Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’...Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.展开更多
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 th...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.展开更多
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 ...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.展开更多
Epidemiological evidence suggests that there is a direct relationship between the degree of obesity and acute pancreatitis severity.Intake of different fatty acids leads to different types of hyperlipidemias.Adipose d...Epidemiological evidence suggests that there is a direct relationship between the degree of obesity and acute pancreatitis severity.Intake of different fatty acids leads to different types of hyperlipidemias.Adipose degradation by pancreatic lipase generates different free fatty acids,which can exacerbate pancreatitis.Saturated fatty acids(SFAs)play an inflammatory role in human metabolic syndrome and obesity,whereas unsaturated fatty acids(UFAs)are“good fats”that are thought to enhance overall health status.However,it appears that serum UFAs correlate with severe acute pancreatitis.Additionally,the“obesity paradox”suggests that UFAs potentially minimize direct harm to the organ.This review provides an in-depth overview of the role of SFAs and UFAs in acute pancreatitis of hyperlipidemia and discusses potential prevention targets for severe acute pancreatitis.展开更多
Heterogeneous metal-catalyzed chemical conversions with a recyclable catalyst are very ideal and challenging for sustainable organic synthesis.A new bipyridyl-Mo(IV)-carbon nitride(CN-K/Mo-Bpy)was prepared by supporti...Heterogeneous metal-catalyzed chemical conversions with a recyclable catalyst are very ideal and challenging for sustainable organic synthesis.A new bipyridyl-Mo(IV)-carbon nitride(CN-K/Mo-Bpy)was prepared by supporting molybdenum complex on C_(3)N_(4)-K and characterized by FT-IR,XRD,SEM,XPS and ICP-OES.Heterogeneous CN–Mo-Bpy catalyst can be applied to the direct amination of nitroarenes and arylboronic acid,thus constructing various valuable diarylamines in high to excellent yields with a wide substrate scope and good functional group tolerance.It is worth noting that this heterogeneous catalyst has high chemical stability and can be recycled for at least five times without reducing its activity.展开更多
Formic and acetic acids are the most abundant gaseous organic acids and play the key role in the atmospheric chemistry.In iodine-adduct chemical ionizationmass spectrometry(CIMS),the low utilization efficiency of meth...Formic and acetic acids are the most abundant gaseous organic acids and play the key role in the atmospheric chemistry.In iodine-adduct chemical ionizationmass spectrometry(CIMS),the low utilization efficiency of methyl iodide and humidity interference are two major issues of the vacuum ultraviolet(VUV)lamp initiated CIMS for on-line gaseous formic and acetic acids analysis.In this work,we present a new CIMS based on VUV lamp,and the ion-molecular reactor is separated into photoionization and chemical ionization zones by a reducer electrode.Acetone was added to the photoionization zone,and the VUV photoionization acetone provided low-energy electrons for methyl iodide to generate I−,and the addition of acetone reduced the amount of methyl iodide by 2/3.In the chemical ionization zone,a headspace vial containing ultrapure water was added for humidity calibration,and the vial changes the sensitivity as a function of humidity from ambiguity to well linear correlation(R2>0.95).With humidity calibration,the CIMS can quantitatively measure formic and acetic acids in the humidity range of 0%-88%RH.In this mode,limits of detection of 10 and 50 pptv are obtained for formic and acetic acids,respectively.And the relative standard deviation(RSD)of quantitation stability for 6 days were less than 10.5%.This CIMS was successfully used to determine the formic and acetic acids in the underground parking and ambient environment of the Shandong University campus(Qingdao,China).In addition,we developed a simple model based formic acid concentration to assess vehicular emissions.展开更多
Morphology and growth rate of carbon dioxide hydrate on the interface between liquid carbon dioxide and humic acid solutions were studied in this work.It was found that after the growth of the hydrate film at the inte...Morphology and growth rate of carbon dioxide hydrate on the interface between liquid carbon dioxide and humic acid solutions were studied in this work.It was found that after the growth of the hydrate film at the interface,further growth of hydrate due to the suction of water in the capillary system formed between the wall of the cuvette and the end boundary of the hydrate layer occurs.Most probably,substantial effects on the formation of this capillary system may be caused by variations in reactor wall properties,for example,hydrophobic-hydrophilic balance,roughness,etc.We found,that the rate of CO_(2) hydrate film growth on the surface of the humic acid aqueous solution is 4-fold to lower in comparison with the growth rate on the surface of pure water.We suppose that this is caused by the adsorption of humic acid associates on the surface of hydrate particles and,as a consequence,by the deceleration of the diffusion of dissolved carbon dioxide to the growing hydrate particle.展开更多
An efficient TfOH-catalyzed O—H insertion reaction of α-aryl diazoesters with carboxylic acids is reported.This metal-free protocol provides an operationally simple method for a one-pot assembly of diverse α-acylox...An efficient TfOH-catalyzed O—H insertion reaction of α-aryl diazoesters with carboxylic acids is reported.This metal-free protocol provides an operationally simple method for a one-pot assembly of diverse α-acyloxy esters in moderate to high yields with a broad substrate scope.All starting materials are readily available,and the reactions can be conducted in the open air at room temperature.展开更多
The optical absorption of large molecular compounds HULIS(humic-like substances)can significantly impact the aerosol light absorption and radiative forcing,influencing cloud condensation nuclei formation and thus the ...The optical absorption of large molecular compounds HULIS(humic-like substances)can significantly impact the aerosol light absorption and radiative forcing,influencing cloud condensation nuclei formation and thus the climate and atmospheric environment.This study collected aerosol(PM_(2.5))samples from the summit of Mount Tai in North China to investigate the concentration,molecular composition,and optical properties of HULIS.The average concentration of HULIS in the PM_(2.5) in this study was 1.26±0.54μg/m^(3),comprising for 56%of the water-soluble organic carbon(WSOC),with levels lower than urban areas but higher than other mountainous regions.Mass spectrometry revealed that CHO and CHON components,with high aromaticity and phenolic groups,are major contributors to absorption and fluorescence.These results indicate that HULIS is mainly composed of lignin and proteins/amino sugars,derived from combustion and secondary formation,and possesses a high light absorption capacity(withMAE365(mass absorption efficiency)and AAE(A˚ngstrom exponent)indices of 0.62m^(2)/g and 4.99,respectively).Parallel factor analysis identified three fluorescence components of HULIS,with proportions of 60.8%for less oxygen humic-like substances,21.0%for high oxygen humic-like substances,and 18.2%for protein-like substances.Our study highlights the significance of the light-absorbing capacity and secondary formation of HULIS at Mount Tai,laying the groundwork for investigation into the climate effects,formation mechanisms,and sources of HULIS generation.展开更多
The aim of the present study was to evaluate the effects of baobab seed washing and origin on the chemical composition of the oil extracted by pressing. Six (6) oil samples were obtained from seeds of three (3) geogra...The aim of the present study was to evaluate the effects of baobab seed washing and origin on the chemical composition of the oil extracted by pressing. Six (6) oil samples were obtained from seeds of three (3) geographical origins. The identification and quantification of fatty acids and the polyphenolic profile were carried out by GC-MS and HPLC-UV, respectively. Analysis of fatty acid methyl esters allowed the identification and quantification of 18 fatty acids. Oils from unwashed seeds were richer in palmitic (C16:0), stearic (C18:0), oleic (C18:1) and arachidic (C20:0) acids. In addition, HPLC-UV analysis at 279 nm shows that oils from unwashed seeds are richer in tyrosol, hydroxytyrosol and caffeic acid. With regard to the polyphenolic profile, gallic acid and quercetin were not detected in these baobab oils. Principal component analysis of fatty acid and phenolic compound content showed that oils from unwashed seeds would best preserve their chemical and associated potential bioactive characteristics.展开更多
Alpha-linolenic acid(ALA)is capable of synthesizing eicosapentaenoic acid(EPA)and docosahexaenoic acid(DHA)in vivo,but the conversion rate is hard to meet the body's need for rapid DHA supplementation.Studies have...Alpha-linolenic acid(ALA)is capable of synthesizing eicosapentaenoic acid(EPA)and docosahexaenoic acid(DHA)in vivo,but the conversion rate is hard to meet the body's need for rapid DHA supplementation.Studies have shown that fucoxanthin can increase DHA content in the liver of mice,but the mechanism is not clear.Moreover,the effect of fucoxanthin and its metabolite fucoxanthinol on the chain lengthening reaction of n-6 polyunsaturated fatty acids(PUFAs)is little studied.In this study,the effects of fucoxanthin and fucoxanthinol on the chain elongation of n-3 and n-6 series PUFAs were investigated in mice.Results showed that fucoxanthin and fucoxanthinol significantly increased the conversion of n-3 series ALA to DHA and n-6 series linolenic acid(LA)to arachidonic acid(AA)in the serum,liver,small intestine,and heart of mice.In addition,fucoxanthin accelerated the rate of DHA supplementation by ALA in the brain.Further mechanistic studies revealed that the role of fucoxanthin in promoting PUFAs conversion was not regulated at transcriptional level,but by increasing the activity of fatty acid desaturase 2(FADS2),a key enzyme of chain elongation reaction of n-3 and n-6 PUFAs.This study fundamentally provided theoretical bases for a new strategy of dietary supplementation of n-3 and n-6 PUFAs.展开更多
Background This study investigated the potential impacts of increasing linoleic andα-linolenic acid intake during lactation and wean-to-breeding on subsequent reproduction of sows.A total of 309 sows(PIC Camborough L...Background This study investigated the potential impacts of increasing linoleic andα-linolenic acid intake during lactation and wean-to-breeding on subsequent reproduction of sows.A total of 309 sows(PIC Camborough L42)were balanced by parity(140 and 169 sows representing parity 1 to 2[P1-2]and 3 to 9[P3+],respectively)and assigned within parity to a 2×2 factorial arrangement.Factors included essential fatty acid(EFA)supplementation(control diets containing 1.2%linoleic and 0.15%α-linolenic acid or diets with 3.0%linoleic and 0.38%α-linolenic acid)and supplementation period(lactation or wean-to-breeding).Tallow(low EFA diets)or soybean oil(high EFA diets)were included at 4%in sorghum-soybean meal-wheat middlings-based diets to attain targeted EFA levels.Results High levels of EFA fed during lactation had no effect on feed intake or litter performance,but increased subsequent farrowing rate(P=0.027;82.1%vs.70.4%),tended to reduce the proportion of sows removed(P=0.070;12.4%vs.20.8%),decreased the number of total pigs born in the following litter(P=0.072;15.3 vs.16.2),and increased total pigs born alive per 100 sows weaned(P=0.062;1,122 vs.974),regardless of sow parity.Young sows(P1-2)consuming the high EFA diet during lactation displayed a shorter wean-to-estrus interval(P=0.035;4.2 vs.4.6),but P3+sows were unaffected.Increasing EFA intake for P3+sows,but not P1-2 sows,resulted in more sows bred by d 5(P=0.028;91.1%vs.81.7%)and more mummies in the subsequent litter(P=0.040;0.32 vs.0.16).Feeding increased EFA to P1-2 sows during the wean-to-breeding period decreased subsequent farrowing rate(P=0.042;72.0%vs.87.7%),and increased removal rate(P=0.003;28.8%vs.9.4%).Total pigs born alive per 100 sows weaned was reduced(P=0.007)in P1-2 sows when supplemented with EFA during wean-breeding(939 vs.1,149)but was not impacted in P3+sows(1,131 vs.982).Conclusions Supplemental EFA in lactation diets benefited subsequent reproduction of sows,regardless of parity.Increasing dietary levels of EFA during the wean-to-breeding period to younger sows negatively impacted subsequent reproduction.展开更多
Alduronic acid lactones and glyconolactones are highly functionalized and versatile chiral building blocks.Herein,we describe a novel approach to these compounds via decarboxylative oxygenation of uronic acids.The tra...Alduronic acid lactones and glyconolactones are highly functionalized and versatile chiral building blocks.Herein,we describe a novel approach to these compounds via decarboxylative oxygenation of uronic acids.The transformations proceed using Selectfluor and TEMPO as oxidants,either in the presence of catalytic amounts of Ag_(2)CO_(3)or in the absence of this catalyst.The methodology provides structurally diverse alduronic acid lactones and enables the preparation of rare sugar glyconolactones from easily available D-C-glycosides.Based on the^(18)O-labeling experiments,control experiments,and isolation of the key intermediates,a radical-polar crossover reaction mechanism is proposed.The utility of this method is demonstrated through efficient conversions of alduronic acid lactones into polyhydroxylated cyclic alkaloids and castanospermine-type architectures.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease worldwide.Its prevalence is closely linked to the dramatic rise in obesity and non-communicable diseas...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease worldwide.Its prevalence is closely linked to the dramatic rise in obesity and non-communicable diseases.MASLD exhibits a progressive trajectory that may culminate in development of hepatic cirrhosis,thereby predisposing affected individuals to an elevated likelihood of hepatocarcinogenesis.Diet,especially dietary fatty acids,serves as a key link between nutrient intake and MASLD pathogenesis.AIM To explore the impact of various omega-6 fatty acid subtypes on the pathogenesis and therapeutic strategies of MASLD.METHODS A systematic literature search was conducted across Web of Science,PubMed,Cochrane Central,Scopus,and Embase databases from inception through June 2024 to identify all original studies linking different subtypes of omega-6 polyunsaturated fatty acids to the pathogenesis and management of MASLD.The search strategy explored the linkage between omega-6 polyunsaturated fatty acids and their subtypes,including linoleic acid(LA),gamma-linolenic acid(GLA),arachidonic acid,conjugated LA,and docosapentaenoic acid,in relation to MASLD and cardiometabolic risk.RESULTS By employing the specified search strategy,a total of 83 articles were identified as potentially eligible.During the title,abstract,and full-text screening phases,27 duplicate records were removed,leaving 56 records for relevance screening.Of these,43 records were excluded for reasons such as irrelevance and language restrictions(limited to English),resulting in 13 full-text articles being included for detailed assessment(10 human studies,1 animal study,and 2 review articles).Although certain subtypes,as GLA,dihomo-GLA,omega-6-derived oxylipins,and most arachidonic acid-derived eicosanoids,exhibit pro-inflammatory effects,our findings suggest that other subtypes such as LA,cis-9,trans-11 conjugated LA,and docosapentaenoic acid have beneficial effects on fatty liver,cardiometabolic risk factors,and inflammation,even at high intake levels.CONCLUSION The varying health effects of omega-6 fatty acids,ranging from anti-inflammatory to pro-inflammatory impacts on the liver,leave the question of their recommendation for MASLD patients unresolved.This underscores the importance of careful selection when considering omega-6 supplementation.展开更多
The anaerobic acid production experiments were conducted with the pretreated kitchen waste under pH adjustment.The results showed that pH 8 was considered to be the most suitable condition for acid production,especial...The anaerobic acid production experiments were conducted with the pretreated kitchen waste under pH adjustment.The results showed that pH 8 was considered to be the most suitable condition for acid production,especially for the formation of acetic acid and propionic acid.The average value of total volatile fatty acid at pH 8 was 8814 mg COD/L,1.5 times of that under blank condition.The average yield of acetic acid and propionic acid was 3302 mg COD/L and 2891 mg COD/L,respectively.The activities of key functional enzymes such as phosphotransacetylase,acetokinase,oxaloacetate transcarboxylase and succinylcoA transferase were all enhanced.To further explore the regulatory mechanisms within the system,the distribution of microorganisms at different levels in the fermentation system was obtained by microbial sequencing,results indicating that the relative abundances of Clostridiales,Bacteroidales,Chloroflexi,Clostridium,Bacteroidetes and Propionibacteriales,which were great contributors for the hydrolysis and acidification,increased rapidly at pH 8 compared with the blank group.Besides,the proportion of genes encoding key enzymes was generally increased,which further verified the mechanism of hydrolytic acidification and acetic acid production of organic matter under pH regulation.展开更多
Background During the transition period,cows are prone to negative energy balance,which can lead to a decline in production performance and health in severe cases.In recent years,it has been discovered that bile acids...Background During the transition period,cows are prone to negative energy balance,which can lead to a decline in production performance and health in severe cases.In recent years,it has been discovered that bile acids(BAs)can act not only as fat emulsifiers but also as signaling molecules to regulate body metabolism.Although BAs have been used to some extent in monogastric and aquatic animals,their role in ruminants,particularly in transition cows,remains unclear.Therefore,this study aimed to determine the effects of BAs on the production performance,milk and plasma fatty acid and BA composition,and fecal microbiota in transition dairy cows.Results Forty-six healthy transition Holstein dairy cows with similar conditions were randomly divided into two groups and supplemented with 0 or 20 g/d of BAs from 21 d before the expected calving to 21 d after calving.The production performance was tracked until 60 d after calving.The results indicated that BA supplementation significantly improved postpartum milk fat content and yields as well as the yields of unsaturated fatty acids,monounsaturated fatty acids,and polyunsaturated fatty acids in milk.There was a significant increase in the concentration of triglyceride and the proportion of C≤16 fatty acids in the plasma of cows supplemented with BAs,while the concentration of β-hydroxybutyrate and the proportion of C>16 fatty acids in the plasma decreased significantly.BA supplementation significantly altered the composition of the fecal bacterial community and increased the relative abundance of bacteria beneficial for BA metabolism and transformation(Romboutsia,Clostridium sensu_stricto_6,and Clostridium sensu_stricto_1).Functional prediction analysis showed that the relative abundance of bile salt hydrolase,7 α-hydroxysteroid dehydrogenase,and BA inducible E as well as the pathways related to BA metabolism also significantly increased in cows supplemented BAs.In addition,BA supplementation significantly altered the composition of plasma and fecal BAs,particularly increasing circulating secondary BA concentration,which might induce the complete oxidation of fatty acids in the liver and further reduce the concentration of β-hydroxybutyrate.Conclusions These findings highlight the potential benefits of BA supplementation in improving milk yields and quality,as well as influencing metabolic pathways in transition dairy cows.Meanwhile,further studies are needed to elucidate the underlying mechanisms and explore the broader implications of these results by using more tissue samples.展开更多
BACKGROUND Barrett esophagus(BE),a metaplastic adaptive process to gastrointestinal reflux,is associated with a higher risk of developing esophageal adenocarcinoma.However,the factors and mechanism that drive the mali...BACKGROUND Barrett esophagus(BE),a metaplastic adaptive process to gastrointestinal reflux,is associated with a higher risk of developing esophageal adenocarcinoma.However,the factors and mechanism that drive the malignant progression of BE is not well understood.AIM To investigate the role of bile acids,a component of the reflux fluid,in the malignant progression of BE.METHODS Using engineered green fluorescent protein-labeled adult tissue-resident stem cells isolated from BE clinical biopsies(BE-ASCs)as the target,we studied the effect of hydrophobic deoxycholic acid(DCA)and hydrophilic tetrahydroxylated bile acids(THBA)on cell viability by fluorescence intensity analysis,mucin production by dark density measurement,tissue structure by pathology analysis,expression of different pro-inflammatory factors gene by quantitative polymerase chain reaction and proteins by Western blot.RESULTS We found that hydrophobic DCA has cytotoxic and proinflammatory effects through activation of interleukin-1β(IL-1β)-nuclear factor kappa-B(NF-κB)inflammatory pathway on BE-ASCs.This action results in impaired cell viability,tissue intactness,reduced mucin production,and increased transition to disorganized atypical cells without intestinal features.In contrast,co-culture with hydrophilic THBA inhibited the IL-1β-NF-κB inflammatory pathway with maintenance of mature intestinal type cellular and histomorphology.CONCLUSION Our data indicates that the hydrophilic bile acid THBA can counteract the cytotoxic and proinflammatory effect of hydrophobic DCA and prevent the malignant progression of BE by inhibiting the IL-1β-NF-κB pathway.展开更多
The tumor immune microenvironment(TIME)represents a complex battlefield where metabolic competition and immune evasion mechanisms converge to drive cancer progression.Amino acids,with their multifaceted biological rol...The tumor immune microenvironment(TIME)represents a complex battlefield where metabolic competition and immune evasion mechanisms converge to drive cancer progression.Amino acids,with their multifaceted biological roles,have emerged as pivotal regulators of tumor cell proliferation and immune cell functionality.The sensing mechanisms by which amino acids within the tumor microenvironment influence cellular growth,survival,and immune function are systematically explored in this review;the latest advances in understanding amino acid metabolism in tumor biology are also reviewed.In addition,the multifaceted roles of key amino acids in shaping the TIME with particular emphasis on tumor immunity and malignant growth were investigated.Finally,emerging therapeutic strategies targeting amino acid metabolism to reprogram the TIME are discussed,highlighting promising approaches,such as CAR-T cell therapy and engineered bacterial interventions.Through this comprehensive analysis,critical insights into future research directions and potential clinical translation of amino acid-targeted interventions are provided.展开更多
Gallic acid(GA),a plant phenol ubiquitously present in fruits and vegetables,has demonstrated efficacy in ameliorating ulcerative colitis(UC).Despite previous reports,the precise mechanism of GA's therapeutic acti...Gallic acid(GA),a plant phenol ubiquitously present in fruits and vegetables,has demonstrated efficacy in ameliorating ulcerative colitis(UC).Despite previous reports,the precise mechanism of GA's therapeutic action remains elusive.Herein,the present study aims to delineate the mechanism underlying the anti-UC effects of GA by focusing on the interplay of gut microbiota,microbial and host cometabolites,and gut immune regulation.The findings revealed that GA treatment improved the colitis symptoms and systematic inflammatory response,reliant on gut microbiota,as evidenced by microbiota depletion and fecal microbiota transplantation.According to the 16S r DNA sequencing results,GA altered the gut microbiota community structure and upregulated the biosynthesis of secondary bile acids(SBAs).Metabolomics and flow cytometry(FCS)analysis revealed a substantial increase in SBAs production,including ursodeoxycholic acid(UDCA),lithocholic acid(LCA),3-oxo-lithocholic acid(3-oxo-LCA)and iso-allolithocholic acid(Isoallo LCA),which further upregulated the proportion of regulatory T(Treg)cells and downregulated the proportion of T helper type 17(Th17)cells in the colon,ultimately resulting in an improved Treg/Th17 balance.Further FCS and real-time quantitative PCR assays provided mechanistic insights,demonstrating that UDCA and Isoallo LCA facilitate Treg cell differentiation through the upregulation of nuclear hormone receptor 4A1(NR4A1).This research elucidated that GA effectively mitigates colitis by modulating the Treg/Th17 balance,facilitated by the enhanced synthesis of microbiota-derived SBAs.These insights unveil innovative pathways through which GA exerts its anti-UC effects,emphasizing the potential therapeutic benefits of incorporating a GAenriched diet into UC management.展开更多
The liver is a central metabolic organ that regulates numerous physiological processes,including glucose and lipid metabolism,detoxification,and the synthesis of essential proteins and bile.Bile acids(BAs),synthesized...The liver is a central metabolic organ that regulates numerous physiological processes,including glucose and lipid metabolism,detoxification,and the synthesis of essential proteins and bile.Bile acids(BAs),synthesized from cholesterol in hepatocytes,not only facilitate the emulsification and absorption of dietary fats but also act as potent signaling molecules through receptors such as the farnesoid X receptor(FXR)and Takeda G-protein-coupled receptor 5.Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally,closely linked with obesity,insulin resis-tance,and other components of metabolic syndrome.In MASLD,the metabolism of BAs is markedly disrupted,resulting in alterations in their synthesis,compo-sition,and signaling activity.These changes contribute to hepatic steatosis,inflammation,and fibrosis,thereby exacerbating metabolic dysfunction and liver damage.The altered profiles and signaling activity of BAs in MASLD patients suggest that BAs act not only as biomarkers of disease severity,but also as active mediators of its pathogenesis.Modulators of BA signaling pathways,especially FXR agonists,are the focus of intense research for their potential to beneficially influence liver steatosis and inflammation in MASLD.Recent research has yielded promising results,indicating potential therapeutic application and the introduction of novel agents aimed at modulating BA homeostasis and function.This minireview outlines the physiological roles of BAs,seeks to advance the elucidation of the mechanisms by which their dysregulation contributes to MASLD progression,and highlights current and emerging therapeutic approa-ches.A deeper understanding of these complex interactions is essential for improving the diagnosis,prognosis and treatment of MASLD.展开更多
基金supported by the National Key R&D Program of China,No.2021YFC2501200(to PC).
文摘Short-chain fatty acids,metabolites produced by the fermentation of dietary fiber by gut microbiota,have garnered significant attention due to their correlation with neurodegenerative diseases,particularly Parkinson’s disease.In this review,we summarize the changes in short-chain fatty acid levels and the abundance of short-chain fatty acid-producing bacteria in various samples from patients with Parkinson’s disease,highlighting the critical role of gut homeostasis imbalance in the pathogenesis and progression of the disease.Focusing on the nervous system,we discuss the molecular mechanisms by which short-chain fatty acids influence the homeostasis of both the enteric nervous system and the central nervous system.We identify key processes,including the activation of G protein-coupled receptors and the inhibition of histone deacetylases by short-chain fatty acids.Importantly,structural or functional disruptions in the enteric nervous system mediated by these fatty acids may lead to abnormalα-synuclein expression and gastrointestinal dysmotility,which could serve as an initiating event in Parkinson’s disease.Furthermore,we propose that short-chain fatty acids help establish communication between the enteric nervous system and the central nervous system via the vagal nerve,immune circulation,and endocrine signaling.This communication may shed light on their potential role in the transmission ofα-synuclein from the gut to the brain.Finally,we elucidate novel treatment strategies for Parkinson’s disease that target short-chain fatty acids and examine the challenges associated with translating short-chain fatty acid-based therapies into clinical practice.In conclusion,this review emphasizes the pivotal role of short-chain fatty acids in regulating gut-brain axis integrity and their significance in the pathogenesis of Parkinson’s disease from the perspective of the nervous system.Moreover,it highlights the potential value of short-chain fatty acids in early intervention for Parkinson’s disease.Future research into the molecular mechanisms of short-chain fatty acids and their synergistic interactions with other gut metabolites is likely to advance the clinical translation of innovative short-chain fatty acid-based therapies for Parkinson’s disease.
基金supported by a grant from the French Society of Sleep Research and Medicine(to LS)The China Scholarship Council(to HL)The CNRS,INSERM,Claude Bernard University Lyon1(to LS)。
文摘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.
基金supported by MICIU(grant number PID2021-128133NB-100/AEI/FEDER10.13039/501100011033 to JMHG)by the National Institutes of Health(grant number R01 NS083858 to SAK)+1 种基金the Intramural Grants Program IGPP00057(to SAK)VIC enjoys a FPU contract from the Comunidad de Madrid(PIPF-2022/SAL-GL-25948)。
文摘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.
文摘Epidemiological evidence suggests that there is a direct relationship between the degree of obesity and acute pancreatitis severity.Intake of different fatty acids leads to different types of hyperlipidemias.Adipose degradation by pancreatic lipase generates different free fatty acids,which can exacerbate pancreatitis.Saturated fatty acids(SFAs)play an inflammatory role in human metabolic syndrome and obesity,whereas unsaturated fatty acids(UFAs)are“good fats”that are thought to enhance overall health status.However,it appears that serum UFAs correlate with severe acute pancreatitis.Additionally,the“obesity paradox”suggests that UFAs potentially minimize direct harm to the organ.This review provides an in-depth overview of the role of SFAs and UFAs in acute pancreatitis of hyperlipidemia and discusses potential prevention targets for severe acute pancreatitis.
基金support for this work by Hebei Education Department(No.JZX2024004)Central Guidance on Local Science and Technology Development Fund of Hebei Province(No.236Z1404G)+3 种基金the National Natural Science Foundation of China(Nos.22301060 and 21272053)China Postdoctoral Science Foundation(No.2023M730914)the Natural Science Foundation of Hebei Province(Biopharmaceutical Joint Fund No.B2022206008)Project of Science and Technology Department of Hebei Province(No.22567622H)。
文摘Heterogeneous metal-catalyzed chemical conversions with a recyclable catalyst are very ideal and challenging for sustainable organic synthesis.A new bipyridyl-Mo(IV)-carbon nitride(CN-K/Mo-Bpy)was prepared by supporting molybdenum complex on C_(3)N_(4)-K and characterized by FT-IR,XRD,SEM,XPS and ICP-OES.Heterogeneous CN–Mo-Bpy catalyst can be applied to the direct amination of nitroarenes and arylboronic acid,thus constructing various valuable diarylamines in high to excellent yields with a wide substrate scope and good functional group tolerance.It is worth noting that this heterogeneous catalyst has high chemical stability and can be recycled for at least five times without reducing its activity.
基金supported by the National Special Fund for the Development of Major Research Equipment and Instrument(No.2020YFF01014503)the Young Taishan Scholars(No.tsqn201909039)the College 20 Project fromJi Nan Science&Technology Bureau(No.2021GXRC058).
文摘Formic and acetic acids are the most abundant gaseous organic acids and play the key role in the atmospheric chemistry.In iodine-adduct chemical ionizationmass spectrometry(CIMS),the low utilization efficiency of methyl iodide and humidity interference are two major issues of the vacuum ultraviolet(VUV)lamp initiated CIMS for on-line gaseous formic and acetic acids analysis.In this work,we present a new CIMS based on VUV lamp,and the ion-molecular reactor is separated into photoionization and chemical ionization zones by a reducer electrode.Acetone was added to the photoionization zone,and the VUV photoionization acetone provided low-energy electrons for methyl iodide to generate I−,and the addition of acetone reduced the amount of methyl iodide by 2/3.In the chemical ionization zone,a headspace vial containing ultrapure water was added for humidity calibration,and the vial changes the sensitivity as a function of humidity from ambiguity to well linear correlation(R2>0.95).With humidity calibration,the CIMS can quantitatively measure formic and acetic acids in the humidity range of 0%-88%RH.In this mode,limits of detection of 10 and 50 pptv are obtained for formic and acetic acids,respectively.And the relative standard deviation(RSD)of quantitation stability for 6 days were less than 10.5%.This CIMS was successfully used to determine the formic and acetic acids in the underground parking and ambient environment of the Shandong University campus(Qingdao,China).In addition,we developed a simple model based formic acid concentration to assess vehicular emissions.
基金supported by the Russian Science Foundation(23-29-00830).
文摘Morphology and growth rate of carbon dioxide hydrate on the interface between liquid carbon dioxide and humic acid solutions were studied in this work.It was found that after the growth of the hydrate film at the interface,further growth of hydrate due to the suction of water in the capillary system formed between the wall of the cuvette and the end boundary of the hydrate layer occurs.Most probably,substantial effects on the formation of this capillary system may be caused by variations in reactor wall properties,for example,hydrophobic-hydrophilic balance,roughness,etc.We found,that the rate of CO_(2) hydrate film growth on the surface of the humic acid aqueous solution is 4-fold to lower in comparison with the growth rate on the surface of pure water.We suppose that this is caused by the adsorption of humic acid associates on the surface of hydrate particles and,as a consequence,by the deceleration of the diffusion of dissolved carbon dioxide to the growing hydrate particle.
文摘An efficient TfOH-catalyzed O—H insertion reaction of α-aryl diazoesters with carboxylic acids is reported.This metal-free protocol provides an operationally simple method for a one-pot assembly of diverse α-acyloxy esters in moderate to high yields with a broad substrate scope.All starting materials are readily available,and the reactions can be conducted in the open air at room temperature.
基金supported by the National Natural Science Foundation of China(Nos.22176112 and 42307134)the Natural Science Foundation of Shandong Province(No.ZR2021MD028)the Natural Science Foundation of Qingdao(No.23–2-1–74-zyyd-jch).
文摘The optical absorption of large molecular compounds HULIS(humic-like substances)can significantly impact the aerosol light absorption and radiative forcing,influencing cloud condensation nuclei formation and thus the climate and atmospheric environment.This study collected aerosol(PM_(2.5))samples from the summit of Mount Tai in North China to investigate the concentration,molecular composition,and optical properties of HULIS.The average concentration of HULIS in the PM_(2.5) in this study was 1.26±0.54μg/m^(3),comprising for 56%of the water-soluble organic carbon(WSOC),with levels lower than urban areas but higher than other mountainous regions.Mass spectrometry revealed that CHO and CHON components,with high aromaticity and phenolic groups,are major contributors to absorption and fluorescence.These results indicate that HULIS is mainly composed of lignin and proteins/amino sugars,derived from combustion and secondary formation,and possesses a high light absorption capacity(withMAE365(mass absorption efficiency)and AAE(A˚ngstrom exponent)indices of 0.62m^(2)/g and 4.99,respectively).Parallel factor analysis identified three fluorescence components of HULIS,with proportions of 60.8%for less oxygen humic-like substances,21.0%for high oxygen humic-like substances,and 18.2%for protein-like substances.Our study highlights the significance of the light-absorbing capacity and secondary formation of HULIS at Mount Tai,laying the groundwork for investigation into the climate effects,formation mechanisms,and sources of HULIS generation.
文摘The aim of the present study was to evaluate the effects of baobab seed washing and origin on the chemical composition of the oil extracted by pressing. Six (6) oil samples were obtained from seeds of three (3) geographical origins. The identification and quantification of fatty acids and the polyphenolic profile were carried out by GC-MS and HPLC-UV, respectively. Analysis of fatty acid methyl esters allowed the identification and quantification of 18 fatty acids. Oils from unwashed seeds were richer in palmitic (C16:0), stearic (C18:0), oleic (C18:1) and arachidic (C20:0) acids. In addition, HPLC-UV analysis at 279 nm shows that oils from unwashed seeds are richer in tyrosol, hydroxytyrosol and caffeic acid. With regard to the polyphenolic profile, gallic acid and quercetin were not detected in these baobab oils. Principal component analysis of fatty acid and phenolic compound content showed that oils from unwashed seeds would best preserve their chemical and associated potential bioactive characteristics.
基金supported by Qingdao Marine Science and Technology Center(2022QNLM030003-1)Taishan Scholars Program(tstp20240812)+3 种基金Youth Innovation Team Program of Universities in Shandong Province(2023KJ040)Open Foundation of State Key Laboratory of Marine Food Processing&Safety Control(SKL202412)China Postdoctoral Science Foundation(2024M763107)Postdoctoral Fellowship Program of CPSF(GZC20241617)。
文摘Alpha-linolenic acid(ALA)is capable of synthesizing eicosapentaenoic acid(EPA)and docosahexaenoic acid(DHA)in vivo,but the conversion rate is hard to meet the body's need for rapid DHA supplementation.Studies have shown that fucoxanthin can increase DHA content in the liver of mice,but the mechanism is not clear.Moreover,the effect of fucoxanthin and its metabolite fucoxanthinol on the chain lengthening reaction of n-6 polyunsaturated fatty acids(PUFAs)is little studied.In this study,the effects of fucoxanthin and fucoxanthinol on the chain elongation of n-3 and n-6 series PUFAs were investigated in mice.Results showed that fucoxanthin and fucoxanthinol significantly increased the conversion of n-3 series ALA to DHA and n-6 series linolenic acid(LA)to arachidonic acid(AA)in the serum,liver,small intestine,and heart of mice.In addition,fucoxanthin accelerated the rate of DHA supplementation by ALA in the brain.Further mechanistic studies revealed that the role of fucoxanthin in promoting PUFAs conversion was not regulated at transcriptional level,but by increasing the activity of fatty acid desaturase 2(FADS2),a key enzyme of chain elongation reaction of n-3 and n-6 PUFAs.This study fundamentally provided theoretical bases for a new strategy of dietary supplementation of n-3 and n-6 PUFAs.
文摘Background This study investigated the potential impacts of increasing linoleic andα-linolenic acid intake during lactation and wean-to-breeding on subsequent reproduction of sows.A total of 309 sows(PIC Camborough L42)were balanced by parity(140 and 169 sows representing parity 1 to 2[P1-2]and 3 to 9[P3+],respectively)and assigned within parity to a 2×2 factorial arrangement.Factors included essential fatty acid(EFA)supplementation(control diets containing 1.2%linoleic and 0.15%α-linolenic acid or diets with 3.0%linoleic and 0.38%α-linolenic acid)and supplementation period(lactation or wean-to-breeding).Tallow(low EFA diets)or soybean oil(high EFA diets)were included at 4%in sorghum-soybean meal-wheat middlings-based diets to attain targeted EFA levels.Results High levels of EFA fed during lactation had no effect on feed intake or litter performance,but increased subsequent farrowing rate(P=0.027;82.1%vs.70.4%),tended to reduce the proportion of sows removed(P=0.070;12.4%vs.20.8%),decreased the number of total pigs born in the following litter(P=0.072;15.3 vs.16.2),and increased total pigs born alive per 100 sows weaned(P=0.062;1,122 vs.974),regardless of sow parity.Young sows(P1-2)consuming the high EFA diet during lactation displayed a shorter wean-to-estrus interval(P=0.035;4.2 vs.4.6),but P3+sows were unaffected.Increasing EFA intake for P3+sows,but not P1-2 sows,resulted in more sows bred by d 5(P=0.028;91.1%vs.81.7%)and more mummies in the subsequent litter(P=0.040;0.32 vs.0.16).Feeding increased EFA to P1-2 sows during the wean-to-breeding period decreased subsequent farrowing rate(P=0.042;72.0%vs.87.7%),and increased removal rate(P=0.003;28.8%vs.9.4%).Total pigs born alive per 100 sows weaned was reduced(P=0.007)in P1-2 sows when supplemented with EFA during wean-breeding(939 vs.1,149)but was not impacted in P3+sows(1,131 vs.982).Conclusions Supplemental EFA in lactation diets benefited subsequent reproduction of sows,regardless of parity.Increasing dietary levels of EFA during the wean-to-breeding period to younger sows negatively impacted subsequent reproduction.
基金financial support from the Marine S&T Fund of Shandong Province for Qingdao Marine Science and Technology Center(No.2022QNLM030003-2)the National Key Research&Development Program of China(No.2022YFA2104902)the National Natural Science Foundation of China(Nos.21977088 and22377114)。
文摘Alduronic acid lactones and glyconolactones are highly functionalized and versatile chiral building blocks.Herein,we describe a novel approach to these compounds via decarboxylative oxygenation of uronic acids.The transformations proceed using Selectfluor and TEMPO as oxidants,either in the presence of catalytic amounts of Ag_(2)CO_(3)or in the absence of this catalyst.The methodology provides structurally diverse alduronic acid lactones and enables the preparation of rare sugar glyconolactones from easily available D-C-glycosides.Based on the^(18)O-labeling experiments,control experiments,and isolation of the key intermediates,a radical-polar crossover reaction mechanism is proposed.The utility of this method is demonstrated through efficient conversions of alduronic acid lactones into polyhydroxylated cyclic alkaloids and castanospermine-type architectures.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common chronic liver disease worldwide.Its prevalence is closely linked to the dramatic rise in obesity and non-communicable diseases.MASLD exhibits a progressive trajectory that may culminate in development of hepatic cirrhosis,thereby predisposing affected individuals to an elevated likelihood of hepatocarcinogenesis.Diet,especially dietary fatty acids,serves as a key link between nutrient intake and MASLD pathogenesis.AIM To explore the impact of various omega-6 fatty acid subtypes on the pathogenesis and therapeutic strategies of MASLD.METHODS A systematic literature search was conducted across Web of Science,PubMed,Cochrane Central,Scopus,and Embase databases from inception through June 2024 to identify all original studies linking different subtypes of omega-6 polyunsaturated fatty acids to the pathogenesis and management of MASLD.The search strategy explored the linkage between omega-6 polyunsaturated fatty acids and their subtypes,including linoleic acid(LA),gamma-linolenic acid(GLA),arachidonic acid,conjugated LA,and docosapentaenoic acid,in relation to MASLD and cardiometabolic risk.RESULTS By employing the specified search strategy,a total of 83 articles were identified as potentially eligible.During the title,abstract,and full-text screening phases,27 duplicate records were removed,leaving 56 records for relevance screening.Of these,43 records were excluded for reasons such as irrelevance and language restrictions(limited to English),resulting in 13 full-text articles being included for detailed assessment(10 human studies,1 animal study,and 2 review articles).Although certain subtypes,as GLA,dihomo-GLA,omega-6-derived oxylipins,and most arachidonic acid-derived eicosanoids,exhibit pro-inflammatory effects,our findings suggest that other subtypes such as LA,cis-9,trans-11 conjugated LA,and docosapentaenoic acid have beneficial effects on fatty liver,cardiometabolic risk factors,and inflammation,even at high intake levels.CONCLUSION The varying health effects of omega-6 fatty acids,ranging from anti-inflammatory to pro-inflammatory impacts on the liver,leave the question of their recommendation for MASLD patients unresolved.This underscores the importance of careful selection when considering omega-6 supplementation.
基金supported by the National Key Research and Development Program of China(No.2019YFC1906304).
文摘The anaerobic acid production experiments were conducted with the pretreated kitchen waste under pH adjustment.The results showed that pH 8 was considered to be the most suitable condition for acid production,especially for the formation of acetic acid and propionic acid.The average value of total volatile fatty acid at pH 8 was 8814 mg COD/L,1.5 times of that under blank condition.The average yield of acetic acid and propionic acid was 3302 mg COD/L and 2891 mg COD/L,respectively.The activities of key functional enzymes such as phosphotransacetylase,acetokinase,oxaloacetate transcarboxylase and succinylcoA transferase were all enhanced.To further explore the regulatory mechanisms within the system,the distribution of microorganisms at different levels in the fermentation system was obtained by microbial sequencing,results indicating that the relative abundances of Clostridiales,Bacteroidales,Chloroflexi,Clostridium,Bacteroidetes and Propionibacteriales,which were great contributors for the hydrolysis and acidification,increased rapidly at pH 8 compared with the blank group.Besides,the proportion of genes encoding key enzymes was generally increased,which further verified the mechanism of hydrolytic acidification and acetic acid production of organic matter under pH regulation.
基金supported by the National Center of Technology Innovation for Dairy(No.2024-JSGG-021)the National Natural Science Foundation of China(No.32102570)the Key Research and Development Project of Ningxia(No.2024BBF01006).
文摘Background During the transition period,cows are prone to negative energy balance,which can lead to a decline in production performance and health in severe cases.In recent years,it has been discovered that bile acids(BAs)can act not only as fat emulsifiers but also as signaling molecules to regulate body metabolism.Although BAs have been used to some extent in monogastric and aquatic animals,their role in ruminants,particularly in transition cows,remains unclear.Therefore,this study aimed to determine the effects of BAs on the production performance,milk and plasma fatty acid and BA composition,and fecal microbiota in transition dairy cows.Results Forty-six healthy transition Holstein dairy cows with similar conditions were randomly divided into two groups and supplemented with 0 or 20 g/d of BAs from 21 d before the expected calving to 21 d after calving.The production performance was tracked until 60 d after calving.The results indicated that BA supplementation significantly improved postpartum milk fat content and yields as well as the yields of unsaturated fatty acids,monounsaturated fatty acids,and polyunsaturated fatty acids in milk.There was a significant increase in the concentration of triglyceride and the proportion of C≤16 fatty acids in the plasma of cows supplemented with BAs,while the concentration of β-hydroxybutyrate and the proportion of C>16 fatty acids in the plasma decreased significantly.BA supplementation significantly altered the composition of the fecal bacterial community and increased the relative abundance of bacteria beneficial for BA metabolism and transformation(Romboutsia,Clostridium sensu_stricto_6,and Clostridium sensu_stricto_1).Functional prediction analysis showed that the relative abundance of bile salt hydrolase,7 α-hydroxysteroid dehydrogenase,and BA inducible E as well as the pathways related to BA metabolism also significantly increased in cows supplemented BAs.In addition,BA supplementation significantly altered the composition of plasma and fecal BAs,particularly increasing circulating secondary BA concentration,which might induce the complete oxidation of fatty acids in the liver and further reduce the concentration of β-hydroxybutyrate.Conclusions These findings highlight the potential benefits of BA supplementation in improving milk yields and quality,as well as influencing metabolic pathways in transition dairy cows.Meanwhile,further studies are needed to elucidate the underlying mechanisms and explore the broader implications of these results by using more tissue samples.
文摘BACKGROUND Barrett esophagus(BE),a metaplastic adaptive process to gastrointestinal reflux,is associated with a higher risk of developing esophageal adenocarcinoma.However,the factors and mechanism that drive the malignant progression of BE is not well understood.AIM To investigate the role of bile acids,a component of the reflux fluid,in the malignant progression of BE.METHODS Using engineered green fluorescent protein-labeled adult tissue-resident stem cells isolated from BE clinical biopsies(BE-ASCs)as the target,we studied the effect of hydrophobic deoxycholic acid(DCA)and hydrophilic tetrahydroxylated bile acids(THBA)on cell viability by fluorescence intensity analysis,mucin production by dark density measurement,tissue structure by pathology analysis,expression of different pro-inflammatory factors gene by quantitative polymerase chain reaction and proteins by Western blot.RESULTS We found that hydrophobic DCA has cytotoxic and proinflammatory effects through activation of interleukin-1β(IL-1β)-nuclear factor kappa-B(NF-κB)inflammatory pathway on BE-ASCs.This action results in impaired cell viability,tissue intactness,reduced mucin production,and increased transition to disorganized atypical cells without intestinal features.In contrast,co-culture with hydrophilic THBA inhibited the IL-1β-NF-κB inflammatory pathway with maintenance of mature intestinal type cellular and histomorphology.CONCLUSION Our data indicates that the hydrophilic bile acid THBA can counteract the cytotoxic and proinflammatory effect of hydrophobic DCA and prevent the malignant progression of BE by inhibiting the IL-1β-NF-κB pathway.
基金supported by grants from the National Key Research and Development Program of China(Grant No.2022YFC3401500 to P.W.Grant No.2021YFA1302200 to L.F.)+1 种基金the National Natural Science Foundation of China(Grant Nos.82341028 and 31920103007 to P.W.Grant Nos.82472815 and U24A20727 to L.F.)。
文摘The tumor immune microenvironment(TIME)represents a complex battlefield where metabolic competition and immune evasion mechanisms converge to drive cancer progression.Amino acids,with their multifaceted biological roles,have emerged as pivotal regulators of tumor cell proliferation and immune cell functionality.The sensing mechanisms by which amino acids within the tumor microenvironment influence cellular growth,survival,and immune function are systematically explored in this review;the latest advances in understanding amino acid metabolism in tumor biology are also reviewed.In addition,the multifaceted roles of key amino acids in shaping the TIME with particular emphasis on tumor immunity and malignant growth were investigated.Finally,emerging therapeutic strategies targeting amino acid metabolism to reprogram the TIME are discussed,highlighting promising approaches,such as CAR-T cell therapy and engineered bacterial interventions.Through this comprehensive analysis,critical insights into future research directions and potential clinical translation of amino acid-targeted interventions are provided.
基金funded by the National Natural Science Foundation of China(82174104 and 22104158)Guangzhou Science and Technology Program(2023B03J1382)+2 种基金Nansha Science and Technology Program(2022ZD004)Science and Technology Innovation Strategy of Guangdong Province(2020A1111350001)Natural Science Foundation of Hunan Province(2021JJ40041)。
文摘Gallic acid(GA),a plant phenol ubiquitously present in fruits and vegetables,has demonstrated efficacy in ameliorating ulcerative colitis(UC).Despite previous reports,the precise mechanism of GA's therapeutic action remains elusive.Herein,the present study aims to delineate the mechanism underlying the anti-UC effects of GA by focusing on the interplay of gut microbiota,microbial and host cometabolites,and gut immune regulation.The findings revealed that GA treatment improved the colitis symptoms and systematic inflammatory response,reliant on gut microbiota,as evidenced by microbiota depletion and fecal microbiota transplantation.According to the 16S r DNA sequencing results,GA altered the gut microbiota community structure and upregulated the biosynthesis of secondary bile acids(SBAs).Metabolomics and flow cytometry(FCS)analysis revealed a substantial increase in SBAs production,including ursodeoxycholic acid(UDCA),lithocholic acid(LCA),3-oxo-lithocholic acid(3-oxo-LCA)and iso-allolithocholic acid(Isoallo LCA),which further upregulated the proportion of regulatory T(Treg)cells and downregulated the proportion of T helper type 17(Th17)cells in the colon,ultimately resulting in an improved Treg/Th17 balance.Further FCS and real-time quantitative PCR assays provided mechanistic insights,demonstrating that UDCA and Isoallo LCA facilitate Treg cell differentiation through the upregulation of nuclear hormone receptor 4A1(NR4A1).This research elucidated that GA effectively mitigates colitis by modulating the Treg/Th17 balance,facilitated by the enhanced synthesis of microbiota-derived SBAs.These insights unveil innovative pathways through which GA exerts its anti-UC effects,emphasizing the potential therapeutic benefits of incorporating a GAenriched diet into UC management.
文摘The liver is a central metabolic organ that regulates numerous physiological processes,including glucose and lipid metabolism,detoxification,and the synthesis of essential proteins and bile.Bile acids(BAs),synthesized from cholesterol in hepatocytes,not only facilitate the emulsification and absorption of dietary fats but also act as potent signaling molecules through receptors such as the farnesoid X receptor(FXR)and Takeda G-protein-coupled receptor 5.Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally,closely linked with obesity,insulin resis-tance,and other components of metabolic syndrome.In MASLD,the metabolism of BAs is markedly disrupted,resulting in alterations in their synthesis,compo-sition,and signaling activity.These changes contribute to hepatic steatosis,inflammation,and fibrosis,thereby exacerbating metabolic dysfunction and liver damage.The altered profiles and signaling activity of BAs in MASLD patients suggest that BAs act not only as biomarkers of disease severity,but also as active mediators of its pathogenesis.Modulators of BA signaling pathways,especially FXR agonists,are the focus of intense research for their potential to beneficially influence liver steatosis and inflammation in MASLD.Recent research has yielded promising results,indicating potential therapeutic application and the introduction of novel agents aimed at modulating BA homeostasis and function.This minireview outlines the physiological roles of BAs,seeks to advance the elucidation of the mechanisms by which their dysregulation contributes to MASLD progression,and highlights current and emerging therapeutic approa-ches.A deeper understanding of these complex interactions is essential for improving the diagnosis,prognosis and treatment of MASLD.
