Fatty Amide Research Articles

Interaction of endocannabinoid system and cyclooxygenase metabolites with fatty acid amide hydrolase and cyclooxygenase enzyme activities on contractile responses in rat vas deferens tissue.

The endocannabinoid system and prostaglandins are important modulators in the genitourinary system. This study aimed to investigate the possible interactions between the endocannabinoid system and the cyclooxygenase (COX) pathway on rat vas deferens. For this purpose, the concentration responses of the endocannabinoid anandamide, prostaglandin F2α analog latanoprost, and prostaglandin E1 analog misoprostol on the electrical field stimulation (EFS)-induced contractile responses were obtained. The concentration responses to anandamide were obtained again in the presence of nonselective COX inhibitor flurbiprofen and prostaglandin analogs, while the concentration responses of latanoprost and misoprostol were obtained in the presence of cannabinoid receptor antagonists and fatty acid amide hydrolase (FAAH) enzyme inhibitor URB597. FAAH, COX-1, and COX-2 enzyme levels in vas deferens tissue samples were also determined. The cumulative addition of anandamide was not different from the vehicle; however, the EFS-induced contractile responses were significantly increased with the incubation of latanoprost or flurbiprofen in the prostatic portion. Flurbiprofen and misoprostol decreased FAAH enzyme levels in both portions of the vas deferens, while latanoprost induced the inhibition in the prostatic portion. The cumulative administration of latanoprost and misoprostol significantly enhanced the contractile responses in the prostatic portion. This effect of latanoprost was significantly antagonized by URB597 and AM251. The enhancing effect of misoprostol was antagonized by anandamide, URB597, AM251, and AM630. Anandamide, AM251, AM630, and URB597 decreased enzyme levels of COX-1 and COX-2 in both portions of the vas deferens. These results demonstrate an intricate crosstalk between endocannabinoids and prostaglandins in modulation of the vas deferens contractility.

Insight into the metabolic pathways of Paracoccus sp. strain DMF: a non-marine halotolerant methylotroph capable of degrading aliphatic amines/amides.

Paracoccus sp. strain DMF (P. DMF from henceforth) is a gram-negative heterotroph known to tolerate and utilize high concentrations of N,N-dimethylformamide (DMF). The work presented here elaborates on the metabolic pathways involved in the degradation of C1 compounds, many of which are well-known pollutants and toxic to the environment. Investigations on microbial growth and detection of metabolic intermediates corroborate the outcome of the functional genome analysis. Several classes of C1 compounds, such as methanol, methylated amines, aliphatic amides, and naturally occurring quaternary amines like glycine betaine, were tested as growth substrates. The detailed growth and kinetic parameter analyses reveal that P. DMF can efficiently aerobically degrade trimethylamine (TMA) and grow on quaternary amines such as glycine betaine. The results show that the mechanism for halotolerant adaptation in the presence of glycine betaine is dissimilar from those observed for conventional trehalose-mediated halotolerance in heterotrophic bacteria. In addition, a close genomic survey revealed the presence of a Co(I)-based substrate-specific corrinoid methyltransferase operon, referred to as mtgBC. This demethylation system has been associated with glycine betaine catabolism in anaerobic methanogens and is unknown in denitrifying aerobic heterotrophs. This report on an anoxic-specific demethylation system in an aerobic heterotroph is unique. Our finding exposes the metabolic potential for the degradation of a variety of C1 compounds by P. DMF, making it a novel organism of choice for remediating a wide range of possible environmental contaminants.

Green synthesis of silver nano particles using Dracaena Trifasciata plant extract and comparison of fatty acids and amides capping agents

Green synthesis of NPs evades many of the deleterious aspects by permitting the synthesis of nanoparticles at relatively low temperatures, pH and pressure, all at a significantly lower cost and short time. A bottom-up approach is used for the synthesis of silver nanoparticles formed due to the reduction of silver ions because of the existence of the phytochemicals contained in the Dracaena Trifasciata plant extract, which is primarily used for the study of green synthesis. X-ray diffraction, scanning electron microscope, UV–vis spectroscopy, and Fast Fourier Infrared spectroscopy characteristic techniques are used to analyze the nature of the silver nanoparticles formed by the green synthesis method. To prevent the over-growth of silver nanoparticles and avoid their aggregation, one fatty acids based and one amides based capping agent has been used for the comparison purpose for the preservation of the silver nanoparticles in term of shape, size and coagulation, which is a novel study. Amides interacted with the silver nanoparticles via electrostatic interactions which result in strong stabilization compared to the fatty acids which make van der wall interactions with the surface of the nanoparticles but for bio compatibility and environmentally friendly applications, fatty acid based capping agent can be preferred as these NPs are also suitable for the use in the field of medicine and pharmaceuticals.

Comparing plasma and skin imprint metabolic profiles in COVID-19 diagnosis and severity assessment.

As SARS-CoV-2 continues to produce new variants, the demand for diagnostics and a better understanding of COVID-19 remain key topics in healthcare. Skin manifestations have been widely reported in cases of COVID-19, but the mechanisms and markers of these symptoms are poorly described. In this cross-sectional study, 101 patients (64 COVID-19 positive patients and 37 controls) were enrolled between April and June 2020, during the first wave of COVID-19, in São Paulo, Brazil. Enrolled patients had skin imprints sampled non-invasively using silica plates; plasma samples were also collected. Samples were used for untargeted lipidomics/metabolomics through high-resolution mass spectrometry. We identified 558 molecular ions, with lipids comprising most of them. We found 245 plasma ions that were significant for COVID-19 diagnosis, compared to 61 from the skin imprints. Plasma samples outperformed skin imprints in distinguishing patients with COVID-19 from controls, with F1-scores of 91.9% and 84.3%, respectively. Skin imprints were excellent for assessing disease severity, exhibiting an F1-score of 93.5% when discriminating between patient hospitalization and home care statuses. Specifically, oleamide and linoleamide were the most discriminative biomarkers for identifying hospitalized patients through skin imprinting, and palmitic amides and N-acylethanolamine 18:0 were also identified as significant biomarkers. These observations underscore the importance of primary fatty acid amides and N-acylethanolamines in immunomodulatory processes and metabolic disorders. These findings confirm the potential utility of skin imprinting as a valuable non-invasive sampling method for COVID-19 screening; a method that may also be applied in the evaluation of other medical conditions. KEY MESSAGES: Skin imprints complement plasma in disease metabolomics. The annotated markers have a role in immunomodulation and metabolic diseases. Skin imprints outperformed plasma samples at assessing disease severity. Skin imprints have potential as non-invasive sampling strategy for COVID-19.

URB937 Prevents the Development of Mechanical Allodynia in Male Rats with Trigeminal Neuralgia.

Cannabinoids are proposed for alleviating neuropathic pain, but their use is limited by cannabimimetic side effects. The inhibition of the fatty acid amide hydrolase (FAAH), the degrading enzyme of the endocannabinoid anandamide, has received attention as an alternative to cannabinoids in the treatment of neuropathic pain. Here, we investigated the effect of URB937, a blood-brain barrier impermeant FAAH inhibitor, on experimentally induced mechanical allodynia in an animal model of trigeminal neuralgia. Male Sprague-Dawley rats were subjected to chronic constriction injury of the infraorbital nerve (IoN-CCI); operated animals were treated sub-chronically with URB937 (1 mg/kg, i.p.) or vehicle before or after trigeminal mechanical allodynia establishment. We also assayed mRNA expression levels of the pain neuropeptide calcitonin gene-related peptide (CGRP) and cytokines in the medulla, cervical spinal cord, and trigeminal ganglion ipsilateral to IoN-CCI using rt-PCR. URB937 treatment prevented the development of mechanical allodynia and IoN-CCI-induced changes in mRNA expression levels of CGRP and cytokines in the evaluated areas. When administered after allodynia development, URB937 prevented IoN-CCI-induced changes in CGRP and cytokine gene expression; this was not associated with a significant abrogation of the mechanical allodynia. These findings suggest that URB937 may counteract, but not reverse, the development of allodynia in trigeminal neuralgia. Further research is needed to elucidate the underlying mechanisms.

Advanced Anticorrosive Graphene Oxide-Doped Organic-Inorganic Hybrid Nanocomposite Coating Derived from Leucaena leucocephala Oil.

Metal corrosion poses a substantial economic challenge in a technologically advanced world. In this study, novel environmentally friendly anticorrosive graphene oxide (GO)-doped organic-inorganic hybrid polyurethane (LFAOIH@GO-PU) nanocomposite coatings were developed from Leucaena leucocephala oil (LLO). The formulation was produced by the amidation reaction of LLO to form diol fatty amide followed by the reaction of tetraethoxysilane (TEOS) and a dispersion of GOx (X = 0.25, 0.50, and 0.75 wt%) along with the reaction of isophorane diisocyanate (IPDI) (25-40 wt%) to form LFAOIH@GOx-PU35 nanocomposites. The synthesized materials were characterized by Fourier transform infrared spectroscopy (FTIR); 1H, 13C, and 29Si nuclear magnetic resonance; and X-ray photoelectron spectroscopy. A detailed examination of LFAOIH@GO0.5-PU35 morphology was conducted using X-ray diffraction, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and transmission electron microscopy. These studies revealed distinctive surface roughness features along with a contact angle of around 88 G.U preserving their structural integrity at temperatures of up to 235 °C with minimal loading of GO. Additionally, improved mechanical properties, including scratch hardness (3 kg), pencil hardness (5H), impact resistance, bending, gloss value (79), crosshatch adhesion, and thickness were evaluated with the dispersion of GO. Electrochemical corrosion studies, involving Nyquist, Bode, and Tafel plots, provided clear evidence of the outstanding anticorrosion performance of the coatings.

Nontargeted identification of disinfection by-product precursors from soluble microbial products in municipal secondary effluent

As soluble microbial products (SMPs) can serve as precursors for disinfection by-products (DBPs), the release of SMPs from municipal secondary effluent has the potential to increase the health hazards associated with reused water. Nontargeted identification of DBPs precursors from SMPs in municipal secondary effluent was explored in the present research. The hydrophobic (HPO) fraction that constituted the major portion of the SMPs was 48.0%, and the majority of organic SMPs were composed of low molecular weight (LMW) compounds. The results showed that the HPO fraction with MW < 1 kDa component has the highest disinfection by-product formation potentials (DBPFPs). X-ray photoelectron spectroscopy (XPS) results showed that the HPO fraction with MW < 1 kDa component was mainly composed of OC–OH (40.2%) and amide/peptide N (46.7%) functional groups. This finding was in line with the results showing the highest yields of DBPFPs in terms of HAAs (haloacetic acids) and trichloroacetamide (TCAcAm). Ultra-performance liquid chromatography coupled with tandem quadrupole-time-of-flight mass spectrometry (UPLC-Q-ToF-MS) data revealed that phospholipids, fatty acids, fatty acyls-fatty amides, phosphatidylcholine, glycosides, fatty acid esters, glycolipid, and steroids were the main chemical classes in SMPs. Among these chemical classes, phospholipids containing amino acids structures and fatty acids containing carboxyl functional groups with the maximum abundance could promote the formation of HAAs. This research offers a thorough characterization of SMPs derived from municipal secondary effluent. These results enable the implementation of targeted methods to decrease the formation of DBPs by identifying potential precursors of DBPs.

Multimodal covarying brain patterns mediate genetic and psychological contributions to individual differences in pain sensitivity.

Individuals vary significantly in their pain sensitivity, with contributions from the brain, genes, and psychological factors. However, a multidimensional model integrating these factors is lacking due to their complex interactions. To address this, we measured pain sensitivity (ie, pain threshold and pain tolerance) using the cold pressor test, collected magnetic resonance imaging (MRI) data and genetic data, and evaluated psychological factors (ie, pain catastrophizing, pain-related fear, and pain-related anxiety) from 450 healthy participants with both sexes (160 male, 290 female). Using multimodal MRI fusion methods, we identified 2 pairs of covarying structural and functional brain patterns associated with pain threshold and tolerance, respectively. These patterns primarily involved regions related to self-awareness, sensory-discriminative, cognitive-evaluative, motion preparation and execution, and emotional aspects of pain. Notably, pain catastrophizing was negatively correlated with pain tolerance, and this relationship was mediated by the multimodal covarying brain patterns in male participants only. Furthermore, we identified an association between the single-nucleotide polymorphism rs4141964 within the fatty acid amide hydrolase gene and pain threshold, mediated by the identified multimodal covarying brain patterns across all participants. In summary, we suggested a model that integrates the brain, genes, and psychological factors to elucidate their role in shaping interindividual variations in pain sensitivity, highlighting the important contribution of the multimodal covarying brain patterns as important biological mediators in the associations between genes/psychological factors and pain sensitivity.

Synthesis of fatty amides from lauric acid and stearic acid for pharmaceutical and cosmetic applications

The research relates to developing a process for making fatty acid-based surfactants from renewable natural resources. At this stage, the potential of stearic acid and lauric acid to be synthesized into fatty amide surfactants was observed using monoethanolamine and urea as an amine source. In this study, the potential utilization of two types of fatty acids, namely lauric acid and stearic acid, was reacted with monoethanolamine using CaO and hexane-isopropanol solvent in a stirred tank reactor. For this reason, the research was planned to study the effect of reaction time, stirring speed, and temperature on the amide recovery. The success of the process is measured by the best conversion of fatty acids produced, as well as observing the effect of the three reaction variables on the conversion of fatty acids. Furthermore, structural tests were carried out with FT-IR spectroscopy. As a result, the lauric acid conversion was 83.33%, and the stearic acid conversion was 82.38%, obtained at a substrate (fatty acid: MEA) ratio of 1:8, a catalyst weight of 5%, and a solvent ratio of 2:1.

High-Dose Acetaminophen with Concurrent CYP2E1 Inhibition Has Profound Anticancer Activity without Liver Toxicity.

Acetaminophen (AAP) is metabolized by a variety of pathways such as sulfation, glucuronidation, and fatty acid amide hydrolase-mediated conversion to the active analgesic metabolite AM404. CYP2E1-mediated metabolism to the hepatotoxic reactive metabolite NAPQI (N-acetyl-p-benzoquinone imine) is a minor metabolic pathway that has not been linked to AAP therapeutic benefits yet clearly leads to AAP liver toxicity. N-acetylcysteine (NAC) (an antioxidant) and fomepizole (a CYP2E1 inhibitor) are clinically used for the treatment of AAP toxicity. Mice treated with AAP in combination with fomepizole (plus or minus NAC) were assessed for liver toxicity by histology and serum chemistry. The anticancer activity of AAP with NAC and fomepizole rescue was assessed in vitro and in vivo. Fomepizole with or without NAC completely prevented AAP-induced liver toxicity. In vivo, high-dose AAP with NAC/fomepizole rescue had profound antitumor activity against commonly used 4T1 breast tumor and lewis lung carcinoma lung tumor models, and no liver toxicity was detected. The antitumor efficacy was reduced in immune-compromised NOD-scid IL2Rgammanull mice, suggesting an immune-mediated mechanism of action. In conclusion, using fomepizole-based rescue, we were able to treat mice with 100-fold higher than standard dosing of AAP (650 mg/kg) without any detected liver toxicity and substantial antitumor activity. SIGNIFICANCE STATEMENT: High-dose acetaminophen can be given concurrently with CYP2E1 inhibition to allow for safe dose escalation to levels needed for anticancer activity without detected evidence of toxicity.

Determination of endocannabinoids in fermented foods of animal and plant origin by liquid chromatography tandem mass spectrometry.

An analytical method was developed for the determination of endocannabinoids and endocannabinoid-like compounds using ultra high performance liquid chromatography tandem mass spectrometry in fermented food products. Extraction optimization and method validation were carried out to detect 36 endocannabinoids and endocannabinoid-like compounds including N-acylethanolamines, N-acylamino acids, N-acylneurotransmitters, monoacylglycerols and primary fatty acid amides using 7 isotope labelled internal standards in foods. The method was able to detect precisely these compounds with good linearity (R2>0.982), reproducibility (0.1-14.4%), repeatability (0.3-18.4%), recovery (>67%) and high sensitivity. The limit of detection ranged between 0.01 and 4.30ng/mL, and of quantitation between 0.02 and 14.2ng/mL. Fermented sausage and cheese as animal-origin fermented foods and cocoa powder as plant-origin fermented foods were found to be rich in endocannabinoids and endocannabinoid-like compounds. N-Acylamino acids and N-acylneurotransmitters detected for the first time in fermented foods will provide important preliminary information for future studies.

Cocaine-induced loss of LTD and social impairments are restored by fatty acid amide hydrolase inhibition

A single dose of cocaine abolishes endocannabinoid-mediated long-term depression (eCB-LTD) in the nucleus accumbens (NAc) within 24 h of administration. However, it is uncertain whether this altered neuroplasticity entails a behavioral deficit. As previously reported, after a single dose of cocaine (20 mg/kg), mice displayed impaired eCB-LTD in the NAc. Such cocaine-induced neuroplastic impairment was accompanied by an altered preference for saccharin and social interactions and a reduction in mRNA levels of the anandamide-catabolizing enzyme NAPE-PLD. The pharmacological increase of anandamide through the fatty acid amide hydrolase (FAAH) inhibitor URB597 (1 mg/kg) reversed the cocaine-induced loss of eCB-LTD in the NAc and restored normal social interaction in cocaine-exposed mice, but it did not affect saccharin preference. Overall, this research underlines the neuroplastic and behavioral alterations occurring after the initial use of cocaine and suggests a potential role for anandamide.

A novel antibacterial and anti-biofilm material: Biosynthetic silver nanoparticles mediated by extract from Oplopanax elatus adventitious roots

The search for plant resources involved in the biosynthesis of silver nanoparticles (AgNPs) is crucial for the diversity of AgNP materials. Oplopanax elatus is a valuable medicinal shrub and its adventitious root (AR) culture is a modern method for producing the raw material. To explore an efficient biosynthetic AgNPs, this study synthesized AgNPs using O. elatus AR extract (OE-AgNPs) and the characterization of OE-AgNPs was performed. Finally, the antibacterial and anti-biofilm effects of OE-AgNPs were investigated. The result showed that OE-AgNPs had an obvious absorption peak of nanosilver with a spherical shape and a silver-like face-centered cubic structure, which the OE-AgNPs were capped by compounds with aliphatic amine, amide, carbonyl, and hydroxyl groups of O. elatus AR extract, indicating a successful synthesis of OE-AgNPs. The 10–40 nm particles were the most abundant in the OE-AgNPs, accounting for 70%. OE-AgNPs had the strongest antibacterial activity against Escherichia coli and Pseudomonas aeruginosa among six bacterial species tested, with a minimum inhibitory concentration (MIC) of 0.75 μg/mL, and the cell contents of E. coli and P. aeruginosa leaked out by OE-AgNP treatment, and bacterial respiration was inhibited. After OE-AgNP treatment, biofilms of E. coli and P. aeruginosa were efficiently scavenged with a scavenging rate of more than 60%; the extracellular polysaccharide concentrations in biofilms were also ruduced. The findings of this study suggested that OE-AgNPs could be used as a potential antibacterial and antibiofilm substance to apply in the product production and indicated the feasibility of expanding the application of O. elatus ARs.

The novel FAAH inhibitor, MCH1, reduces the infarction area in the motor cortex-related region but does not affect the sensorimotor function or memory and spatial learning in rats exposed to transient middle cerebral artery occlusion

Macamides, amides of fatty acids first isolated from maca (Lepidium meyenii) are potentially responsible for the reduction of ischemic injury in the stroke animal model followed by maca extract administration. This deduction comes from its ability to inhibit the fatty acid amide hydrolase activity, an enzyme related to the endocannabinoid anandamide hydrolysis. However, no study about the effects of isolated macamides on in-vivo models has been published yet. Our objective was to evaluate the effect of a 10-day 30 mg/kg i.p. MCH1 administration, the macamide with the higher FAAH inhibition capability, on the neurological recovery and brain infarction area of Sprague-Dawley rats exposed to the transient middle cerebral artery occlusion (MCAO) model. Our results showed that the group receiving MCH1 for 10 days did not improve Garcia’s neurological score compared to receiving the vehicle only. Likewise, the MCH1 group did not improve their sensorimotor dysfunction as indicated by the latency to detect and remove the tape from the contralateral forepaw in the adhesive removal test, and a similar number of errors with the contralateral forepaw in the foot fault test compared to the vehicle group at the 10th day. Evaluation of the spatial memory and learning using the Barnes test showed longer latency to reach the escape box in the Vehicle and MCH1 groups compared to the control group (no MCAO) only in the retrieval test, while no effect of MCAO procedure or MCH1 administration was observed in the reversal learning test. Despite the lack of behavioral effect of MCH1, analysis of the infarcted areas in the brain using the 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining method in the seven consecutive coronal sections revealed that the infarcted area in the first (bregma + 4.2 mm) and fifth (bregma −3.8 mm) coronal sections of the MCAO + MCH1 group remained similar to the Control group. These results provide evidence that MCH1 can limit damage from ischemic stroke, although it is not reflected in neurological or sensorimotor behavior and spatial learning and memory.

Mechanistic interplay of different mediators involved in mediating the anti-depressant effect of isoflavones.

Depression is one of the most prevalent severe CNS disorders, which negatively affects social lives, the ability to work, and the health of people. As per the World Health Organisation (WHO), it is a psychological disorder that is estimated to be a leading disease by 2030. Clinically, various medicines have been formulated to treat depression but they are having a setback due to their side effects, slow action, or poor bioavailability. Nowadays, flavonoids are regarded as an essential component in a variety of nutraceutical, pharmaceutical and medicinal. Isoflavones are a distinctive and important subclass of flavonoids that are generally obtained from soybean, chickpeas, and red clover. The molecules of this class have been extensively explored in various CNS disorders including depression and anxiety. Isoflavones such as genistein, daidzein, biochanin-A, formononetin, and glycitein have been reported to exert an anti-depressant effect through the modulation of different mediators. Fatty acid amide hydrolase (FAAH) mediated depletion of anandamide and hypothalamic-pituitary-adrenal (HPA) axis-mediated modulation of brain-derived neurotrophic factor (BDNF), monoamine oxidase (MAO) mediated depletion of biogenic amines and inflammatory signaling are the important underlying pathways leading to depression. Upregulation in the levels of BDNF, anandamide, antioxidants and monoamines, along with inhibition of MAO, FAAH, HPA axis, and inflammatory stress are the major modulations produced by different isoflavones in the observed anti-depressant effect. Therefore, the present review has been designed to explore the mechanistic interplay of various mediators involved in mediating the anti-depressant action of different isoflavones.

Anxiogenic doses of rapamycin prevent URB597-induced anti-stress effects in socially defeated mice

Repeated exposure to psychosocial stress modulates the endocannabinoid system, particularly anandamide (AEA) signaling in brain regions associated with emotional distress. The mTOR protein regulates various neuroplastic processes in the brain disrupted by stress, including adult hippocampal neurogenesis. This kinase has been implicated in multiple effects of cannabinoid drugs and the anti-stress behavioral effects of psychoactive drugs. Therefore, our hypothesis is that enhancing AEA signaling via pharmacological inhibition of the fatty acid amide hydrolase (FAAH) enzyme induces an anti-stress behavioral effect through an mTOR-dependent mechanism. To test this hypothesis, male C57Bl6 mice were exposed to social defeat stress (SDS) for 7 days and received daily treatment with either vehicle or different doses of the FAAH inhibitor, URB597 (0.1; 0.3; 1 mg/Kg), alone or combined with rapamycin. The results suggested that URB597 induced an inverted U-shaped dose–response curve in mice subjected to SDS (with the intermediate dose of 0.3 mg/kg being anxiolytic, and the higher tested dose of 1 mg/Kg being anxiogenic). In a second independent experiment, rapamycin treatment induced an anxiogenic-like response in control mice. However, in the presence of rapamycin, the anxiolytic dose of URB597 treatment failed to reduce stress-induced anxiety behaviors in mice. SDS exposure altered the hippocampal expression of the mTOR scaffold protein Raptor. Furthermore, the anxiogenic dose of URB597 decreased the absolute number of migrating doublecortin (DCX)-positive cells in the dentate gyrus, suggesting an anti-anxiety effect independent of newly generated/immature neurons. Therefore, our results indicate that in mice exposed to repeated psychosocial stress, URB597 fails to counteract the anxiogenic-like response induced by the pharmacological dampening of mTOR signaling.

FAAH rs324420 Polymorphism: Biological Pathways, Impact on Elite Athletic Performance and Insights for Sport Medicine.

Gene variation linked to physiological functions is recognised to affect elite athletic performance by modulating training and competition-enabling behaviour. The fatty acid amide hydrolase (FAAH) has been investigated as a good candidate for drug targeting, and recently, its single-nucleotide polymorphism (SNP) rs324420 was reported to be associated with athletic performance. Given the implications, the biological pathways of this genetic polymorphism linked to elite athletic performance, considering sport type, psychological traits and sports injuries, need to be dissected. Thus, a narrative review of the literature concerning the biological mechanisms of this SNP was undertaken. In addition to its role in athletic performance, FAAH rs324420 is also involved in important mechanisms underlying human psychopathologies, including substance abuse and neural dysfunctions. However, cumulative evidence concerning the C385A variant is inconsistent. Therefore, validation studies considering homogeneous sports modalities are required to better define the role of this SNP in elite athletic performance and its impact on stress coping, pain regulation and inflammation control.

Multiomics Revealed the Multi-Dimensional Effects of Late Sleep on Gut Microbiota and Metabolites in Children in Northwest China.

Background Sleep plays a pivotal role in children's mental and physical development and has been linked to the gut microbiota in animals and adults. However, the characteristics of the gut microbiota and metabolites and the relationship to late bedtimes in children remain unclear. Methods In total, 88 eligible children, aged from 3 to 8 years, were recruited and divided into two groups according to the bedtime collected by designed questionnaires (early, before 22:00: n = 48; late, after 22:00, n = 40). Stools and plasma samples were collected to examine the characteristics of the gut microbiota and metabolites by shotgun metagenomics and metabolomics. Results The richness and diversity of the gut microbiota in children with early bedtime were significantly increased compared with the late ones. Coprococcus, Collinsella, Akkermansia muciniphila, and Bifidobacterium adolescentis were significantly more abundant in children with early bedtime, while Bacteroides and Clostridium sp. CAG-253 were obviously enriched in the late ones. A total of 106 metabolic pathways, including biosynthesis of ribonucleotide, peptidoglycan, and amino acids, and starch degradation were enriched in children with early bedtime, while 42 pathways were abundant in those with late bedtime. Notably, more gut microbial metabolites were observed in children with late bedtime, which included aldehyde, ketones, esters, amino acids and their metabolites, benzene and substituted derivatives, bile acids, heterocyclic compounds, nucleotide and metabolites, organic acid and derivatives, sugars and acyl carnitine. In plasma, fatty amides, lipids, amino acids, metabolites, hormones, and related compounds were enriched in children with early bedtime, while bile acids were higher in children with late bedtime. Association studies revealed that the different microbial species were correlated with metabolites from gut microbiota and plasma. Conclusions The results of our study revealed that the gut microbiota diversity and richness, and metabolic pathways were significantly extensive in children with early bedtime, whereas the gut microbial metabolites were significantly decreased, which might be related to gut microbial differences.

Catalytic enantioselective reductive alkynylation of amides enables one-pot syntheses of pyrrolidine, piperidine and indolizidine alkaloids

The primary objective in synthetic organic chemistry is to develop highly efficient, selective, and versatile synthetic methodologies, which are essential for discovering new drug candidates and agrochemicals. In this study, we present a unified strategy for a one-pot, catalytic enantioselective synthesis of α-alkyl and α,α′-dialkyl pyrrolidine, piperidine, and indolizidine alkaloids using readily available amides and alkynes. This synthesis is enabled by the identification and development of an Ir/Cu/N-PINAP catalyzed highly enantioselective and chemoselective reductive alkynylation of α-unbranched aliphatic amides, which serves as the key reaction. This reaction is combined with Pd-catalyzed tandem reactions in a one-pot approach, enabling the collective, catalytic enantioselective total syntheses of eight alkaloids and an anticancer antipode with 90–98% ee. The methodology’s enantio-divergence is exemplified by the one-step access to either enantiomer of alkaloid bgugaine.

L-Asparaginase from an acrylamide degrader, Cupriavidus oxalaticus ICTDB921: Production, kinetic modelling, purification and characterization

In the present study, a novel soil isolate and previously reported acrylamide degrader, Cupriavidus oxalaticus ICTDB921, was found to have better and significantly higher l-asparaginase (LAase) activity than other bacterial strains that were screened for the same. The medium and fermentation conditions were optimized for maximizing LAase production followed by its purification and biochemical characterization. The optimum conditions of pH (7), temperature (30 °C) and agitation (180 rpm), showed the highest biomass accumulation (DCW 3.15 g/L) and LAase activity (22.94 IU/mL) after 12 h at 160 mM l-asparagine. Kinetic modelling of optimized batch data showed the biomass accumulation, LAase formation and l-asparagine utilization to best fit with the logistic model, Leudeking-Piret model and exponential decay model, respectively. The crude LAase from this isolate showed high potency at pH 7 to 9, and temperatures from 30 to 40 °C with reasonable pH (6–9) and thermal (up to 50 °C) stability. The LAase was stable against most amino acids and metal ions, and it could degrade aliphatic amides like urea and formamide. A sequential purification by ammonium sulphate precipitation, thermal treatment and chromatographic separation achieved approximately 8-fold purity. The purified subunit showed a molecular weight of 78 kDa, and km and Vmax of 24.1 mM and 40 μmol/min, respectively. The study demonstrates the potential of LAase from Cupriavidus oxalaticus in the mitigation of asparagine in food as well as for therapeutic applications.