Decoding the nexus:branched-chain amino acids and their connection with sleep,circadian rhythms,and cardiometabolic health

The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other organs.Among these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral processes.Among the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of rapamycin.Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared transporter.Beyond their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy metabolism.Notably,they impact GABAergic neurons and the excitation/inhibition balance.The rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock control.The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood.Disturbed sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics.The mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies.In this context,the Drosophila model,though underutilized,holds promise in shedding new light on these mechanisms.Initial findings indicate its potential to introduce novel concepts,particularly in elucidating the intricate connections between the circadian clock,sleep/wake,and metabolism.Consequently,the use and transport of branched-chain amino acids emerge as critical components and orchestrators in the web of interactions across multiple organs throughout the sleep/wake cycle.They could represent one of the so far elusive mechanisms connecting sleep patterns to metabolic and cardiovascular health,paving the way for potential therapeutic interventions.

Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is well-documented.Nevertheless,the role of non-excitatory amino acids in brain damage following a stroke or brain trauma remains largely understudied.The release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the penumbra.Our findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma concentrations.These amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate receptors.Blocking N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during hypoxia.It is likely that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor activation.Thus,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as stroke and traumatic brain injury.Understanding these pathways co uld highlight new therapeutic targets to mitigate brain injury.

Evaluating the Potential of Birch Bark Suberinic Acids for Solid Wood Impregnation

Instead of the traditional linear model of taking,making,and disposing,the circular bio-economy promotes a regenerative approach.Although there is potential to create valuable products like betulin,lupeol,and suberinic acids(SA)from outer birch bark,many industries,such as plywood and pulp,often choose to incinerate substan-tial amounts of leftover birch bark to meet their energy needs.This highlights the importance of obtaining valu-able products from wood.The objective of this study was to examine various fractions of SA and assess their potential for wood impregnation.The fractions included SA potassium salts in ethanol(SAK-EtOH)and water(SAK-H2O),SA suspension in water(SAS-H2O)and dried SA,which was subsequently diluted in ethanol(DSA-EtOH).There is significant potential for utilizing SA in wood treatment formulations as a sustainable alternative to harmful petroleum-derived chemicals.This approach not only addresses environmental concerns but also enhances the functionality of wood in construction applications,such as improving impregnation for moisture and fungal protection.Among the solutions tested,the ethanol solution of SA,specifically DSA-EtOH,showed the highest weight percent gain(WPG)and the greatest leaching resistance.GPC analysis showed that SA salts in ethanol(SAK-EtOH)and water(SAK-H2O)predominantly consist of low molecular fractions and each process(acidification and drying)reduces the low molecular content in the sample.This suggests that SA polymerizes after drying,making it necessary to dissolve it in ethanol to meet the requirements for impregnation.Further opti-mization,including adjustments in the concentration of the SA ethanol solution and the curing temperature,is essential to identify the optimal conditions for more in-depth impregnation studies.

Integrated multi-omics analysis reveals liver metabolic reprogramming by fish iridovirus and antiviral function of alpha-linolenic acid

Iridovirus poses a substantial threat to global aquaculture due to its high mortality rate;however,the molecular mechanisms underpinning its pathogenesis are not well elucidated.Here,a multi-omics approach was applied to groupers infected with Singapore grouper iridovirus(SGIV),focusing on the roles of key metabolites.Results showed that SGIV induced obvious histopathological damage and changes in metabolic enzymes within the liver.Furthermore,SGIV significantly reduced the contents of lipid droplets,triglycerides,cholesterol,and lipoproteins.Metabolomic analysis indicated that the altered metabolites were enriched in 19 pathways,with a notable down-regulation of lipid metabolites such as glycerophosphates and alpha-linolenic acid(ALA),consistent with disturbed lipid homeostasis in the liver.Integration of transcriptomic and metabolomic data revealed that the top enriched pathways were related to cell growth and death and nucleotide,carbohydrate,amino acid,and lipid metabolism,supporting the conclusion that SGIV infection induced liver metabolic reprogramming.Further integrative transcriptomic and proteomic analysis indicated that SGIV infection activated crucial molecular events in a phagosome-immune depression-metabolism dysregulation-necrosis signaling cascade.Of note,integrative multi-omics analysis demonstrated the consumption of ALA and linoleic acid(LA)metabolites,and the accumulation of L-glutamic acid(GA),accompanied by alterations in immune,inflammation,and cell death-related genes.Further experimental data showed that ALA,but not GA,suppressed SGIV replication by activating antioxidant and anti-inflammatory responses in the host.Collectively,these findings provide a comprehensive resource for understanding host response dynamics during fish iridovirus infection and highlight the antiviral potential of ALA in the prevention and treatment of iridoviral diseases.

Anti-inflammatory Mechanism of Gamma-linolenic Acid in RAW264.7 Cells

[Objective] The aim was to investigate the anti-inflammatory effect and the mechanism of gamma-linolenic acid on lipopolysaccharide-induced RAW264.7 cells.[Method] Macrophagic system RAW 264.7 cells were cultured in vitro,when cells grew to fusion state,they were pretreated with 0,12.5,25.0,50.0 μmol/L of GLA for 4 h,and then 100 ng/ml of LPS were added to induce for 12 h or 30 min.Meanwhile,the blank control and LPS control were set.And the expression of iNOS,COX-2 and the effect of GLA on IκBα,p-JNK/SAPK（Thr183/Tyr185）,p38 MAPK,p-p38 MAPK（Thr180/Tyr182）,ERK1/2,p-ERK1/2 were detected by Western blot.[Result] GLA significantly inhibited the expression of iNOS and COX-2 in RAW264.7 cells induced by LPS,and in the range of 0-50 μmol/L of GLA,the inhibition effect was concentration-dependent（P0.05）.GLA could significantly inhibited the degradation of IκBα（P0.05）,thereby inhibited the activation of NF-κB.GLA could significantly inhibited the phosphorylation of LPS-induced JNK1/2 and ERK1/2（P0.05）,while it had not significantly effect on the phosphorylation of p38（P0.05）.[Conclusion] GLA had excellent anti-inflammation effect.The inhibition of the phosphorylation of JNK1/2,ERK1/2 and the inhibition of activation of NF-κB might be the important mechanism for the educing of its biological effect.

Recovery of Li, Ni, Co and Mn from spent lithium-ion batteries assisted by organic acids: Process optimization and leaching mechanism

The proper recycling of spent lithium-ion batteries(LIBs)can promote the recovery and utilization of valuable resources,while also negative environmental effects resulting from the presence of toxic and hazardous substances.In this study,a new environmentally friendly hydro-metallurgical process was proposed for leaching lithium(Li),nickel(Ni),cobalt(Co),and manganese(Mn)from spent LIBs using sulfuric acid with citric acid as a reductant.The effects of the concentration of sulfuric acid,the leaching temperature,the leaching time,the solid-liquid ratio,and the reducing agent dosage on the leaching behavior of the above elements were investigated.Key parameters were optimized using response surface methodology(RSM)to maximize the recovery of metals from spent LIBs.The maxim-um recovery efficiencies of Li,Ni,Co,and Mn can reach 99.08%,98.76%,98.33%,and 97.63%.under the optimized conditions(the sulfuric acid concentration was 1.16 mol/L,the citric acid dosage was 15wt%,the solid-liquid ratio was 40 g/L,and the temperature was 83℃ for 120 min),respectively.It was found that in the collaborative leaching process of sulfuric acid and citric acid,the citric acid initially provided strong reducing CO_(2)^(-),and the transition metal ions in the high state underwent a reduction reaction to produce transition metal ions in the low state.Additionally,citric acid can also act as a proton donor and chelate with lower-priced transition metal ions,thus speeding up the dissolution process.

Enabling heterogeneous catalysis to achieve carbon neutrality: Directional catalytic conversion of CO_(2) into carboxylic acids

The increase in anthropogenic carbon dioxide(CO_(2))emissions has exacerbated the deterioration of the global environment,which should be controlled to achieve carbon neutrality.Central to the core goal of achieving carbon neutrality is the utilization of CO_(2) under economic and sustainable conditions.Recently,the strong need for carbon neutrality has led to a proliferation of studies on the direct conversion of CO_(2) into carboxylic acids,which can effectively alleviate CO_(2) emissions and create high-value chemicals.The purpose of this review is to present the application prospects of carboxylic acids and the basic principles of CO_(2) conversion into carboxylic acids through photo-,electric-,and thermal catalysis.Special attention is focused on the regulation strategy of the activity of abundant catalysts at the molecular level,inspiring the preparation of high-performance catalysts.In addition,theoretical calculations,advanced technologies,and numerous typical examples are introduced to elaborate on the corresponding process and influencing factors of catalytic activity.Finally,challenges and prospects are provided for the future development of this field.It is hoped that this review will contribute to a deeper understanding of the conversion of CO_(2) into carboxylic acids and inspire more innovative breakthroughs.

Bile acids inhibit ferroptosis sensitivity through activating farnesoid X receptor in gastric cancer cells

BACKGROUND Gastric cancer(GC)is associated with high mortality rates.Bile acids(BAs)reflux is a well-known risk factor for GC,but the specific mechanism remains unclear.During GC development in both humans and animals,BAs serve as signaling molecules that induce metabolic reprogramming.This confers additional cancer phenotypes,including ferroptosis sensitivity.Ferroptosis is a novel mode of cell death characterized by lipid peroxidation that contributes universally to malignant progression.However,it is not fully defined if BAs can influence GC progression by modulating ferroptosis.AIM To reveal the mechanism of BAs regulation in ferroptosis of GC cells.METHODS In this study,we treated GC cells with various stimuli and evaluated the effect of BAs on the sensitivity to ferroptosis.We used gain and loss of function assays to examine the impacts of farnesoid X receptor(FXR)and BTB and CNC homology 1(BACH1)overexpression and knockdown to obtain further insights into the molecular mechanism involved.RESULTS Our data suggested that BAs could reverse erastin-induced ferroptosis in GC cells.This effect correlated with increased glutathione(GSH)concentrations,a reduced GSH to oxidized GSH ratio,and higher GSH peroxidase 4(GPX4)expression levels.Subsequently,we confirmed that BAs exerted these effects by activating FXR,which markedly increased the expression of GSH synthetase and GPX4.Notably,BACH1 was detected as an essential intermediate molecule in the promotion of GSH synthesis by BAs and FXR.Finally,our results suggested that FXR could significantly promote GC cell proliferation,which may be closely related to its anti-ferroptosis effect.CONCLUSION This study revealed for the first time that BAs could inhibit ferroptosis sensitivity through the FXR-BACH1-GSHGPX4 axis in GC cells.This work provided new insights into the mechanism associated with BA-mediated promotion of GC and may help identify potential therapeutic targets for GC patients with BAs reflux.

Gut microbiota induced abnormal amino acids and their correlation with diabetic retinopathy

AIM:To explore the correlation of gut microbiota and the metabolites with the progression of diabetic retinopathy(DR)and provide a novel strategy to elucidate the pathological mechanism of DR.METHODS:The fecal samples from 32 type 2 diabetes patients with proliferative retinopathy(PDR),23 with nonproliferative retinopathy(NPDR),27 without retinopathy(DM),and 29 from the sex-,age-and BMI-matched healthy controls(29 HC)were analyzed by 16S rDNA gene sequencing.Sixty fecal samples from PDR,DM,and HC groups were assayed by untargeted metabolomics.Fecal metabolites were measured using liquid chromatographymass spectrometry(LC-MS)analysis.Associations between gut microbiota and fecal metabolites were analyzed.RESULTS:A cluster of 2 microbiome and 12 metabolites accompanied with the severity of DR,and the close correlation of the disease progression with PDR-related microbiome and metabolites were found.To be specific,the structure of gut microbiota differed in four groups.Diversity and richness of gut microbiota were significantly lower in PDR and NPDR groups,than those in DM and HC groups.A cluster of microbiome enriched in PDR group,including Pseudomonas,Ruminococcaceae-UCG-002,Ruminococcaceae-UCG-005,Christensenellaceae-R-7,was observed.Functional analysis showed that the glucose and nicotinate degradations were significantly higher in PDR group than those in HC group.Arginine,serine,ornithine,and arachidonic acid were significantly enriched in PDR group,while proline was enriched in HC group.Functional analysis illustrated that arginine biosynthesis,lysine degradation,histidine catabolism,central carbon catabolism in cancer,D-arginine and D-ornithine catabolism were elevated in PDR group.Correlation analysis revealed that Ruminococcaceae-UCG-002 and Christensenellaceae-R-7 were positively associated with L-arginine,ornithine levels in fecal samples.CONCLUSION:This study elaborates the different microbiota structure in the gut from four groups.The relative abundance of Ruminococcaceae-UCG-002 and Parabacteroides are associated with the severity of DR.Amino acid and fatty acid catabolism is especially disordered in PDR group.This may help provide a novel diagnostic parameter for DR,especially PDR.

Bile acids,gut microbiota,and therapeutic insights in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver malignancy.The interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and progression.Under normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and BAs.The gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal homeostasis.Of note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC development.Therefore,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying hepatocarcinogenesis.In this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in HCC.Additionally,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered bacteria.In summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.

Synergistic microcystin degradation by a novel bacterium isolated from shrimp pond and fulvic acids

Using the Widdel medium with extracted microcystin(MC)as the sole carbon and nitrogen sources,the MC-degrading bacteria community S_6 was enriched from the sediment of Litopenaeus vannamei pond,and a novel MC-degrading bacteria strain was isolated from S_6.According to 16S rDNA gene sequence and biochemical characteristics,the isolated strain was identified and named Nitratireductor aquimarinus D_(1).Fulvic acid(FA),as a widely existing photosensitizer involved in MC photodegradation,coexists with MC-degrading bacteria in natural water.The synergistic effects of N.aquimarinus D_(1) and FA on MC degradation were evaluated via comparing the degradation rate of MC induced by N.aquimarinus D_(1) and FA alone and in combination under natural light conditions.Compared with the control group,the supplementation of N.aquimarinus D_(1) and FA alone or in combination could significantly increase the degradation rate of MC(P<0.05).In the first 36 h,the degradation effect of FA on MC was better than that of N.aquimarinus D_(1),but the degradation effect was opposite at 48 h.N.aquimarinus D_(1) and FA did not show synergistic effect on MC degradation until 48 h.In the application of N.aquimarinus and FA to degrade MC in aquaculture pond,there might be a time-lag effect in the synergistic degradation.

Formulation ofα-linolenic acid microemulsion free of co-surfactant

A novel class ofα-linolenic acid-in-water microemulsion free of co-surfactant was investigated as potential food delivery systems.Rough demarcation within the transparent region was deduced from the results of conductivity and polarizing optical microscopy.The microemulsion mean hydrodynamic diameter and characterization were determined by dynamic light scattering and negative-staining TEM.The location of ALA molecules in the microemulsion formulations was determined by ~1H NMR spectroscopy.

Effect of different drying methods on the amino acids,α-dicarbonyls and volatile compounds of rape bee pollen

The significant demand for high quality food has motivated us to adopt appropriate processing methods to improve the food nutritional quality and flavors.In this study,the effects of five drying methods,namely,pulsed vacuum drying(PVD),freeze drying(FD),infrared drying(IRD),hot-air drying(HAD)and sun drying(SD)on free amino acids(FAAs),α-dicarbonyl compounds(α-DCs)and volatile compounds(VOCs)in rape bee pollen(RBP)were determined.The results showed that FD significantly released the essential amino acids(EAAs)compared with fresh samples while SD caused the highest loss.Glucosone was the dominantα-DCs in RBP and the highest loss was observed after PVD.Aldehydes were the dominant volatiles of RBP and SD samples contained more new volatile substances(especially aldehydes)than the other four drying methods.Comprehensively,FD and PVD would be potential methods to effectively reduce the quality deterioration of RBP in the drying process.

Palm oil protectsα-linolenic acid from rumen biohydrogenation and muscle oxidation in cashmere goat kids

Background:In ruminants,dietary C18:3n-3 can be lost through biohydrogenation in the rumen;and C18:3n-3 that by-passes the rumen still can be lost through oxidation in muscle,theoretically reducing the deposition of C18:3n-3,the substrate for synthesis of poly-unsaturated fatty acids(n-3 LCPUFA)in muscle.In vitro studies have shown that rumen hydrogenation of C18:3n-3 is reduced by supplementation with palm oil(rich in cis-9 C18:1).In addition,in hepatocytes,studies with neonatal rats have shown that cis-9 C18:1 inhibits the oxidation of C18:3n-3.It therefore seems likely that palm oil could reduce both rumen biohydrogenation of C18:3n-3 and muscle oxidation of C18:3n-3.The present experiment tested whether the addition of palm oil to a linseed oil supplement for goat kids would prevent the losses of C18:3n-3 and thus improve the FA composition in two muscles,Longissimus dorsi and Biceps femoris.To investigate the processes involved,we studied the rumen bacterial communities and measured the mRNA expression of genes related to lipid metabolism in Longissimus dorsi.Sixty 4-month-old castrated male Albas white cashmere kids were randomly allocated among three dietary treatments.All three diets contained the same ingredients in the same proportions,but differed in their fat additives:palm oil(PMO),linseed oil(LSO)or mixed oil(MIX;2 parts linseed oil plus 1 part palm oil on a weight basis).Results:Compared with the LSO diet,the MIX diet decreased the relative abuandance of Pseudobutyrivibrio,a bacterial species that is positively related to the proportional loss rate of dietary C18:3n-3 and that has been reported to generate the ATP required for biohydrogenation(reflecting a decrease in the abundance of rumen bacteria that hydrogenate C18:3n-3 in MIX kids).In muscle,the MIX diet increased concentrations of C18:3n-3,C20:5n-3,C22:6n-3,and n-3 LCPUFA,and thus decreased the n-6/n-3 ratio;decreased the mRNA expression of CPT1β(a gene associated with fatty acid oxidation)and increased the mRNA expression of FADS1 and FADS2(genes associated with n-3 LCPUFA synthesis),compared with the LSO diet.Interestingly,compared to Longissimus dorsi,Biceps femoris had greater concentrations of PUFA,greater ratios of unsaturated fatty acids/saturated fatty acids(U/S),and poly-unsaturated fatty acids/saturated fatty acids(P/S),but a lesser concentration of saturated fatty acids(SFA).Conclusions:In cashmere goat kids,a combination of linseed and palm oils in the diet increases the muscle concentration of n-3 LCPUFA,apparently by decreasing the relative abundance of rumen bacteria that are positively related to the proportional loss rate of dietary C18:3n-3,by inhibiting mRNA expression of genes related to C18:3n-3 oxidation in muscle,and by up-regulating mRNA expression of genes related to n-3 LCPUFA synthesis in muscle,especially in Longissimus dorsi.

α-Linolenic acid alleviates aluminium chloride-induced toxicity in PC12 cells by activation of PKA-CREB-BDNF signaling pathway

Aluminum has been associated with neurodegenerative diseases.ALA(α-linolenic acid),an essential dietary component for human health,possesses prominent biological activities.Herein,we aim to explore the neuroprotective effects of ALA on aluminum toxicity and reveal the underlying mechanism.Results show that aluminum chloride(denoted as Al)enabled cell viability decline and apoptosis with oxidative stress and mitochondrial damage in differentiated rat pheochromocytoma cells(PC12)for 24 h incubation.Compared with Al(10 mmol/L)treatment alone,ALA(50μmol/L)pretreatment for 24 h significantly enhanced cell viability by 28.40%,and hindered cell apoptosis by 12.35%,together with recovering redox state balance and alleviating mitochondrial damage.It was measured that ALA treatment upregulated Bcl-2 expression and down-regulated Bax level,accompanied with an expression decline of caspase-3 and caspase-9.Meanwhile,ALA pretreatment was proved to increase protein kinase A(PKA)expression and to promote phosphorylation of cAMP response element-binding protein(p-CREB),resulting in elevation on the level of brain-derived neurotrophic factor(BDNF).The above results showed that ALA attenuated Al toxicity in PC12 cells by mediating the PKA-CREBBDNF signaling pathway.

Milk fat globule membrane supplementation protects againstβ-lactoglobul-ininduced food allergy in mice via upregulation of regulatory T cells and enhancement of intestinal barrier in a microbiota-derived short-chain fatty acids manner

Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.

Production of γ-linolenic acid and stearidonic acid by Synechococcus sp.PCC7002 containing cyanobacterial fatty acid desaturase genes

Genetic modifi cation is useful for improving the nutritional qualities of cyanobacteria. To increase the total unsaturated fatty acid content, along with the ratio of ω-3/ω-6 fatty acids, genetic engineering can be used to modify fatty acid metabolism. S ynechococcus sp. PCC7002, a fast-growing cyanobacterium, does not contain a Δ6 desaturase gene and is therefore unable to synthesize γ-linolenic acid(GLA) and stearidonic acid(SDA), which are important in human health. In this work, we constructed recombinant vectors Syd6 D, Syd15 D and Syd6Dd15 D to express the Δ15 desaturase and Δ6 desaturase genes from Synechocystis PCC6803 in Synechococcus sp. PCC7002, with the aim of expressing polyunsaturated fatty acids. Overexpression of the Δ15 desaturase gene in S ynechococcus resulted in 5.4 times greater accumulation of α-linolenic acid compared with the wild-type while Δ6 desaturase gene expression produced both GLA and SDA. Co-expression of the two genes resulted in low-level accumulation of GLA but much larger amounts of SDA, accounting for as much to 11.64% of the total fatty acid content.

Oleanolic acid improved intestinal immune function by activating and potentiating bile acids receptor signaling in E. coli-challenged piglets

Background Infection with pathogenic bacteria during nonantibiotic breeding is one of the main causes of animal intestinal diseases.Oleanolic acid(OA)is a pentacyclic triterpene that is ubiquitous in plants.Our previous work demonstrated the protective effect of OA on intestinal health,but the underlying molecular mechanisms remain unclear.This study investigated whether dietary supplementation with OA can prevent diarrhea and intestinal immune dysregulation caused by enterotoxigenic Escherichia coli(ETEC)in piglets.The key molecular role of bile acid receptor signaling in this process has also been explored.Results Our results demonstrated that OA supplementation alleviated the disturbance of bile acid metabolism in ETEC-infected piglets(P<0.05).OA supplementation stabilized the composition of the bile acid pool in piglets by regulating the enterohepatic circulation of bile acids and significantly increased the contents of UDCA and CDCA in the ileum and cecum(P<0.05).This may also explain why OA can maintain the stability of the intestinal microbiota structure in ETEC-challenged piglets.In addition,as a natural ligand of bile acid receptors,OA can reduce the severity of intestinal inflammation and enhance the strength of intestinal epithelial cell antimicrobial programs through the bile acid receptors TGR5 and FXR(P<0.05).Specifically,OA inhibited NF-κB-mediated intestinal inflammation by directly activating TGR5 and its downstream c AMP-PKA-CREB signaling pathway(P<0.05).Furthermore,OA enhanced CDCA-mediated MEK-ERK signaling in intestinal epithelial cells by upregulating the expression of FXR(P<0.05),thereby upregulating the expression of endogenous defense molecules in intestinal epithelial cells.Conclusions In conclusion,our findings suggest that OA-mediated regulation of bile acid metabolism plays an important role in the innate immune response,which provides a new diet-based intervention for intestinal diseases caused by pathogenic bacterial infections in piglets.

Biomass-based production of trimellitic and trimesic acids

The production of industrial chemicals with renewable biomass feedstock holds potential to aid the world in pursuing a carbon-neutral society.Trimellitic and trimesic acids are important commodity chemicals in industry that are prepared by the oxidation of petroleum-derived trimethylbenzene.To reduce the dependence on the limited oil source,we develop a potential sustainable alternative towards trimellitic and trimesic acids using biomass-based 2-methyl-2,4-pentandiol(MPD),acrylate and crotonaldehyde as starting materials.The process for trimellitic acid includes dehydration/D-A reaction of MPD and acrylate,flow aromatization over Pd/C catalyst,hydrolysis and catalytic aerobic oxidation(60%overall yield).The challenging regioselectivity issue of D-A reaction is tackled by a matched combination of temperature and deep eutectic solvent ChCl/HCO_(2)H.Crotonaldehyde can also participate in the reaction,followed by Pd/C-catalyzed decarbonylation/dehydrogenation and oxidation to provide trimesic acid in 54%overall yield.Life cycle assessment implies that compared to conventional fossil process,our biomass-based routes present a potential in reducing carbon emissions.

Mapping and identification of QTLs for seed fatty acids in soybean(Glycine max L.)

Soybean is one of the most important sources of vegetable oil.The oil content and fatty acid ratio have attracted significant attention due to their impacts on the shelf-life of soybean oil products and consumer health.In this study,a high-density genetic map derived from Guizao 1 and Brazil 13 was used to analyze the quantitative trait loci of palmitic acid(PA),stearic acid(SA),oleic acid(OA),linoleic acid(LA),linolenic acid(LNA),and oil content(OC).A total of 54 stable QTLs were detected in the genetic map linkage analysis,which shared six bin intervals.Among them,the bin interval on chromosome 13(bin106-bin118 and bin123-bin125)was found to include stable QTLs in multiple environments that were linked to OA,LA,and LNA.Eight differentially expressed genes(DEGs)within these QTL intervals were determined as candidate genes according to the combination of parental resequencing,bioinformatics and RNA sequencing data.All these results are conducive to breeding soybean with the ideal fatty acid ratio for food,and provide the genetic basis for mining genes related to the fatty acid and oil content traits in soybean.