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BACKGROUND: Oxidized phospholipids play a key role in the atherogenic potential of lipoprotein(a) (Lp[a]); however, Lp(a) is a complex particle that warrants research into additional proinflammatory mediators. We hypothesized that additional Lp(a)-associated lipids contribute to the atherogenicity of Lp(a). METHODS: Untargeted lipidomics was performed on plasma and isolated lipoprotein fractions. The atherogenicity of the observed Lp(a)-associated lipids was tested ex vivo in primary human monocytes by RNA sequencing, ELISA, Western blot, and transendothelial migratory assays. Using immunofluorescence staining and single-cell RNA sequencing, the phenotype of macrophages was investigated in human atherosclerotic lesions. RESULTS: Compared with healthy individuals with low/normal Lp(a) levels (median, 7 mg/dL [18 nmol/L]; n=13), individuals with elevated Lp(a) levels (median, 87 mg/dL [218 nmol/L]; n=12) demonstrated an increase in lipid species, particularly diacylglycerols (DGs) and lysophosphatidic acid (LPA). DG and the LPA precursor lysophosphatidylcholine were enriched in the Lp(a) fraction. Ex vivo stimulation with DG(40:6) demonstrated a significant upregulation in proinflammatory pathways related to leukocyte migration, chemotaxis, NF-κB (nuclear factor kappa B) signaling, and cytokine production. Functional assessment showed a dose-dependent increase in the secretion of IL (interleukin)-6, IL-8, and IL-1β after DG(40:6) and DG(38:4) stimulation, which was, in part, mediated via the NLRP3 (NOD [nucleotide-binding oligomerization domain]-like receptor family pyrin domain containing 3) inflammasome. Conversely, LPA-stimulated monocytes did not exhibit an inflammatory phenotype. Furthermore, activation of monocytes by DGs and LPA increased their transendothelial migratory capacity. Human atherosclerotic plaques from patients with high Lp(a) levels demonstrated colocalization of Lp(a) with M1 macrophages, and an enrichment of CD68+IL-18+TLR4+ (toll-like receptor) TREM2+ (triggering receptor expressed on myeloid cells) resident macrophages and CD68+CASP1+ (caspase) IL-1B+SELL+ (selectin L) inflammatory macrophages compared with patients with low Lp(a). Finally, potent Lp(a)-lowering treatment (pelacarsen) resulted in a reduction in specific circulating DG lipid subspecies in patients with cardiovascular disease with elevated Lp(a) levels (median, 82 mg/dL [205 nmol/L]). CONCLUSIONS: Lp(a)-associated DGs and LPA have a potential role in Lp(a)-induced monocyte inflammation by increasing cytokine secretion and monocyte transendothelial migration. This DG-induced inflammation is, in part, NLRP3 inflammasome dependent.

BACKGROUND RESULTS CONCLUSION The transesterification of butteroil has been shown to alter its lipid chemistry and thus alter the crystallization of the fat. The reaction kinetics and resulting crystallization of the butteroil differ depending on the nature of the catalyst used. Modeling the reaction with vegetable oils is a simpler method for the analysis of resulting products to understand the chemical and physiochemical changes that occur based on catalyst selection. The objective of this work is to perform a chemical transesterification of coconut and corn oil using monovalent and divalent catalysts to investigate the chemical and crystal changes that occur.Coconut and corn oil were subjected to chemical transesterification using both Ca(OH)2 and KOH as catalysts. In both the coconut and corn oil samples, transesterification caused monoglycerides (MAGs) and diacylglycerides (DAGs) to form from the most abundant fatty acid found in each sample. Coconut oil's melting temperature, solid fat content (SFC), and storage modulus decreased as a result of the transesterification, and crystals began to form in the corn oil causing melting thermograms to be evident, higher SFC, and a more viscous oil as a result. Using Ca(OH)2 as a catalyst resulted in more MAG formation, and a higher SFC and melting temperature than when KOH was used as a catalyst.The results demonstrate that the chemical changes that result from transesterification of plant‐based oils change the crystallization behavior of the oils and can therefore be used for different applications in the food industry. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Here, we introduce the full functional reconstitution of genetically validated core protein machinery (SNAREs, Munc13, Munc18, Synaptotagmin, and Complexin) for synaptic vesicle priming and release in a geometry that enables detailed characterization of the fate of docked vesicles both before and after release is triggered with Ca2+. Using this setup, we identify new roles for diacylglycerol (DAG) in regulating vesicle priming and Ca2+-triggered release involving the SNARE assembly chaperone Munc13. We find that low concentrations of DAG profoundly accelerate the rate of Ca2+-dependent release, and high concentrations reduce clamping and permit extensive spontaneous release. As expected, DAG also increases the number of docked, release-ready vesicles. Dynamic single-molecule imaging of Complexin binding to release-ready vesicles directly establishes that DAG accelerates the rate of SNAREpin assembly mediated by chaperones, Munc13 and Munc18. The selective effects of physiologically validated mutations confirmed that the Munc18-Syntaxin-VAMP2 template complex is a functional intermediate in the production of primed, release-ready vesicles, which requires the coordinated action of Munc13 and Munc18.

Background Methods Results Conclusions Hereditary angioedema (HAE) is a rare genetic disorder characterized by local, self‐limiting edema due to temporary increase in vascular permeability. HAE with normal C1 esterase inhibitor (C1INH) activity includes the form with mutations in the F12 gene encoding for coagulation factor XII (FXII‐HAE) causing an overproduction of bradykinin (BK) leading to angioedema attack. BK binding to B2 receptors (BK2R) leads to an activation of phospholipase C (PLC) and subsequent generation of second messengers: diacylglycerols (DAGs) and possibly the endocannabinoids (eCBs), 2‐arachidonoylglycerol (2‐AG) and anandamide (AEA), and eCB‐related N‐acylethanolamines [palmitoylethanolamide (PEA) and oleoylethanolamide (OEA)]. To date, there are no data on the role of these lipid mediators in FXII‐HAE.Here, we analyzed plasma levels of PLC, DAGs, and eCBs in 40 patients with FXII‐HAE and 40 sex‐ and age‐matched healthy individuals.Plasma PLC activity was increased in FXII‐HAE patients compared to controls. Concentrations of DAG 18:1–20:4, a lipid second messenger produced by PLC, were higher in FXII‐HAE compared to controls, and positively correlated with PLC activity and cleaved high molecular kininogen (cHK). Also the concentrations of the DAG metabolite, 2‐AG were altered in FXII‐HAE. AEA and OEA were decreased in FXII‐HAE patients compared to controls; by contrast, PEA, was increased. The levels of all tested mediators did not differ between symptomatic and asymptomatic patients. Moreover, C1INH‐HAE patients had elevated plasma levels of PLC, which correlated with cHK, but the levels of DAGs and eCBs were the same as controls.BK overproduction and BKR2 activation are linked to alteration of PLCs and their metabolites in patients with FXII‐HAE. Our results may pave way to investigations on the functions of these mediators in the pathophysiology of FXII‐HAE, and provide new potential biomarkers and therapeutic targets. [ABSTRACT FROM AUTHOR]

In the context of growing interest in plant-based food products for their potential health benefits and sustainability, this study investigates the effect of mono- and diglycerides of fatty acids application on physico-chemical properties of various plant-based cream products, compared to lecithin application in rice cream. Rheological and textural parameters, colour profile, and colloidal stability were analysed. The application of mono- and diglycerides modified the creams' viscoelastic behaviour, showing a decrease in viscoelasticity across the samples; although in oat–coconut cream resulted in a higher viscoelasticity, indicating the formation of a gel-like structure. Rice cream with lecithin emulsifier showed lower viscoelastic properties characterised by higher phase angle (tan δ). All samples behaved as pseudoplastic materials (with a flow behaviour index n < 1). For coconut and almond creams, the consistency coefficient increased and flow behaviour index decreased after emulsifier application. Interestingly, the emulsifier addition did not significantly affect the cream's colour profile, characterised by yellow hue angle (h*) as a dominant spectral component. The colloidal stability, indicated by a stability index (SI), was determined as well. [ABSTRACT FROM AUTHOR]

Simple Summary: This review summarizes the available literature on the impact of monoglycerides and diglycerides on poultry productivity and health. Consumption of poultry meat and eggs continues to increase in all geographies. Monoglycerides and diglycerides are products that producers can use to help fill the demand for their products while meeting the needs of today's consumers, retailers, and policymakers. Consumer preference dictates not only what food is consumed but also how that food is produced. Ingredients in livestock feed that are not antibiotics, not genetically modified, and not of animal origin but that are nutrient-like tend to be more acceptable to consumers, retailers, and producers. Mono- and diglycerides (MDG) fit these criteria, are commonly used in food, and are generally recognized as safe. But beyond being emulsifiers and a source of energy, MDG are also known to have antimicrobial, immune, and microbiome modulation and angiogenic activity. MDG in broiler diets have been shown to impact a variety of immune-related functions such as the regulation of circulating antibodies, as well as decreased gene expression or protein concentration of pro-inflammatory cytokines like TNF-α, IL-1β, IL-6, and IFN-γ. In addition, MDG can affect metabolic function and intestinal integrity. Results of this review show that MDG can serve as antimicrobial and growth-supporting alternatives for reducing poultry production losses, improving resource utilization and meeting consumer demand for sustainably produced and safe animal protein. [ABSTRACT FROM AUTHOR]

When low blood pressure is detected, angiotensin II, a protein hormone, binds to two receptors, one of which is AT1-R (angiotensin II receptor type 1), resulting in three major signaling pathways leading to regulated blood pressure. Binding to its receptor, Angiotensin II (Ang II) activates PLC (phospholipase C) signaling pathway, which branches out and activates an instantaneous rapid production of 1,4,5-inositol triphosphate (IP3) and a sustainable release of diacylglycerol (DAG). IP3 will increase in cytosolic free Calcium concentration ([Ca2+]i) by increasing Ca2+ influx and mobilizing intracellular Ca2+. Increasing calcium concentration results in vascular smooth muscle cell contraction (VSMC), increasing vessel resistance and rapidly increasing blood pressure. Additionally, DAG production activates PKC (protein kinase C) mechanisms, which elicit an increase in intracellular pH [pHi]. Such alkalinization is only dependent on Na+/H+ exchangers. This increase in pH with the activation of Na+/H+ induces vasoconstriction in various vascular vessels, thus increasing blood pressure. Ang II binding to AT1-R also activates Src and PLC / DAG signaling pathways. This activation stimulates the expression of CYP11B2 in H295R cells. If regularly expressed, the CYP11B2 gene will, in turn, result in aldosterone secretion from the adrenal cortex in the zona glomerulosa. On the other hand, if the CYP11B2 gene is not expressed normally, it will result in several gene mutations causing several diseases, including aldosterone synthase deficiency, which exposes infants to electrolyte abnormalities and failure to thrive. Aldosterone secretion will result in the activation of the Na+/K+ pump. With Na+/H+ exchangers already induced, the result will be increased sodium concentrations, leading to an increased stroke volume and blood pressure increase, and understanding the mechanism of how angiotensin works yields several advantages. These include understanding hypertension treatment, explaining renal disorders linked to fluid retention, fostering drug innovation, and empowering patients with insights into the necessity of lifestyle adjustments, including the crucial role of salt intake in increasing blood pressure. [ABSTRACT FROM AUTHOR]

Lipases can catalyze synthesis reactions in a micro aqueous system, producing useful partial glycerides (mono- and diglycerides), and these compounds are commonly utilized in different products as surfactants. Depending on the microbial sources for lipases, immobilization conditions, and starting substrates for synthesis reaction, the composition and yields of the resulting partial glycerides could be variable. These differences could lead to the final efficacy of partial glycerides as surfactants in targeted products. Therefore, it is necessary to establish a group of immobilized lipases from different microbial sources with information about substrate specificity to produce effective partial glycerides for various product types. Here, lipases from thermophilic Geobacillus stearothermophilus and Anoxybacillus flavithermus were prepared with a simple partial purification method, and after immobilization, these lipases were tested to synthesize partial glycerides using different types of decanoic acids. The distinct product patterns were analyzed using HPLC. Both immobilized lipases showed the highest substrate selectivity to decanoic acids in common, producing mainly glyceryl monodecanoate. However, commercial immobilized lipases from Thermomyces lanuginosus produced the largest glyceryl monodecanoate from methyl decanoate. These results indicate the importance of immobilization conditions like different microbial sources and substrates and the need for their optimal combination. [ABSTRACT FROM AUTHOR]

As a commercially available ingredient, the mono- and diglycerides (MDG) were widely used in a plant protein-based emulsion to provide effective, functional, emulsifying properties. The simultaneous addition of the MDG and pea protein isolate (PPI) was investigated by the methods of interfacial rheology and quantitative protein proteomics. The physicochemical quantitative analysis of the oil–water interface revealed an interfacial stability mechanism for the protein adsorption layer. For a low MDG concentration, the interfacial quantities of vicilin and albumin were increased, which could be attributed to the adsorption rate. For a high MDG concentration, both vicilin and albumin were displaced by MDG and desorbed from the interface, while legumin was more difficult to displace due to its slow adsorption and the complex structure of protein molecules. The protein molecules with the structural rearrangement interacted with MDG, exhibiting potential effects on the interfacial film structure. Combined with some nanotechnologies, the new comprehension of protein-emulsifier interactions may promote food delivery systems. The research aims to develop an in-depth analysis of interfacial proteins, and provide more innovative and tailored functionalities for the application of the plant protein emulsion. [ABSTRACT FROM AUTHOR]

Unsaturated diacylglycerols are a class of antioxidant compounds with the potential to positively impact human health. Their ability to combat oxidative stress through radical scavenger activity underscores their significance in the context of preventive and therapeutic strategies. In this paper we highlight the role of Anabaena flos-aquae as a producer of unsaturated mono and diacylglycerols, and then demonstrate the antioxidant activity of its methanolic extract, which has as its main components a variety of acylglycerol analogues. This finding was revealed using a sustainable strategy in which the One Strain Many Compounds (OSMAC) cultivation in microscale was coupled with a bioinformatic approach to analyze a large dataset of mass spectrometry data using the molecular networking analyses. This strategy reduces time and costs, avoiding long and expensive steps of purification and obtaining informative data on the metabolic composition of the extracts. This study highlights the role of Anabaena as a sustainable and green source of novel bioactive compounds. [ABSTRACT FROM AUTHOR]

Hypoxic-ischemic encephalopathy (HIE), resulting from a lack of blood flow and oxygen before or during newborn delivery, is a leading cause of cerebral palsy and neurological disability in children. Therapeutic hypothermia (TH), the current standard of care in HIE, is only beneficial in 1 of 7–8 cases. Therefore, there is a critical need for more efficient treatments. We have previously reported that omega-3 (n-3) fatty acids (FA) carried by triglyceride (TG) lipid emulsions provide neuroprotection after experimental hypoxic-ischemic (HI) injury in neonatal mice. Herein, we propose a novel acute therapeutic approach using an n-3 diglyceride (DG) lipid emulsions. Importantly, n-3 DG preparations had much smaller particle size compared to commercially available or lab-made n-3 TG emulsions. We showed that n-3 DG molecules have the advantage of incorporating at substantially higher levels than n-3 TG into an in vitro model of phospholipid membranes. We also observed that n-3 DG after parenteral administration in neonatal mice reaches the bloodstream more rapidly than n-3 TG. Using neonatal HI brain injury models in mice and rats, we found that n-3 DG emulsions provide superior neuroprotection than n-3 TG emulsions or TH in decreasing brain infarct size. Additionally, we found that n-3 DGs attenuate microgliosis and astrogliosis. Thus, n-3 DG emulsions are a superior, promising, and novel therapy for treating HIE.

Spinocerebellar ataxia type 14 (SCA14) is a neurodegenerative disease caused by germline variants in the diacylglycerol (DAG)/Ca2+-regulated protein kinase Cγ (PKCγ), leading to Purkinje cell degeneration and progressive cerebellar dysfunction. Most of the identified mutations cluster in the DAG-sensing C1 domains. Here, we found with a FRET-based activity reporter that SCA14-associated PKCγ mutations, including a previously undescribed variant, D115Y, enhanced the basal activity of the kinase by compromising its autoinhibition. Unlike other mutations in PKC that impair its autoinhibition but lead to its degradation, the C1 domain mutations protected PKCγ from such down-regulation. This enhanced basal signaling rewired the brain phosphoproteome, as revealed by phosphoproteomic analysis of cerebella from mice expressing a human SCA14-associated H101Y mutant PKCγ transgene. Mutations that induced a high basal activity in vitro were associated with earlier average age of onset in patients. Furthermore, the extent of disrupted autoinhibition, but not agonist-stimulated activity, correlated with disease severity. Molecular modeling indicated that almost all SCA14 variants not within the C1 domain were located at interfaces with the C1B domain, suggesting that mutations in and proximal to the C1B domain are a susceptibility for SCA14 because they uniquely enhance PKCγ basal activity while protecting the enzyme from down-regulation. These results provide insight into how PKCγ activation is modulated and how deregulation of the cerebellar phosphoproteome by SCA14-associated mutations affects disease progression.

BackgroundAlterations in gut microbiota and blood metabolomic profiles have been implicated in HIV infection and cardiovascular disease. However, it remains unclear whether alterations in gut microbiota may contribute to disrupted host blood metabolomic profiles in relation to atherosclerosis, especially in the context of HIV infection.MethodsWe analyzed cross-sectional associations between gut microbiota features and carotid artery plaque in 361 women with or at high risk of HIV (67% HIV+), and further integrated plaque-associated microbial features with plasma lipidomic/metabolomic profiles. Furthermore, in 737 women and men, we examined prospective associations of baseline gut bacteria-associated lipidomic and metabolomic profiles with incident carotid artery plaque over 7-year follow-up.ResultsWe found 2 potentially pathogenic bacteria, Fusobacterium and Proteus, were associated with carotid artery plaque; while the beneficial butyrate producer Odoribacter was inversely associated with plaque. Fusobacterium and Proteus were associated with multiple lipids/metabolites which were clustered into 8 modules in network. A module comprised of 9 lysophosphatidylcholines and lysophosphatidylethanolamines and a module comprised of 9 diglycerides were associated with increased risk of carotid artery plaque (risk ratio [95% CI], 1.34 [1.09-1.64] and 1.24 [1.02-1.51] per SD increment, respectively). Functional analyses identified bacterial enzymes in lipid metabolism associated with these plasma lipids. In particular, phospholipase A1 and A2 are the key enzymes in the reactions producing lysophosphatidylcholines and lysophosphatidylethanolamines.ConclusionsAmong individuals with or at high risk of HIV infection, we identified altered gut microbiota and related functional capacities in the lipid metabolism associated with disrupted plasma lipidomic profiles and carotid artery atherosclerosis.

Mono- and diacylglycerols of fatty acids are widely used as lipophilic nonionic emulsifiers and emulsion stabilizers in the production of food products. The identified deficiencies in the composition and properties of existing additives in this group created prerequisites for new developments. An acylglycerol emulsifier with essential unsaturated fatty acids based on sunflower oil was obtained under mild conditions (35–40 °C) that are harmless to human health and the environment. The evaluation of its surface-active properties was carried out using the ring tear-off and the laying drop methods. The aggregative stability of the emulsion and the number of hydrophilic-lipophilic balances were evaluated by the lifetime of individual drops of the emulsion near the interfacial surface. The results of determining the functional properties of the additive allowed us to establish its technological usage as an effective emulsifier for food systems. [ABSTRACT FROM AUTHOR]

Introduction: The marula fruit is an important indigenous African fruit since various commercial products are produced from the pulp and the seed oil. The increased demand requires methods for authentication, quality control and determination of geographical origin. Objective: The study aimed to establish a fast and reliable method for characterisation and authentication of marula seed oil. Furthermore, to identify marker compounds that can distinguish marula seed oils from other commercial oils and indicate regional differences. Materials and Methods: Metabolic profiling of 44 commercial marula seed oils was performed using proton nuclear magnetic resonance (1H NMR). For rapid classification similarity calculations were compared with principal component analysis. Differential NMR was used to determine marker compounds. Results: Marula seed oil was found to be similar to macadamia and olive oils and was distinguished from these oils by the detection of minor components. Marula seed oil is differentiated from the other two oils by the absence of α‐linolenic acid, relatively high levels of monoglycerides and diglycerides, and an approximately 1:1 ratio of 1,2‐ and 1,3‐diglycerides. When comparing marula seed oils from various regions using hierarchical cluster analysis, clustering of the marula seed oils from Namibia and Zimbabwe was observed and was related to the quantities of linoleic acid and monoglycerides and diglycerides. Some samples displayed deviations in their composition which might indicate adulteration or contamination during the production process. Conclusion: The study demonstrates the potential of NMR as a tool in the quality control of marula seed oil. This technique requires very little sample preparation, circumvents derivatisation of the oil components with fast run‐times. In addition, samples with chemical profiles that differ from the general signature profile can easily be identified. 1H NMR fingerprints of 44 marula oils were compared with those of other vegetable oils. By similarity calculations and PCA, the marula oils were found to be most similar to olive and macadamia oil. Differential NMR revealed compared to these oils the absence of α‐linolenic acid and relatively high levels of mono‐ and diglycerides and an approximate 1:1 ratio of 1,2‐ and 1,3‐diglycerides. HCA revealed clustering by the geographical origin and potential marker compounds were indicated. [ABSTRACT FROM AUTHOR]

Oleogels and emulgels were developed with winterized algal oil from Schizochytrium spp. rich in ω‐3 fatty acids (FAs) to overcome physical limitations of using a highly unsaturated lipid source in food applications. Both gel types were developed using monolaurin or a combination of mono‐ and diacylglycerols (MAG/DAG) as the gelator at concentrations of 8%, 10%, or 12% (w/w) in oil or emulsion. A 30‐day oxidation study was conducted using peroxide value, p‐Anisidine value, and change in FA composition to measure the level of oxidation. Oleogel and emulgel samples exhibited a higher oxidative stability than bulk algal oil and oil‐in‐water emulsion as control groups, respectively. The 12% monolaurin oleogel outperformed others in oxidative stability, preventing oxidation of approximately 11.66% and 7.86% of EPA and DHA, respectively, compared to algal oil. Physical characteristics including thermal behavior, solid fat content (SFC), rheology, morphology, and polymorphism were studied. Results indicated that MAG/DAG oleogels and monolaurin emulgels were the most physically stable. The SFC of 12% MAG/DAG oleogel at 30°C was 10.27% whereas 12% monolaurin oleogel was only 4.51%. Both gel types developed with monolaurin and MAG/DAG could be used for different applications as they exhibited desirable qualities such as oxidative stability and improved physical characteristics. [ABSTRACT FROM AUTHOR]

A total number of 247 participants were inquired via a questionnaire, 125 women and 122 men (sex ration 0.97). 142 (57,48%) of consumers had no information on potentially harmful food additives while 105 (42,10%) were aware but despite this, they have never consulted the labeling and do not use this information when buying their food products. According the age, the rate of sensitized consumers was 57,08% for individuals under the age of 40 years and 42,91% for individuals over the age of 40 years. This rate was 55,2% and 41,8% for women and men, respectively. A total of 101 food product labels were subjected for the study, including 71 products of local origin and 30 products from Europe marketed in Algeria. Potentially harmful food additives mentioned on packaging, for local products, were: tartrazine (E102), sunset yellow FCF S(E110), Cochineal Red A (E124), caramel (E150), carotenoids (E160), sodium benzoate (E211), carboxymethylcellulose (E466), mono- and diglycerides of fatty acids (E471), lecithin (E322). titanium dioxide (E171), natamycin (235), phosphoric acid (338), gum arabic (414), mono sodium glutamate (621), and xylitol (967). Whereas, for the imported products, harmful food additives, were the following: Copper-chlorophyll and chlorophyllin complexes (E141), caramel (E150), lecithin (E322), calcium orthophosphates (E341), mono and diglycerides of fatty acids (E471), polyglycerol polyricinoleate (E476), and propylene glycol esters fatty acids (E477). In conclusion, the Algerian consumer, although he is informed of the potential danger of food additives, he is nevertheless neglectful when it comes to the consumption of these products. Further studies should evaluate the impact of harmful food additives on the health of the consumer. [ABSTRACT FROM AUTHOR]

T cells use kinetic proofreading to discriminate antigens by converting small changes in antigen-binding lifetime into large differences in cell activation, but where in the signaling cascade this computation is performed is unknown. Previously, we developed a light-gated immune receptor to probe the role of ligand kinetics in T cell antigen signaling. We found significant kinetic proofreading at the level of the signaling lipid diacylglycerol (DAG) but lacked the ability to determine where the multiple signaling steps required for kinetic discrimination originate in the upstream signaling cascade (Tiseher and Weiner, 2019). Here, we uncover where kinetic proofreading is executed by adapting our optogenetic system for robust activation of early signaling events. We find the strength of kinetic proofreading progressively increases from Zap70 recruitment to LAT clustering to downstream DAG generation. Leveraging the ability of our system to rapidly disengage ligand binding, we also measure slower reset rates for downstream signaling events. These data suggest a distributed kinetic proofreading mechanism, with proofreading steps both at the receptor and at slower resetting downstream signaling complexes that could help balance antigen sensitivity and discrimination.

The main aim of this work was to develop a heterogeneous Fe2O3/CaO2 bifunctional catalyst prepared from iron sand and 3 different CaO2 sources (CaCO3, Ca (OH)2, and limestone) using wet impregnation and calcination methods for biodiesel production. The effects of different CaO2 sources and Fe/Ca ratio in the catalyst were investigated to provide insight into the catalyst character and biodiesel yield. X-ray diffraction, X-ray fluorescence, and scanning electron microscopy analyses were used to characterize the catalyst. CaCO3 was concluded as the best CaO2 source, while the best Fe/Ca configuration was found to be 1:4, giving the highest biodiesel yield (97.0401%) with no diglycerides. Greater addition of Fe loading would result in an amorphous structure, and all catalysts were relatively crystalline. Fe was concluded to favor the esterification reaction and biodiesel formation, while CaO2 was seen to favor the transesterification reaction and fatty acid methyl ester (FAME) formation. The catalyst mechanism was also established in this study, where esterification of free fatty acid (FFA) and glycerol took place on the acid site to produce diglyceride and transesterification of triglyceride by methanol occurred on the basic site. [ABSTRACT FROM AUTHOR]

The purpose of this study was to analyze the stability of new emulsions prepared on the basis of modified fats with varying amounts of hydroxypropylmethylcellulose. Selected techniques for evaluating the stability of emulsion systems, such as Turbiscan analysis, and the evaluation of microstructure, texture, particle size and viscosity were used. The evaluation of the above-mentioned studied parameters allowed us to indicate differentiated stability and their properties. The most desired results in terms of stability evaluation were determined for the emulsion prepared on the basis of modified mutton tallow with hemp seed oil in a ratio 3:1 (by weight) containing 0.6% (by weight) of hydroxypropylmethylcellulose. In addition, as the hemp seed oil content in the interesterified fat phase increased, a decrease in the stability of the emulsion systems was noted. Mentioned emulsions were characterized with the lowest value of TSI. Moreover, for those emulsions, the smallest increment in the droplet diameter values of systems after 31 days was recorded. The prepared model formulation can serve as a starting material for new emulsion chemical, cosmetic or food systems. [ABSTRACT FROM AUTHOR]

The manufacturing process for ointments typically involves a series of heating, cooling, and mixing steps. Precise control of the level of mixing through homogenization and the cooling rate, as well as temperature at different stages, is important in delivering ointments with the desired quality attributes, stability, and performance. In this work, we investigated the influence of typical plant processing conditions on the microstructure, stability, and sensorial properties of a model ointment system through a Design of Experiments (DoE) approach. Homogenization speed at the cooling stage after the addition of the solvent (propylene glycol, PG) was found to be the critical processing parameter that affects stability and the rheological and sensorial properties of the ointment. A lower PG addition temperature was also found to be beneficial. The stabilization of the ointment at a lower PG addition temperature was hypothesized to be due to more effective encapsulation by crystallizing mono- and diglycerides at the lower temperature. The in vitro release profiles were found to be not influenced by the processing parameters, suggesting that for the ointment platform studied, processing affects the microstructure, but the effects do not translate into the release profile, a key performance indicator. Our systematic study represents a Quality-by-Design (QbD) approach to the design of a robust manufacturing process for delivering stable ointments with the desired performance attributes and properties. [ABSTRACT FROM AUTHOR]

Performing pre‐deacidification using short‐path distillation at high temperatures and vacuum levels is a general application for fats and oils with high free fatty acids (FFA) to reduce their FFA contents to reasonable levels before steam distillation or neutralization. This study aims to determine the changes in 3‐chloropropane‐1,2‐diol esters (3‐MCPDE), glycidyl esters (GE), and diglyceride (DG) as well as the losses in tocopherols during this process. A bleached hazelnut oil having 12.10% FFA content was distilled using a molecular distillation unit at 200 °C, 220 °C, and 240°C temperatures and 0.25, 0.5, 1, and 2 mbar absolute pressures. The target was to reduce FFA content to less than 2% with minimum tocopherol loss. The results showed that considerable removals in FFA and GE contents were achieved by increasing the temperature and vacuum, while fewer decreases were detected in 3‐MCPDE and DG concentrations. Tocopherols were dramatically decreased by temperature rising, therefore, the lowest temperature (200°C) and absolute pressures (0.25–0.5 mbar) might be suitable for pre‐deacidification of hazelnut oil, where the distilled oil contained 1.78%–1.90% FFA, 243.11–286.76 mg kg–1 tocopherol, 0.50–0.55 mg kg–1 3‐MCPDE, 0.03–0.05 mg kg–1 GE and 4.00–4.22 mg kg–1 DG. Practical Application: Vegetable oils with high free fatty acid (FFA) contents are generally subjected to physical refining to avoid considerable refining loss. However, high temperatures applied to vegetable oils during physical refining result in the formation of 3‐MCPDE&GE, and the loss of some nutrients, such as tocopherols. These adverse effects can be reduced through application of lower temperatures and shorter time during physical refining. This can be applied after the FFA contents of the oils are decreased to reasonable levels (less than 2%) by distillation (pre‐deacidification) before the deodorization. Although this technique has been implemented in many plants, there is almost no information on the effects of applied conditions on 3‐MCPDE and GE and some other minor constituents. This manuscript explains the changes in these compounds during the pre‐deacidification of hazelnut oil by molecular distillation. Suitable distillation conditions were also suggested, which would be very useful for industrial refining plants. [ABSTRACT FROM AUTHOR]

Glycerol oligomerization in a liquid phase was studied over the acid‐base bifunctional catalysts for the following oxides: TiO2, ZrO2, CeO2, binary CeO2−ZrO2 systems, and purely basic oxide MgO. The phase composition and surface area have been estimated by XRD and BET. The acid and basic properties of catalysts have been characterized using the quasi‐equilibrium thermal desorption (QE‐TD) of NH3 (acidity) and CO2 (basicity). Attenuated total reflectance FTIR (ATR‐FTIR) spectroscopy provided qualitative insights into the interactions in the oxide‐glycerol systems. A comparison of catalytic and acid‐base properties of the oxide systems showed that the reaction requires the presence of both acid and base sites in the catalyst. Moreover, the strength of base sites should exceed the strength of acid sites. [ABSTRACT FROM AUTHOR]

With the global demand for lipid compounds on the rise, concerns are growing about the environmental and economic impact of traditional lipid sources. This concern is exacerbated by the ever‐increasing demand for plant‐based lipids, which is contributing to unsustainable production practices and competition for land and food. Considering this challenge, this work aimed at exploring the potential of black soldier fly larvae (BSFL) as a low‐cost and ecofriendly source of lipid classes. A fractionation scheme consisting of a mixture of polar and nonpolar solvents at different ratios was employed to isolate the lipid classes from BSFL oil using silica gel column chromatography, which is a conventional method of chromatography. The fraction's separation efficiency was validated using thin‐layer chromatography and characterized with Fourier‐transformed infrared spectroscopy and gas chromatography flame ionization (GC‐FID). Triglycerides (30%) were found to be the most abundant component while cholesterols (0.6%) were the least abundant lipid fractions in the lipid mixture. GC‐FID in the various lipid fractions analyzed, lauric acid exhibited the highest percentage among the triglycerides (16.64%), diglycerides (19.10%), monoglycerides (22.70%), and free fatty acids (27.65%) fractions. The fractionation scheme proposed achieves high efficiency in separating and recovering different lipid classes extracted from the BSFL. [ABSTRACT FROM AUTHOR]

Alternatives to oils with high saturated fatty acid content are often liquid oils (high in unsaturated fatty acids) that have a modified structure created either through additives or processing. Emulsifiers are additives that can be used as structuring agents of liquid fats; this process results in products such as oleogels, which can broaden the applications of these oils. This study assessed and compared the effects of mono- and diglycerides at 3%, 5%, 7% and 10% w/w on the mechanical and thermal properties of high-oleic palm oil (HOPO) oleogels. HOPO was heated to 75 °C and mixed with mono- or diglycerides at those four concentrations. The thermomechanical properties of the melted oleogels were assessed using differential scanning calorimetry (DSC). The melted oleogels were cooled to final temperatures of 5 °C, 10 °C and 15 °C under identical cooling rates, after which a puncture test (via a texture analyzer) was used to assess their textures. Finally, polarized light microscopy was used to assess the mechanical changes induced through emulsifier addition. The results showed that the use of mono- and diglycerides significantly modified the thermal and mechanical properties of the oleogels. The addition of saturated monoglycerides promoted a higher-temperature nucleation stage that did not previously occur in HOPO. The onset crystallization temperature increased with the addition of diglycerides, promoting crystallization at higher temperatures of the high-melting fraction of HOPO. The hardness of the oleogel generally increased with emulsifier addition and a reduction of the temperature. The effect of the temperature on the hardness was significantly greater in the diglyceride oleogel than in the monoglyceride oleogel. This study shows that the addition of mono- and diglycerides allows companies to customize their formulations to achieve desired results that may not previously have been possible, thereby facilitating novel uses for these oils within the industry. [ABSTRACT FROM AUTHOR]

BackgroundSouth Asians are at higher risk for diabetes (DM) than many other racial/ethnic groups. Circulating metabolites are measurable products of metabolic processes that may explain the aetiology of elevated risk. We characterized metabolites associated with prevalent DM and glycaemic measures in South Asians.MethodsWe included 717 participants from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study, aged 40-84 years. We used baseline fasting serum for metabolomics and demographic, behavioural, glycaemic data from baseline and at 5 years. We performed LC-MS untargeted metabolomic and lipidomic analysis with targeted integration of known signals. Individual linear and ordinal logistic regression models were adjusted for age, sex, BMI, diet, exercise, alcohol, smoking and family history of DM followed by elastic net regression to identify metabolites most associated with the outcome.ResultsThere were 258 metabolites with detectable signal in >98% of samples. Thirty-four metabolites were associated with prevalent DM in an elastic net model. Predominant metabolites associated with DM were sphingomyelins, proline (OR 15.86; 95% CI 4.72, 53.31) and betaine (OR 0.03; 0.004, 0.14). Baseline tri- and di-acylglycerols [DG (18:0/16:0) (18.36; 11.79, 24.92)] were positively associated with fasting glucose and long-chain acylcarnitines [CAR 26:1 (-0.40; -0.54, -0.27)] were inversely associated with prevalent DM and HbA1c at follow-up.DiscussionA metabolomic signature in South Asians may help determine the unique aetiology of diabetes in this high-risk ethnic group. Future work will externally validate our findings and determine the effects of modifiable risk factors for DM.

Copyright of Indonesian Journal of Animal & Veterinary Sciences / Jurnal Ilmu Ternak dan Veteriner is the property of Indonesian Center for Animal Science Research & Development and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aspergillus niger is a primary cell factory for food-grade protein (enzyme) production due to its strong protein secretion capacity and unique safety characteristics. The bottleneck issue for the current A. niger expression system is the difference in expression yield of heterologous proteins of non-fungal origin compared to those of fungal origin, which is about three orders of magnitude. The sweet protein monellin, derived from West African plants, has the potential to become a food-grade sweetener due to its high sweetness and the benefit of not containing sugar itself, but it is extremely difficult to establish a research model for heterologous expression in A. niger, owing to extremely low expression, a small molecular weight, and being undetectable with conventional protein electrophoresis. HiBiT-Tag was fused with low-expressing monellin in this work to create a research model for heterologous protein expression in A. niger at ultra-low levels. We increased monellin expression by increasing the monellin copy number, fusing monellin with the endogenous highly expressed glycosylase glaA, and eliminating extracellular protease degradation, among other strategies. In addition, we investigated the effects of overexpression of molecular chaperones, inhibiting the ERAD pathway, and enhancing the synthesis of phosphatidylinositol, phosphatidylcholine, and diglycerides in the biomembrane system. Using medium optimization, we finally obtained 0.284 mg/L of monellin in the supernatant of the shake flask. This is the first time recombinant monellin has been expressed in A. niger, with the goal of investigating ways to improve the secretory expression of heterologous proteins at ultra-low levels, which can serve as a model for the expression of other heterologous proteins in A. niger. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the effects of fat levels (200 g·kg–1 meat and 500 g·kg–1 meat) and types [lard, glycerolised lard (GL), and purified glycerolised lard (PGL)] on the quality and sensory characteristics of emulsion-type sausages. As observed, at the same type of fat, the low-fat sausage (200 g·kg–1 meat) had a significantly higher L*-value (lightness) and lower cooking loss and total expressible fluid (P < 0.05) than the high-fat sausage (500 g·kg–1 meat) and exhibited a denser and more homogeneous microstructure. Additionally, T23 (relaxation time) of the low-fat sausage shifted toward a slower relaxation time, and higher A23 (peak area) was found, which suggested the water mobility was restricted. However, at the same fat content, the low-GL and low-PGL sausages showed better textural properties and superior overall acceptability from sensory evaluation compared with the low-lard sausage (P < 0.05). Still, they have no significant differences (P > 0.05). Therefore, lard-based diacylglycerol could be effectively applied as a fat replacer in emulsion-type sausages with low-fat contents to produce healthier meat products. [ABSTRACT FROM AUTHOR]

As side products of concern, glycidyl fatty acid esters (GE) are an unwanted impurity in food emulsifier production. This study investigates the reduction of the GE content in such monoglycerides and their blends with diglycerides (mono‐/diglycerides) by thermal post‐treatment. The results indicate that the kinetics of GE reduction and equilibrium concentrations largely depend on the specific temperatures applied. For instance, while reaching equilibrium levels of GE can take several weeks at 80°C, they can be reached within hours at 150°C. The thermal treatment can have, however, also negative impact on other quality parameters, like the content of monoglycerides in both, distilled monoglycerides and mono‐/diglycerides. Based on 47 laboratory and pilot trials the influence of post‐treatment temperatures between 80 and 200°C on reducing GE levels has been systematically investigated. The obtained data were analyzed by mathematical modeling. [ABSTRACT FROM AUTHOR]

Many signaling enzymes have multiple isozymes that are localized discretely at varying molecular levels in different compartments of cells where they play specific roles. In this study, among the various isozymes of phospholipase C (PLC) and diacylglycerol kinase (DGK), which work sequentially in the phosphoinositide cycle, both PLCβ3 and DGKι were found in renal brush-border microvilli, but found to replace each other along the proximal tubules: PLCβ3 in the proximal straight tubules (PST) of the outer stripe of the outer medulla (OSOM) and the medullary ray (MR), and DGKι in the proximal convoluted tubules (PCT) in the cortex and partially in the PST of the MR. Following daily injection of gentamicin for 1 week, the expression of PLCβ3 and DGKι was transiently enhanced, as demonstrated by western blot, and the increases were found to most likely occur in their original sites, that is, in the brush borders of the PST for PLCβ3 and in the PCT for DGKι. These findings showing differences in expression along the tubules suggest that the exertion of reabsorption and secretion through various ion channels and transporters in the microvillus membranes and the maintenance of microvillus turnover are regulated by a PLC-mediated signal with the balance shifted toward relative augmentation of the DAG function in the PST, and by a DGK-mediated signal with the balance shifted to relative augmentation of the phosphatidic acid function in the PCT. Our results also suggest the possibility that these isozymes are potential diagnostic signs for the early detection of acute kidney injury caused by gentamicin. [ABSTRACT FROM AUTHOR]

Objective: To define the lipidomic profile in plasma across pregnancy, and identify lipid biomarkers for gestational diabetes mellitus (GDM) prediction in early pregnancy. Design: Case–control study. Setting: Tertiary referral maternity unit. Population or Sample: Plasma samples from 100 GDM and 100 normal glucose tolerance (NGT) women, divided into a training set (GDM first trimester = 50, GDM second trimester = 40, NGT first trimester = 50, NGT second trimester = 50) and a validation set (GDM first trimester = 45, GDM second trimester = 34, NGT first trimester = 44, NGT second trimester = 40). Methods: Plasma samples were collected in the first (11+0 to 13+6 weeks), second (19+0 to 24+6 weeks), and third trimesters (30+0 to 34+6 weeks), and tested by ultra‐high‐performance liquid chromatography coupled with electrospray ionisation‐quadrupole‐time of flight‐mass spectrometry; The GDM prediction model was established by the machine‐learning method of random forest. Main outcome measures: Gestational diabetes mellitus. Results: In both the GDM and NGT group, lyso‐glycerophospholipids were down‐regulated, whereas ceramides, sphingomyelins, cholesteryl ester, diacylglycerols (DGs) and triacylglycerols (TGs) and glucosylceramide were up‐regulated across the three trimesters of pregnancy. In the training dataset, seven TGs and five DGs demonstrated good performance in the prediction of GDM in the first and second trimesters (area under the curve [AUC] = 0.96 with 95% confidence interval [CI] of 0.93–1 and AUC = 0.97 with 95% CI of 0.95–1, respectively), independent of maternal body mass index (BMI) and ethnicity. In the validation dataset, the predictive model achieved an AUC of 0.88 and 0.94 at the first and second trimesters, respectively. Conclusions: Our results have proposed new lipid biomarkers for the first trimester prediction of GDM, independent of ethnicity and BMI. [ABSTRACT FROM AUTHOR]

[Display omitted] Dairy proteins and mono- and diglycerides (MDG) are often used in unison to tailor the properties of dairy-based emulsions. However, there are significant gaps in our understanding of how proteins affect lipid crystallisation at the oil–water interface. We have used a unique combination of interfacially-sensitive techniques to elucidate the impact of dairy proteins on interfacial MDG crystal formation. The formation temperature of interfacial MDG crystals was assessed through interfacial tension studies via drop shape analysis. Small and Wide-Angle X-ray Scattering measurements were performed on isolated oil–water interfaces, allowing for in-situ interrogation of MDG crystal structure and concentration at and near the interface. Dairy proteins are seen to reduce the temperature at which MDG crystals form at the oil–water interface. The displacement of proteins upon interfacial crystal formation was also clearly observed in interfacial tension measurements. For the first time, lipid crystals formed at the oil–water interface have been characterised using X-ray scattering. All scattering studies showed no change to the MDG crystal structures at the oil–water interface in the presence of adsorbed proteins. The results demonstrate that informed selection of emulsifier components is critical to controlling interfacial crystallisation with concomitant impact on emulsion stability. [ABSTRACT FROM AUTHOR]

The production of preparations based on natural ingredients has become a priority in the cosmetic and pharmaceutical industries. The novelty of the study was to present a possible method for obtaining pure diacylglycerols (DAG) from natural raw materials like fats (hemp seed oil and mutton tallow). We have determined the optimum water content for enzymatic interesterification to shift the reaction equilibrium towards hydrolysis and obtain the highest DAG formation yield. Then, DAG were separated and purified by column chromatography. Raw fats were characterized by fatty acids composition and their positional distribution using gas chromatography. Triacylglycerols, diacylglycerols, monoacylglycerols, and free fatty acid contents were determined using gel permeation chromatography. The main fatty acid found in sn-2 MAG of hemp seed oil was linoleic acid, which was followed by oleic acid. Saturated fatty acids in hemp seed oil's TAG showed a preference for the outer sn-1,3 positions. For mutton tallow, the majority of oleic acid was found at sn-2 position. The optimum water content applied during enzymatic interesterification for DAG formation was estimated to be 2.0% w/w, using the following conditions: 5% w/w of catalyst, 200 rpm, 60°C, 6 h. DAG yield was 27%. Purification of the mutton tallow-based and hemp seed oil-based DAG yielded 83% w/w and 82% w/w, respectively. High-purity DAG could be applied as effective emulsifiers in food, cosmetic or pharmaceutical emulsions. [ABSTRACT FROM AUTHOR]

Diacylglycerols (DAGs) display huge application prospectives in food industries. Therefore, new strategies to produce diacylglycerides are needed. Malassezia globose lipase (SMG1) could be used to synthesize DAGs. However, the poor thermostability of SMG1 seriously hampers its application. Herein, a rational design was used to generate a more thermostable SMG1. Compared with the wild type (WT), the M5D mutant (Q34P/A37P/M176V/G177A/M294R/ G28C-P206C), which contains five single-point mutations and one additional disulfide bond, displayed a 14.0 °C increase in the melting temperature (Tm), 5 °C in the optimal temperature, and 1154.3-fold in the half-life (t1/2) at 55 °C. Meanwhile, the specific activity towards DAGs of the M5D variant was improved by 3.0-fold compared to the WT. Molecular dynamics (MD) simulations revealed that the M5D mutant showed an improved rigid structure. Additionally, the WT and the M5D variants were immobilized and used for the production of DAGs. Compared with the WT, the immobilized M5D-catalyzed esterification showed a 9.1% higher DAG content and a 22.9% increase in residual activity after nine consecutive cycles. This study will pave the way for the industrial application of SMG1. [ABSTRACT FROM AUTHOR]

Oleogelation is an efficient way to offer healthy substitutes for trans and saturated fatty acids in processed foods. Multicomponent gels are of particular interest due to the ability to tune gel properties by altering the component proportions. In this study, monoacylglycerol (MAG) and diacylglycerol (DAG) are used as gelator blends and the influence of the gelator ratio on the characteristics of oleogels was investigated. The crystallization and melting behavior, solid fat content (SFC), crystal morphology, polymorphism and mechanical properties of the oleogels were characterized. The oleogels with higher gelator level displayed increased oil binding ability and shorter crystal formation time. The oleogels with higher MAG ratio exhibited more fibrillar‐like crystals, and the mixed oleogels with MAG:DAG of 5:5 showed altered crystal morphology with finer crystal size, reduced crystallization enthalpies and solid state possibly due to the increased nucleation seeds promoted by MAG. The oleogels with high MAG level showed lower equilibrium SFC during isothermal crystallization but faster crystallization rate, higher hardness and elasticity. Therefore, by changing the ratio of DAG to MAG, the crystallization profile and rheological properties of oleogels can be tailored. The oleogels can be used as traditional solid fat substitutes to reduce saturated fatty acid content in lipid‐based products. [ABSTRACT FROM AUTHOR]

[Display omitted] • Esters nature affects the reaction kinetics and the time required for the products. • Precise MG, DG, FFA selectivity achieved by temperature and reaction time control. • MG and DG can be obtained in SCW at 375 °C and times of less than 40 s. • SCW shows the intensification of a hydrolysis reaction dropping time from h to s. • SCW hydrolysis of triglycerides may be a key for future FFA production reactors. This study focuses on utilizing subcritical and supercritical water technology to produce intensive and selective diglycerides, monoglycerides, and fatty acids. The water properties can be easily modified by adjusting pressure and temperature, which promotes an improving solubility of the triglycerides in water and a selective production of glycerides. Triacetin and sunflower oil were used as models for short and long-chain components, exploring a range of temperatures (250 to 400 °C), pressures (22.0 to 25.0 MPa), and reaction times (0.7 to 29 s). A conversion of 98.5 % of sunflower oil is reached at 375 °C and 25.0 MPa in 29 s. The resulting products are 16.3 % diglycerides, 27.9 % monoglycerides, 48.9 % fatty acids, and 5.3 % glycerol. On the other hand, only 13 % of the oil is hydrolyzed at 300 °C, 22.0 MPa, with a reaction time of 23.6 s. The main product at this condition was fatty acids with a yield of 3.7 %. Furthermore, a kinetic model was developed to obtain comprehensive kinetic parameters for both raw materials to evaluate their reactivity during hydrolysis. This study provides valuable insights into the hydrolysis kinetics and the most promising conditions to make valuable products like fatty acids, mono and diglycerides, and glycerol. [ABSTRACT FROM AUTHOR]

[Display omitted] • Enzymatic transesterification with natural oils allows for the preparation of PEs. • One-step transesterification yields an oil rich in two functional substances. • AYS "Amano" exhibits the highest catalytic activity in the transesterification. • Over 70% phytosterol is converted to PEs in the reaction catalyzed by AYS "Amano". • Manipulation of oil species enables regulation of the fatty acid composition of PEs. Phytosterol esters (PEs) and diacylglycerols (DAGs) have various health benefits in humans. In this study, PEs and DAGs were synthesized by lipase-catalyzed transesterification between a natural oil and phytosterols. First, commercial lipases were screened for transesterification and were further verified using multiple-ligand molecular docking. AYS "Amano" (a lipase from Candida rugosa) was found to be the optimum lipase. Subsequently, the enzymatic transesterification conditions were optimized. The optimized conditions were determined to be a 1:2 M ratio of phytosterols to oil, 100 mmol/L phytosterols, and 9 % AYS "Amano", and 50 °C for 24 h in 20 mL n -hexane. Under these conditions, over 70 % of phytosterols were converted to PEs. In this study, an efficient enzymatic process was developed to produce value-added functional oils rich in PEs and DAGs, with PEs content ≥ 31.6 %, DAGs content ≥ 11.2 %, acid value ≤ 0.91 mg KOH/g, and peroxide value ≤ 2.38 mmol/kg. [ABSTRACT FROM AUTHOR]

PurposeNitrogen mustard (NM), which simulates the effects of sulfur mustard (SM), is a potent vesicant known to cause irreversible corneal damage. This study investigates the mechanisms by which NM induces corneal damage by examining the impact of NM exposure on the morphology and lipidome of the cornea.MethodsIntact ex vivo rabbit eyes were placed in serum-free DMEM organ culture. NM (0, 1, 2.5, 5 or 10 mg/ml) was applied to the central cornea for 5, 10 or 15 min using a 5 mm filter disk and subsequently rinsed with DMEM. Corneas were then cultured for 3, 24, or 48 h before being fixed for morphological analysis or for 24 h before being snap frozen for lipidomic analysis.ResultsNo morphological changes were detected 3 h after NM exposure. Twenty-four h after exposure, 1 mg/ml NM caused erosion of the corneal epithelium, but no damage to the underlying stroma. Damage caused by 2.5 mg/ml NM extended almost two thirds through the corneal stroma, while 5 mg/ml completely penetrated the corneal stroma. An altered lipid profile occurred 24 h after corneas were exposed to NM. Specific sphingomyelins, ceramides, and diacylglycerols were increased up to 9-, 60- and 10-fold, respectively.ConclusionsNM induces concentration- and exposure time-dependent damage to the cornea that increases in severity over time. Alterations in the sphingomyelin-ceramide pathway may contribute to the damaging effects of NM exposure.

The most widely used commercial biodiesel production technique, alkali-catalysed transesterification, requires only moderate temperatures and pressures to achieve a more than 98% conversion yield. Unfortunately, oil feedstock's high free fatty acid (FFA) content limits the technology's usefulness. A heterogeneous base catalysed glycerolysis process was investigated in this study to lower the FFA and meet these requirements. The response surface methodology (RSM) based on I-optimal design was used to model and optimize a CaO catalysed glycerolysis reaction under the influence of five reaction variables: temperature (60–180 °C), residence time (30–120 min), FFA concentration (6–50%), catalyst amount (0.4–0.6 wt (g/g)), and Glycerol to Oil ratio (G/O) (1–1.5). The data were fitted in a quadratic model, and R2 of 0.986 was observed, signifying that the model well defined the experimental data. The model was validated by running four replicates of the experiment, and a residual standard error of 2.7% was obtained, indicating the model would accurately predict future observations. The 48.584% FFA in oil was reduced to 0.98% under optimal conditions of 170 °C, 39.9 min of residence time, 0.591 wt g catalyst concentration, and 1.026 g/g glycerol/oil (G/O) ratio. CaO catalysed glycerolysis has significantly reduced FFA to less than 3% in less than an hour in biodiesel feedstock for biodiesel production.

It has been previously shown that the MRS sequence stimulated echo acquisition mode (STEAM; mixing time, TM = 20 ms) with an echo time (TE) of 100 ms resolves triglyceride glycerol resonances from that of water at 3 T. The purpose of this work is to determine if STEAM with a TE of 100 ms facilitates relative quantification of diglyceride/triglyceride levels at 3 T. Spectra were obtained from tricaprylin (triglyceride) and dicaprylin (diglyceride) with a range of STEAM TE values (TM = 20 ms). TE values that resulted in two resolved glycerol resonances for triglycerides (rendering them suitable for distinguishing triglyceride contributions from those of diglycerides) were selected. One resonance resides in the 3.85–4.2 ppm spectral range (overlapping the 1,3‐diglyceride resonance) and the other in the 4.2–4.6 ppm spectral range (overlapping one of the 1,2‐diglyceride resonances). STEAM with TE values of 40 ms and 100 ms (TM = 20 ms) yielded two resolvable triglyceride resonances (tricaprylin phantom), at about 4 ppm and 4.4 ppm. Direct integration of the resonances showed that the former peak has 0.86 and 0.17 times the area of the latter for TE = 40 ms and 100 ms, respectively. Spectra obtained from the phantoms containing mixtures of diglyceride (1,3‐dicaprylin) and triglyceride (tricaprylin) were acquired. The triglyceride contribution to the 4 ppm glycerol resonance, a mixture of signal from 1,3‐diglyceride and triglyceride, can be approximated from the area of the 4.4 ppm peak, resulting in an estimate of the 1,3‐diglyceride contribution. Analysis was performed for STEAM TE = 40 ms and TE = 100 ms spectra acquired from phantoms with 1,3‐dicaprylin/tricaprylin weight/weight contents of 2.5%/97.5%, 5%/95%, 10%/90% and 20%/80%. Concentration ratios of 1,3‐dicaprylin/tricaprylin estimated with both STEAM TE values resulted in linear correlations with expected concentration ratios (R2 > 0.99). [ABSTRACT FROM AUTHOR]

Asthma is a chronic lung disease with persistent airway inflammation, bronchial hyper-reactivity, mucus overproduction, and airway remodeling. Antagonizing T2 responses by triggering the immune system with microbial components such as Toll-like receptors (TLRs) has been suggested as a therapeutic concept for allergic asthma. The aim of this study was to evaluate the effect of a TLR2/6 agonist, FSL-1 (Pam2CGDPKHPKSF), administered by intranasal instillation after an allergic airway reaction was established in the ovalbumin (OVA) mouse model and to analyze the role of natural killer (NK) cells in this effect. We showed that FSL-1 decreased established OVA-induced airway hyper-responsiveness and eosinophilic inflammation but did not reduce the T2 or T17 response. FSL-1 increased the recruitment and activation of NK cells in the lung parenchyma and modified the repartition of NK cell subsets in lung compartments. Finally, the transfer or depletion of NK cells did not modify airway hyper-responsiveness and eosinophilia after OVA and/or FSL-1 treatment. Thus, the administration of FSL-1 reduces airway hyper-responsiveness and bronchoalveolar lavage eosinophilia. However, despite modifications of their functions following OVA sensitization, NK cells play no role in OVA-induced asthma and its inhibition by FSL-1. Therefore, the significance of NK cell functions and localization in the airways remains to be unraveled in asthma.

The objective of this study was to assess intermediary metabolic alterations that link sugar-sweetened beverage (SSB) intake to cardiometabolic (CM) risk factors in youth. A total of 597 participants from the multi-ethnic, longitudinal Exploring Perinatal Outcomes among CHildren (EPOCH) Study were followed in childhood (median 10 yrs) and adolescence (median 16 yrs). We used a multi-step approach: first, mixed models were used to examine the associations of SSB intake in childhood with CM measures across childhood and adolescence, which revealed a positive association between SSB intake and fasting triglycerides (β (95% CI) for the highest vs. lowest SSB quartile: 8.1 (−0.9,17.0); p-trend = 0.057). Second, least absolute shrinkage and selection operator (LASSO) regression was used to select 180 metabolite features (out of 767 features assessed by untargeted metabolomics) that were associated with SSB intake in childhood. Finally, 13 of these SSB-associated metabolites (from step two) were also prospectively associated with triglycerides across follow-up (from step one) in the same direction as with SSB intake (Bonferroni-adj. p < 0.0003). All annotated compounds were lipids, particularly dicarboxylated fatty acids, mono- and diacylglycerols, and phospholipids. In this diverse cohort, we identified a panel of lipid metabolites that may serve as intermediary biomarkers, linking SSB intake to dyslipidemia risk in youth. [ABSTRACT FROM AUTHOR]

Bladder Cancer (BLCA) is the ninth most frequently diagnosed cancer globally and the sixth most common cancer in the US. African Americans (AA) exhibit half the BLCA incidence compared to European Americans (EA), but they have a 70% higher risk of cancer-related death; unfortunately, this disparity in BLCA mortality remains poorly understood. In this study, we have used an ethnicity-balanced cohort for unbiased lipidomics profiling to study the changes in the lipid fingerprint for AA and EA BLCA tissues collected from similar geographical regions to determine a signature of ethnic-specific alterations. We identified 86 lipids significantly altered between self-reported AA and EA BLCA patients from Augusta University (AU) cohort. The majority of altered lipids belong to phosphatidylcholines (PCs), phosphatidylethanolamines (PEs), ly sophosphatidylcholines (lysoPCs), phosphatidylserines (PSs), and diglycerides (DGs). Interestingly, levels of four lysoPCs (lyso PCs 20:3, lyso PCs 22:1, lyso PCs 22:2, and lyso PCs 26:1) were elevated while, in contrast, the majority of the PCs were reduced in AA BLCA. Significant alterations in long-chain monounsaturated (MonoUN) and polyunsaturated (PolyUN) lipids were also observed between AA and EA BLCA tumor tissues. These first-in-field results implicate ethnic-specific lipid alterations in BLCA. [ABSTRACT FROM AUTHOR]

Currently, the poor whipping capabilities of anhydrous milk fat (AMF) in aerated emulsion products are a major obstacle for their use in beverages like tea and coffee, as well as in cakes and desserts, presenting fresh hurdles for the food industry. In this study, the mechanism of action of diacylglycerols (DAGs) with different carbon chain lengths and degrees of saturation on the partial coalescence of aerated emulsions was systematically investigated from three fundamental perspectives: fat crystallization, air-liquid interface rheology, and fat globule interface properties. The optimized crystallization of long carbon chain length diacylglycerol (LCD) based on stearate enhances interactions between fat globules at the air-liquid interface (with an elastic modulus E' reaching 246.42 mN/m), leading to a significantly reduced interface membrane strength. This promotes fat crystal-membrane interactions during whipping, resulting in a thermally stable foam structure with excellent shaping capability due to enhanced partial coalescence of fat globules. Although Laurate based medium carbon chain length diacylglycerol (MCD) promoted fat crystallization and optimized interface properties, it showed weaker foam properties because it did not adequately encapsulate air bubbles during whipping. Conversely, oleate long carbon chain length diacylglycerol (OCD) proved to be ineffective in facilitating fat crystal-membrane interaction, causing foam to have a subpar appearance. Hence, drawing from the carefully examined fat crystal-membrane interaction findings, a proposed mechanism sheds light on how DAGs impact the whipping abilities of aerated emulsions. This mechanism serves as a blueprint for creating aerated emulsions with superior whipping capabilities and foam systems that are resistant to heat. [Display omitted] • The mechanism of DAGs on the whipping capability of aerated emulsion was systematically studied. • Enhancing fat crystal-membrane interactions is essential for high-quality foam systems. • High air wrapping capacity is a necessary condition for heat-resistant foam systems. • 1.00% LCD facilitated the formation of surprisingly high-quality heat-resistant foam systems. [ABSTRACT FROM AUTHOR]

[Display omitted] • Examining the effect of multiple cooking parameters on PDAG oils, provides new insights into PDAG as a healthy alternative to conventional TAG. • PDAG-58 exhibited comparable oxidative stability to PO during short heating periods. • Reducing NaCl, temperature, and cooking time minimized processing contaminants formation and preserved phytonutrients. Diacylglycerol (DAG) is generally considered one of the precursors of 3-chloropropanol esters (3-MCPDE) and glycidyl esters (GEs). This study aimed to evaluate static heating and stir-frying properties of peanut oil (PO) and PO based 58% and 82% DAG oils (PDAG-58 and PDAG-82). Observations revealed that, phytonutrient levels notably diminished during static heating, with PDAG exhibiting reduced oxidative stability, but maintaining a stability profile similar to PO over a short period. During stir-frying, 3-MCPDE content initially increased and then decreased whereas the opposite was observed for GEs. Furthermore, as temperature, and NaCl concentration increased, there was a corresponding increase in the levels of 3-MCPDE and GEs, although remained within safe limits. When used in suitable concentrations, these findings underscore the potential of DAG, as a nutritionally rich and oxidatively stable alternative to conventional cooking oils, promoting the use of DAG edible oil in heat-cooked food systems. [ABSTRACT FROM AUTHOR]

Background & aimsNonalcoholic fatty liver disease (NAFLD) is a consequence of defects in diverse metabolic pathways that involve hepatic accumulation of triglycerides. Features of these aberrations might determine whether NAFLD progresses to nonalcoholic steatohepatitis (NASH). We investigated whether the diverse defects observed in patients with NAFLD are caused by different NAFLD subtypes with specific serum metabolomic profiles, and whether these can distinguish patients with NASH from patients with simple steatosis.MethodsWe collected liver and serum from methionine adenosyltransferase 1a knockout (MAT1A-KO) mice, which have chronically low levels of hepatic S-adenosylmethionine (SAMe) and spontaneously develop steatohepatitis, as well as C57Bl/6 mice (controls); the metabolomes of all samples were determined. We also analyzed serum metabolomes of 535 patients with biopsy-proven NAFLD (353 with simple steatosis and 182 with NASH) and compared them with serum metabolomes of mice. MAT1A-KO mice were also given SAMe (30 mg/kg/day for 8 weeks); liver samples were collected and analyzed histologically for steatohepatitis.ResultsLivers of MAT1A-KO mice were characterized by high levels of triglycerides, diglycerides, fatty acids, ceramides, and oxidized fatty acids, as well as low levels of SAMe and downstream metabolites. There was a correlation between liver and serum metabolomes. We identified a serum metabolomic signature associated with MAT1A-KO mice that also was present in 49% of the patients; based on this signature, we identified 2 NAFLD subtypes. We identified specific panels of markers that could distinguish patients with NASH from patients with simple steatosis for each subtype of NAFLD. Administration of SAMe reduced features of steatohepatitis in MAT1A-KO mice.ConclusionsIn an analysis of serum metabolomes of patients with NAFLD and MAT1A-KO mice with steatohepatitis, we identified 2 major subtypes of NAFLD and markers that differentiate steatosis from NASH in each subtype. These might be used to monitor disease progression and identify therapeutic targets for patients.

Constitutive activation of Gαq signaling by mutations in GNAQ or GNA11 occurs in over 80% of uveal melanomas (UMs) and activates MAPK. Protein kinase C (PKC) has been implicated as a link, but the mechanistic details remained unclear. We identified PKC δ and ɛ as required and sufficient to activate MAPK in GNAQ mutant melanomas. MAPK activation depends on Ras and is caused by RasGRP3, which is significantly and selectively overexpressed in response to GNAQ/11 mutation in UM. RasGRP3 activation occurs via PKC δ- and ɛ-dependent phosphorylation and PKC-independent, DAG-mediated membrane recruitment, possibly explaining the limited effect of PKC inhibitors to durably suppress MAPK in UM. The findings nominate RasGRP3 as a therapeutic target for cancers driven by oncogenic GNAQ/11.

Hypoxic-ischemic encephalopathy (HIE), resulting from a lack of blood flow and oxygen before or during newborn delivery, is a leading cause of cerebral palsy and neurological disability in children. Therapeutic hypothermia (TH), the current standard of care in HIE, is only beneficial in 1 of 7–8 cases. Therefore, there is a critical need for more efficient treatments. We have previously reported that omega-3 (n-3) fatty acids (FA) carried by triglyceride (TG) lipid emulsions provide neuroprotection after experimental hypoxic-ischemic (HI) injury in neonatal mice. Herein, we propose a novel acute therapeutic approach using an n-3 diglyceride (DG) lipid emulsions. Importantly, n-3 DG preparations had much smaller particle size compared to commercially available or lab-made n-3 TG emulsions. We showed that n-3 DG molecules have the advantage of incorporating at substantially higher levels than n-3 TG into an in vitro model of phospholipid membranes. We also observed that n-3 DG after parenteral administration in neonatal mice reaches the bloodstream more rapidly than n-3 TG. Using neonatal HI brain injury models in mice and rats, we found that n-3 DG emulsions provide superior neuroprotection than n-3 TG emulsions or TH in decreasing brain infarct size. Additionally, we found that n-3 DGs attenuate microgliosis and astrogliosis. Thus, n-3 DG emulsions are a superior, promising, and novel therapy for treating HIE. [Display omitted] • Therapeutic hypothermia (TH), the standard of care in HIE, has substantial limitations in the clinical practice. • To improve n-3 FA bioavailability, we formulated a diglyceride (DG) lipid emulsion for acute parenteral administration. • n-3 DG emulsion showed superior neuroprotection compared to TH and other n-3 based lipid emulsions. [ABSTRACT FROM AUTHOR]