥2-fold depletion in the HP and WCF frass ferments. In gut extract and frass-fermented canola meal, particularly of the HP group, tryptophan, tyrosine, and cysteine and glutathione metabolism were the most impactful pathways, aiding biogenic amine and branched-SCFA synthesis. S-adenosyl methionine (SAM) led salvaging, playing a key role in amino acid recycling via mercapturate metabolism, oxidative stress handling via the methionine and cysteine metabolism pathway, and sinapin metabolism through syringate degradation. These findings highlight the metabolic mechanism of brassica herbivore insect gut microbiome in detoxifying and adding value to canola meal. Such microbial communities have the potential to upcycle canola meal into a nutrient-rich feed additive with gut-health-promoting properties. Full article

Walnut (Juglans regia L.), an ecologically and economically important species, requires the elucidation of its salt stress response mechanisms for improved salt tolerance breeding. This study elucidates the physiological and molecular mechanisms through which exogenous methyl jasmonate (MeJA) mitigates salt stress in walnut, providing novel strategies for salt-tolerant cultivar development. This integrated study combined physiological, biochemical, and multi-omics analyses to decipher how exogenous MeJA enhances ROS scavenging through the synergistic activation of phenylalanine (Phe), tryptophan (Trp), and α-linolenic acid pathways, establishing a multilevel antioxidant defense network. MeJA treatment effectively mitigated salt stress-induced oxidative damage, as demonstrated by a significant 16.83% reduction in malondialdehyde (MDA) content, concurrent 11.60%, 10.73% and 22.25% increases in superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities, respectively, the elevation of osmoregulatory soluble sugars (SS), and 1.2- to 2.0-fold upregulation of key antioxidant enzyme genes (SOD, POD, APX, GPX, DHAR) and elevated osmoregulatory substances (soluble sugars, SS). Improved photosynthetic parameters (P_n, G_s) and chlorophyll fluorescence efficiency (F_v/F_m) collectively indicated reduced oxidative stress (improved by 7.97–23.71%). Joint metabolomic-transcriptomic analyses revealed MeJA-enhanced ROS scavenging via the coordinated regulation of Phe, Trp, and α-linolenic acid pathways. In summary, MeJA significantly enhanced reactive oxygen species (ROS) scavenging efficiency and comprehensive antioxidant capacity in walnut seedlings through the synergistic regulation of key metabolic pathways, effectively mitigating salt stress. These findings establish a crucial mechanistic foundation for understanding plant salt stress responses and advance the utilization of MeJA-mediated strategies for the genetic improvement of salinity tolerance in walnut. Future research should prioritize optimizing MeJA application protocols and functionally validating key regulatory genes for breeding applications. Full article

Background and Objectives: Effective myocardial protection is essential for successful cardiac surgery outcomes, especially in complex and prolonged procedures. To this end, Del Nido (DN) and histidine-tryptophan-ketoglutarate (HTK) cardioplegia solutions are widely used; however, their comparative efficacy in adult surgeries with prolonged aortic cross-clamp (ACC) times remains unclear. This study aimed to compare the efficacy and safety of DN and HTK for myocardial protection during prolonged ACC times in adult cardiac surgery and to define clinically relevant thresholds. Materials and Methods: This retrospective study included a total of 320 adult patients who underwent cardiac surgery under cardiopulmonary bypass (CPB) with an aortic cross-clamp time ≥ 90 min. Data were collected from the medical records of elective adult cardiac surgery cases performed at a single center between 2019 and 2025. Patients were categorized into two groups based on the type of cardioplegia received: Del Nido (n = 160) and HTK (n = 160). The groups were compared using 1:1 propensity score matching. Clinical and biochemical outcomes—including troponin I (TnI), CK-MB, lactate levels, incidence of low cardiac output syndrome (LCOS), and need for mechanical circulatory support—were analyzed between the two cardioplegia groups. Subgroup analyses were performed according to ACC duration (90–120, 120–150, 150–180 and >180 min). The predictive threshold of ACC duration for each complication was determined by ROC analysis, followed by the analysis of independent predictors of each endpoint by multivariate logistic regression. Results: Intraoperative cardioplegia volume and transfusion requirements were lower in the DN group (p < 0.05). HTK was associated with lower TnI levels and less intra-aortic balloon pump (IABP) requirement at ACC times exceeding 180 min. Markers of myocardial injury were lower in patients with an ACC duration of 120–150 min in favor of HTK. The propensity for ventricular fibrillation after ACC was significantly lower in the DN group. Significantly lower postoperative sodium levels were observed in the HTK group. Prolonged ACC duration was an independent risk factor for LCOS (odds ratio [OR]: 1.023, p < 0.001), VIS > 15 (OR, 1.015; p < 0.001), IABP requirement (OR: 1.020, p = 0.002), and early mortality (OR: 1.016, p = 0.048). Postoperative ejection fraction (EF), troponin I, and CK-MB levels were associated with the development of LCOS and a VIS > 15. Furthermore, according to ROC analysis, HTK cardioplegia was able to tolerate ACC for up to a longer duration in terms of certain complications, suggesting a higher physiological tolerance to ischemia. Conclusions: ACC duration is a strong predictor of major adverse outcomes in adult cardiac surgeries. Although DN cardioplegia is effective and economically advantageous for shorter procedures, HTK may provide superior myocardial protection in operations with long ACC duration. This study supports the need to individualize cardioplegia choice according to ACC duration. Further prospective studies are needed to establish standard dosing protocols and to optimize cardioplegia selection according to surgical duration and complexity. Full article

Quinoa (Chenopodium quinoa), a stress-tolerant pseudocereal ideal for studying abiotic stress responses, was used to systematically identify optimal reference genes for qPCR normalization under gradient stresses: low temperatures (LT group: −2 °C to −10 °C), heat (HT group: 39° C to 45 °C), and drought (DR group: 7 to 13 days). Through multi-algorithm evaluation (GeNorm, NormFinder, BestKeeper, the ΔCt method, and RefFinder) of eleven candidates, condition-specific optimal genes were established as ACT16 (Actin), SAL92 (IT4 phosphatase-associated protein), SSU32 (Ssu72-like family protein), and TSB05 (Tryptophan synthase beta-subunit 2) for the LT group; ACT16 and NRP13 (Asparagine-rich protein) for the HT group; and ACT16, SKP27 (S-phase kinase), and NRP13 for the DR group, with ACT16, NRP13, WLIM96 (LIM domain-containing protein), SSU32, SKP27, SAL92, and UBC22 (ubiquitin-conjugating enzyme E2) demonstrating cross-stress stability (global group). DHDPS96 (dihydrodipicolinate synthase) and EF03 (translation elongation factor) showed minimal stability. Validation using stress-responsive markers—COR72 (LT), HSP44 (HT), COR413-PM (LT), and DREB12 (DR)—confirmed reliability; COR72 and COR413-PM exhibited oscillatory cold response patterns, HSP44 peaked at 43 °C before declining, and DREB12 showed progressive drought-induced upregulation. Crucially, normalization with unstable genes (DHDPS96 and EF03) distorted expression profiles. This work provides validated reference standards for quinoa transcriptomics under abiotic stresses. Full article

Ericoid mycorrhizal fungi (EMF) enhance plant fitness and metabolic regulations in nutrient-poor soils, though the mechanisms diving these interactions require further elucidation. This study investigated the physiological and metabolic responses of blueberry seedlings following 2- and 3-weeks inoculation with Oidiodendron maius H14. The results indicated that EMF could significantly increases plant biomass, improve the accumulation of osmoregulatory substances in leaves. Additionally, the colonization rate of EMF are 26.18% and 30.22% after 2- and 3-weeks, respectively. The Metabolomics analysis identified 758 (593 up- and 165 down-regulated) and 805 (577 up- and 228 down-regulated) differential metabolites in roots at 2- and 3-weeks inoculation with O. maius H14, respectively. KEGG pathway annotation revealed that O. maius H14 triggered various amino acid metabolism pathways, including tryptophan metabolism and arginine and proline metabolism. These findings suggested that O. maius H14 stimulated root-specific biosynthesis of growth-promoting compounds and antimicrobial compounds. Concomitant downregulation of stress-associated genes and upregulation of glutamine synthetase suggest EMF modulates host defense responses to facilitate symbiosis. Thus, our results demonstrated that O. maius H14 orchestrates a metabolic reprogramming in blueberry roots, enhancing growth and stress tolerance through coordinated changes in primary and specialized metabolism, which could inform strategies for improving symbiosis and metabolic engineering in horticultural practices. Full article

Cancer-related cognitive impairment (CRCI)—encompassing anxiety, depression, and memory deficits—significantly diminishes the quality of life in patients with cancer, yet remains underrecognized in clinical practice. In this study, we investigated the therapeutic potential of tabernanthalog (TBG), a non-hallucinogenic analog of psychedelic compounds, as a novel intervention for CRCI using a Lewis lung carcinoma (3LL) mouse model. Behavioral assessments revealed heightened anxiety-like behavior and memory impairment following 3LL cell transplantation. Biochemical analysis revealed reduced tryptophan levels in both blood and hippocampal tissue, accompanied by the downregulation of serotonergic receptor genes and upregulation of pro-inflammatory cytokine genes in the hippocampus of tumor-bearing mice. Additionally, microglial density and morphological activation were markedly elevated. TBG treatment reversed these behavioral deficits, improving both anxiety-related behavior and memory performance. These effects were associated with the normalization of microglial density and morphology, as well as the restoration of serotonergic receptor and cytokine gene expression. In vitro, TBG partially suppressed neuroinflammatory gene expression in BV-2 microglial cells exposed to conditioned medium from 3LL cells. Collectively, these findings suggest that TBG alleviates CRCI-like symptoms by modulating neuroinflammation and microglial activation. This study highlights TBG as a promising therapeutic candidate for improving cognitive and emotional functioning in patients with cancer. Full article

Carboxypeptidase A4 (CPA4) is an exopeptidase that cleaves peptide bonds at the C-terminal domain within peptides and proteins. It preferentially cleaves peptides with terminal aromatic or branched chain amino acid residues such as phenylalanine, tryptophan, or leucine. CPA4 was first discovered in prostate cancer cells, but it is now known to be expressed in various tissues throughout the body. Its physiologic expression is governed by latexin, a noncompetitive endogenous inhibitor of CPA4. Nevertheless, the overexpression of CPA4 has been associated with the progression and aggressiveness of many malignancies, including prostate, pancreatic, breast and lung cancer, to name a few. CPA4’s role in cancer has been attributed to its disruption of many cellular signaling pathways, e.g., PI3K-AKT-mTOR, STAT3-ERK, AKT-cMyc, GPCR, and estrogen signaling. The dysregulation of these pathways by CPA4 could be responsible for inducing epithelial--mesenchymal transition (EMT), tumor invasion and drug resistance. Although CPA4 has been found to regulate cancer aggressiveness and poor prognosis, no comprehensive review summarizing the role of CPA4 in cancer is available so far. In this review, we provide a brief description of peptidases, their classification, history of CPA4, mechanism of action of CPA4 as a peptidase, its expression in various tissues, including cancers, its role in various tumor types, the associated molecular pathways and cellular processes. We further discuss the limitations of current literature linking CPA4 to cancers and challenges that prevent using CPA4 as a biomarker for cancer aggressiveness and predicting drug response and highlight a number of future strategies that can help to overcome the limitations. Full article

Background: Secondary (nosocomial) bacterial meningitis remains a serious problem in patients with severe brain damage. The aim of this study was to assess the differences in the aromatic metabolites of tryptophan, phenylalanine, and tyrosine, in serum and cerebrospinal fluid (CSF) samples collected simultaneously from patients with long-term sequelae of severe brain damage with suspected secondary bacterial meningitis. Methods: Group I included 16 paired serum and CSF samples from patients (N = 11) without secondary bacterial meningitis; group II included 13 paired serum and CSF samples from patients (N = 4) with secondary bacterial meningitis. Results: The median concentrations of serum 5-hydroxyindole-3-acetic, CSF 4-hydroxyphenyllactic (p-HPhLA), CSF 4-hydroxyphenylacetic, CSF phenyllactic, and indole-3-lactic acids in serum and CSF were statistically higher in group II compared to group I (p-value ≤ 0.03), while 4-hydroxyphenylpropionic and indole-3-acetic in serum were lower in group II compared to group I (p-value = 0.04). In group I, p-HPhLA serum concentrations were greater than or equal to its CSF concentrations in 14 paired samples; in group II, p-HPhLA concentrations in serum were lower than in CSF in all paired samples. Conclusions: The obtained results demonstrate the differences in the profile of aromatic metabolites in serum and CSF and may confirm the hypothesis of the p-HPhLA microbial origin in the CSF of patients with secondary bacterial meningitis. Full article

Understanding the metabolic characteristics of pineapple varieties is crucial for market expansion and diversity. This study performed comparative metabolomic analysis on the “Comte de Paris” (BL) and three Taiwan-introduced varieties: “Tainong No. 11” (XS), “Tainong No. 23” (MG), and “Tainong No. 13” (DM). A total of 551 metabolites were identified across the four varieties, with 231 metabolites exhibiting no significant differences between all varieties. This included major sugars such as sucrose, glucose, and fructose, as well as key acids like citric, malic, and quinic acids, indicating that the in-season maturing fruits of different pineapple varieties can all achieve good sugar–acid accumulation under suitable conditions. The differentially accumulated metabolites (DAMs) that were identified among the four varieties all primarily belonged to several major subclasses, including phenolic acids, flavonoids, amino acids and derivatives, and alkaloids, but the preferentially accumulated metabolites in each variety varied greatly. Specifically, branched-chain amino acids (L-leucine, L-isoleucine, and L-valine) and many DAMs in the flavonoid, phenolic acid, lignan, and coumarin categories were most abundant in MG, which might contribute to its distinct and enriched flavor and nutritional value. XS, meanwhile, exhibited a notable accumulation of aromatic amino acids (L-phenylalanine, L-tryptophan), various phenolic acids, and many lignans and coumarins, which may be related to its unique flavor profile. In DM, the dominant accumulation of jasmonic acid might contribute to its greater adaptability to low temperatures during autumn and winter, allowing off-season fruits to maintain good quality. The main cultivar BL exhibited the highest accumulation of L-ascorbic acid and many relatively abundant flavonoids, making it a good choice for antioxidant benefits. These findings offer valuable insights for promoting different varieties and advancing metabolome-based pineapple improvement programs. Full article

Faecal microbiota transplantation (FMT) is an emerging therapy for gastrointestinal and neurological disorders, acting via the microbiota–gut–brain axis. Altering gut microbial composition may influence cognitive function, but this has not been tested in cognitively healthy adults. This randomised, double-blinded, placebo-controlled pilot trial investigates whether FMT is feasible and improves cognition in adults with irritable bowel syndrome (IBS). Participants receive a single dose of FMT or placebo via rectal retention enema. Cognitive performance is the primary outcome, assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). Secondary outcomes include IBS symptom severity and mood. Tertiary outcomes include microbiome composition and plasma biomarkers related to inflammation, short-chain fatty acids, and tryptophan metabolism. Outcomes are assessed at baseline and at one, three, six, and twelve months following treatment. We hypothesise that FMT will lead to greater improvements in cognitive performance than placebo, with benefits extending beyond practice effects, emerging at one month and persisting in the long term. The findings will contribute to evaluating the safety and efficacy of FMT and enhance our understanding of gut–brain interactions. Full article

The use of methane as a carbon source for producing bacterial single-cell protein (SCP) has been one of the most interesting developments in recent years. Most of these upcoming industries are using a methanotroph, Methylococcus capsulatus Bath, for SCP production using natural gas as the substrate. In the present study, we have explored the possibility of using an indigenously isolated methanotroph from a rice field in India, Methylomagnum ishizawai strain KRF4, for producing SCP from biogas [derived from cow dung]. The process was eco-friendly, required minimal instruments and chemicals, and was carried out under semi-sterile conditions in a tabletop fish tank. As the name suggests, Methylomagnum is a genus of large methanotrophs, and the strain KRF4 had elliptical to rectangular size and dimensions of ~4–5 µm × 1–2 µm. In static cultures, when biogas and air were supplied in the upper part of the growing tank, the culture grew as a thick pellicle/biofilm that could be easily scooped. The grown culture was mostly pure, from the microscopic observations where the large size of the cells, with rectangular-shaped cells and dark granules, could easily help identify any smaller contaminants. Additionally, the large cell size could be advantageous for separating biomass during downstream processing. The amino acid composition of the lyophilized biomass was analyzed using HPLC, and it was seen that the amino acid composition was comparable to commercial fish meal, soymeal, Pruteen, and the methanotroph-derived SCP-UniProtein^®. The only difference was that a slightly lower percentage of lysine, tryptophan, and methionine was observed in Methylomagnum-derived SCP. Methylomagnum ishizawai could be looked at as an alternative for SCP derived from methane or biogas due to the comparable SCP produced, on the qualitative level. Further intensive research is needed to develop a continuous, sustainable, and economical process to maximize biomass production and downstream processing. Full article

Tryptophan is synthesized in microorganisms via a five-step enzymatic pathway originating from chorismate, which is a product of the shikimate pathway. As a biosynthetic precursor to a wide range of high-value compounds such as indole-3-acetic acid, indigo, indirubin, and violacein, this pathway has been a central target for metabolic engineering to enhance microbial production. Anthranilate phosphoribosyltransferase (AnPRT) catalyzes the second step of the pathway by transferring a phosphoribosyl group from PRPP to anthranilate, forming phosphoribosyl anthranilate (PRA). AnPRT, the sole member of class IV phosphoribosyltransferases, adopts a unique fold and functions as a homodimer. While the structural basis of AnPRT activity has been elucidated in several organisms, thermostable variants remain underexplored despite their relevance for high-temperature bioprocessing. In this study, the crystal structure of AnPRT from the thermophilic archaeon Methanocaldococcus jannaschii (MjAnPRT) was determined at a 2.16 Å resolution. The enzyme exhibits a conserved dimeric architecture and key catalytic motifs. Comparative structural analysis with mesophilic and hyper thermophilic homologs revealed that MjAnPRT possesses enhanced local stability in catalytically important regions and strengthened inter-subunit interactions. These features likely contribute to its thermostability and provide a valuable framework for the rational design of robust AnPRTs for industrial and synthetic biology applications. Full article

Background/Objectives: Blunt cardiac injury (BCI) is a severe medical condition that may arise as a result of various traumas, including motor vehicle accidents and falls. The main objective of this study was to explore the role and underlying mechanisms of the TRPV4 gene in BCI. Elucidating the function of TRPV4 in BCI may reveal potential novel therapeutic targets for the treatment of this condition. Methods: Rats in each group, including the SD control group (SDCON), the SD blunt-trauma group (SDBT), the TRPV4 gene-knockout control group (KOCON), and the TRPV4 gene-knockout blunt-trauma group (KOBT), were all freely dropped from a fixed height with a weight of 200 g and struck in the left chest with a certain energy, causing BCI. After the experiment, the levels of serum IL-6 and IL-1β were detected to evaluate the inflammatory response. The myocardial tissue structure was observed by HE staining. In addition, cardiac transcriptome analysis was conducted to identify differentially expressed genes, and metabolomics studies were carried out using UHPLC-Q-TOF/MS technology to analyze metabolites. The results of transcriptomics and metabolomics were verified by qRT-PCR and Western blot analysis. Results: Compared with the SDCON group, the levels of serum IL-6 and IL-1β in the SDBT group were significantly increased (p < 0.001), while the levels of serum IL-6 and IL-1β in the KOBT group were significantly decreased (p < 0.001), indicating that the deletion of the TRPV4 gene alleviated the inflammation induced by BCI. HE staining showed that myocardial tissue injury was severe in the SDBT group, while myocardial tissue structure abnormalities were mild in the KOBT group. Transcriptome analysis revealed that there were 1045 upregulated genes and 643 downregulated genes in the KOBT group. These genes were enriched in pathways related to inflammation, apoptosis, and tissue repair, such as p53, apoptosis, AMPK, PPAR, and other signaling pathways. Metabolomics studies have found that TRPV4 regulates nucleotide metabolism, amino-acid metabolism, biotin metabolism, arginine and proline metabolism, pentose phosphate pathway, fructose and mannose metabolism, etc., in myocardial tissue. The combined analysis of metabolic and transcriptional data reveals that tryptophan metabolism and the protein digestion and absorption pathway may be the key mechanisms. The qRT-PCR results corroborated the expression of key genes identified in the transcriptome sequencing, while Western blot analysis validated the protein expression levels of pivotal regulators within the p53 and AMPK signaling pathways. Conclusions: Overall, the deletion of the TRPV4 gene effectively alleviates cardiac injury by reducing inflammation and tissue damage. These findings suggest that TRPV4 may become a new therapeutic target for BCI, providing new insights for future therapeutic strategies. Full article

T-2 toxin and HT-2 toxin are commonly found in agricultural products and animal feed, posing serious effects to both humans and animals. This study employed combination index (CI) modeling and metabolomics to assess the combined cytotoxic effects of T-2 and HT-2 on four porcine cell types: intestinal porcine epithelial cells (IPEC-J2), porcine Leydig cells (PLCs), porcine ear fibroblasts (PEFs), and porcine hepatocytes (PHs). Cell viability assays revealed a dose-dependent reduction in viability across all cell lines, with relative sensitivities in the order: IPEC-J2 > PLCs > PEFs > PHs. Synergistic cytotoxicity was observed at low concentrations, while antagonistic interactions emerged at higher doses. Untargeted metabolomic profiling identified consistent and significant metabolic perturbations in four different porcine cell lines under co-exposure conditions. Notably, combined treatment with T-2 and HT-2 resulted in a uniform downregulation of LysoPC (22:6), LysoPC (20:5), and LysoPC (20:4), implicating disruption of membrane phospholipid integrity. Additionally, glycerophospholipid metabolism was the most significantly affected pathway across all cell lines. Ether lipid metabolism was markedly altered in PLCs and PEFs, whereas PHs displayed a unique metabolic response characterized by dysregulation of tryptophan metabolism. This study identified markers of synergistic toxicity and common alterations in metabolic pathways across four homologous porcine cell types under the combined exposure to T-2 and HT-2 toxins. These findings enhance the current understanding of the molecular mechanisms underlying mycotoxin-induced the synergistic toxicity. Full article

This story began half a century ago with the discovery of an unusually high presence of tryptophan (Trp, W) in transthyretin (TTR), one of the three carrier proteins of thyroid hormones. With the Trp-rich retinol-binding protein (RBP), TTR forms a plasma complex implicated in the delivery of retinoid compounds to body tissues. W has the lowest concentration among all AAs involved in the sequencing of human body proteins. The present review proposes molecular maps focusing on the ratio of W/AA residues found in the sequence of proteins involved in immune events, allowing us to ascribe the guidance of inflammatory processes as fully under the influence of W. Under the control of cytokine stimulation, plasma biomarkers of protein nutritional status work in concert with major acute-phase reactants (APRs) and with carrier proteins to release, in a free and active form, their W and hormonal ligands, interacting to generate hot spots affecting the course of acute stress disorders. The prognostic inflammatory and nutritional index (PINI) scoring formula contributes to identifying the respective roles played by each of the components prevailing during the progression of the disease. Glucagon demonstrates ambivalent properties, remaining passive under steady-state conditions while displaying stronger effects after cytokine activation. In developing countries, inappropriate weaning periods lead to toddlers eating W-deficient cereals as a staple, causing a dramatic reduction in the levels of W-rich biomarkers in plasma, constituting a novel nutritional deficiency at the global scale. Appropriate counseling should be set up using W implementations to cover the weaning period and extended until school age. In adult and elderly subjects, the helpful immune protections provided by W may be hindered by the surge in harmful catabolites with the occurrence of chronic complications, which can have a significant public health impact but lack the uncontrolled surges in PINI observed in young infants and teenagers. Biomarkers of neurodegenerative and neoplastic disorders measured in elderly patients indicate the slow-moving elevation of APRs due to rampant degradation processes. Full article