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42 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/11/26PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

23 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/11/25PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

23 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/11/25PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

26 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/11/24PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

26 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/11/24PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Related Articles Microbiome-Metabolomic Analyses of the Impacts of Dietary Stachyose on Fecal Microbiota and Metabolites in Infants Intestinal Microbiota-associated Mice. J Sci Food Agric. 2020 Nov 22;: Authors: Xi M, Tang H, Zhang Y, Ge W, Chen Y, Cui X Abstract BACKGROUND: The intestinal microbiota and metabolites play an important role in human health and immunity. However, few studies have investigated the long-term effects of stachyose on the human intestinal microbiota and metabolism. Therefore, in this study, the feces of infants were transplanted into germ-free mice, and the effect of long-term stachyose intake on intestinal metabolism was examined by comparing the results of microbiome and metabolome analyses. Ultra-high performance liquid chromatography/tandem mass spectrometry (UHPLC-MS/MS) was used to study the effects of stachyose intake on the metabolites and metabolic pathways of the transplanted human intestinal microbiota. RESULTS: We observed that stachyose significantly altered the composition of the intestinal microbiota and metabolites, upregulated production of the metabolite taurocholic acid, downregulated amino acid metabolism, and significantly regulated the metabolism of taurine and hydroxytaurine, pantothenate and CoA biosynthesis, and other signaling pathways. CONCLUSION: These findings may provide a basis for elucidating the mechanism by which stachyose promotes host health. This article is protected by copyright. All rights reserved. PMID: 33222240 [PubMed - as supplied by publisher]

Related Articles Hippocampal Sector-Specific Metabolic Profiles Reflect Endogenous Strategy for Ischemia-Reperfusion Insult Resistance. Mol Neurobiol. 2020 Nov 22;: Authors: Krupska O, Kowalczyk T, Beręsewicz-Haller M, Samczuk P, Pietrowska K, Zabłocki K, Kretowski A, Ciborowski M, Zabłocka B Abstract The gerbil is a well-known model for studying cerebral ischemia. The CA1 of the hippocampus is vulnerable to 5 min of ischemia, while the CA2-4 and dentate gyrus (DG) are resistant to it. Short-lasting ischemia, a model of transient ischemic attacks in men, results in CA1 neuron death within 2-4 days of reperfusion. Untargeted metabolomics, using LC-QTOF-MS, was used to enrich the knowledge about intrinsic vulnerability and resistance of hippocampal regions and their early post-ischemic response (IR). In total, 30 significant metabolites were detected. In controls, taurine was significantly lower and guanosine monophosphate was higher in CA1, as compared to that in CA2-4,DG. LysoPG and LysoPE were more abundant in CA1, while LysoPI 18:0 was detected only in CA2-4,DG. After IR, a substantial decrease in the citric acid level in CA1, an accumulation of pipecolic acid in both regions, and opposite changes in the amount of PE and LysoPE were observed. The following metabolic pathways were identified as being differentially active in control CA1 vs. CA2-4,DG: metabolism of taurine and hypotaurine, glycerophospholipid, and purine. These results may indicate that a regulation of cell volume, altered structure of cell membranes, and energy metabolism differentiate hippocampal regions. Early post-ischemia, spatial differences in the metabolism of aminoacyl-tRNA biosynthesis, and amino acids and their metabolites with a predominance of those which upkeep their well-being in CA2-4,DG are shown. Presented results are consistent with genetic, morphological, and functional data, which may be useful in further study on endogenous mechanisms of neuroprotection and search for new targets for therapeutic interventions. PMID: 33222147 [PubMed - as supplied by publisher]

Related Articles Applying NMR compound identification using NMRfilter to match predicted to experimental data. Metabolomics. 2020 Nov 21;16(12):123 Authors: Kuhn S, Colreavy-Donnelly S, de Andrade Silva Quaresma LE, de Andrade Silva Quaresma E, Borges RM Abstract INTRODUCTION: Metabolomics is the approach of choice to guide the understanding of biological systems and its molecular intricacies, but compound identification is yet a bottleneck to be overcome. OBJECTIVE: To assay the use of NMRfilter for confidence compound identification based on chemical shift predictions for different datasets. RESULTS: We found comparable results using the lead tool COLMAR and NMRfilter. Then, we successfully assayed the use of HMBC to add confidence to the identified compounds. CONCLUSIONS: NMRfilter is currently under development to become a stand-alone interactive software for high-confidence NMR compound identification and this communication gathers part of its application capabilities. PMID: 33222074 [PubMed - as supplied by publisher]

Related Articles Nonfasting Lipids for All Patients? Clin Chem. 2020 Nov 22;: Authors: Farukhi Z, Mora S PMID: 33221866 [PubMed - as supplied by publisher]

Related Articles Metabolic profiles of socio-economic position: a multi-cohort analysis. Int J Epidemiol. 2020 Nov 21;: Authors: Robinson O, Carter AR, Ala-Korpela M, Casas JP, Chaturvedi N, Engmann J, Howe LD, Hughes AD, Järvelin MR, Kähönen M, Karhunen V, Kuh D, Shah T, Ben-Shlomo Y, Sofat R, Lau CE, Lehtimäki T, Menon U, Raitakari O, Ryan A, Providencia R, Smith S, Taylor J, Tillin T, Viikari J, Wong A, Hingorani AD, Kivimäki M, Vineis P Abstract BACKGROUND: Low socio-economic position (SEP) is a risk factor for multiple health outcomes, but its molecular imprints in the body remain unclear. METHODS: We examined SEP as a determinant of serum nuclear magnetic resonance metabolic profiles in ∼30 000 adults and 4000 children across 10 UK and Finnish cohort studies. RESULTS: In risk-factor-adjusted analysis of 233 metabolic measures, low educational attainment was associated with 37 measures including higher levels of triglycerides in small high-density lipoproteins (HDL) and lower levels of docosahexaenoic acid (DHA), omega-3 fatty acids, apolipoprotein A1, large and very large HDL particles (including levels of their respective lipid constituents) and cholesterol measures across different density lipoproteins. Among adults whose father worked in manual occupations, associations with apolipoprotein A1, large and very large HDL particles and HDL-2 cholesterol remained after adjustment for SEP in later life. Among manual workers, levels of glutamine were higher compared with non-manual workers. All three indicators of low SEP were associated with lower DHA, omega-3 fatty acids and HDL diameter. At all ages, children of manual workers had lower levels of DHA as a proportion of total fatty acids. CONCLUSIONS: Our work indicates that social and economic factors have a measurable impact on human physiology. Lower SEP was independently associated with a generally unfavourable metabolic profile, consistent across ages and cohorts. The metabolites we found to be associated with SEP, including DHA, are known to predict cardiovascular disease and cognitive decline in later life and may contribute to health inequalities. PMID: 33221853 [PubMed - as supplied by publisher]

Related Articles The effect of antecedent exercise on the acute stress response and subsequent food consumption: a preliminary investigation. Physiol Behav. 2020 Nov 19;:113256 Authors: Leow S, Beer NJ, Dimmock JA, Jackson B, Alderson JA, Clarke MW, Guelfi KJ Abstract Physical activity has been shown to be protective against many of the deleterious consequences of stress; however, the effects of exercise on stress-induced food consumption are unclear. This study examined the effect of an acute bout of exercise prior to exposure to an acute stressor on subsequent eating behavior, together with the physiological (e.g., heart rate, blood pressure, salivary cortisol) and psychological (e.g., mood, perceived stress) responses to stress. Twenty-three men and women completed four experimental conditions (control, exercise only, stress only, and exercise prior to stress) conducted in a counterbalanced order using a within-subjects repeated measures design. Ad libitum energy intake from a laboratory test meal was assessed at each trial, together with monitoring of physiological and psychological responses. No difference in total energy intake (p = 0.146) or energy intake from 'unhealthy' foods was noted between conditions (p = 0.783), despite lower circulating ghrelin when antecedent exercise was performed compared with stress alone (p < 0.05). Exposure to an acute stressor is not necessarily associated with alterations in subsequent food intake, nor does antecedent exercise prior to stress exposure affect food choices, despite transient alterations in the hunger hormone ghrelin. PMID: 33221392 [PubMed - as supplied by publisher]

Related Articles Autonomous climbing: An effective exercise mode with beneficial outcomes of aerobic exercise and resistance training. Life Sci. 2020 Nov 19;:118786 Authors: Shen F, Zhao Y, Ding W, Liu K, Ren X, Zhang Q, Yu J, Hu Y, Zuo H, Guo M, Jin L, Gong M, Wu W, Gu X, Xu L, Yang F, Lu J Abstract AIMS: To assess the effects of three specific exercise training modes, aerobic exercise (A), resistance training (R) and autonomous climbing (AC), aimed at proposing a cross-training method, on improving the physical, molecular and metabolic characteristics of mice without many side effects. MATERIALS AND METHODS: Seven-week-old male mice were randomly divided into four groups: control (C), aerobic exercise (A), resistance training (R), and autonomous climbing (AC) groups. Physical changes in mice were tracked and analysed to explore the similarities and differences of these three exercise modes. Histochemistry, quantitative real-time PCR (RT-PCR), western blot (WB) and metabolomics analysis were performed to identify the underlying relationships among the three training modes. KEY FINDINGS: Mice in the AC group showed better body weight control, glucose and energy homeostasis. Molecular markers of myogenesis, hypertrophy, antidegradation and mitochondrial function were highly expressed in the muscle of mice after autonomous climbing. The serum metabolomics landscape and enriched pathway comparison indicated that the aerobic oxidation pathway (pentose phosphate pathway, galactose metabolism and fatty acid degradation) and amino acid metabolism pathway (tyrosine, arginine and proline metabolism) were significantly enriched in group AC, suggesting an increased muscle mitochondrial function and protein balance ability of mice after autonomous climbing. SIGNIFICANCE: We propose a new exercise mode, autonomous climbing, as a convenient but effective training method that combines the beneficial effects of aerobic exercise and resistance training. PMID: 33221346 [PubMed - as supplied by publisher]

Related Articles Comparison of the contents of phenolic compounds including flavonoids and antioxidant activity of rice (Oryza sativa) and Chinese wild rice (Zizania latifolia). Food Chem. 2020 Nov 11;:128600 Authors: Yu X, Yang T, Qi Q, Du Y, Shi J, Liu X, Liu Y, Zhang H, Zhang Z, Yan N Abstract The contents of phenolic compounds, especially flavonoids, and antioxidant activity of rice (Oryza sativa, Os) and Chinese wild rice (Zizania latifolia, Zl) harvested in China were compared. Zl possessed significantly higher contents of total phenolics, flavonoids, and proanthocyanidins and exhibited higher antioxidant activity than in the Os Xian group, the Os Geng group, and red rice. The flavonoid contents of Os and Zl were compared using a UHPLC-QqQ-MS-based metabolomics approach. A total of 159 flavonoids were identified, among which 78 showed differential expression (72 up-regulated and six down-regulated in the Zl group). The Kyoto Encyclopaedia of Genes and Genomes annotation and classification indicated that the differentially expressed flavonoids were mainly related to anthocyanin biosynthesis. Moreover, candidate genes for flavonoid biosynthesis in Os and Zl were identified in this study. Compared with non-pigmented and red rice, Zl may be more nutritious and is thus considered a better source of natural antioxidants. PMID: 33221101 [PubMed - as supplied by publisher]

Related Articles Evaluating the effect of cooking and gastrointestinal digestion in modulating the bio-accessibility of different bioactive compounds of eggs. Food Chem. 2020 Nov 13;:128623 Authors: Nolasco E, Yang J, Ciftci O, Vu DC, Alvarez S, Purdum S, Majumder K Abstract Eggs' nutritional value has been enhanced by enriching hen's diet with bioactive compounds, but factors influencing bio-accessibility are unspecified. This study investigated the effect of hen breed, diet enrichment, and cooking methods in modulating the egg compounds' bio-accessibility after gastrointestinal (GI) digestion. White Leghorn (WLH) and Rhode Island Red (RIR) hens were fed a corn-soybean-based diet enriched with flaxseed and carotenoids; eggs were collected, cooked, and subjected to simulated GI digestion. The results showed that egg proteins were equally digestible with no change in the degree of hydrolysis (DH). The linolenic fatty acid in enriched-cooked samples remained bio-accessible after GI digestion. The lutein bio-accessibility in enriched eggs decreased after GI digestion except in RIR fried sample. Eggs from WLH and RIR achieved similar peptide content after GI digestion. These results elucidate the bio-accessibility of different bioactive compounds in cooked eggs and the use of eggs as potential functional foods. PMID: 33221100 [PubMed - as supplied by publisher]

Related Articles How to outwit nature: Omics insight into butanol tolerance. Biotechnol Adv. 2020 Nov 18;:107658 Authors: Arsov A, Petrov K, Petrova P Abstract The energy crisis, depletion of oil reserves, and global climate changes are pressing problems of developed societies. One possibility to counteract that is microbial production of butanol, a promising new fuel and alternative to many petrochemical reagents. However, the high butanol toxicity to all known microbial species is the main obstacle to its industrial implementation. The present state of the art review aims to expound the recent advances in modern omics approaches to resolving this insurmountable to date problem of low butanol tolerance. Genomics, transcriptomics, and proteomics show that butanol tolerance is a complex phenomenon affecting multiple genes and their expression. Efflux pumps, stress and multidrug response, membrane transport, and redox-related genes are indicated as being most important during butanol challenge, in addition to fine-tuning of global regulators of transcription (Spo0A, GntR), which may further improve tolerance. Lipidomics shows that the alterations in membrane composition (saturated lipids and plasmalogen increase) are very much species-specific and butanol-related. Glycomics discloses the pleiotropic effect of CcpA, the role of alternative sugar transport, and the production of exopolysaccharides as alternative routes to overcoming butanol stress. Unfortunately, the strain that simultaneously syntheses and tolerates butanol in concentrations that allow its commercialization has not yet been discovered or produced. Omics insight will allow the purposeful increase of butanol tolerance in natural and engineered producers and the effective heterologous expression of synthetic butanol pathways in strains hereditary butanol-resistant up to 3.2 - 4.9% (w/v). Future breakthrough can be achieved by a detailed study of the membrane proteome, of which 21% are proteins with unknown functions. PMID: 33220435 [PubMed - as supplied by publisher]

Related Articles Plasma metabolomics analysis of the effects of drinking soda water on hyperglycemia mice by UPLC/Q-TOF MS. Biomed Chromatogr. 2020 Nov 21;:e5032 Authors: Han D, Shi L, Pan H Abstract The purpose of this study is to evaluate the effects of a natural soda Shi Han Quan (SHQ) water on hyperglycemia and plasma metabolic profiling, and explore the mechanism using metabolomics techniques. KM mice weighing 26 ± 2g were used for the hyperglycemia animal model with alloxan, and divided into control, hyperglycemia (HG), and hyperglycemia + SHQ soda water (SHQ) groups. The experiment lasted for 30 days. The plasma metabolomic profiling of mice were determined with ultrahigh pressure liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC/Q-TOF MS). After drinking SHQ soda water, the levels of insulin and blood glucose were significantly lower in SHQ group compared with control group, and the level of insulin sensitivity (ISI) was significantly higher in SHQ group compared with HG group. The mice in different groups after SHQ intervention could be separated into distinct clusters, and nine major plasma metabolites with significant differences between groups were found closely associated with blood glucose and ISI. Metabolic pathway analysis of these metabolites involved abnormal fatty acids oxidation, phospholipid, acylcarnitine, and corticoid metabolism. The results suggested the metabolic changes and possible mechanism of SHQ improving the alloxan-induced hyperglycemia, and the findings provided insights for the prevention and control of hyperglycemia and diabetes. PMID: 33220100 [PubMed - as supplied by publisher]

Related Articles Serum aromatic and branched-chain amino acids associated with NASH demonstrate divergent associations with serum lipids. Liver Int. 2020 Nov 20;: Authors: de Mello VD, Sehgal R, Männistö V, Klåvus A, Nilsson E, Perfilyev A, Kaminska D, Miao Z, Pajukanta P, Ling C, Hanhineva K, Pihlajamäki J Abstract BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) has been associated with multiple metabolic abnormalities. By applying a non-targeted metabolomics approach, we aimed at investigating whether serum metabolite profile that associates with NAFLD would differ in its association with NAFLD-related metabolic risk factors. METHODS & RESULTS: A total of 233 subjects (mean ± SD: 48.3±9.3 years old; BMI: 43.1±5.4 kg/m2 ; 64 male) undergoing bariatric surgery were studied. Of these participants, 164 with liver histology could be classified as normal liver (n=79), simple steatosis (SS, n=40) or non-alcoholic steatohepatitis (NASH, n=45). Among the identified fasting serum metabolites with higher levels in those with NASH when compared to those with normal phenotype were the aromatic amino acids (AAAs: tryptophan, tyrosine and phenylalanine) and branched-chain amino acids (BCAAs: leucine and isoleucine), a phosphatidylcholine (PC(16:0/16:1)) and uridine (all FDRp<0.05). Only tryptophan was significantly higher in those with NASH compared to those with SS (FDRp<0.05). Only the AAAs tryptophan and tyrosine correlated positively with serum total and LDL cholesterol (FDRp<0.1), and accordingly, with liver LDLR at mRNA expression level. In addition, tryptophan was the single AA associated with liver DNA methylation of CpG sites known to be differentially methylated in those with NASH. CONCLUSIONS: We found that serum levels of the NASH-related AAAs and BCAAs demonstrate divergent associations with serum lipids. The specific correlation of tryptophan with LDL-c may result from the molecular events affecting LDLR mRNA expression and NASH-associated methylation of genes in the liver. PMID: 33219609 [PubMed - as supplied by publisher]

Related Articles A review of applications of metabolomics in osteoarthritis. Clin Rheumatol. 2020 Nov 20;: Authors: Li JT, Zeng N, Yan ZP, Liao T, Ni GX Abstract Osteoarthritis (OA) represents the most prevalent and disabling arthritis worldwide due to its heterogeneous and progressive articular degradation. However, effective and timely diagnosis and fundamental treatment for this disorder are lacking. Metabolomics, a growing field in life science research in recent years, has the potential to detect many metabolites and thus explains the underlying pathophysiological processes. Hence, new specific metabolic markers and related metabolic pathways can be identified for OA. In this review, we aimed to provide an overview of studies related to the metabolomics of OA in animal models and humans to describe the metabolic changes and related pathways for OA. The present metabolomics studies reveal that the pathogenesis of OA may be significantly related to perturbations of amino acid metabolism. These altered amino acids (e.g., branched-chain amino acids, arginine, and alanine), as well as phospholipids, were identified as potential biomarkers to distinguish patients with OA from healthy individuals. PMID: 33219452 [PubMed - as supplied by publisher]

Related Articles Oxalobacter formigenes produces metabolites and lipids undetectable in oxalotrophic Bifidobacterium animalis. Metabolomics. 2020 Nov 21;16(12):122 Authors: Chamberlain CA, Hatch M, Garrett TJ Abstract INTRODUCTION: In the search for new potential therapies for pathologies of oxalate, such as kidney stone disease and primary hyperoxaluria, the intestinal microbiome has generated significant interest. Resident oxalate-degrading bacteria inhabit the gastrointestinal tract and reduce absorption of dietary oxalate, thereby potentially lowering the potency of oxalate as a risk factor for kidney stone formation. Although several species of bacteria have been shown to degrade oxalate, select strains of Oxalobacter formigenes (O. formigenes) have thus far demonstrated the unique ability among oxalotrophs to initiate a net intestinal oxalate secretion into the lumen from the bloodstream, allowing them to feed on both dietary and endogenous metabolic oxalate. There is significant interest in this function as a potential therapeutic application for circulating oxalate reduction, although its mechanism of action is still poorly understood. Since this species-exclusive, oxalate-regulating function is reported to be dependent on the use of a currently unidentified secreted bioactive compound, there is much interest in whether O. formigenes produces unique biochemicals that are not expressed by other oxalotrophs which lack the ability to transport oxalate. Hence, this study sought to analyze and compare the metabolomes of O. formigenes and another oxalate degrader, Bifidobacterium animalis subsp. lactis (B. animalis), to determine whether O. formigenes could produce features undetectable in another oxalotroph, thus supporting the theory of a species-exclusive secretagogue compound. METHODS: A comparative metabolomic analysis of O. formigenes strain HC1 (a human isolate) versus B. animalis, another oxalate-degrading human intestinal microbe, was performed by ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). Bacteria were cultured independently in anaerobic conditions, harvested, lysed, and extracted by protein precipitation. Metabolite extracts were chromatographically separated and analyzed by UHPLC-HRMS using reverse phase gradient elution (ACE Excel 2 C18-Pentafluorophenyl column) paired with a Q Exactive™ mass spectrometer. OBJECTIVES: The purpose of this study was to assess whether O. formigenes potentially produces unique biochemicals from other oxalate degraders to better understand its metabolic profile and provide support for the theoretical production of a species-exclusive secretagogue compound responsible for enhancing intestinal oxalate secretion. RESULTS: We report a panel of metabolites and lipids detected in the O. formigenes metabolome which were undetectable in B. animalis, several of which were identified either by mass-to-charge ratio and retention time matching to our method-specific metabolite library or MS/MS fragmentation. Furthermore, re-examination of data from our previous work showed most of these features were also undetected in the metabolomes of Lactobacillus acidophilus and Lactobacillus gasseri, two other intestinal oxalate degraders. CONCLUSIONS: Our observation of O. formigenes metabolites and lipids which were undetectable in other oxalotrophs suggests that this bacterium likely holds the ability to produce biochemicals not expressed by at least a selection of other oxalate degraders. These findings provide support for the hypothesized biosynthesis of a species-exclusive secretagogue responsible for the stimulation of net intestinal oxalate secretion. PMID: 33219444 [PubMed - as supplied by publisher]

Related Articles Comparative use of aqueous humour 1H NMR metabolomics and potassium concentration for PMI estimation in an animal model. Int J Legal Med. 2020 Nov 20;: Authors: Locci E, Stocchero M, Gottardo R, De-Giorgio F, Demontis R, Nioi M, Chighine A, Tagliaro F, d'Aloja E Abstract Estimation of the post-mortem interval (PMI) remains a matter of concern in the forensic scenario. Traditional and novel approaches are not yet able to fully address this issue, which relies on complex biological phenomena triggered by death. For this purpose, eye compartments may be chosen for experimental studies because they are more resistant to post-mortem modifications. Vitreous humour, in particular, has been extensively investigated, with potassium concentration ([K+]) being the marker that is better correlated with PMI estimation. Recently, a 1H nuclear magnetic resonance (NMR) metabolomic approach based on aqueous humour (AH) from an animal model was proposed for PMI estimation, resulting in a robust and validated regression model. Here we studied the variation in [K+] in the same experimental setup. [K+] was determined through capillary ion analysis (CIA) and a regression analysis was performed. Moreover, it was investigated whether the PMI information related to potassium could improve the metabolome predictive power in estimating the PMI. Interestingly, we found that a part of the metabolomic profile is able to explain most of the information carried by potassium, suggesting that the rise in both potassium and metabolite concentrations relies on a similar biological mechanism. In the first 24-h PMI window, the AH metabolomic profile shows greater predictive power than [K+] behaviour, suggesting its potential use as an additional tool for estimating the time since death. PMID: 33219398 [PubMed - as supplied by publisher]