Metabolite Concentrations Research Articles

Metabolomics Reveal the Chemical Characteristic of Cigar Tobacco Leaves During Air-Curing Process

Air-curing is a critical process in the production of cigar tobacco leaves. This process involves the vital degradation and transformation of macromolecular substances into micromolecular chemical compounds. In this study, three different varieties of tobacco leaves harvested from the Wuzhishan and Danzhou areas of Hainan, China were used as materials. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was employed to investigate the chemical changes before and after air-curing in the metabolites. Metabolic analysis revealed significant stepwise alterations in the tobacco leaf metabolome during the air-curing process. A total of 172 differential metabolites were identified as significant contributors in the biosynthesis pathways of flavonoids, flavone, flavonol, and other secondary metabolites, among the total analyzed 1841 metabolites obtained from the tobacco leaves. Notably, the contents of flavonoid metabolites, including kaempferol, rutin, chlorogenic acid, and quercetin, exhibited a significant decrease throughout the air-curing period. Correlation analysis indicated a strong association between the biosynthesis of flavonoids and the contents of chlorogenic acid and kaempferol, suggesting their role in regulation the formation of yellow and brown colors in tobacco leaves. These findings provide valuable insights for future investigations into the quality, commercial value, and chemical properties of cigar tobacco.

Coronary circulation enhances the aerobic performance of wild Pacific salmon.

Female Pacific salmon often experience higher mortality than males during their once-in-a-lifetime up-river spawning migration, particularly when exposed to secondary stressors (e.g. high temperatures). However, the underlying mechanisms remain unknown. One hypothesis is that female Pacific salmon hearts are more oxygen-limited than males and are less able to supply oxygen to the body's tissues during this demanding migration. Notably, female hearts have higher coronary blood flow, which could indicate a greater reliance on this oxygen source. Oxygen limitations can develop from naturally occurring coronary blockages (i.e., coronary arteriosclerosis) found in mature salmon hearts. If female hearts rely more heavily on coronary blood flow but experience similar arteriosclerosis levels as males, they will have disproportionately impaired aerobic performance. To test this hypothesis, we measured resting (RMR) and maximum metabolic rate (MMR), aerobic scope (AS) and acute upper thermal tolerance in coho salmon (Oncorhynchus kisutch) with an intact or artificially blocked coronary oxygen supply. We also assessed venous blood oxygen and chemistry (cortisol, ions, and metabolite concentrations) at different time intervals during recovery from exhaustive exercise. We found that coronary blockage impaired MMR, AS, and the partial pressure of oxygen in venous blood (PvO2) during exercise recovery but did not differ between sexes. Coronary ligation lowered acute upper thermal tolerance by 1.1°C. Though we did not find evidence of enhanced female reliance on coronary supply, our findings highlight the importance of coronary blood supply for mature wild salmon, where migration success may be linked to cardiac performance, particularly during warm water conditions.

Higher exposure to 1,3-butadiene is associated with more severe hearing loss

While volatile organic compounds (VOCs) impair various organs, their influence on hearing loss (HL) has not been extensively researched. We aimed to identify the association between VOCs and HL or high-frequency hearing loss (HFHL). We extracted data on age, sex, pure tone audiometry, hypertension, occupational noise exposure, and creatinine-corrected urine VOC metabolite concentrations from the eighth Korea National Health and Nutrition Survey. Among the VOC metabolites, N-acetyl-S-(benzyl)-L-cysteine (BMA, P = 0.004), N-acetyl-S-(phenyl)-l-cysteine (SPMA, P = 0.027), and N-acetyl-S-(3,4-dihydroxybutyl)-l-cysteine (DHBMA, P < 0.001) showed associations with HL. Additionally, HFHL exhibited significant associations with BMA (P = 0.005), 3- and 4-methylhippuric acid (3, 4 MHA, P = 0.049), mandelic acid (MA, P = 0.015), SPMA (P < 0.001), N-acetyl-S-(3-hydroxypropyl)-l-cysteine (3-HPMA, P < 0.001), and DHBMA (P < 0.001). After controlling other factors, DHBMA were associated with HL (P = 0.021) and HFHL (P = 0.014) and exhibited a linear association with the mean hearing level (β = 0.054, P = 0.024) and high-frequency hearing level (β = 0.045, P = 0.037). Since 1,3-butadiene may act as an ototoxic material, early screening for workers exposed to 1,3-butadiene and reducing exposure to 1,3-butadiene in everyday life may be helpful to prevent further HL.

Development of a Novel Non-invasive Metabolomics Assay to Predict Implantation Potential of Human Embryos.

Can a set of metabolites present in embryo culture media correlate with embryo implantation? Case-control study in two phases: discovery phase (101 samples) and validation phase (169 samples), collected between 2018 and 2022, with a total of 218 participants. Culture media samples with known implantation outcomes were collected after blastocyst embryo transfer (including both PGT and non-PGT cycles) and were analyzed using chromatography followed by mass spectrometry. The spectra were processed and analyzed using statistical and machine learning techniques to identify biomarkers associated with embryo implantation, and to develop a predictive model. In the discovery phase, 148 embryo implantation biomarkers were identified using high resolution equipment, and 47 of them were characterized. Our results indicate a significant enrichment of tryptophan metabolism, arginine and proline metabolism, and lysine degradation biochemical pathways. After transferring the method to a lower resolution equipment, a model able to assign a Metabolite Pregnancy Index (MPI) to each embryo culture media was developed, taking the concentration of 36 biomarkers as input. Applying this model to 20% of the validation samples (N=34) used as the test set, an accuracy of 85.29% was achieved, with a PPV (Positive Predictive Value) of 88% and a NPV (Negative Predictive Value) of 77.78%. Additionally, informative results were obtained for all the analyzed samples. Metabolite concentration in the media after in vitro culture shows correlation with embryo implantation potential. Furthermore, the mathematical combination of biomarker concentrations using Artificial Intelligence techniques can be used to predict embryo implantation outcome with an accuracy of around 85%.

Moderate concentration of Lactobacillus metabolites does not adversely affect mouse sperm

Many couples in contemporary societies suffer from infertility of unexplained origins (idiopathic). A promising treatment strategy within this context involves the administration to women of preparations containing lactic acid bacteria (Lactobacillus) and/or their metabolites. Recent investigations underscore the role of lactobacilli in sustaining female fertility and enhancing the effectiveness of assisted reproductive techniques. There have also been reports describing the effect of lactobacilli on sperm functions, but our knowledge in this domain remains uncertain. In this study, the effect of supernatant from Lactobacillus rhamnosus culture on mouse sperm viability and motility was tested. The protective properties of lactobacilli metabolites against hydrogen peroxide-induced DNA damage were also verified. It was shown that the metabolites have no effect on viability, motility, and genome integrity of spermatozoa, but in excessive concentrations they become toxic. The obtained results imply that probiotic and/or postbiotic preparations taken by women should not adversely affect the sperm of their partners, provided the dose is correctly selected.

Lockbox enrichment facilitates manipulative and cognitive activities for mice

Background Due to the lack of complexity and variety of stimuli, conventional housing conditions of laboratory mice do not allow these animals to fully express their behavioral repertoire, including manipulative and cognitive activities. Therefore, we designed mechanical puzzles, so-called lockboxes, for mice that can be provided in their home cages. We investigated the impact of the lockbox enrichment on their phenotype and affective state when compared to conventional housing and super-environmental enrichment. Methods Young adult female C57BL/6JCrl mice were examined before and after 2-month exposure to the different types of enrichment in a phenotyping test battery, including tests for trait and state anxiety-related behavior, calorimetric measurements, body weight measurements, and the analysis of stress hormone metabolite concentrations as well as sequential problem-solving abilities. At the end of the study, adrenal gland weights were determined and pathohistological evaluation was performed. For all continuous variables, the relative variability was calculated. Results We demonstrated that lockbox enrichment decreased trait anxiety-related behavior compared to conventional housing in the Grid Exploratory Paradigm. In contrast, the different types of enrichment neither influenced state anxiety-related behavior in the Open Field and Elevated Plus Maze Test nor physiological variables (i.e., bodyweight, resting metabolic rate, stress hormone metabolite concentrations, and adrenal gland weights). Lockbox enrichment improved sequential problem-solving when compared to super-environmental enrichment. Regardless of the housing condition, the relative variability increased in most variables over time, although the coefficient of variation decreased for some variables, especially in animals with access to the lockbox enrichment. A pathohistological evaluation revealed no evidence of toxicopathological effects associated with the material from which the lockbox enrichment was made. Conclusions Overall, the lockbox enrichment revealed beneficial effects on the affective state and sequential problem-solving abilities of laboratory mice. The reproducibility was demonstrated not to be compromised by lockbox enrichment, similar to super-environmental enrichment.

A pilot case-control study on the fecal microbiota of pediatric functional abdominal pain-not otherwise specified and the role of early life stress

Background: Gut microbial features and the role of early life stress in pediatric functional abdominal pain-not otherwise specified (FAP-NOS) have never been investigated before. Here, we hypothesize that early life stress is more prevalent in FAP-NOS compared to healthy controls and that fecal microbial profiles and related metabolites differ between groups. Methods: In an international multicenter case-control study, FAP-NOS patients (n = 40) were compared to healthy controls (n = 55). Stool samples and demographic and clinical data including early life traumatic events and antibiotics treatments were collected from children aged four to twelve years. Fecal microbial profiles were assessed with 16S rRNA gene amplicon sequencing. Microbial metabolite concentrations in fecal supernatant, including short-chain fatty acids and amino acids, were detected via liquid chromatography. Results: Microbial richness was increased in FAP-NOS compared to healthy controls and microbial composition (unweighted UniFrac) differed between groups. Three distinct amplicon sequencing variants and two distinct species were enriched in FAP-NOS compared to controls, with no observed changes at higher taxonomic levels. No differences in microbial metabolites and early life stress were observed between groups. Conclusion: The presented hypothesis could not be proven, with no observed differences in occurrence of early life stress, and fecal microbial metabolic profiles between pediatric FAP-NOS and healthy controls. Pediatric FAP-NOS patients exhibited mild differences in the fecal microbial community compared with controls. Further large-scale studies with high-resolution techniques are warranted to address the biological relevance of present observations.

Rhizosphere metagenomics provides insights into the environmental effect on the secondary metabolism of Ligusticum chuanxiong

Rhizosphere microbiomes influence the secondary metabolism of plants, but the mechanism has not been analyzed. This study aimed to explore relationship between abiotic environments, microbiomes and secondary metabolites of Ligusticum chuanxiong. By combining metagenomic, metatranscriptomic, and high-performance liquid chromatography, the microbial community structure and key microbiomes in Ligusticum chuanxiong were identified. Furthermore, the relationship between root-associated microbiomes and the secondary metabolites in Ligusticum chuanxiong was revealed. The microbial community structures of L. chuanxiong differed in each individual. The key microbiome related to secondary metabolism were similar, while there were significant differences in relative abundance across all samples. Four families (Burkholderiaceae, Comamonadaceae, Pseudomonadaceae, and Streptomycetaceae) and four species (Gemmatirosa kalamazoonesis, Luteitalea pratensis, Candidatus Solibacter usitatus, and Sorangium cellulosum) were identified as conservative core microbes, and Chloroflexi was the main biomarker. Functional annotation results showed that the metabolic function strength of the microbial community was positively correlated with the secondary metabolite content. According to correlation results, rhizosphere microbiomes related with secondary metabolites in two aspects including community diversity and microbial abundance. In conclusion, environmental factors might affect secondary metabolites of Ligusticum chuanxiong Hort. by influencing microbial diversity and the abundance of key microbes. This study can provide references for improving the artificial cultivation of Ligusticum chuanxiong, further developing and utilizing this medicinal resource.

Effects of priming duration and concentration of metabolites from rhizosphere bacteria on the germinability of cowpea, soybean, sesame, and okra seeds

Seed priming enhances germination and growth, which are important determinants of crop yield. This study was carried out to assess the effect of priming duration and metabolite concentration on the priming of five (5) different crops, using the metabolites of five (5) bacterial isolates. The crop seeds were treated in the cold-extracted metabolites of the five isolates at five (5) different priming durations (1, 2, 3, 4, and 5 h) and then in five metabolite concentrations (200, 400, 600, 800, and 1000 mg/L) of the five extracted metabolites at the optimal priming duration determined in the first experiment. Characterization of the cold-extracted metabolites was also carried out using gas-chromatography-mass spectrometry (GC-MS). Results revealed that priming cowpea and soybean for longer durations (&lt; 3 h) could hinder their growth and development. Lower concentrations were observed to be optimal for cowpea and soybean, but for sesame and okra, there was no detectable pattern with metabolite concentration. The GC-MS revealed the presence of some molecules (e.g. hexadecanoic acid) that have shown plant growth promotion potential in other studies. This study showed that seeds with large endosperm, such as, cowpea and soybean, are more prone to the deleterious effects of treatment for longer durations. Further experiments should be carried out to isolate and purify the bioactive moieties for further studies and onward application.

Metabolomics-based study on the significance of differential metabolite binding IgG isoforms in Hemolytic disease of newborn

ABSTRACT Background: Hemolytic disease of the newborn (HDN) is a common condition that can have a severe impact on the health of newborns due to the hemolytic reactions it triggers. Although numerous studies have focused on understanding the pathogenesis of HDN, there are still many unanswered questions. Methods: In this retrospective study, serum samples were collected from 15 healthy newborns and 8 infants diagnosed with hemolytic disease. The relationship between different metabolites and various IgG subtypes in Healthy, HDN and BLI groups was studied by biochemical technique and enzyme-linked immunosorbent assay (ELISA). Metabolomics analysis was conducted to identify the differential metabolites associated with HDN. Subsequently, Pearson's correlation analysis was used to determine the relation of these differential metabolites with IgG isoforms. The relationship between the metabolites and IgG subtypes was observed after treatment. Results: The study results revealed that infants with hemolytic disease exhibited abnormal elevations in TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4 levels when compared to healthy newborns. Additionally, differences in metabolite contents were also observed. N, N-DIMETHYLARGININE showed negative correlations with TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4, while 2-HYDROXYBUTYRATE, AMINOISOBUTANOATE, Inosine, and ALLYL ISOTHIOCYANATE exhibited positive correlations with TBA, IgG1, IgG2a, IgG2b, IgG3, and IgG4. Through metabolomics-based research, we have discovered associations between differential metabolites and different IgG isoforms during the onset of HDN. Conclusion: These findings suggest that changes in metabolite and IgG isoform levels are linked to HDN. Understanding the involvement of IgG isoforms and metabolites can provide valuable guidance for the diagnosis and treatment of HDN.

Differential responses of primary neuron-secreted MCP-1 and IL-9 to type 2 diabetes and Alzheimer’s disease-associated metabolites

Type 2 diabetes (T2D) is implicated as a risk factor for Alzheimer’s disease (AD), the most common form of dementia. In this work, we investigated neuroinflammatory responses of primary neurons to potentially circulating, blood–brain barrier (BBB) permeable metabolites associated with AD, T2D, or both. We identified nine metabolites associated with protective or detrimental properties of AD and T2D in literature (lauric acid, asparagine, fructose, arachidonic acid, aminoadipic acid, sorbitol, retinol, tryptophan, niacinamide) and stimulated primary mouse neuron cultures with each metabolite before quantifying cytokine secretion via Luminex. We employed unsupervised clustering, inferential statistics, and partial least squares discriminant analysis to identify relationships between cytokine concentration and disease-associations of metabolites. We identified MCP-1, a cytokine associated with monocyte recruitment, as differentially abundant between neurons stimulated by metabolites associated with protective and detrimental properties of AD and T2D. We also identified IL-9, a cytokine that promotes mast cell growth, to be differentially associated with T2D. Indeed, cytokines, such as MCP-1 and IL-9, released from neurons in response to BBB-permeable metabolites associated with T2D may contribute to AD development by downstream effects of neuroinflammation.

Genome-wide profiling of WRKY genes involved in flavonoid biosynthesis in Erigeron breviscapus.

The transcription factors of WRKY genes play essential roles in plant growth, stress responses, and metabolite biosynthesis. Erigeron breviscapus, a traditional Chinese herb, is abundant in flavonoids and has been used for centuries to treat cardiovascular and cerebrovascular diseases. However, the WRKY transcription factors that regulate flavonoid biosynthesis in E. breviscapus remain unknown. In this study, a total of 75 EbWRKY transcription factors were predicted through comprehensive genome-wide characterization of E. breviscapus and the chromosomal localization of each EbWRKY gene was investigated. RNA sequencing revealed transient responses of 74 predicted EbWRKY genes to exogenous abscisic acid (ABA), salicylic acid (SA), and gibberellin 3 (GA3) after 4h of treatment. In contrast, the expression of key structural genes involved in flavonoid biosynthesis increased after 4h in GA3 treatment. However, the content of flavonoid metabolites in leaves significantly increased at 12h. The qRT-PCR results showed that the expression patterns of EbWRKY11, EbWRKY30, EbWRKY31, EbWRKY36, and EbWRKY44 transcription factors exhibited a high degree of similarity to the 11 structural genes involved in flavonoid biosynthesis. Protein-DNA interactions were performed between the key genes involved in scutellarin biosynthesis and candidate WRKYs. The result showed that F7GAT interacts with EbWRKY11, EbWRKY36, and EbWRKY44, while EbF6H has a self-activation function. This study provides comprehensive information on the regulatory control network of flavonoid accumulation mechanisms, offering valuable insights for breeding E. breviscapus varieties with enhanced scutellarin content.

Chemical and Biological Characterization of the Ethyl Acetate Fraction from the Red Sea Marine Sponge Hymedesmia sp.

Hymedesmiidae is one of the largest families of marine sponges and stands out as an exceptional source of variable metabolites with diverse biological activities. In this study, the ethyl acetate fraction (HE) of a Hymedesmia sp. marine sponge from the Red Sea, Egypt, was analyzed for the first time using Ultra-performance liquid chromatography electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) analysis. The analysis tentatively identified 29 compounds in this fraction, including the isolation and identification of six compounds (two pyrimidine nucleosides, one purine, and two pyrimidine bases in addition to one cerebroside) for the first time. The structures of the isolated compounds were established by 1D and 2D NMR (nuclear magnetic resonance), MS (mass spectrometry), and IR (infrared) spectroscopy. Furthermore, the cytotoxic, antioxidant, and antimicrobial activities of the ethyl acetate fraction were evaluated in vitro. The fraction exhibited strong DPPH scavenging activity with an IC50 of 78.7 µg/mL, compared to ascorbic acid as a positive control with an IC50 of 10.6 µg/mL. It also demonstrated significant cytotoxic activity with IC50 values of 13.5 µg/mL and 25.3 µg/mL against HCT-116 and HEP-2 cell lines, respectively, compared to vinblastine as a positive control with IC50 values of 2.34 µg/mL and 6.61 µg/mL against HCT-116 and HEP-2, respectively. Additionally, the ethyl acetate fraction displayed promising antibacterial activity against S. aureus with a MIC value of 62.5 µg/mL, compared to ciprofloxacin as a positive control with MIC values of 1.56 µg/mL for Gram-positive bacteria and 3.125 µg/mL for Gram-negative bacteria. It also exhibited activity against E. coli and P. aeruginosa with MIC values of 250 µg/mL and 500 µg/mL, respectively. Briefly, this is the first report on the biological activities and secondary metabolite content of the ethyl acetate fraction of Hymedesmia sp. marine sponge, emphasizing the potential for further research against resistant bacterial and fungal strains, as well as different cancer cell lines. The ethyl acetate fraction of Hymedesmia sp. is a promising source of safe and unique natural drugs with potential therapeutic and pharmaceutical benefits.

Analgesic Activity Combination of Dry Extract of Meniran Leaves (Phyllanthus niruri L.) and Moringa Leaves (Moringa oleifera L.) Using the Chemical Induction Method: Invivo Study

Analgesics are drugs that selectively reduce pain in the central nervous system or peripheral pain mechanisms without significantly changing consciousness. This study aims to determine the analgesic activity of a combination of dry extracts of meniran leaves (Phyllanthus niruri l.) and moringa leaves (Moringa oleifera l.) against Swiss Webster rats with chemical induction methods. This research proves the presence of secondary metabolite content in the dry extract of meniran leaves and moringa leaves which have analgesic activity. The research used 30 male Swiss Webster rats divided into 5 groups. Group 1 is the negative control (CMC-Na 0.5%), group 2 is the positive control (diclofenac Na), group 3 (Dry extract of meniran leaves), group 4 (Dry extract of moringa leaves) and Group 5 (Combination of dry extracts). meniran and moringa leaves). Each was given 1 mL of 1% acetic acid induction chemical stimulation, then the writhing response was observed and recorded at 5-minute intervals for 30 minutes. The results showed that the K3 group combined dry extract of meniran leaves (Phyllanthus niruri L.) and moringa leaves (Moringa oleifera L) is not statistically significantly different from the positive control diclofenac sodium, p-value = 0.183. In conclusion, dry extract of meniran leaves (Phyllanthus niruri L.) and Moringa leaves (Moringa oleifera L.) has been proven to contain secondary metabolites of flavonoids, alkaloids, tannins, and saponins which have analgesic activity.

Associations between neonicotinoids and liver function measures in US adults: National Health and Nutrition Examination Survey 2015–2016

Background: Toxicological studies indicate that neonicotinoids may be associated with disruptions in liver function due to an increase in oxidative stress. There are scant epidemiological studies investigating the chronic hepatotoxic effects of neonicotinoids. Objective: To examine the association between detectable concentrations of parent neonicotinoids and neonicotinoid metabolites with liver function markers among US adults, and whether sex modifies this association. Methods: National Health and Nutrition Examination Survey 2015–2016 data were used to estimate associations between detectable neonicotinoids and serum alkaline phosphatase (ALP), alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transaminase (GGT), albumin, total bilirubin, total protein, and Hepatic Steatosis Index (HSI) using multiple linear regression. Results: Detectable levels of N-desmethyl-acetamiprid were associated with a decrease in GGT (β = −3.54 unit/l; 95% confidence interval [CI] = −6.48, −0.61) and detectable levels of 5-hydroxy-imidacloprid were associated with a decrease in HSI (β = −1.11; 95% CI = −2.14, −0.07). Sex modified the association between any parent neonicotinoid and ALP (P int = 0.064) and the association between clothianidin and ALP (P int = 0.019), with a pattern of positive associations in males and inverse associations in females, though stratified associations did not reach statistical significance. Sex also modified the association between 5-hydroxy-imidacloprid and total protein (P int = 0.062), with a significant positive association in females (β = 0.14 g/dl; 95% CI = 0.03, 0.25) and a null association in males. Conclusion: Detectable concentrations of neonicotinoid metabolites were inversely associated with GGT and HSI in US adults. Evidence suggests neonicotinoids may influence liver function differently depending on sex. Future research is recommended to replicate the findings as the study was limited in its cross-sectional nature and inability to examine continuous neonicotinoid concentrations with liver function.

Investigation of virginiamycin to improve health of growing and finishing steers: I. Effects on ruminal acidosis and liver health*

ObjectiveOur objective was to observe the effects of the interrelationship among virginiamycin (VM) inclusion (240 mg/d), ruminal pH dynamics, and hepatic plasma metabolites on rumen and animal health during a 150-d feeding trial. Materials and MethodsSteers (304 ± 27 kg; n = 120) were assigned randomly to 1 of 6 dietary treatments: no VM (T000); VM for the last 50 d (T001); VM for the last 100 d (T011); VM for the first 50 d (T100); VM for the first 100 d (T110); and VM for 150 d (T111). All animals were orally administered 2 indwelling rumen pH and temperature recording boli on d 0 and 84. Blood samples were collected via jugular venipuncture on d −7, 28, 56, 84, 112, and 140, and plasma was analyzed for concentrations of albumin, alkaline phosphatase, direct bilirubin, total bilirubin, gamma-glutamyl transferase, and total protein using an automated blood analyzer. Concurrently, haptoglobin (HPT) was measured following a colorimetric method based on peroxidase activity. A random coefficients model with pen and animals within treatment as a random effect was used. Results and DiscussionAnimals that received VM for the first 100 d (T110 and T111) had greater mean ruminal pH during d 50 to 100 when compared with animals that did not receive VM (T000 and T001; 6.12 vs. 6.00, respectively). Moreover, T111 tended to have less time under pH 5.8 (3.01 h/d) when compared with T100 and T001 (5.83 and 6.45 h/d, respectively). At slaughter, overall, 3.36% of cattle in the study were identified with liver abscesses (A and A−), and 24.3% had lung lesions. Plasma metabolite concentrations before slaughter did not predict the presence of liver abscesses (P ≥ 0.182). Based on acute phase responses, HPT was notably lower on d 84 after diet transition in VM-treated animals (46.1 vs. 68.9 mg/L). Additionally, VM inclusion boosted indicators of overall health with greater alkaline phosphatase levels and albumin-toglobulin ratios. Implications and ApplicationsVirginiamycin has practical implications for rumen health and overall cattle health, where supplementation during the whole growing to finishing phases was more effective in capturing its full potential.

Magnetic Resonance Spectroscopy Quantification Aided by Deep Estimations of Imperfection Factors and Macromolecular Signal.

Magnetic Resonance Spectroscopy (MRS) is an important technique for biomedical detection. However, it is challenging to accurately quantify metabolites with proton MRS due to serious overlaps of metabolite signals, imperfections because of non-ideal acquisition conditions, and interference with strong background signals mainly from macromolecules. The most popular method, LCModel, adopts complicated non-linear least square to quantify metabolites and addresses these problems by designing empirical priors such as basis-sets, imperfection factors. However, when the signal-to-noise ratio of MRS signal is low, the solution may have large deviation. Linear Least Squares (LLS) is integrated with deep learning to reduce the complexity of solving this overall quantification. First, a neural network is designed to explicitly predict the imperfection factors and the overall signal from macromolecules. Then, metabolite quantification is solved analytically with the introduced LLS. In our Quantification Network (QNet), LLS takes part in the backpropagation of network training, which allows the feedback of the quantification error into metabolite spectrum estimation. This scheme greatly improves the generalization to metabolite concentrations unseen in training compared to the end-to-end deep learning method. Experiments show that compared with LCModel, the proposed QNet, has smaller quantification errors for simulated data, and presents more stable quantification for 20 healthy in vivo data at a wide range of signal-to-noise ratio. QNet also outperforms other end-to-end deep learning methods. This study provides an intelligent, reliable and robust MRS quantification. QNet is the first LLS quantification aided by deep learning.

Temporal fiber-optic fluorescence study of FAD-NADH interactions in phantoms for potential applications in rapid liquid optical biopsy procedures

Body fluids carry several biomarkers and genetic material that enable the detection of carcinogenesis and tumor metastasis. Owing to this, liquid biopsy is gaining importance and entering clinical practice as an adjunct modality to the current standard of practice in cancer detection. Liquid biopsy involving specimens such as urine is non-invasive and has biomarkers reflecting the tumor microenvironment. We investigate the normal and altered levels of cellular metabolic by-products in liquid phantoms and demonstrate their photon-induced excited-state interaction behaviour for potential diagnostic applications. Short-span temporal analysis of metabolic by-products FAD and NADH in liquid phantoms with fiber optic fluorescence spectroscopy is carried out. The mixed liquid phantom of FAD and NADH, showed excited state interactions that manifested as simultaneous inverse variation in the fluorescence emission from FAD and NADH in varying pH environments. Linear discriminant analysis of the time-varying integrated fluorescence intensity resulted in a 100% accuracy in classifying liquid samples between high and low metabolite concentrations. An extension of application of the experiment model for analysis of body fluids such as urine is also discussed.

Integrative Metabolomics, Enzymatic Activity, and Gene Expression Analysis Provide Insights into the Metabolic Profile Differences between the Slow-Twitch Muscle and Fast-Twitch Muscle of Pseudocaranx dentex.

The skeletal muscles of teleost fish encompass heterogeneous muscle types, termed slow-twitch muscle (SM) and fast-twitch muscle (FM), characterized by distinct morphological, anatomical, histological, biochemical, and physiological attributes, driving different swimming behaviors. Despite the central role of metabolism in regulating skeletal muscle types and functions, comprehensive metabolomics investigations focusing on the metabolic differences between these muscle types are lacking. To reveal the differences in metabolic characteristics between the SM and FM of teleost, we conducted an untargeted metabolomics analysis using Pseudocaranx dentex as a representative model and identified 411 differential metabolites (DFMs), of which 345 exhibited higher contents in SM and 66 in FM. KEGG enrichment analysis showed that these DFMs were enriched in the metabolic processes of lipids, amino acids, carbohydrates, purines, and vitamins, suggesting that there were significant differences between the SM and FM in multiple metabolic pathways, especially in the metabolism of energy substances. Furthermore, an integrative analysis of metabolite contents, enzymatic activity assays, and gene expression levels involved in ATP-PCr phosphate, anaerobic glycolysis, and aerobic oxidative energy systems was performed to explore the potential regulatory mechanisms of energy metabolism differences. The results unveiled a set of differential metabolites, enzymes, and genes between the SM and FM, providing compelling molecular evidence of the FM achieving a higher anaerobic energy supply capacity through the ATP-PCr phosphate and glycolysis energy systems, while the SM obtains greater energy supply capacity via aerobic oxidation. These findings significantly advance our understanding of the metabolic profiles and related regulatory mechanisms of skeletal muscles, thereby expanding the knowledge of metabolic physiology and ecological adaptation in teleost fish.

Energy supply during nocturnal endurance flight of migrant birds: effect of energy stores and flight behaviour

BackgroundMigrating birds fly non-stop for hours or even for days. They rely mainly on fat as fuel complemented by a certain amount of protein. Studies on homing pigeons and birds flying in a wind-tunnel suggest that the shares of fat and protein on total energy expenditure vary with flight duration and body fat stores. Also, flight behaviour, such as descending flight, is expected to affect metabolism. However, studies on free flying migrant birds under natural conditions are lacking.MethodsOn a Swiss Alpine pass, we caught three species of nocturnal migrant passerines out of their natural migratory flight. Since most night migrants start soon after dusk, we used time since dusk as a measure of flight duration. We used plasma concentrations of metabolites of the fat, protein, and carbohydrate metabolism as indicators of relative fuel use. We used flight altitudes of birds tracked with radar and with atmospheric pressure loggers to characterize flight behaviour.ResultsThe indicators of fat catabolism (triglycerides, very low-density lipoproteins, glycerol) were positively correlated with body energy stores, supporting earlier findings that birds with high fat stores have a higher fat catabolism. As expected, plasma levels of triglycerides, very low-density lipoproteins, glycerol and ß-hydroxy-butyrate increased at the beginning of the night, indicating that nocturnal migrants increased their fat metabolism directly after take-off. Surprisingly, fat catabolism as well as glucose levels decreased in the second half of the night. Data from radar observations showed that the number of birds aloft, their mean height above ground and vertical flight speed decreased after midnight. Together with the findings from atmospheric pressure-loggers put on three species, this shows that nocturnal migrants migrating over continental Europe descend slowly during about 1.5 h before final landfall at night, which results in 11–30% energy savings according to current flight models.ConclusionsWe suggest that this slow descent reduces energy demands to an extent which is noticeable in the plasma concentration of lipid, protein, and carbohydrate metabolites. The slow descent may facilitate the search for a suitable resting habitat and serve to refill glycogen stores needed for foraging and predator escape when landed.