Chain Unsaturated Fatty Acids Research Articles

Abstract A065: Spatial and single cell transcriptomics uncovers metabolic reprogramming and NETosis of neutrophils in human pancreatic cancer

Abstract Pancreatic ductal adenocarcinoma is the most hypovascular solid tumor, imposing harsh constraints on tumor metabolism. Cancer cells adapt to reduced access to vascular-derived nutrients and O2 by cooperating with abundant stromal cells. Specifically, critical nutrients including alanine, proline, glycosaminoglycans, branched chain ketoacids, lysophosphatidic acid, and unsaturated fatty acids can be provided by fibroblasts in vitro and in vivo. However, the extent of metabolic support provided by other cell types in the PDAC TME is relatively unexplored. We hypothesized that cell types that are cooperating metabolically with cancer cells will be spatially positioned near cancer cells in these tumors. We performed Xenium spatial transcriptomics on 8 treatment-naive PDAC resections and generated a spatial atlas of nearly 700,000 cells across a range of expected cell types. We noted striking neutrophil aggregates, nucleating in the glands of classical-like malignant cells and elaborating extraglandularly. Cellular neighborhood analysis demonstrates neutrophil aggregation is strongly correlated with malignant cell proliferation and low endothelial content, suggesting neutrophils may be an important source of pro-tumoral, non-vascular nutrients in the PDAC TME. Reanalysis of published scRNAseq data revealed 3 neutrophil metabolic states in human PDAC tumors. Metabolic cluster 7 neutrophils were found only in PDAC patient samples but not healthy controls and were enriched for Type I interferon response as well as pentose phosphate pathway and iron uptake. Metabolic cluster 2 neutrophils were strikingly depleted from PDAC tumor samples compared to blood, suggesting decreased infiltration or increased cell death. Cluster 2 neutrophils were enriched for several catabolic pathways including glycogenolysis, autophagy, and proteasome, and selectively express the NETosis gene PADI4. Multiplexed immunofluorescence demonstrated that neutrophil aggregates in PDAC are citH3+/MPO+ large neutrophil extracellular traps (NETs). We reasoned pancreatic cancer cells could proliferate under tumor-like metabolic stress by repurposing amino acids liberated by autophagy, glucose liberated by glycogenolysis, or simply consuming bulk neutrophil dead cell debris via macropinocytosis. Using tumor interstitial fluid media (TIFM) and 0.5% O2 to mimic tumor-like metabolic stress, we cocultured pancreatic cancer cells with human primary neutrophils and HL60-derived neutrophil-like cells. However, under tumor-like metabolic conditions, coculture with human primary neutrophils failed to substantially increase cancer cell proliferation and NETotic neutrophils were cytotoxic. However, we noticed enhanced neutrophil viability in tumor-like metabolic conditions, suggesting metabolic regulation of neutrophil cell death. Together, these data shed light on the metabolic phenotypes and interactions with cancer cells of neutrophils in the PDAC tumor microenvironment. Citation Format: Carson D Poltorack, Sydney M Shaffer, M Celeste Simon. Spatial and single cell transcriptomics uncovers metabolic reprogramming and NETosis of neutrophils in human pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr A065.

Effect of Continuous Cropping on Growth and Lobetyolin Synthesis of the Medicinal Plant Codonopsis pilosula (Franch.) Nannf. Based on the Integrated Analysis of Plant-Metabolite-Soil Factors.

The integrated plant-metabolite-soil regulation model of C. Pilosula growth and lobetyolin synthesis in response to continuous cropping lacks systematic investigation. In this study, we investigated the regulatory mechanisms of growth and lobetyolin synthesis in C. pilosula under continuous cropping stress based on high-performance liquid chromatography, transcriptome, and microbial sequencing on the root system and rhizosphere soil of C. pilosula from one year of cultivation and five years of continuous cropping. The findings of this study revealed that continuous cropping significantly inhibited the growth of C. pilosula and led to a notable decrease in the lobetyolin content. An effort was made to propose a potential pathway for lobetyolin biosynthesis in C. pilosula, which is closely linked to the expression of genes responsible for glucoside and unsaturated fatty acid chain synthesis. In addition, soil physicochemical properties and soil microorganisms had strong correlations with root growth and synthesis of lobetyolin, suggesting that soil physicochemical properties and microorganisms are the main factors triggering the succession disorder in C. pilosula. This study provides an in-depth interpretation of the regulatory mechanism of acetylenic glycoside synthesis and offers new insights into the triggering mechanism of C. pilosula succession disorder, which will guide future cultivation and industrial development.

Dietary astaxanthin alleviates negative changes of flesh quality, long chain unsaturated fatty acids content and muscle growth on rainbow trout (Oncorhynchus mykiss) induced by black soldier fly oil via mammalian target of rapamycin and AMP-activated protein kinase α pathway: Evidence of transcripts and proteomics

This study evaluated the effect of black soldier fly (Hermetia illucens) larvae oil (BO) produced by a novel technique, subcritical butane extraction, on the muscle growth, flesh quality and lipid nutrients of rainbow trout (Oncorhynchus mykiss), and investigated the alleviating mechanisms of dietary astaxanthin supplementation. Two hundred and forty fish (215.16 ± 2.30 g) were distributed to three groups with four replicates. Fish were fed three experimental diets for 8 weeks: the control diet (CD diet), total fish oil of the CD diet was replaced with BO to formulate the BO100 diet, and then 1 g/kg astaxanthin was supplemented with the BO100 diet to formulate the AST diet. Results showed that the final body weight and the sarcomere length of fillet were significantly increased and the protein phosphorylation levels of mammalian target of rapamycin (mTOR) and p70 S6 kinase were enhanced in the BO100 group compared to the CD group (P < 0.05). However, there was a reduction in the hardness, springiness and chewiness of fillets, with a decrease in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) levels in the fish of the BO100 group (P < 0.05). Supplementation of astaxanthin in the BO100 diet mitigated the impairment of springiness and chewiness and further promoted the sarcomere length of fillet (P < 0.05). Furthermore, dietary astaxanthin partially restored the EPA and DHA content of fillet by increasing the phosphorylation levels of serine/threonine kinase (AKT) and AMP-activated protein kinase α (AMPKα) (P < 0.05) and activating the gene expression of unsaturated fatty acid synthesis. To conclude, BO produced by subcritical butane extraction can be a readily available oil source for rainbow trout feed that can be used to promote muscle growth in rainbow trout. Further dietary astaxanthin supplementation can alleviate BO-induced lipid accumulation, restore DHA levels and improve the flesh quality of rainbow trout fillet.

Comprehensive foodomics analysis reveals key lipids affect aroma generation in beef

Lipids are vital precursors to beef aroma compounds, but the exact lipid molecules influencing aroma generation remain unconfirmed. This study employs gas chromatography–olfactometry–mass spectrometry and absolute quantitative lipidomics to identify beef's aroma and lipid profiles and to examine lipid alterations post-thermal processing. The aim is to understand the role of lipids in aroma generation during beef's raw-to-cooked transition. Eighteen key aroma compounds were identified as significant contributors to the aroma of beef. 265 lipid molecules were quantified accurately, and we found that triglycerides containing C18:1 or C18:2 chains, such as TG(16:0_18:1_18:1), TG(16:0_18:1_18:2), TG(16:0_16:1_18:1), as well as phosphatidylcholine and phosphatidylethanolamine containing PC(16:1e_20:4), PC(16:0e_20:4), PC(18:2e_18:2), and PE(16:1e_20:4), played important roles in the generation of key aroma compounds in beef. C18:1, C18:2, C18:3, and C20:4 were key substrates for the formation of aroma compounds. In addition, lysophosphatidylcholine and lysophosphatidylethanolamine containing unsaturated fatty acid chains may serve as important aroma retainers.

Effect of Th2 cytokines on ceramide subclasses based on a model of reconstructed human epidermis.

Atopic dermatitis (AD) is associated with chronic inflammation and an altered skin barrier. Lipids of the stratum corneum of AD patients are known to differ substantially in composition from those of healthy subjects. A reconstructed human epidermis (RHE) model has been developed in vitro in order to mimic the characteristics of AD. In this study, using this model, we compared lipid profile modifications between control RHE and RHE treated with Th2 cytokines in order to mimic AD. We focused particularly on the lipid profile of the ceramide subclasses: non-hydroxy sphingosine (NS) and esterified ω-hydroxy sphingosine (EOS), which have been reported to be clearly modified in atopic skin. RHE lipids were extracted and analysed using high-performance liquid chromatography coupled to high-resolution mass spectrometry. The following lipid profile changes were observed in Th2-cytokine-treated RHE: (i) an increase in ceramide NS composed of an unsaturated fatty acid chain; (ii) an increase in saturated ceramide NS with small total carbon content (≤40 carbon atoms), whereas NS with a higher total carbon content (≥42 carbon atoms) was decreased; and (iii) a decrease in ceramide EOS. These results are in accordance with reported lipid profiles of human atopic skin in vivo. Moreover, the in vitro model represents a useful tool to better understand the pathogenesis of AD which may be used for future screening of new effective treatments.

Penetration of oils into hair.

The objective of this work was to understand how triglyceride plant oils can deliver strength and softness benefits to hair by their penetration. These plant oils are complex mixtures of TAGs, so the initial studies performed were with pure TAGs and then these data compared to plant oils and their measured TAG compositions. LC-MS was used to identify the di and triglycerides in coconut oil, Camellia oleifera oil and safflower seed oil. Penetration of these plant oils and pure individual triglycerides was measured by a differential extraction method. Cross-sections of oils treated with 13C-labelled triolein were studied by NanoSIMS to visualize location of triglyceride inside hair. Fatigue strength was measured using constant stress to generate a survival distribution. Models of the lipid-rich cell membrane complex (CMC) were created with the equimolar ratio of 18-methyl-eicosanoic acid (MEAS), palmitic acid (C16:0) and oleic acid (C18:1). Penetration of the individual pure TAGs was confirmed for all chain lengths and degree of unsaturation tested with higher penetration for shorter chain lengths and unsaturated fatty acids. Detailed compositional analysis of selected plant oils showed a wide variety of TAGs and penetration was also demonstrated for these oils. NanoSIMS and modelling confirmed these TAGs are penetrating the lipid-rich CMC of hair and are interacting with the fatty acids that make up the CMC. All plant oils delivered a fatigue strength improvement by penetration into the CMC and it is proposed that these oils prevent formation and/or propagation of flaws in the CMC network that leads to breakage. Many plant oils with a wide range of triglyceride compositions can penetrate into hair and NanoSIMS data confirmed these oils partition into the lipid-rich cell membrane complex. Penetration studies of individual TAGs shown to be present in these oils confirmed TAGs of varying chain length can penetrate and there is a correlation between increased penetration efficacy and shorter chain lengths and presence of unsaturation in the fatty acid chains. All the oils studied delivered single fibre fatigue strength benefits.

Fecal short chain fatty acids role in atrial fibrillation paroxysm pathogenesis through coronary artery disease patients

gut microbiota composition and its metabolites is an essential part of human health. Short chain fatty acids (SCFA) are known gut microbiota metabolites. Lack of them is common for dyslipidemia and inflammatory changes. But their role in atrial fibrillation (AF) and coronary artery disease (CAD) pathogenesis is still uninvestigated. The aim: to estimate the fecal short chain fatty acids changes in patients with atrial fibrillation paroxysm and coronary artery disease and found their connections with known cardiometabolic risk factors. Materials and methods: 300 patients were investigated. We divided them into 3 groups: I group – 149 CAD patients without rhythm disorders, II group – 124 patients with CAD and AF paroxysm and control group (CG) – 27 patients without CAD and arrhythmias. Fecal SCFA was checked by gas chromatography with mass electron detection. Results: Fecal SCFA changes in patients with AF paroxysm and CAD were found in our investigation. Isocaproic and isobutyric fecal acids appears in CAD and AF patients’ samples in comparison with control group. In the patients with AF and CAD significant increasing of valeric (1128,43%) and decreasing butyric (78,75%), isovaleric (56,29%), caprylic (99,21%) acids, medium chain fatty acids (95,54%) and unsaturated fatty acids (38,76%) levels was revealed in comparison with CAD patients without arrhythmias (P&lt;0,05). The largest amount of correlations was between total amount of SCFA, medium chain fatty acids (total amount = 7), butyric acid (total number = 6) and cardiometabolic risk factors (P&lt;0,05). The acceptable role of total amount of short chain fatty acids (AUC = 0.7907) and butyric acid (AUC=0.7127) in AF paroxysm occurrence in CAD patients was proven by ROC-analysis. Conclusions: SCFA-synthesis violations were reveled in patients with atrial fibrillation paroxysm and coronary artery disease. To propose the new ways of gut microbiota and cardiometabolic risk factors correction will be interesting for future investigations.

Low temperature promotes the production and efflux of terpenoids in yeast

Altering the fermentation environment provides an effective approach to optimizing the production efficiency of microbial cell factories globally. Here, lower fermentation temperatures of yeast were found to significantly improve the synthesis and efflux of terpenoids, including glycyrrhetinic acid (GA), β-caryophyllene, and α-amyrin. The production of GA at 22°C increased by 5.5 times compared to 30°C. Yeast subjected to lower temperature showed substantial changes at various omics levels. Certain genes involved in maintaining cellular homeostasis that were upregulated under the low temperature conditions, leading to enhanced GA production. Substituting Mvd1, a thermo-unstable enzyme in mevalonate pathway identified by transcriptome and proteome, with a thermo-tolerant isoenzyme effectively increased GA production. The lower temperature altered the composition of phospholipids and increased the unsaturation of fatty acid chains, which may influence GA efflux. This study presents a strategy for optimizing the fermentation process and identifying key targets of cell factories for terpenoid production.

Composites produced from waste plastic with agricultural and energy sector by‐products

AbstractA three‐stage route to chemically upcycle post‐consumer poly(ethylene terephthalate) (PET) to produce high compressive strength composites is reported. This procedure involves initial glycolysis with diethylene glycol to produce a mixture (GPET) comprising oligomers of 2–7 terephthalate units followed by trans/esterification of GPET with fatty acid chains supplied by brown grease, an agricultural by‐product of animal fat of relatively low nutritional or fuel value. This process yields PGB comprising a mixture of mono‐terephthalate ester derivatives. The olefin units provided by unsaturated fatty acid chains in brown grease were crosslinked by an inverse vulcanization reaction with elemental sulfur to give composites GBSx (x = wt% S, varied from 80%–90%). The compressive strengths of GBS80 (27.5 ± 2.6 MPa) and GBS90 (19.2 ± 0.8 MPa) exceed the compressive strength required of ordinary Portland cement (17 MPa) for its use in residential building foundations. The current route represents a way to repurpose waste plastic, energy sector by‐product sulfur, and agricultural by‐product brown grease to give high strength composites with mechanical properties suggesting their possible use to replace less sustainably sourced legacy structural materials.

Mechanisms of nucleic acid degradation and high hydrostatic pressure tolerance of a novel deep-sea wall-less bacterium.

Wall-less bacteria are broadly distributed in diverse habitats. They evolved from a common ancestor within the Firmicutes phylum through reductive evolution. Here, we report the cultivation, characterization, and polyphasic taxonomic analysis of the novel free-living wall-less bacterium, Hujiaoplasma nucleasis zrk29. We demonstrated that strain zrk29 had a strong ability to degrade DNA and RNA both under laboratory conditions and in the deep sea. We found that nucleic acids induced strain zrk29 to release chronic bacteriophages which supported strain zrk29 and other marine bacteria to metabolize nucleic acids without lysing host cells. We also showed that strain zrk29 tolerated high hydrostatic pressure via two pathways: (i) by transporting cations into its cells to increase intracellular osmotic pressure and (ii) by adjusting the unsaturated fatty acid chain content in its cell membrane phospholipids to increase cell membrane fluidity. This study extends our understanding of free-living wall-less bacteria and provides a useful model to explore the unique adaptation mechanisms of deep-sea microbes. IMPORTANCE The unique physiology and survival strategies of the Tenericutes bacterium-a typical wall-less bacterium-have fascinated scientists and the public, especially in extreme deep-sea environments where there is high hydrostatic pressure (HHP) and limited availability of nutrients. Here, we have isolated a novel free-living Tenericutes strain from deep-sea sediment and have found that it metabolizes nucleic acids with the support of chronic bacteriophages. This Tenericutes strain tolerates HHP stress by increasing intracellular osmotic pressure and the unsaturated fatty acid chain content of phospholipids in its cell membrane. Our results provide insights into the unique physiology of deep-sea free-living Tenericutes bacteria and highlight the significant role that chronic bacteriophages play in assisting wall-less bacteria to adapt to harsh conditions.

Non-interference delivery of Ce6 and DOX in NIR light-responsive liposomes for synergetic cervical cancer therapy

Multi-model combination treatment of malignant tumors can make up for the shortcomings of single treatment through multi-target and multi-path to achieve more ideal tumor treatment effect. However, the mutual interference of different drugs in the delivery process in vivo and the difficulty of effective drug accumulation in tumor cells are the bottlenecks of combined therapy. To this project, light-responsive liposomes loading doxorubicin (DOX) and chlorin e6 (Ce6) (DOX-Ce6-Lip) without mutual interference were engineered by thin film hydration method. This kind of nano-drug delivery system increased the drugs concentration accumulated in tumor sites through enhanced permeability and retention effect, and reduced the toxic and side effects of drugs on normal tissues in vivo. In addition, after entering the tumor cells, Ce6 produced a large number of reactive oxygen species under 660 nm NIR laser irradiation, which further oxidized the unsaturated fatty acid chain in the liposomes and caused the collapse of the liposomes, thus realizing the stimulus-responsive release of Ce6 and DOX. The concentrations of DOX and Ce6 in the tumor cells rapidly reached the peak and achieved a more effective combination of chemotherapy and photodynamic therapy (PDT). Consequently, DOX-Ce6-Lip followed by 660 nm NIR irradiation achieved an efficient tumor growth inhibition of 71.90 ± 3.14%, indicating the versatile potential of chemotherapy and PDT. In conclusion, this study provides a delivery scheme for drugs with different solubilities and an effectively combined anti-tumor therapy method.

GPCR-mediated effects of fatty acids and bile acids on glucose homeostasis.

Fatty acids and glucose are key biomolecules that share several commonalities including serving as energy substrates and as signaling molecules. Fatty acids can be synthesized endogenously from intermediates of glucose catabolism via de-novo lipogenesis. Bile acids are synthesized endogenously in the liver from the biologically important lipid molecule, cholesterol. Evidence abounds that fatty acids and bile acids play direct and indirect roles in systemic glucose homeostasis. The tight control of plasma glucose levels during postprandial and fasted states is principally mediated by two pancreatic hormones, insulin and glucagon. Here, we summarize experimental studies on the endocrine effects of fatty acids and bile acids, with emphasis on their ability to regulate the release of key hormones that regulate glucose metabolism. We categorize the heterogenous family of fatty acids into short chain fatty acids (SCFAs), unsaturated, and saturated fatty acids, and highlight that along with bile acids, these biomolecules regulate glucose homeostasis by serving as endogenous ligands for specific G-protein coupled receptors (GPCRs). Activation of these GPCRs affects the release of incretin hormones by enteroendocrine cells and/or the secretion of insulin, glucagon, and somatostatin by pancreatic islets, all of which regulate systemic glucose homeostasis. We deduce that signaling induced by fatty acids and bile acids is necessary to maintain euglycemia to prevent metabolic diseases such as type-2 diabetes and related metabolic disorders.

Oxidation of Phospholipids by OH Radical Coordinated to Copper Amyloid-β Peptide—A Density Functional Theory Modeling

Oxidative stress and metal dyshomeostasis are considered crucial factors in the pathogenesis of Alzheimer’s disease (AD). Indeed, transition metal ions such as Cu(II) can generate reactive oxygen species (ROS) via O2 Fenton-like reduction, catalyzed by Cu(II) coordinated to the amyloid-beta (Aβ) peptide. Despite intensive efforts, the mechanisms of ROS-induced molecular damage remain poorly understood. In the present paper, we investigate, on the basis of Density Functional Theory (DFT) computations, a possible mechanism of the OH radical propagation toward membrane phospholipid polar head and fatty acid chains starting from the end-product of the OH radical generation by Cu(II)-Aβ. Using phosphatidylcholine as a model of a single unit inside a membrane, we evaluated the thermochemistry of the OH propagation with the oxidation of a C-H bond and the formation of the radical moiety. The DFT results show that Cu(II)-Aβ-OH can oxidize only sn-2 C-H bonds of the polar head and can easily oxidize the C-H bond adjacent to the carbon–carbon double bond in a mono or bis unsaturated fatty acid chain. These results are discussed on the basis of the recent literature on in vitro Aβ metal-catalyzed oxidation and on the possible implications in the AD oxidative stress mechanism.

The Heat Shock Transcription Factor HsfA Plays a Role in Membrane Lipids Biosynthesis Connecting Thermotolerance and Unsaturated Fatty Acid Metabolism in Aspergillus fumigatus.

Thermotolerance is a remarkable virulence attribute of Aspergillus fumigatus, but the consequences of heat shock (HS) to the cell membrane of this fungus are unknown, although this structure is one of the first to detect changes in ambient temperature that imposes on the cell a prompt adaptative response. Under high-temperature stress, fungi trigger the HS response controlled by heat shock transcription factors, such as HsfA, which regulates the expression of heat shock proteins. In yeast, smaller amounts of phospholipids with unsaturated fatty acid (FA) chains are synthesized in response to HS, directly affecting plasma membrane composition. The addition of double bonds in saturated FA is catalyzed by Δ9-fatty acid desaturases, whose expression is temperature-modulated. However, the relationship between HS and saturated/unsaturated FA balance in membrane lipids of A. fumigatus in response to HS has not been investigated. Here, we found that HsfA responds to plasma membrane stress and has a role in sphingolipid and phospholipid unsaturated biosynthesis. In addition, we studied the A. fumigatus Δ9-fatty acid desaturase sdeA and discovered that this gene is essential and required for unsaturated FA biosynthesis, although it did not directly affect the total levels of phospholipids and sphingolipids. sdeA depletion significantly sensitizes mature A. fumigatus biofilms to caspofungin. Also, we demonstrate that hsfA controls sdeA expression, while SdeA and Hsp90 physically interact. Our results suggest that HsfA is required for the adaptation of the fungal plasma membrane to HS and point out a sharp relationship between thermotolerance and FA metabolism in A. fumigatus. IMPORTANCE Aspergillus fumigatus causes invasive pulmonary aspergillosis, a life-threatening infection accounting for high mortality rates in immunocompromised patients. The ability of this organism to grow at elevated temperatures is long recognized as an essential attribute for this mold to cause disease. A. fumigatus responds to heat stress by activating heat shock transcription factors and chaperones to orchestrate cellular responses that protect the fungus against damage caused by heat. Concomitantly, the cell membrane must adapt to heat and maintain physical and chemical properties such as the balance between saturated/unsaturated fatty acids. However, how A. fumigatus connects these two physiological responses is unclear. Here, we explain that HsfA affects the synthesis of complex membrane lipids such as phospholipids and sphingolipids and controls the enzyme SdeA, which produces monounsaturated fatty acids, raw material for membrane lipids. These findings suggest that forced dysregulation of saturated/unsaturated fatty acid balance might represent novel strategies for antifungal therapy.

Design, synthesis, antibacterial/antitumor activity and in vitro stability of novel cordycepin derivatives with unsaturated fatty acid chain

To overcome the metabolic instability of cordycepin (adenosine deaminase (ADA) metabolic deamination and plasma degradation) and obtain better bioactivity, three novel kinds of cordycepin derivatives 1a-1c containing unsaturated fatty acids including linoleic acid, arachidonic acid and α-linolenic acid, respectively, were designed and synthesized. In terms of antibacterial activity, the synthesized compounds 1a and 1c showed enhanced activity than cordycepin in the tested bacterial strains. 1a-1c also exhibited enhanced antitumor activity against four cancer cell lines (human cervical cancer cell line HeLa, human non-small cell lung cancer cell line A549, human breast cancer cell line MCF-7, and human hepatoma cell line SMMC-7721) compared with cordycepin. Notably, 1a and 1b showed better antitumor activity even compared with positive control 5-Fluorouracil (5-FU) in HeLa, MCF-7 and SMMC-7721. The cell cycle assay indicated that when compared with cordycepin, 1a and 1b could significantly inhibit the cell propagation trapped in S and G2/M phases and increase the percentage of cells trapped in G0/G1 in HeLa and A549, which might provide a synergistic antitumor mechanism evidence different from cordycepin. Last but not the least, 1a and 1b displayed improved stability both in ADA solution and mouse plasma compared with cordycepin and 1a owns a solubility of 130 μg/mL in PBS. These results offer a novel insight into the primary structure and activity relationship of how the unsaturated fatty acid chain could affect the bioactivity of cordycepin, which also represents a series of cordycepin analogs with obviously improved bioactivity and enhanced stability, therefore promoting its druggable enhancement.

NMR and GPC Analysis of Alkyd Resins: Influence of Synthesis Method, Vegetable Oil and Polyol Content.

Alkyd resins are oil-based polymers that have been widely used for generations in the surface coating industry and beyond. Characterization of these resins is of high importance to understand the influence of its components on its behavior, compatibility with other resins, and final quality to ensure high durability. Here, NMR spectroscopy and GPC were used for characterizing differences in the chemical structure, molecular distribution, and dispersity between oil-based and fatty acid-based alkyd polymers made from sacha inchi and linseed oils. Sancha inchi (Plukentia volubilis L.) is a fruit-bearing plant native to South America and the Caribbean, and has a rich unsaturated fatty acid content. The effect of vegetable oil and polyol selection on the synthesis of alkyd resins for coating applications was analyzed. The influence of two different synthesis methods, monoglyceride and fatty acid processes, was also compared. Important structural differences were observed using NMR: one-dimensional spectra revealed the degree of unsaturated fatty acid chains along the polyester backbone, whereas, 2D NMR experiments facilitated chemical shift assignments of all signals. GPC analysis suggested that alkyd resins with homogeneous and high molecular weights can be obtained with the fatty acid process, and that resins containing pentaerythritol may have uniform chain lengths.

RETRACTED: Integrated the embedding delivery system and targeted oxygen scavenger enhances free radical scavenging capacity

World trends in oil crop growing area, yield, and production over the last 10years exhibited an increase of 48%, 82%, and 240%, respectively. Concerning reduced shelf-life of oil-containing food products caused by oil oxidation and the demand for sensory quality of oil, the development of methods the improvement oil quality is urgently required. This critical review presented a concise overview of the recent literature related to the inhibition ways of oil oxidation. The mechanism of different antioxidants and nanoparticle delivery systems on oil oxidation was also explored. The current review provides scientific findings on control strategies: (i) design oxidation quality assessment model; (ii) packaging by antioxidant coatings and eco-friendly film nanocomposite: ameliorate physicochemical properties; (iii) molecular investigations on inhibitory effects of selected antioxidants and underlying mechanisms; (iv) explore the interrelationship between the cysteine/citric acid and lipoxygenase pathway in the progression of oxidative/fragmentation degradation of unsaturated fatty acid chains.

Characterization of the Biosynthetic Gene Cluster and Shunt Products Yields Insights into the Biosynthesis of Balmoralmycin.

Angucyclines are a family of structurally diverse, aromatic polyketides with some members that exhibit potent bioactivity. Angucyclines have also attracted considerable attention due to the intriguing biosynthetic origins that underlie their structural complexity and diversity. Balmoralmycin (compound 1) represents a unique group of angucyclines that contain an angular benz[α]anthracene tetracyclic system, a characteristic C-glycosidic bond-linked deoxy-sugar (d-olivose), and an unsaturated fatty acid chain. In this study, we identified a Streptomyces strain that produces balmoralmycin and seven biosynthetically related coproducts (compounds 2-8). Four of the coproducts (compounds 5-8) are novel compounds that feature a highly oxygenated or fragmented lactone ring, and three of them (compounds 3-5) exhibited cytotoxicity against the human pancreatic cancer cell line MIA PaCa-2 with IC50 values ranging from 0.9 to 1.2 μg/mL. Genome sequencing and CRISPR/dCas9-assisted gene knockdown led to the identification of the ~43 kb balmoralmycin biosynthetic gene cluster (bal BGC). The bal BGC encodes a type II polyketide synthase (PKS) system for assembling the angucycline aglycone, six enzymes for generating the deoxysugar d-olivose, and a hybrid type II/III PKS system for synthesizing the 2,4-decadienoic acid chain. Based on the genetic and chemical information, we propose a mechanism for the biosynthesis of balmoralmycin and the shunt products. The chemical and genetic studies yielded insights into the biosynthetic origin of the structural diversity of angucyclines. IMPORTANCE Angucyclines are structurally diverse aromatic polyketides that have attracted considerable attention due to their potent bioactivity and intriguing biosynthetic origin. Balmoralmycin is a representative of a small family of angucyclines with unique structural features and an unknown biosynthetic origin. We report a newly isolated Streptomyces strain that produces balmoralmycin in a high fermentation titer as well as several structurally related shunt products. Based on the chemical and genetic information, a biosynthetic pathway that involves a type II polyketide synthase (PKS) system, cyclases/aromatases, oxidoreductases, and other ancillary enzymes was established. The elucidation of the balmoralmycin pathway enriches our understanding of how structural diversity is generated in angucyclines and opens the door for the production of balmoralmycin derivatives via pathway engineering.

Stimulating the sir2-spargel axis rescues exercise capacity and mitochondrial respiration in a Drosophila model of Barth syndrome.

ABSTRACTCardiolipin (CL) is a phospholipid required for proper mitochondrial function. Tafazzin remodels CL to create highly unsaturated fatty acid chains. However, when TAFAZZIN is mutated, CL remodeling is impeded, leading to mitochondrial dysfunction and the disease Barth syndrome. Patients with Barth syndrome often have severe exercise intolerance, which negatively impacts their overall quality of life. Boosting NAD+ levels can improve symptoms of other mitochondrial diseases, but its effect in the context of Barth syndrome has not been examined. We demonstrate, for the first time, that nicotinamide riboside can rescue exercise tolerance and mitochondrial respiration in a Drosophila Tafazzin mutant and that the beneficial effects are dependent on sir2 and spargel. Overexpressing spargel increased the total abundance of CL in mutants. In addition, muscles and neurons were identified as key targets for future therapies because sir2 or spargel overexpression in either of these tissues is sufficient to restore the exercise capacity of Drosophila Tafazzin mutants.

Fabrication and characterizations of cyclic amylopectin-based delivery system incorporated with β-carotene

The aim of this work was to investigate the encapsulation potential of cyclic amylopectin (CA) as a novel delivery carrier for fortifying the solubility and environmental stability of β-carotene (βC). After measuring solubility, recovery, encapsulation rate and loading rate, the optimum ratio of CA to βC in the composite (CA-βC) was 5:1. The solubility of βC in the optimal composite reached a maximum value of 179.1 μg/mL and was significantly higher than that of raw βC. Structural characterizations showed that the βC crystals were successfully entrapped into the hydrophobic cavity of CA, resulting in a composite with an amorphous state. A higher stability of βC to light or chemical oxidation was observed. Additionally, in-silico simulations showed that the partially unsaturated fatty acid chain of the βC molecule was bound into the hydrophobic core of CA through hydrophobic interaction. Results indicate that CA is a suitable compound to encapsulate and improve the functionality of lipophilic phytochemicals. • CA-based delivery system significantly enhanced the water solubility of βC. • Composite showed the higher stability of βC against light and chemical oxidation. • Crystal βC was successfully entrapped into the hydrophobic cavity of CA. • CA is an attractive platform to improve the functionalities of phytochemicals.