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Interstitial lung diseases (ILDs) include a variety of inflammatory and fibrotic pulmonary conditions. This study employs high-resolution metabolomics (HRM) to explore plasma metabolites and pathways across ILD phenotypes, including non-fibrotic ILD, idiopathic pulmonary fibrosis (IPF), and non-IPF fibrotic ILD. The study used 80 plasma samples for HRM, and involved linear trend and group-wise analyses of metabolites altered in ILD phenotypes. We utilized limma one-way ANOVA and mummichog algorithms to identify differences in metabolites and pathways across ILD groups. Then, we focused on metabolites within critical pathways, indicated by high pathway overlap sizes and low p-values, for further analysis. Targeted HRM identified putrescine, hydroxyproline, prolyl-hydroxyproline, aspartate, and glutamate with significant linear increases in more fibrotic ILD phenotypes, suggesting their role in ILD fibrogenesis. Untargeted HRM highlighted pathway alterations in lysine, vitamin D3, tyrosine, and urea cycle metabolism, all associated with pulmonary fibrosis. In addition, methylparaben level had a significantly increasing linear trend and was higher in the IPF than fibrotic and non-ILD groups. This study highlights the importance of specific amino acids, metabolic pathways, and xenobiotics in the progression of pulmonary fibrosis., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Vanadium pentoxide (V +5 ) is a hazardous material that has drawn considerable attention due to its wide use in industrial sectors and increased release into environment from human activities. It poses potential adverse effects on animals and human health, with pronounced impact on lung physiology and functions. In this study, we investigated the metabolic response of human bronchial epithelial BEAS-2B cells to low-level V +5 exposure (0.01, 0.1, and 1 ppm) using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Exposure to V +5 caused extensive changes to cellular metabolism in BEAS-2B cells, including TCA cycle, glycolysis, fatty acids, amino acids, amino sugars, nucleotide sugar, sialic acid, vitamin D 3 , and drug metabolism, without causing cell death. Altered mitochondrial structure and function were observed with as low as 0.01 ppm (0.2 μM) V +5 exposure. In addition, decreased level of E-cadherin, the prototypical epithelial marker of epithelial-mesenchymal transition (EMT), was observed following V +5 treatment, supporting potential toxicity of V +5 at low levels. Taken together, the present study shows that V +5 has adverse effects on mitochondria and the metabolome which may result in EMT activation in the absence of cell death. Furthermore, results suggest that high-resolution metabolomics could serve as a powerful tool to investigate metal toxicity at levels which do not cause cell death., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests. Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Little is known about lipid changes that occur in the setting of metabolic-dysfunction-associated steatotic liver disease (MASLD) regression. We previously reported improvements in hepatic steatosis, de novo lipogenesis (DNL), and metabolomic profiles associated with oxidative stress, inflammation, and selected lipid metabolism in 40 adolescent boys (11-16 y) with hepatic steatosis ≥5% (98% meeting the definition of MASLD). Participants were randomized to a low-free-sugar diet (LFSD) (n = 20) or usual diet (n = 20) for 8 weeks. Here, we employed untargeted/targeted lipidomics to examine lipid adaptations associated with the LFSD and improvement of hepatic steatosis. Our LC-MS/MS analysis revealed decreased triglycerides (TGs), diacylglycerols (DGs), cholesteryl esters (ChE), lysophosphatidylcholine (LPC), and phosphatidylcholine (PC) species with the diet intervention ( p < 0.05). Network analysis demonstrated significantly lower levels of palmitate-enriched TG species post-intervention, mirroring the previously shown reduction in DNL in response to the LFSD. Targeted oxylipins analysis revealed a decrease in the abundance of 8-isoprostane and 14,15-DiHET and an increase in 8,9-DiHET ( p < 0.05). Overall, we observed reductions in TGs, DGs, ChE, PC, and LPC species among participants in the LFSD group. These same lipids have been associated with MASLD progression; therefore, our findings may indicate normalization of key biological processes, including lipid metabolism, insulin resistance, and lipotoxicity. Additionally, our targeted oxylipins assay revealed novel changes in eicosanoids, suggesting improvements in oxidative stress. Future studies are needed to elucidate the mechanisms of these findings and prospects of these lipids as biomarkers of MASLD regression.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as NAFLD, is the most common liver disease in children. Liver biopsy remains the gold standard for diagnosis, although more efficient screening methods are needed. We previously developed a novel NAFLD screening panel in youth using machine learning applied to high-resolution metabolomics and clinical phenotype data. Our objective was to validate this panel in a separate cohort, which consisted of a combined cross-sectional sample of 161 children with stored frozen samples (75% male, 12.8±2.6 years of age, body mass index 31.0±7.0 kg/m2, 81% with MASLD, 58% Hispanic race/ethnicity)., Methods: Clinical data were collected from all children, and high-resolution metabolomics was performed using their fasting serum samples. MASLD was assessed by MRI-proton density fat fraction or liver biopsy and cardiometabolic factors. Our previously developed panel included waist circumference, triglycerides, whole-body insulin sensitivity index, 3 amino acids, 2 phospholipids, dihydrothymine, and 2 unknowns. To improve feasibility, a simplified version without the unknowns was utilized in the present study. Since the panel was modified, the data were split into training (67%) and test (33%) sets to assess the validity of the panel., Results: Our present highest-performing modified model, with 4 clinical variables and 8 metabolomics features, achieved an AUROC of 0.92, 95% sensitivity, and 80% specificity for detecting MASLD in the test set., Conclusions: Therefore, this panel has promising potential for use as a screening tool for MASLD in youth., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

Cadmium (Cd) is a naturally occurring, toxic environmental metal found in foods. Humans do not have an efficient mechanism for Cd elimination; thus, Cd burden in humans increases with age. Cell and mouse studies show that Cd burden from low environmental levels of exposure impacts lung cell metabolism, proliferation signaling and cell growth as part of disease-promoting profibrotic responses in the lungs. Prior integrative analysis of metabolomics and transcriptomics identified the zDHHC11 transcript as a central functional hub in response to Cd dose. zDHHC11 encodes a protein S-palmitoyltransferase, but no evidence is available for effects of Cd on protein S-palmitoylation. In the present research, we studied palmitoylation changes in response to Cd and found increased protein S-palmitoylation in human lung fibroblasts that was inhibited by 2-bromopalmitate (2-BP), an irreversible palmitoyltransferase inhibitor. Mass spectrometry-based proteomics showed palmitoylation of proteins involved in divalent metal transport and in fibrotic signaling. Mechanistic studies showed that 2-BP inhibited palmitoylation of divalent metal ion transporter ZIP14 and also inhibited cellular Cd uptake. Transcription analyses showed that Cd stimulated transforming growth factor (TGF)-β1 and β3 expression within 8 h and lung fibrotic markers α-smooth muscle actin, matrix metalloproteinase-2, and collagen 1α1 gene expression and that these effects were blocked by 2-BP. Because 2-BP also blocked palmitoylation of proteins controlled by TGFβ1, these results show that palmitoylation impacts Cd-dependent fibrotic signaling both by enhancing cellular Cd accumulation and by supporting post-translational processing of TGFβ1-dependent proteins., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Early-life respiratory syncytial virus (RSV) infection (eRSV) is one of the leading causes of serious pulmonary disease in children. eRSV is associated with higher risk of developing asthma and compromised lung function later in life. Cadmium (Cd) is a toxic metal, widely present in the environment and in food. We recently showed that eRSV re-programs metabolism and potentiates Cd toxicity in the lung, and our transcriptome-metabolome-wide study showed strong associations between S-palmitoyl transferase expression and Cd-stimulated lung inflammation and fibrosis signaling. Limited information is available on the mechanism by which eRSV re-programs metabolism and potentiates Cd toxicity in the lung. In the current study, we used a mouse model to examine the role of protein S-palmitoylation (Pr-S-Pal) in low dose Cd-elevated lung metabolic disruption and inflammation following eRSV. Mice exposed to eRSV were later treated with Cd (3.3 mg CdCl2/L) in drinking water for 6 weeks (RSV+Cd). The role of Pr-S-Pal was studied using a palmitoyl transferase inhibitor, 2-bromopalmitate (BP, 10 µM). Inflammatory marker analysis showed that cytokines, chemokines and inflammatory cells were highest in the RSV+Cd group, and BP decreased inflammatory markers. Lung metabolomics analysis showed that pathways including phenylalanine, tyrosine and tryptophan, phosphatidylinositol and sphingolipid were altered across treatments. BP antagonized metabolic disruption of sphingolipid and glycosaminoglycan metabolism by RSV+Cd, consistent with BP effect on inflammatory markers. This study shows that Cd exposure following eRSV has a significant impact on subsequent inflammatory response and lung metabolism, which is mediated by Pr-S-Pal, and warrants future research for a therapeutic target., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This report identifies, for the first time, a phytochelatin compound, phytochelatin 2 [γ-E-C-γ-E-C-G], and related metabolites in human urine. Phytochelatins are metal-binding peptides produced by plants. They are present in nearly all human diets, due to their ubiquity in plants. The urinary concentration of phytochelatin 2 among 143 adults was in the low micromolar range, and phytochelatin 2 and its metabolites had differential correlations with urinary selenium and toxic metals. Activities of ingested phytochelatins are largely undescribed. Observed urinary metal interactions were investigated further in cell and animal models. Selenite reacted with phytochelatin to form a phytochelatin selenotrisulfide, and the preformed selenotrisulfide showed increased selenium uptake by renal proximal tubule cells. In vivo studies further showed that oral phytochelatin increased renal selenium content and decreased lung cadmium in mice. Presence of phytochelatin in human urine combined with its function in selenium and heavy metal distribution present a new route by which diet may influence metal disposition and bioavailability., Competing Interests: The authors declare that they have no conflicts of interest with the contents of this article., (© 2023 The Authors. FASEB BioAdvances published by Wiley Periodicals LLC on behalf of The Federation of American Societies for Experimental Biology.)

Vanadium is available as a dietary supplement and also is known to be toxic if inhaled, yet little information is available concerning the effects of vanadium on mammalian metabolism when concentrations found in food and water. Vanadium pentoxide (V +5 ) is representative of the most common dietary and environmental exposures, and prior research shows that low-dose V +5 exposure causes oxidative stress measured by glutathione oxidation and protein S-glutathionylation. We examined the metabolic impact of V +5 at relevant dietary and environmental doses (0.01, 0.1, and 1 ppm for 24 h) in human lung fibroblasts (HLFs) and male C57BL/6J mice (0.02, 0.2, and 2 ppm in drinking water for 7 mo). Untargeted metabolomics using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) showed that V +5 induced significant metabolic perturbations in both HLF cells and mouse lungs. We noted 30% of the significantly altered pathways in HLF cells, including pyrimidines and aminosugars, fatty acids, mitochondrial and redox pathways, showed similar dose-dependent patterns in mouse lung tissues. Alterations in lipid metabolism included leukotrienes and prostaglandins involved in inflammatory signaling, which have been associated with the pathogenesis of idiopathic pulmonary fibrosis (IPF) and other disease processes. Elevated hydroxyproline levels and excessive collagen deposition were also present in lungs from V +5 -treated mice. Taken together, these results show that oxidative stress from environmental V +5 , ingested at low levels, could alter metabolism to contribute to common human lung diseases. NEW & NOTEWORTHY We used relevant dietary and environmental doses of Vanadium pentoxide (V +5 ) to examine its metabolic impact in vitro and in vivo. Using liquid chromatography-high-resolution mass spectrometry (LC-HRMS), we found significant metabolic perturbations, with similar dose-dependent patterns observed in human lung fibroblasts and male mouse lungs. Alterations in lipid metabolism included inflammatory signaling, elevated hydroxyproline levels, and excessive collagen deposition were present in V +5 -treated lungs. Our findings suggest that low levels of V +5 could trigger pulmonary fibrotic signaling.

Cadmium (Cd) is a toxic environmental metal that interacts with selenium (Se) and contributes to many lung diseases. Humans have widespread exposures to Cd through diet and cigarette smoking, and studies in rodent models show that Se can protect against Cd toxicities. We sought to identify whether an antagonistic relationship existed between Se and Cd burdens and determine whether this relationship may associate with metabolic variation within human lungs. We performed metabolomics of 31 human lungs, including 25 with end-stage lung disease due to idiopathic pulmonary fibrosis, cystic fibrosis, chronic obstructive lung disease (COPD)/emphysema and other causes, and 6 non-diseased lungs. Results showed pathway associations with Cd including amino acid, lipid and energy-related pathways. Metabolic pathways varying with Se had considerable overlap with these pathways. Hierarchical cluster analysis (HCA) of individuals according to metabolites associated with Cd showed partial separation of disease types, with COPD/emphysema in the cluster with highest Cd, and non-diseased lungs in the cluster with the lowest Cd. When compared to HCA of metabolites associated with Se, the results showed that the cluster containing COPD/emphysema had the lowest Se, and the non-diseased lungs had the highest Se. A greater number of pathway associations occurred for Cd to Se ratio than either Cd or Se alone, indicating that metabolic patterns were more dependent on Cd to Se ratio than on either alone. Network analysis of interactions of Cd and Se showed network centrality was associated with pathways linked to polyunsaturated fatty acids involved in inflammatory signaling. Overall, the data show that metabolic pathway responses in human lung vary with Cd and Se in a pattern suggesting that Se is antagonistic to Cd toxicity in humans., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests.

Vanadium is a toxic metal listed by the IARC as possibly carcinogenic to humans. Manufactured nanosize vanadium pentoxide (V 2 O 5 ) materials are used in a wide range of industrial sectors and recently have been developed as nanomedicine for cancer therapeutics, yet limited information is available to evaluate relevant nanotoxicity. In this study we used high-resolution metabolomics to assess effects of two V 2 O 5 nanomaterials, nanoparticles and nanofibers, at exposure levels (0.01, 0.1, and 1 ppm) that did not cause cell death (i.e., non-cytotoxic) in a human airway epithelial cell line, BEAS-2B. As prepared, V 2 O 5 nanofiber exhibited a fibrous morphology, with a width approximately 63 ± 12 nm and length in average 420 ± 70 nm; whereas, V 2 O 5 nanoparticles showed a typical particle morphology with a size 36 ± 2 nm. Both V 2 O 5 nanoparticles and nanofibers had dose-response effects on aminosugar, amino acid, fatty acid, carnitine, niacin and nucleotide metabolism. Differential effects of the particles and fibers included dibasic acid, glycosphingolipid and glycerophospholipid pathway associations with V 2 O 5 nanoparticles, and cholesterol and sialic acid metabolism associations with V 2 O 5 nanofibers. Examination by transmission electron microscopy provided evidence for mitochondrial stress and increased lysosome fusion by both nanomaterials, and these data were supported by effects on mitochondrial membrane potential and lysosomal activity. The results showed that non-cytotoxic exposures to V 2 O 5 nanomaterials impact major metabolic pathways previously associated with human lung diseases and suggest that toxico-metabolomics may be useful to evaluate health risks from V 2 O 5 nanomaterials., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Both environmental exposure to vanadium pentoxide (V 2 O 5 , V +5 for its ionic counterparts) and fibroblast senescence are associated with pulmonary fibrosis, but whether V +5 causes fibroblast senescence remains unknown. We found in a dose-response study that 2-40 μM V +5 caused human lung fibroblasts (HLF) senescence with increased senescence-associated β-galactosidase activity and p16 expression, while cell death occurred at higher concentration (LC 50 , 82 μM V +5 ). Notably, measures of reactive oxygen species (ROS) production with fluorescence probes showed no association of ROS with V +5 -dependent senescence. Preloading catalase (polyethylene-conjugated), a H 2 O 2 scavenger, did not alleviate the cellular senescence induced by V +5 . Analyses of the cellular glutathione (GSH) system showed that V +5 oxidized GSH, increased GSH biosynthesis, stimulated cellular GSH efflux and increased protein S-glutathionylation, and addition of N-acetyl cysteine inhibited V +5 -elevated p16 expression, suggesting that thiol oxidation mediates V +5 -caused senescence. Moreover, strong correlations between GSSG/GSH redox potential (E h ), protein S-glutathionylation, and cellular senescence (R 2  > 0.99, p < 0.05) were present in V +5 -treated cells. Studies with cell-free and enzyme-free solutions showed that V +5 directly oxidized GSH with formation of V +4 and GSSG in the absence of O 2 . Analyses of V +5 and V +4 in HLF and culture media showed that V +5 was reduced to V +4 in cells and that a stable V +4 /V +5 ratio was rapidly achieved in extracellular media, indicating ongoing release of V +4 and reoxidation to V +5 . Together, the results show that V +5 -dependent fibroblast senescence is associated with a cellular/extracellular redox cycling mechanism involving the GSH system and occurring under conditions that do not cause cell death. These results establish a mechanism by which environmental vanadium from food, dietary supplements or drinking water, can cause or contribute to lung fibrosis in the absence of high-level occupational exposures and cytotoxic cell death., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Respiratory syncytial virus (RSV) infection causes serious pulmonary disease and death in high-risk infants and elderly. Cadmium (Cd) is a toxic environmental metal contaminant and constantly exposed to humans. Limited information is available on Cd toxicity after early-life respiratory virus infection. In this study, we examined the effects of low-dose Cd exposure following early-life RSV infection on lung metabolism and inflammation using mouse and fibroblast culture models. C57BL/6J mice at 8 days old were exposed to RSV 2 times with a 4-week interval. A subset of RSV-infected mice was subsequently treated with Cd at a low dose in drinking water (RSV infection at infant age [RSVinf]+Cd) for 16 weeks. The results of inflammatory marker analysis showed that the levels of cytokines and chemokines were substantially higher in RSVinf+Cd group than other groups, implying that low-dose Cd following early-life RSV infection enhanced lung inflammation. Moreover, histopathology data showed that inflammatory cells and thickening of the alveolar walls as a profibrotic signature were evident in RSVinf+Cd. The metabolomics data revealed that RSVinf+Cd-caused metabolic disruption in histamine and histidine, vitamin D and urea cycle, and pyrimidine pathway accompanying with mechanistic target of rapamycin complex-1 activation. Taken together, our study demonstrates for the first time that cumulative Cd exposure following early-life RSV infection has a significant impact on subsequent inflammation and lung metabolism. Thus, early-life respiratory infection may reprogram metabolism and potentiate Cd toxicity, enhance inflammation, and cause fibrosis later in life., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

To prevent broiler breeders from growing too quickly and becoming too large for optimum reproduction, their dietary intake is restricted. While current restricted feeding programs, such as skip-a-day feeding (SAD), improve the economic efficiency of broiler breeder operations, this management practice impacts bird welfare. There is an interest in finding strategies that could reduce the impact of feed restriction during broiler breeder rearing. This research investigated the effects of feeding pullets on an advanced growth curve for early photostimulation at 15 wk (15P) or standard growth curve for photostimulation at 21 wk (21P), using either an every-day-spin feeding program (EDS) or SAD feeding, on the reproductive parameters of broiler breeder hens in a 2 × 2 factorial arrangement. Overall, advancing the growth curve (15P) decreased blood corticosterone levels compared to 21P, but EDS resulted in higher blood corticosterone levels compared to SAD. At the end of rearing in both 15P and 21P, EDS pullets weighed less than SAD pullets. The onset of egg production was 20 and 24 wk of age for the 15P and 21P hens, respectively. Despite an earlier onset, 15P hens did not produce more eggs than 21P hens through 65 wk of age. Egg weight was reduced for 15P compared to 21P until 30 wk of age. The 15P hens had a greater number of double yolk eggs than the 21P hens. Fertility and hatch were not impacted by the advanced growth curve and early photostimulation. Although the current research indicates the potential to reduce feed restriction associated welfare issues by rearing broiler breeder pullets for an earlier photostimulation onset, further research in needed to determine if this management technique can be improved to optimize hen reproductive efficiency., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Glyphosate-based herbicides (GBHs) such as RoundUp® are a staple of modern crop production, and as a result, residues of their ingredients are typically found in animal feeds. GBH ingredients have repeatedly been shown to impact the male reproductive health of various animals, but at present, the impact of GBH exposures on reproductive health have not been investigated in broiler breeder roosters. This study sought to determine the effect of these exposures on roosters as well as the ability of humic acids (HA) to counteract the effect of GBH exposure. Through 18 weeks of treatment with Roundup®-added or HA-added feeds compared against a common broiler breeder mash, negative effects of Roundup® exposure were seen on testis morphology as well as sperm quality. Increased exposure to Roundup® ingredients resulted in increased vacuolation of seminiferous tubule epithelium. Exposure to Roundup® impacted assessments of sperm quality including sperm mobility, viability and count during the experimental trail. HA supplementation served as a promising adsorptive additive by improving both morphology and sperm quality during the trial. Roundup® exposure was shown to have a negative influence on broiler breeder rooster reproductive health while HA improved reproductive health. The use of HA as an absorbent additive in broiler breeder feeds shows promise in improving reproductive efficiency in broiler breeders., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors. Published by Elsevier Ltd.)

Electronic nicotine delivery system (ENDS) use has become a popular, generally regarded as safe, alternative to tobacco use. The e-liquids used for ENDS vapor generation commonly contain flavoring agents, such as maltol, which have been subjected to little investigation of their effects on lung health from ENDS usage. In the present study, we examined the impacts of firsthand (3.9 mM) and secondhand (3.9 µM) exposure levels to maltol-flavored ENDS vapors on lung metabolism. Human lung bronchial epithelial cells were exposed to ENDS vapors using a robotic system for controlled generation and delivery of exposures, and the effects on metabolism were evaluated using high-resolution metabolomics. The results show that maltol in e-liquids impacts lung airway epithelial cell metabolism at both firsthand and secondhand exposure levels. The effects of maltol were most notably seen in amino acid metabolism while oxidative stress was observed with exposure to all ENDS vapors including e-liquids alone and maltol-contained e-liquids. Many effects of firsthand exposure were also observed with secondhand exposure, suggesting need for systematic investigation of both firsthand and secondhand effects of flavored ENDS vapors on lung metabolism and risk of lung disease., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society of Toxicology.All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Electronic cigarettes (e-cig) are an increasingly popular alternative to traditional smoking but have been in use for too short of a period of time to fully understand health risks. Furthermore, associated health risks are difficult to evaluate because of a large range of flavoring agents and their combinations for use with e-cig. Many flavoring agents are generally regarded as safe but have limited studies for effects on lung. Vanillin, an aromatic aldehyde, is one of the most commonly used flavoring agents in e-cig. Vanillin is electrophilic and can be redox active, with chemical properties expected to interact within biologic systems. Because accumulating lung metabolomics studies have identified metabolic disruptions associated with idiopathic pulmonary fibrosis, asthma and acute respiratory distress syndrome, we used human bronchial epithelial cells (BEAS-2B) with high-resolution metabolomics analysis to determine whether these disease-associated pathways are impacted by vanillin over the range used in e-cig. A metabolome-wide association study showed that vanillin perturbed specific energy, amino acid, antioxidant and sphingolipid pathways previously associated with human disease. Analysis of a small publicly available human dataset showed associations with several of the same pathways. Because vanillin is a common and high-abundance flavorant in e-cig, these results show that vanillin has potential to be mechanistically important in lung diseases and warrants in vivo toxicity testing in the context of e-cig use., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Sperm mobility is a major determinant of sperm quality in the domesticated chicken (Gallus domesticus) and is therefore an area of interest for improving fertility. Sperm-associated antigen 6 (SPAG6) is an important flagellar protein implicated to be necessary for flagellar function but negatively associated with rooster fertility. This study was aimed to characterize the expression of SPAG6 and investigate its utility as a protein biomarker of sperm mobility. By western analysis, relative SPAG6 abundances were compared between the testicular, epididymal, and vasal tissues and in sequentially maturing sperm. Immunocytochemistry techniques were used to detect localization of SPAG6 in chicken sperm. Last, western analysis was used to compare relative SPAG6 abundances in sperm of differing mobility. SPAG6 was found in higher abundance in epididymal tissues and in highest abundance in vasal tissues, relative to that of the testis. SPAG6 was also found to sequentially increase in abundance in maturing sperm. SPAG6 localizes between the axonemal central pair of microtubules in the sperm flagella, but it is also found in lower concentration in the acrosomal region. SPAG6 was not a significant predictor of sperm mobility. SPAG6 abundance, alone, is not a strong predictor of sperm mobility. Its impact on rooster fertility is likely unrelated to its impact on sperm mobility., (Copyright © 2020. Published by Elsevier Inc.)

The adoption of genetically engineered (GE) crops in agriculture has increased dramatically over the last few decades. Among the transgenic plants, those tolerant to the herbicide glyphosate are among the most common. Weed resistance to glyphosate-based herbicides (GBHs) has been on the rise, leading to increased herbicide applications. This, in turn, has led to increased glyphosate residues in feed. Although glyphosate has been considered to be generally safe to animal health, recent studies have shown that GBHs have potential to cause adverse effects in animal reproduction, including disruption of key regulatory enzymes in androgen synthesis, alteration of serum levels of estrogen and testosterone, damage to reproductive tissues and impairment of gametogenesis. This review emphasizes known effects of GBHs on reproductive health as well as the potential risk GBH residues pose to animal agriculture., Competing Interests: All authors have participated in (a) conception and design, or analysis and interpretation of the data; (b) drafting the article or revising it critically for important intellectual content; and (c) approval of the final version. This manuscript has not been submitted to, nor is under review at, another journal or other publishing venue. The authors have no affiliation with any organization with a direct or indirect financial interest in the subject matter discussed in the manuscript, (© 2020 The Author(s).)

Acylcarnitines transport fatty acids into mitochondria and are essential for β-oxidation and energy metabolism. Decreased mitochondrial activity results in increased plasma acylcarnitines, and increased acylcarnitines activate proinflammatory signaling and associate with age-related disease. Changes in acylcarnitines associated with healthy aging, however, are not well characterized. In the present study, we examined the associations of plasma acylcarnitines with age (range: 20-90) in 163 healthy, non-diseased individuals from the predictive medicine research cohort (NCT00336570) and tested for gender-specific differences. The results show that long-chain and very long-chain acylcarnitines increased with age, while many odd-chain acylcarnitines decreased with age. Gender-specific differences were observed for several acylcarnitines, e.g., eicosadienoylcarnitine varied with age in males, and hydroxystearoylcarnitine varied in females. Metabolome-wide association study (MWAS) of age-associated acylcarnitines with all untargeted metabolic features showed little overlap between genders. These results show that plasma concentrations of acylcarnitines vary with age and gender in individuals selected for criteria of health. Whether these variations reflect mitochondrial dysfunction with aging, mitochondrial reprogramming in response to chronic environmental exposures, early pre-disease change, or an adaptive response to healthy aging, is unclear. The results highlight a potential utility for untargeted metabolomics research to elucidate gender-specific mechanisms of aging and age-related disease.

In sexual reproduction, a male gamete or sperm cell fuses with a female gamete to bring about fertilization. However, a large number of sperm cells with fertilizing ability are required to interact with a female gamete to ensure fertilization. As such, the fertilizing ability of individual sperm cells is critical for successful reproduction. Density gradient centrifugation has been utilized for several decades as a reproducible, fast, efficient, effective and extremely adaptable method to collect only high-quality sperm to be used in assisted reproductive technology. The protocols we described herein focus on the utilization of the discontinuous Percoll density gradient centrifugation (PDGC) technique to isolate three distinct populations of rooster sperm by their quality. We were able to collect low-, medium- and high-quality sperm. We also describe reproducible protocols that entail determining fertility potential of sperm by assessing their viability, mobility and penetrability. Collection of sperm by their quality using PDGC technique would be useful to accurately and thoroughly characterize sperm with differential fertility potential.