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
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
The skeletal muscle is the largest organ present in the body and is responsible for mechanical activities like maintaining posture,movement,respiratory function,and support for the health and functioning of other syst...The skeletal muscle is the largest organ present in the body and is responsible for mechanical activities like maintaining posture,movement,respiratory function,and support for the health and functioning of other systems of the body.Skeletal muscle atrophy is a condition characterized by a reduction in muscle size,strength,and activity,which leads to an increased dependency on others for movement,an increased risk of falls,and a reduced quality of life.Various conditions like osteoarthritis,osteoporosis,and fractures are directly associated with increased muscle atrophy.Additionally,numerous risk factors,like aging,malnutrition,physical inactivity,and certain disease conditions,through distinct pathways,negatively affect skeletal muscle health and lead to muscle atrophy.Among various determinants of overall muscle health,the rate of muscle protein synthesis and degradation is an important parameter that eventually alters the fate of overall muscle health.In conditions of excessive skeletal muscle atrophy,including sarcopenia,the rate of muscle protein degradation usually exceeds the rate of protein synthesis.The availability of amino acids in the systemic circulation is a crucial step in muscle protein synthesis.The current review aims to consolidate the existing evidence on amino acids,highlight their mechanisms of action,and assess their roles and effectiveness in enhancing skeletal muscle health.展开更多
Prolonged lack of rain and high-temperature lead to soil water deficits,inhibiting cereal crop growth in early ontogenesis and reducing grain quality and yield.Rye(Secale cereale L.)is a key grain crop,particularly in...Prolonged lack of rain and high-temperature lead to soil water deficits,inhibiting cereal crop growth in early ontogenesis and reducing grain quality and yield.Rye(Secale cereale L.)is a key grain crop,particularly in regions where wheat cultivation is challenging or unfeasible.To clarify its drought adaptation mechanisms,we analyzed the effects of moderate soil drought on growth,hormonal homeostasis,and the dynamics and distribution of free amino acids and phenolic compounds in rye at early vegetative stages and post-recovery.Drought triggered both general and organ-specific changes in endogenous phytohormones.A nonspecific response involved the accumulation of stress hormones abscisic acid(ABA)and salicylic acid(SA),alongside the suppression of growth hormones indole-3-acetic acid(IAA)and gibberellins.However,hormone dynamics and localization varied across plant organs.ABA and SA levels significantly increased in shoots of drought-stressed and recovered plants,corresponding with inhibited growth.Prolonged drought further enhanced ABA accumulation in both shoots and roots of recovered plants,while SA levels declined in roots but remained elevated in shoots.Drought also caused a substantial reduction in IAA,particularly in shoots,while gibberellins(GA_(3)+GA_(4))significantly decreased in roots.GA_(3)was predominant in most samples,except in the shoots of 2-day-old control plants.Post-recovery,IAA levels increased but remained below control values,while GA_(4)accumulation in roots led to a rise in total gibberellin levels.In contrast,shoot GA_(3)+GA_(4)levels declined,primarily due to GA_(3)reduction.The dominant free amino acids:aspartic acid,glutamic acid,glycine,alanine,and leucinedecreased significantly,underscoring their key role in stress adaptation.Increased flavonoid accumulation,especially in roots,suggests their involvement in antioxidant defense against oxidative stress.A significant increase in ABA and SA levels,along with a marked reduction in IAA and GA content in stressed rye plants occurred alongside a reduction in free amino acid content,accumulation of phenolic compounds,and an increase in flavonoid levels.These findings indicate distinct adaptation strategies in rye shoots and roots undermoderate soil drought.They provide a foundation for further research on drought resistance mechanisms in cereals and the development of strategies to enhance their adaptive potential.展开更多
Carbon dioxide(CO_(2))marine sequestration by hydrate method is considered as one of the options to effectively achieve carbon reduction.However,the slow rate of hydrate formation becomes a major limiting factor.In vi...Carbon dioxide(CO_(2))marine sequestration by hydrate method is considered as one of the options to effectively achieve carbon reduction.However,the slow rate of hydrate formation becomes a major limiting factor.In view of the gas-water mass transfer problem which is the main obstacle,this paper explored the amphiphilic amino acids to promote the formation of CO_(2)hydrate and used low-field nuclear magnetic resonance(LNMR)to conduct an innovative study on its kinetics and spatiotemporal distribution.By comparing the promotion performance of L-methionine(L-met),L-cysteine(L-cys),and L-valine(L-val),the comprehensive kinetic promotion ability of L-met was the highest,reducing the induction time by 60.0%,achieving the maximum water conversion of about 57.0%within only 1 h,and reaching a final CO_(2)storage efficiency of 84.6%.LNMR results showed that hydrates were preferentially formed in large and medium pores in the reservoir region.Interestingly,we found that the combined effect of hydrophilic groups and the hydrophobic side chain of L-met not only promoted the rearrangement of water molecules and provided more nucleation sites,but also created a localized CO_(2)supersaturated environment and facilitated gas-water redistribution.Meanwhile,L-met promoted the formation of a hydrate porous structure to ensure the continuous formation of hydrates.This study innovatively explored CO_(2)hydrate formation behavior in amphiphilic amino acids and laid a theoretical foundation for the realization of CO_(2)marine sequestration by hydrate method.展开更多
Although the parallel incorporation of fluorinated aromatic amino acids(FAAAs)into proteins has been explored since 2010,the corresponding ^(19)F NMR investigation has been lacking to date.To assess the potential of t...Although the parallel incorporation of fluorinated aromatic amino acids(FAAAs)into proteins has been explored since 2010,the corresponding ^(19)F NMR investigation has been lacking to date.To assess the potential of the parallel incorporation of FAAAs in studies of protein structure,dynamics and interactions,we examine the protein yields,fluorine incorporation efficiencies,and ^(19)F NMR spectra upon simultaneously incorporating FAAAs including 3-fluorotyrosine(3FY),4-fluorophenylalanine(4FF)and 5-fluorotryptophan(5FW)into two model proteins:the structured protein GB1 domain(GB1)and the intrinsically disordered protein a-synuclein(a-syn).We found that the simultaneous incorporation of 3FY and 5FW achieved higher efficiency than combinations of 4FF and 5FW,4FF and 3FY,or 3FY,4FF and 5FW.Moreover,incorporating more types of FAAAs leads to a reduction in overall yield.The ^(19)F spectra of 3FY,4FF and 5FW residues in α-syn and GB1 exhibited good dispersion of chemical shifts.However,the GB1 spectrum showed complexity due to incomplete fluorination and interactions within aromatic cluster.This complexity could be significantly reduced by supplementing the medium with natural aromatic amino acids.To validate the advantage of ^(19)F NMR spectrum,we use 3FY-4FF-5FW-F94W-α-syn to investigate the interaction between α-syn and sodium dodecyl sulphate(SDS)micelle.Our study demonstrates that ^(19)F NMR spectroscopy of proteins with parallel incorporation of FAAAs provides a valuable tool for investigating protein conformation,dynamics and interactions.展开更多
Background The synchronized absorption of amino acids(AAs)and glucose in the gut is crucial for effective AA utilization and protein synthesis in the body.The study investigated how the starch digestion rate and AA le...Background The synchronized absorption of amino acids(AAs)and glucose in the gut is crucial for effective AA utilization and protein synthesis in the body.The study investigated how the starch digestion rate and AA levels impact intestinal AA digestion,transport and metabolism,breast muscle protein metabolism,and growth in grower broilers.A total of 72021-day-old healthy male Arbor Acres Plus broilers were randomly assigned to 12 treatments,each with 6 replicates of 10 birds.The treatments comprised 3 different starch[corn:control,cassava:rapidly digestible starch(RDS),and pea:slowly digestible starch(SDS)]with 4 different AA levels[based on standardized ileal digestible lysine(SID Lys),0.92%,1.02%(as the standard),1.12%and 1.22%].Results An interaction between dietary starch sources and SID Lys levels significantly affected breast muscle yield(P=0.033).RDS and SDS diets,or SID Lys levels of 0.92%,1.02%,or 1.22%,significantly decreased the breast muscle yield of broilers in contrast to the corn starch diet with 1.12%SID Lys(P=0.033).The SID Lys levels of 1.12%and 1.22%markedly improved body weight(BW),body weight gain(BWG)from 22 to 42 days of age,and mRNA expression of y^(+)LAT1 and mTOR while reducing feed intake(FI)and feed/gain ratio(F/G)compared to the 0.92%SID Lys level(P<0.05).The SDS diet significantly decreased BW and BWG of broilers from 22 to 42 days of age,distal ileal starch digestibility,jejunal amylase and chymotrypsin activities,and mRNA expression of GLUT2 and y^(+)LAT1 compared to the corn starch diet(P<0.05).The RDS diet suppressed the breast muscle mass by down-regulating expression of mTOR,S6K1,and eIF4E and up-regulating expression of MuRF,CathepsinB,Atrogin-1,and M-calpain compared to the corn starch diet(P<0.05).Targeted metabolomics analysis revealed that the SDS diet significantly increased acetyl-CoA andα-ketoglutaric acid levels in the tricarboxylic acid(TCA)cycle(P<0.05)but decreased the ileal digestibility of Lys,Tyr,Leu,Asp,Ser,Gly,Pro,Arg,Ile,and Val compared to the corn starch group(P<0.05).Conclusion The SDS diet impaired broiler growth by reducing intestinal starch digestibility,which inhibited intestinal AA and glucose absorption and utilization,increased AA oxidation for energy supply,and lowered the efficiency of protein synthesis.Although the RDS diet resulted in growth performance similar to the corn starch diet,it reduced breast muscle mass by inhibiting protein synthesis and promoting degradation.展开更多
The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain functio...The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.展开更多
Background Low crude protein(CP)formulations with supplemental amino acids(AA)are used to enhance intestinal health,reduce costs,minimize environmental impact,and maintain growth performance of pigs.However,extensive ...Background Low crude protein(CP)formulations with supplemental amino acids(AA)are used to enhance intestinal health,reduce costs,minimize environmental impact,and maintain growth performance of pigs.However,extensive reduction of dietary CP can compromise growth performance due to limited synthesis of non-essential AA and limited availability of bioactive compounds from protein supplements even when AA requirements are met.Moreover,implementing a low CP formulation can increase the net energy(NE)content in feeds causing excessive fat deposition.Additional supplementation of functional AA,coupled with low CP formulation could further enhance intestinal health and glucose metabolism,improving nitrogen utilization,and growth performance.Three experiments were conducted to evaluate the effects of low CP formulations with supplemental AA on the intestinal health and growth performance of growing-finishing pigs.Methods In Exp.1,90 pigs(19.7±1.1 kg,45 barrows and 45 gilts)were assigned to 3 treatments:CON(18.0%CP,supplementing Lys,Met,and Thr),LCP(16.0%CP,supplementing Lys,Met,Thr,Trp,and Val),and LCPT(16.1%CP,LCP+0.05%SID Trp).In Exp.2,72 pigs(34.2±4.2 kg BW)were assigned to 3 treatments:CON(17.7%CP,meeting the requirements of Lys,Met,Thr,and Trp);LCP(15.0%CP,meeting Lys,Thr,Trp,Met,Val,Ile,and Phe);and VLCP(12.8%CP,meeting Lys,Thr,Trp,Met,Val,Ile,Phe,His,and Leu).In Exp.3,72 pigs(54.1±5.9 kg BW)were assigned to 3 treatments and fed experimental diets for 3 phases(grower 2,finishing 1,and finishing 2).Treatments were CON(18.0%,13.8%,12.7%CP for 3 phases;meeting Lys,Met,Thr,and Trp);LCP(13.5%,11.4%,10.4%CP for 3 phases;meeting Lys,Thr,Trp,Met,Val,Ile,and Phe);and LCPG(14.1%,12.8%,11.1%CP for 3 phases;LCP+Glu to match SID Glu with CON).All diets had 2.6 Mcal/kg NE.Results In Exp.1,overall,the growth performance did not differ among treatments.The LCPT increased(P<0.05)Claudin-1 expression in the duodenum and jejunum.The LCP and LCPT increased(P<0.05)CAT-1,4F2hc,and B0AT expressions in the jejunum.In Exp.2,overall,the VLCP reduced(P<0.05)G:F and BUN.The LCP and VLCP increased(P<0.05)the backfat thickness(BFT).In Exp.3,overall,growth performance and BFT did not differ among treatments.The LCPG reduced(P<0.05)BUN,whereas increased the insulin in plasma.The LCP and LCPG reduced(P<0.05)the abundance of Streptococcaceae,whereas the LCP reduced(P<0.05)Erysipelotrichaceae,and the alpha diversity.Conclusions When implementing low CP formulation,CP can be reduced by supplementation of Lys,Thr,Met,Trp,Val,and Ile without affecting the growth performance of growing-finishing pigs when NE is adjusted to avoid increased fat deposition.Supplementation of Trp above the requirement or supplementation of Glu in low CP formulation seems to benefit intestinal health as well as improved nitrogen utilization and glucose metabolism.展开更多
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 ...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.展开更多
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...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.展开更多
Amino acids are the primary form of nitrogen utilization in higher plants,mainly transported by amino acid transporters.In this study,we analyzed the natural variation of amino acid transporter-like 4(OsATL4)in rice g...Amino acids are the primary form of nitrogen utilization in higher plants,mainly transported by amino acid transporters.In this study,we analyzed the natural variation of amino acid transporter-like 4(OsATL4)in rice germplasm resources,identified its spatiotemporal expression characteristics,determined its substrate transport,and validated its function using transgenic plants.We found that the promoter sequence of OsATL4 varied across 498 rice varieties.The expression level of OsATL4 was higher in japonica rice,which was negatively correlated with tiller number and grain yield.OsATL4 was highly expressed in the basal part,leaf sheath,stem,and young panicle,with its two splicing variants localized to the cell membrane.OsATL4a(the long splicing variant)had a high affinity for transporting Ser,Leu,Phe,and Thr,while OsATL4b(the short splicing variant)had a high affinity for transporting Ser,Leu,and Phe.Blocking OsATL4 promoted axillary bud outgrowth,rice tillering,and grain yield,whereas overexpression lines exhibited the opposite phenotype.Exogenous application of low concentrations of Ser promoted axillary bud outgrowth in overexpression lines,while high concentrations of Ser inhibited it.Conversely,the mutant lines showed the opposite response.Altered expression of OsATL4 might affect the expression of genes in nitrogen,auxin,and cytokinin pathways.We propose that two splicing variants of OsATL4 negatively regulate rice tillering and yield by mediating the transport of amino acids,making it a significant target for high-yield rice breeding.展开更多
A novel and readily available binaphthyl-based fluorescent probe(S)-1 was designed and synthesized.(S)-1 can be used to not only chemoselectively discriminate 3 basic amino acids out of common amino acids,but also ena...A novel and readily available binaphthyl-based fluorescent probe(S)-1 was designed and synthesized.(S)-1 can be used to not only chemoselectively discriminate 3 basic amino acids out of common amino acids,but also enantioselectively recognize histidine.Encouragingly,enantioselective imaging of histidine in cells was achieved for the first time by the probe(S)-1.These performances endowed it potential application in the chiral analysis of basic amino acids in asymmetric synthesis and cell imaging for diagnosis of diseases caused by racemization of histidine.Nuclear magnetic resonance(NMR)and mass spectrometry investigations suggested that different reaction extent of(S)-1 with L/D-histidine and different product structures generated the observed enantioselective fluorescent response.The molecular structures and thermodynamic stability of the complexes,formed from(S)-1+Zn2+and enantiomers of histidine,were calculated by Gaussian 16 based on density functional theory(DFT)to validate the above action mechanism.展开更多
Background Dairy cows are at high risk of fatty liver disease in early lactation,but current preventative measures are not always effective.Cows with fatty liver have lower circulating branched-chain amino acid(BCAA)c...Background Dairy cows are at high risk of fatty liver disease in early lactation,but current preventative measures are not always effective.Cows with fatty liver have lower circulating branched-chain amino acid(BCAA)concentra-tions whereas cows with high circulating BCAA levels have low liver triglyceride(TG).Our objective was to determine the impact of BCAA and their corresponding ketoacids(branched-chain ketoacids,BCKA)on production performance and liver TG accumulation in Holstein cows in the first 3 weeks postpartum.Methods Thirty-six multiparous Holstein cows were used in a randomized block design experiment.Cows were abomasally infused for the first 21 d postpartum with solutions of 1)saline(CON,n=12);2)BCA(67 g valine,50 g leu-cine,and 34 g isoleucine,n=12);and 3)BCK(77 g 2-ketovaline calcium salt,57 g 2-ketoleucine calcium salt,and 39 g 2-ketoisoleucine calcium salt,n=12).All cows received the same diet.Treatment effects were determined using PROC GLIMMIX in SAS.Results No differences were detected for body weight,body condition score,or dry matter intake averaged over the first 21 d postpartum.Cows receiving BCK had significantly lower liver TG concentrations compared to CON(6.60%vs.4.77%,standard error of the mean(SEM)0.49)during the first 3 weeks of lactation.Infusion of BCA increased milk yield(39.5 vs.35.3 kg/d,SEM 1.8),milk fat yield(2.10 vs.1.69 kg/d,SEM 0.08),and lactose yield(2.11 vs.1.67 kg/d,SEM 0.07)compared with CON.Compared to CON,cows receiving BCA had lower plasma glucose(55.0 vs.59.2 mg/dL,SEM 0.86)but higherβ-hydroxybutyrate(9.17 vs.6.00 mg/dL,SEM 0.80).Conclusions Overall,BCAA supplementation in this study improved milk production,whereas BCKA supplementa-tion reduced TG accumulation in the liver of fresh cows.展开更多
The digestibility of cadmium(Cd)in brown rice is directly related to amino acid metabolism in rice and human health.In our field study,three kinds of alkaline calcium-rich soil inorganic amendments(SIAs)at three dosag...The digestibility of cadmium(Cd)in brown rice is directly related to amino acid metabolism in rice and human health.In our field study,three kinds of alkaline calcium-rich soil inorganic amendments(SIAs)at three dosages were applied to produce safe rice and improve the quality of rice in Cd-contaminated paddy.With the increased application of SIA,Cd content in iron plaque on rice root significantly increased,the transfer of Cd from rice root to grain significantly decreased,and then Cd content in brown rice decreased synchronously.The vitro digestibility of Cd in brown rice was estimated by a physiologically based extraction test.Results showed that more than 70%of Cd in brown rice could be digested by simulated gastrointestinal juice.Based on the total and digestible Cd contents in brown rice to evaluate the health risk,the application of 2.25 ton SIA/ha could produce safe rice in acidic slightly Cd-contaminated paddy soils.The amino acids(AAs)in brown rice were determined by high-performance liquid chromatography.The contents of 5 key AAs(KAAs)that actively respond to environmental changes increased significantly with the increased application of SIA.The structural equation model indicated that KAAs could be affected by the Cd translocation capacity from rice root to grain,and consequently altered the ratio of indigestible Cd in brown rice.The formation of indigestible KAAs-Cd complexes by combining KAAs(phenylalanine,leucine,histidine,glutamine,and asparagine)with Cd in brown rice could be considered a potential mechanism for reducing the digestibility of Cd.展开更多
Lactic acid bacteria and coagulase-negative staphylococci play an important role in the production of fermented sausages,such as inhibiting the growth of undesirable bacteria and antioxidant.In this study,the effects ...Lactic acid bacteria and coagulase-negative staphylococci play an important role in the production of fermented sausages,such as inhibiting the growth of undesirable bacteria and antioxidant.In this study,the effects of inoculation with different starter cultures(Lactiplantibacillus plantarum HN108 and Staphylococcus simulans NJ209)on the free amino acids(FAAs),biogenic amines(BAs)and volatile compounds of fermented sausages were investigated using an amino acid analyzer,ultra performance liquid chromatography and gas chromatography-ion mobility spectrometry,respectively.The pH and carbonyl content of the inoculated group was significantly lower than those in the control group(P<0.05).L.plantarum HN108 significantly reduced the content of FAAs and BAs in fermented sausage production(P<0.05),while S.simulans NJ209 promoted the formation of FAAs(especially bitter amino acids)and exhibited slight BAs-reducing activity.In addition,L.plantarum HN108 promoted the formation of volatile compounds such as ketones,alcohols and alkenes in sausages.In conclusion,L.plantarum HN108 could contribute to reducing the content of putrescine and tyramine and forming the desirable flavor compounds in fermented sausages.Thus,L.plantarum HN108 is expected to be a starter culture that can improve the safety and flavor of fermented sausages.展开更多
BACKGROUND The lack of specific predictors for type-2 diabetes mellitus(T2DM)severely impacts early intervention/prevention efforts.Elevated branched-chain amino acids(BCAAs:Isoleucine,leucine,valine)and aromatic amin...BACKGROUND The lack of specific predictors for type-2 diabetes mellitus(T2DM)severely impacts early intervention/prevention efforts.Elevated branched-chain amino acids(BCAAs:Isoleucine,leucine,valine)and aromatic amino acids(AAAs:Tyrosine,tryptophan,phenylalanine)show high sensitivity and specificity in predicting diabetes in animals and predict T2DM 10-19 years before T2DM onset in clinical studies.However,improvement is needed to support its clinical utility.AIM To evaluate the effects of body mass index(BMI)and sex on BCAAs/AAAs in new-onset T2DM individuals with varying body weight.METHODS Ninety-seven new-onset T2DM patients(<12 mo)differing in BMI[normal weight(NW),n=33,BMI=22.23±1.60;overweight,n=42,BMI=25.9±1.07;obesity(OB),n=22,BMI=31.23±2.31]from the First People’s Hospital of Yunnan Province,Kunming,China,were studied.One-way and 2-way ANOVAs were conducted to determine the effects of BMI and sex on BCAAs/AAAs.RESULTS Fasting serum AAAs,BCAAs,glutamate,and alanine were greater and high-density lipoprotein(HDL)was lower(P<0.05,each)in OB-T2DM patients than in NW-T2DM patients,especially in male OB-T2DM patients.Arginine,histidine,leucine,methionine,and lysine were greater in male patients than in female patients.Moreover,histidine,alanine,glutamate,lysine,valine,methionine,leucine,isoleucine,tyrosine,phenylalanine,and tryptophan were significantly correlated with abdominal adiposity,body weight and BMI,whereas isoleucine,leucine and phenylalanine were negatively correlated with HDL.CONCLUSION Heterogeneously elevated amino acids,especially BCAAs/AAAs,across new-onset T2DM patients in differing BMI categories revealed a potentially skewed prediction of T2DM development.The higher BCAA/AAA levels in obese T2DM patients would support T2DM prediction in obese individuals,whereas the lower levels of BCAAs/AAAs in NW-T2DM individuals may underestimate T2DM risk in NW individuals.This potentially skewed T2DM prediction should be considered when BCAAs/AAAs are to be used as the T2DM predictor.展开更多
Athletes often use branched-chain amino acid (BCAAs) supplements with a ratio of 2:1:1 (leucine:isoleucine:valine) for their impact on muscle building. Research suggests that by altering the ratio, an improvement in g...Athletes often use branched-chain amino acid (BCAAs) supplements with a ratio of 2:1:1 (leucine:isoleucine:valine) for their impact on muscle building. Research suggests that by altering the ratio, an improvement in glucose metabolism might be possible. The purpose of this study was to examine how isoleucine would influence glucose tolerance. We recruited healthy male (n = 13) and female (n = 5) participants who were asked to fast for 12 hours before coming to the laboratory. A fasting blood sample was collected, followed by the subjects consuming a breakfast containing 113 g carbohydrates, 8 g protein, 1.5 g fat, and BCAA powder in the 2:1:1 ratio (Control) or BCAA powder enriched with Isoleucine (2:6:1), both added to orange juice. The opposite meal was consumed on a second visit one week apart. Blood was collected at 30, 60, 90, and 120 minutes post-meal. No differences were observed between the Control and Isoleucine for changes in serum glucose or insulin response when examining all subjects together. However, when comparing between genders, males tended to have a significantly lower serum glucose response compared to females when consuming the Isoleucine, with no difference between the genders when consuming the Control. Also, males had significantly lower serum glucose responses when consuming the Isoleucine compared to when they consumed the Control, while females had significantly higher serum glucose responses when consuming the Isoleucine compared to when they consumed the Control. In general, males tended to have a lower serum insulin response than females when consuming both the Control and the Isoleucine. Our study indicates a significant difference in the way genders respond to BCAA supplementation, where isoleucine may improve glucose tolerance and insulin response in males but not females.展开更多
Background Research on low-protein-level diets has indicated that even though the profiles of essential amino acids(EAAs)follow the recommendation for a normal-protein-level diet,broilers fed low-protein diets failed ...Background Research on low-protein-level diets has indicated that even though the profiles of essential amino acids(EAAs)follow the recommendation for a normal-protein-level diet,broilers fed low-protein diets failed to achieve pro-ductive performance compared to those fed normal diets.Therefore,it is imperative to reassess the optimum profile of EAAs in low-protein diets and establish a new ideal pattern for amino acid balance.Furthermore,identifying novel sensitive biomarkers for assessing amino acid balance will greatly facilitate the development of amino acid nutrition and application technology.In this study,12 dietary treatments[Con(+),Con(-),L&A(-),L&A(+),M&C(-),M&C(+),BCAA(-),BCAA(+),Thr(-),Thr(+),Trp(-)and Trp(+)]were established by combining different EAAs including lysine and argi-nine,methionine and cysteine,branched-chain amino acid(BCAA),threonine,and tryptophan to observe the growth and development of the broiler chickens fed with low-protein-level diets.Based on the biochemical parameters and untargeted metabolomic analysis of animals subjected to different treatments,biomarkers associated with opti-mal and suboptimal amino acid balance were identified.Results Growth performance,carcass characteristics,hepatic enzyme activity,serum biochemical parameters,and breast muscle mRNA expression differed significantly between male and female broilers under different dietary amino acid patterns.Male broilers exhibited higher sensitivity to the adjustment of amino acid patterns than female broilers.For the low-protein diet,the dietary concentrations of lysine,arginine,and tryptophan,but not of methionine,cystine,or threonine,needed to be increased.Therefore,further research on individual BCAA is required.For untar-geted metabolomic analysis,Con(+)was selected as a normal diet(NP)while Con(-)represented a low-protein diet(LP).L&A(+)denotes a low-protein amino acid balanced diet(LPAB)and Thr(+)represents a low-protein amino acid imbalance diet(LPAI).The metabolites oxypurinol,pantothenic acid,and D-octopine in birds were significantly influ-enced by different dietary amino acid patterns.Conclusion Adjusting the amino acid profile of low-protein diets is required to achieve normal growth performance in broiler chickens fed normal-protein diets.Oxypurinol,pantothenic acid,and D-octopine have been identified as potentially sensitive biomarkers for assessing amino acid balance.展开更多
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.
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.
文摘The skeletal muscle is the largest organ present in the body and is responsible for mechanical activities like maintaining posture,movement,respiratory function,and support for the health and functioning of other systems of the body.Skeletal muscle atrophy is a condition characterized by a reduction in muscle size,strength,and activity,which leads to an increased dependency on others for movement,an increased risk of falls,and a reduced quality of life.Various conditions like osteoarthritis,osteoporosis,and fractures are directly associated with increased muscle atrophy.Additionally,numerous risk factors,like aging,malnutrition,physical inactivity,and certain disease conditions,through distinct pathways,negatively affect skeletal muscle health and lead to muscle atrophy.Among various determinants of overall muscle health,the rate of muscle protein synthesis and degradation is an important parameter that eventually alters the fate of overall muscle health.In conditions of excessive skeletal muscle atrophy,including sarcopenia,the rate of muscle protein degradation usually exceeds the rate of protein synthesis.The availability of amino acids in the systemic circulation is a crucial step in muscle protein synthesis.The current review aims to consolidate the existing evidence on amino acids,highlight their mechanisms of action,and assess their roles and effectiveness in enhancing skeletal muscle health.
基金This publication presents findings from research conducted under Project No.III-99-24.489Natural Growth Regulators in the Induction of Resistance of Cereal Plants to HeavyMetals(2024-2028)funded by the NationalAcademy of Sciences of Ukraine.
文摘Prolonged lack of rain and high-temperature lead to soil water deficits,inhibiting cereal crop growth in early ontogenesis and reducing grain quality and yield.Rye(Secale cereale L.)is a key grain crop,particularly in regions where wheat cultivation is challenging or unfeasible.To clarify its drought adaptation mechanisms,we analyzed the effects of moderate soil drought on growth,hormonal homeostasis,and the dynamics and distribution of free amino acids and phenolic compounds in rye at early vegetative stages and post-recovery.Drought triggered both general and organ-specific changes in endogenous phytohormones.A nonspecific response involved the accumulation of stress hormones abscisic acid(ABA)and salicylic acid(SA),alongside the suppression of growth hormones indole-3-acetic acid(IAA)and gibberellins.However,hormone dynamics and localization varied across plant organs.ABA and SA levels significantly increased in shoots of drought-stressed and recovered plants,corresponding with inhibited growth.Prolonged drought further enhanced ABA accumulation in both shoots and roots of recovered plants,while SA levels declined in roots but remained elevated in shoots.Drought also caused a substantial reduction in IAA,particularly in shoots,while gibberellins(GA_(3)+GA_(4))significantly decreased in roots.GA_(3)was predominant in most samples,except in the shoots of 2-day-old control plants.Post-recovery,IAA levels increased but remained below control values,while GA_(4)accumulation in roots led to a rise in total gibberellin levels.In contrast,shoot GA_(3)+GA_(4)levels declined,primarily due to GA_(3)reduction.The dominant free amino acids:aspartic acid,glutamic acid,glycine,alanine,and leucinedecreased significantly,underscoring their key role in stress adaptation.Increased flavonoid accumulation,especially in roots,suggests their involvement in antioxidant defense against oxidative stress.A significant increase in ABA and SA levels,along with a marked reduction in IAA and GA content in stressed rye plants occurred alongside a reduction in free amino acid content,accumulation of phenolic compounds,and an increase in flavonoid levels.These findings indicate distinct adaptation strategies in rye shoots and roots undermoderate soil drought.They provide a foundation for further research on drought resistance mechanisms in cereals and the development of strategies to enhance their adaptive potential.
基金supported by the National Key Research and Development Program of China for Young Scientists(Grant No.2023YFB4104100)the National Natural Science Foundation of China(Grant 52176057)+3 种基金the National Key Research and Development Program of China(Grant No.2023YFB4104201)supported by the Unveiling and Commanding Foundation of Liaoning Province(Grant 2023JH1/10400003)the Shenzhen Science and Technology Program(No.JCYJ20220818095605012)supported by the Young Changjiang Scholars programme of China。
文摘Carbon dioxide(CO_(2))marine sequestration by hydrate method is considered as one of the options to effectively achieve carbon reduction.However,the slow rate of hydrate formation becomes a major limiting factor.In view of the gas-water mass transfer problem which is the main obstacle,this paper explored the amphiphilic amino acids to promote the formation of CO_(2)hydrate and used low-field nuclear magnetic resonance(LNMR)to conduct an innovative study on its kinetics and spatiotemporal distribution.By comparing the promotion performance of L-methionine(L-met),L-cysteine(L-cys),and L-valine(L-val),the comprehensive kinetic promotion ability of L-met was the highest,reducing the induction time by 60.0%,achieving the maximum water conversion of about 57.0%within only 1 h,and reaching a final CO_(2)storage efficiency of 84.6%.LNMR results showed that hydrates were preferentially formed in large and medium pores in the reservoir region.Interestingly,we found that the combined effect of hydrophilic groups and the hydrophobic side chain of L-met not only promoted the rearrangement of water molecules and provided more nucleation sites,but also created a localized CO_(2)supersaturated environment and facilitated gas-water redistribution.Meanwhile,L-met promoted the formation of a hydrate porous structure to ensure the continuous formation of hydrates.This study innovatively explored CO_(2)hydrate formation behavior in amphiphilic amino acids and laid a theoretical foundation for the realization of CO_(2)marine sequestration by hydrate method.
基金supported by the Ministry of Science and Technology of China[grants 2021YFA1302602]the National Natural Science Foundation of China[grants 21925406,21991082,21921004]the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0540000 and YSBR-068).
文摘Although the parallel incorporation of fluorinated aromatic amino acids(FAAAs)into proteins has been explored since 2010,the corresponding ^(19)F NMR investigation has been lacking to date.To assess the potential of the parallel incorporation of FAAAs in studies of protein structure,dynamics and interactions,we examine the protein yields,fluorine incorporation efficiencies,and ^(19)F NMR spectra upon simultaneously incorporating FAAAs including 3-fluorotyrosine(3FY),4-fluorophenylalanine(4FF)and 5-fluorotryptophan(5FW)into two model proteins:the structured protein GB1 domain(GB1)and the intrinsically disordered protein a-synuclein(a-syn).We found that the simultaneous incorporation of 3FY and 5FW achieved higher efficiency than combinations of 4FF and 5FW,4FF and 3FY,or 3FY,4FF and 5FW.Moreover,incorporating more types of FAAAs leads to a reduction in overall yield.The ^(19)F spectra of 3FY,4FF and 5FW residues in α-syn and GB1 exhibited good dispersion of chemical shifts.However,the GB1 spectrum showed complexity due to incomplete fluorination and interactions within aromatic cluster.This complexity could be significantly reduced by supplementing the medium with natural aromatic amino acids.To validate the advantage of ^(19)F NMR spectrum,we use 3FY-4FF-5FW-F94W-α-syn to investigate the interaction between α-syn and sodium dodecyl sulphate(SDS)micelle.Our study demonstrates that ^(19)F NMR spectroscopy of proteins with parallel incorporation of FAAAs provides a valuable tool for investigating protein conformation,dynamics and interactions.
基金supported by the National Key R&D Program of China(2021YFD1300404)。
文摘Background The synchronized absorption of amino acids(AAs)and glucose in the gut is crucial for effective AA utilization and protein synthesis in the body.The study investigated how the starch digestion rate and AA levels impact intestinal AA digestion,transport and metabolism,breast muscle protein metabolism,and growth in grower broilers.A total of 72021-day-old healthy male Arbor Acres Plus broilers were randomly assigned to 12 treatments,each with 6 replicates of 10 birds.The treatments comprised 3 different starch[corn:control,cassava:rapidly digestible starch(RDS),and pea:slowly digestible starch(SDS)]with 4 different AA levels[based on standardized ileal digestible lysine(SID Lys),0.92%,1.02%(as the standard),1.12%and 1.22%].Results An interaction between dietary starch sources and SID Lys levels significantly affected breast muscle yield(P=0.033).RDS and SDS diets,or SID Lys levels of 0.92%,1.02%,or 1.22%,significantly decreased the breast muscle yield of broilers in contrast to the corn starch diet with 1.12%SID Lys(P=0.033).The SID Lys levels of 1.12%and 1.22%markedly improved body weight(BW),body weight gain(BWG)from 22 to 42 days of age,and mRNA expression of y^(+)LAT1 and mTOR while reducing feed intake(FI)and feed/gain ratio(F/G)compared to the 0.92%SID Lys level(P<0.05).The SDS diet significantly decreased BW and BWG of broilers from 22 to 42 days of age,distal ileal starch digestibility,jejunal amylase and chymotrypsin activities,and mRNA expression of GLUT2 and y^(+)LAT1 compared to the corn starch diet(P<0.05).The RDS diet suppressed the breast muscle mass by down-regulating expression of mTOR,S6K1,and eIF4E and up-regulating expression of MuRF,CathepsinB,Atrogin-1,and M-calpain compared to the corn starch diet(P<0.05).Targeted metabolomics analysis revealed that the SDS diet significantly increased acetyl-CoA andα-ketoglutaric acid levels in the tricarboxylic acid(TCA)cycle(P<0.05)but decreased the ileal digestibility of Lys,Tyr,Leu,Asp,Ser,Gly,Pro,Arg,Ile,and Val compared to the corn starch group(P<0.05).Conclusion The SDS diet impaired broiler growth by reducing intestinal starch digestibility,which inhibited intestinal AA and glucose absorption and utilization,increased AA oxidation for energy supply,and lowered the efficiency of protein synthesis.Although the RDS diet resulted in growth performance similar to the corn starch diet,it reduced breast muscle mass by inhibiting protein synthesis and promoting degradation.
基金supported by the National Natural Science Foundation of China,Nos.32371070 (to JT),31761163005 (to JT),32100824 (to QX)the Shenzhen Science and Technology Program,Nos.RCBS20210609104606024 (to QX),JCY20210324101813035 (to DL)+4 种基金the Guangdong Provincial Key S&T Program,No.2018B030336001 (to JT)the Key Basic Research Program of Shenzhen Science and Technology Innovation Commission,Nos.JCYJ20200109115405930 (to JT),JCYJ20220818101615033 (to DL),JCYJ20210324115811031 (to QX),JCYJ20200109150717745 (to QX)Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases,No.ZDSYS20220304163558001 (to JT)Guangdong Provincial Key Laboratory of Brain Connectome and Behavior,No.2023B1212060055 (to JT)the China Postdoctoral Science Foundation,No.2021M693298 (to QX)。
文摘The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with emotions.Specifically, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal mice.After knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was obviously mitigated. Additionally, administration of an excitatory amino acid transporter 2 inhibitor in the basolateral amygdala yielded a notable reduction in anxiety level among mice subjected to stress. These results suggest that basolateral amygdala astrocytic excitatory amino acid transporter 2 plays a role in in the regulation of unpredictable chronic mild stress-induced anxiety-like behavior by impacting the activity of local glutamatergic neurons, and targeting excitatory amino acid transporter 2 in the basolateral amygdala holds therapeutic promise for addressing anxiety disorders.
基金funded by USDA-NIFA Hatch Fund(#02893,Washington DC,USA)North Carolina Agricultural Foundation(#660101,Raleigh,NC,USA)+3 种基金Ajinomoto Co.,Inc(Tokyo,Japan)CJ Cheil Jedang Corp.(Seoul,Korea)Daesang Corp(Seoul,Korea)Fellowship to support MLTA from CNPq(Brasilia,Brazil).CNPq 305869/2018-3 to support MLTA。
文摘Background Low crude protein(CP)formulations with supplemental amino acids(AA)are used to enhance intestinal health,reduce costs,minimize environmental impact,and maintain growth performance of pigs.However,extensive reduction of dietary CP can compromise growth performance due to limited synthesis of non-essential AA and limited availability of bioactive compounds from protein supplements even when AA requirements are met.Moreover,implementing a low CP formulation can increase the net energy(NE)content in feeds causing excessive fat deposition.Additional supplementation of functional AA,coupled with low CP formulation could further enhance intestinal health and glucose metabolism,improving nitrogen utilization,and growth performance.Three experiments were conducted to evaluate the effects of low CP formulations with supplemental AA on the intestinal health and growth performance of growing-finishing pigs.Methods In Exp.1,90 pigs(19.7±1.1 kg,45 barrows and 45 gilts)were assigned to 3 treatments:CON(18.0%CP,supplementing Lys,Met,and Thr),LCP(16.0%CP,supplementing Lys,Met,Thr,Trp,and Val),and LCPT(16.1%CP,LCP+0.05%SID Trp).In Exp.2,72 pigs(34.2±4.2 kg BW)were assigned to 3 treatments:CON(17.7%CP,meeting the requirements of Lys,Met,Thr,and Trp);LCP(15.0%CP,meeting Lys,Thr,Trp,Met,Val,Ile,and Phe);and VLCP(12.8%CP,meeting Lys,Thr,Trp,Met,Val,Ile,Phe,His,and Leu).In Exp.3,72 pigs(54.1±5.9 kg BW)were assigned to 3 treatments and fed experimental diets for 3 phases(grower 2,finishing 1,and finishing 2).Treatments were CON(18.0%,13.8%,12.7%CP for 3 phases;meeting Lys,Met,Thr,and Trp);LCP(13.5%,11.4%,10.4%CP for 3 phases;meeting Lys,Thr,Trp,Met,Val,Ile,and Phe);and LCPG(14.1%,12.8%,11.1%CP for 3 phases;LCP+Glu to match SID Glu with CON).All diets had 2.6 Mcal/kg NE.Results In Exp.1,overall,the growth performance did not differ among treatments.The LCPT increased(P<0.05)Claudin-1 expression in the duodenum and jejunum.The LCP and LCPT increased(P<0.05)CAT-1,4F2hc,and B0AT expressions in the jejunum.In Exp.2,overall,the VLCP reduced(P<0.05)G:F and BUN.The LCP and VLCP increased(P<0.05)the backfat thickness(BFT).In Exp.3,overall,growth performance and BFT did not differ among treatments.The LCPG reduced(P<0.05)BUN,whereas increased the insulin in plasma.The LCP and LCPG reduced(P<0.05)the abundance of Streptococcaceae,whereas the LCP reduced(P<0.05)Erysipelotrichaceae,and the alpha diversity.Conclusions When implementing low CP formulation,CP can be reduced by supplementation of Lys,Thr,Met,Trp,Val,and Ile without affecting the growth performance of growing-finishing pigs when NE is adjusted to avoid increased fat deposition.Supplementation of Trp above the requirement or supplementation of Glu in low CP formulation seems to benefit intestinal health as well as improved nitrogen utilization and glucose metabolism.
基金supported by National Natural Science Foundation of China(Nos.31871861 and 31501548)The Apicultural Industry Technology System(NCYTI-43-KXJ17)The Science and Technology Innovation Project of Chinese Academy of Agricultural Sciences(CAAS-ASTIP-2015-IAR)。
文摘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.
文摘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.
基金supported by the National Natural Science Foundation of China (32060064/32260498)the Guizhou Provincial Excellent Young Talents Project of Science and Technology (Qiankehepingtairencai-YQK (2023)002)+6 种基金the Guizhou Provincial Science and Technology Projects (Qiankehejichu-ZK (2021)General 128Qiankehejichu-ZK (2022)Key 008Qiankehechengguo (2024)General 116Qiankehepingtairencai-BQW (2024)001,qiankehepingtai-YWZ (2024)004)the Key Laboratory of Molecular Breeding for Grain and Oil Crops in Guizhou Province (Qiankehezhongyindi (2023)008)the Key Laboratory of Functional Agriculture of Guizhou Provincial Department of Education (Qianjiaoji (2023)007)the Qiandongnan Science and Technology Support Project (Qiandongnan Kehe Support (2023)06).
文摘Amino acids are the primary form of nitrogen utilization in higher plants,mainly transported by amino acid transporters.In this study,we analyzed the natural variation of amino acid transporter-like 4(OsATL4)in rice germplasm resources,identified its spatiotemporal expression characteristics,determined its substrate transport,and validated its function using transgenic plants.We found that the promoter sequence of OsATL4 varied across 498 rice varieties.The expression level of OsATL4 was higher in japonica rice,which was negatively correlated with tiller number and grain yield.OsATL4 was highly expressed in the basal part,leaf sheath,stem,and young panicle,with its two splicing variants localized to the cell membrane.OsATL4a(the long splicing variant)had a high affinity for transporting Ser,Leu,Phe,and Thr,while OsATL4b(the short splicing variant)had a high affinity for transporting Ser,Leu,and Phe.Blocking OsATL4 promoted axillary bud outgrowth,rice tillering,and grain yield,whereas overexpression lines exhibited the opposite phenotype.Exogenous application of low concentrations of Ser promoted axillary bud outgrowth in overexpression lines,while high concentrations of Ser inhibited it.Conversely,the mutant lines showed the opposite response.Altered expression of OsATL4 might affect the expression of genes in nitrogen,auxin,and cytokinin pathways.We propose that two splicing variants of OsATL4 negatively regulate rice tillering and yield by mediating the transport of amino acids,making it a significant target for high-yield rice breeding.
基金financial support from the National Natural Science Foundation of China(Nos.22074114,22377097,21877087)Natural Science Foundation of Hubei Province of China(Nos.2020CFB623,2021CFB556)+2 种基金Engineering Research Center of Phosphorus Resources Development and Utilization of Ministry of Education(No.LCX202305)Wuhan Institute of Technology Graduate Education and Teaching Reform Research Project(Nos.2022JYXM09,2021JYXM07)Wuhan Institute of Technology Graduate Innovation Fund(No.CX2022450)are greatly appreciated。
文摘A novel and readily available binaphthyl-based fluorescent probe(S)-1 was designed and synthesized.(S)-1 can be used to not only chemoselectively discriminate 3 basic amino acids out of common amino acids,but also enantioselectively recognize histidine.Encouragingly,enantioselective imaging of histidine in cells was achieved for the first time by the probe(S)-1.These performances endowed it potential application in the chiral analysis of basic amino acids in asymmetric synthesis and cell imaging for diagnosis of diseases caused by racemization of histidine.Nuclear magnetic resonance(NMR)and mass spectrometry investigations suggested that different reaction extent of(S)-1 with L/D-histidine and different product structures generated the observed enantioselective fluorescent response.The molecular structures and thermodynamic stability of the complexes,formed from(S)-1+Zn2+and enantiomers of histidine,were calculated by Gaussian 16 based on density functional theory(DFT)to validate the above action mechanism.
基金This work is supported by the Agriculture and Food Research Initiative competitive grant No.2021-67015-33383 from the USDA National Institute of Food and Agriculture(Washington,DC)and USDA,AgBioResearch,Michigan State University.
文摘Background Dairy cows are at high risk of fatty liver disease in early lactation,but current preventative measures are not always effective.Cows with fatty liver have lower circulating branched-chain amino acid(BCAA)concentra-tions whereas cows with high circulating BCAA levels have low liver triglyceride(TG).Our objective was to determine the impact of BCAA and their corresponding ketoacids(branched-chain ketoacids,BCKA)on production performance and liver TG accumulation in Holstein cows in the first 3 weeks postpartum.Methods Thirty-six multiparous Holstein cows were used in a randomized block design experiment.Cows were abomasally infused for the first 21 d postpartum with solutions of 1)saline(CON,n=12);2)BCA(67 g valine,50 g leu-cine,and 34 g isoleucine,n=12);and 3)BCK(77 g 2-ketovaline calcium salt,57 g 2-ketoleucine calcium salt,and 39 g 2-ketoisoleucine calcium salt,n=12).All cows received the same diet.Treatment effects were determined using PROC GLIMMIX in SAS.Results No differences were detected for body weight,body condition score,or dry matter intake averaged over the first 21 d postpartum.Cows receiving BCK had significantly lower liver TG concentrations compared to CON(6.60%vs.4.77%,standard error of the mean(SEM)0.49)during the first 3 weeks of lactation.Infusion of BCA increased milk yield(39.5 vs.35.3 kg/d,SEM 1.8),milk fat yield(2.10 vs.1.69 kg/d,SEM 0.08),and lactose yield(2.11 vs.1.67 kg/d,SEM 0.07)compared with CON.Compared to CON,cows receiving BCA had lower plasma glucose(55.0 vs.59.2 mg/dL,SEM 0.86)but higherβ-hydroxybutyrate(9.17 vs.6.00 mg/dL,SEM 0.80).Conclusions Overall,BCAA supplementation in this study improved milk production,whereas BCKA supplementa-tion reduced TG accumulation in the liver of fresh cows.
基金supported by the National Key R&D Program of China (No.2019YFC1803704)。
文摘The digestibility of cadmium(Cd)in brown rice is directly related to amino acid metabolism in rice and human health.In our field study,three kinds of alkaline calcium-rich soil inorganic amendments(SIAs)at three dosages were applied to produce safe rice and improve the quality of rice in Cd-contaminated paddy.With the increased application of SIA,Cd content in iron plaque on rice root significantly increased,the transfer of Cd from rice root to grain significantly decreased,and then Cd content in brown rice decreased synchronously.The vitro digestibility of Cd in brown rice was estimated by a physiologically based extraction test.Results showed that more than 70%of Cd in brown rice could be digested by simulated gastrointestinal juice.Based on the total and digestible Cd contents in brown rice to evaluate the health risk,the application of 2.25 ton SIA/ha could produce safe rice in acidic slightly Cd-contaminated paddy soils.The amino acids(AAs)in brown rice were determined by high-performance liquid chromatography.The contents of 5 key AAs(KAAs)that actively respond to environmental changes increased significantly with the increased application of SIA.The structural equation model indicated that KAAs could be affected by the Cd translocation capacity from rice root to grain,and consequently altered the ratio of indigestible Cd in brown rice.The formation of indigestible KAAs-Cd complexes by combining KAAs(phenylalanine,leucine,histidine,glutamine,and asparagine)with Cd in brown rice could be considered a potential mechanism for reducing the digestibility of Cd.
基金supported by the Priority Academic Program Development of Jiangsu Higher Education Institution(PAPD).
文摘Lactic acid bacteria and coagulase-negative staphylococci play an important role in the production of fermented sausages,such as inhibiting the growth of undesirable bacteria and antioxidant.In this study,the effects of inoculation with different starter cultures(Lactiplantibacillus plantarum HN108 and Staphylococcus simulans NJ209)on the free amino acids(FAAs),biogenic amines(BAs)and volatile compounds of fermented sausages were investigated using an amino acid analyzer,ultra performance liquid chromatography and gas chromatography-ion mobility spectrometry,respectively.The pH and carbonyl content of the inoculated group was significantly lower than those in the control group(P<0.05).L.plantarum HN108 significantly reduced the content of FAAs and BAs in fermented sausage production(P<0.05),while S.simulans NJ209 promoted the formation of FAAs(especially bitter amino acids)and exhibited slight BAs-reducing activity.In addition,L.plantarum HN108 promoted the formation of volatile compounds such as ketones,alcohols and alkenes in sausages.In conclusion,L.plantarum HN108 could contribute to reducing the content of putrescine and tyramine and forming the desirable flavor compounds in fermented sausages.Thus,L.plantarum HN108 is expected to be a starter culture that can improve the safety and flavor of fermented sausages.
基金Supported by the Open Project Grant for Clinical Medical Center of Yunnan Province,No.2019LCZXKF-NM03Medical Leader Training Grant,No.L-201624and Yunnan Province Ten Thousand Talents:“Medical Expert”grant,No.YNWR-MY-2019-020.
文摘BACKGROUND The lack of specific predictors for type-2 diabetes mellitus(T2DM)severely impacts early intervention/prevention efforts.Elevated branched-chain amino acids(BCAAs:Isoleucine,leucine,valine)and aromatic amino acids(AAAs:Tyrosine,tryptophan,phenylalanine)show high sensitivity and specificity in predicting diabetes in animals and predict T2DM 10-19 years before T2DM onset in clinical studies.However,improvement is needed to support its clinical utility.AIM To evaluate the effects of body mass index(BMI)and sex on BCAAs/AAAs in new-onset T2DM individuals with varying body weight.METHODS Ninety-seven new-onset T2DM patients(<12 mo)differing in BMI[normal weight(NW),n=33,BMI=22.23±1.60;overweight,n=42,BMI=25.9±1.07;obesity(OB),n=22,BMI=31.23±2.31]from the First People’s Hospital of Yunnan Province,Kunming,China,were studied.One-way and 2-way ANOVAs were conducted to determine the effects of BMI and sex on BCAAs/AAAs.RESULTS Fasting serum AAAs,BCAAs,glutamate,and alanine were greater and high-density lipoprotein(HDL)was lower(P<0.05,each)in OB-T2DM patients than in NW-T2DM patients,especially in male OB-T2DM patients.Arginine,histidine,leucine,methionine,and lysine were greater in male patients than in female patients.Moreover,histidine,alanine,glutamate,lysine,valine,methionine,leucine,isoleucine,tyrosine,phenylalanine,and tryptophan were significantly correlated with abdominal adiposity,body weight and BMI,whereas isoleucine,leucine and phenylalanine were negatively correlated with HDL.CONCLUSION Heterogeneously elevated amino acids,especially BCAAs/AAAs,across new-onset T2DM patients in differing BMI categories revealed a potentially skewed prediction of T2DM development.The higher BCAA/AAA levels in obese T2DM patients would support T2DM prediction in obese individuals,whereas the lower levels of BCAAs/AAAs in NW-T2DM individuals may underestimate T2DM risk in NW individuals.This potentially skewed T2DM prediction should be considered when BCAAs/AAAs are to be used as the T2DM predictor.
文摘Athletes often use branched-chain amino acid (BCAAs) supplements with a ratio of 2:1:1 (leucine:isoleucine:valine) for their impact on muscle building. Research suggests that by altering the ratio, an improvement in glucose metabolism might be possible. The purpose of this study was to examine how isoleucine would influence glucose tolerance. We recruited healthy male (n = 13) and female (n = 5) participants who were asked to fast for 12 hours before coming to the laboratory. A fasting blood sample was collected, followed by the subjects consuming a breakfast containing 113 g carbohydrates, 8 g protein, 1.5 g fat, and BCAA powder in the 2:1:1 ratio (Control) or BCAA powder enriched with Isoleucine (2:6:1), both added to orange juice. The opposite meal was consumed on a second visit one week apart. Blood was collected at 30, 60, 90, and 120 minutes post-meal. No differences were observed between the Control and Isoleucine for changes in serum glucose or insulin response when examining all subjects together. However, when comparing between genders, males tended to have a significantly lower serum glucose response compared to females when consuming the Isoleucine, with no difference between the genders when consuming the Control. Also, males had significantly lower serum glucose responses when consuming the Isoleucine compared to when they consumed the Control, while females had significantly higher serum glucose responses when consuming the Isoleucine compared to when they consumed the Control. In general, males tended to have a lower serum insulin response than females when consuming both the Control and the Isoleucine. Our study indicates a significant difference in the way genders respond to BCAA supplementation, where isoleucine may improve glucose tolerance and insulin response in males but not females.
基金Shenyang Governmental Science and Technology Program(Project No.22-316-2-02)China Agriculture Research System Program(Project No.CARS-41-G04).
文摘Background Research on low-protein-level diets has indicated that even though the profiles of essential amino acids(EAAs)follow the recommendation for a normal-protein-level diet,broilers fed low-protein diets failed to achieve pro-ductive performance compared to those fed normal diets.Therefore,it is imperative to reassess the optimum profile of EAAs in low-protein diets and establish a new ideal pattern for amino acid balance.Furthermore,identifying novel sensitive biomarkers for assessing amino acid balance will greatly facilitate the development of amino acid nutrition and application technology.In this study,12 dietary treatments[Con(+),Con(-),L&A(-),L&A(+),M&C(-),M&C(+),BCAA(-),BCAA(+),Thr(-),Thr(+),Trp(-)and Trp(+)]were established by combining different EAAs including lysine and argi-nine,methionine and cysteine,branched-chain amino acid(BCAA),threonine,and tryptophan to observe the growth and development of the broiler chickens fed with low-protein-level diets.Based on the biochemical parameters and untargeted metabolomic analysis of animals subjected to different treatments,biomarkers associated with opti-mal and suboptimal amino acid balance were identified.Results Growth performance,carcass characteristics,hepatic enzyme activity,serum biochemical parameters,and breast muscle mRNA expression differed significantly between male and female broilers under different dietary amino acid patterns.Male broilers exhibited higher sensitivity to the adjustment of amino acid patterns than female broilers.For the low-protein diet,the dietary concentrations of lysine,arginine,and tryptophan,but not of methionine,cystine,or threonine,needed to be increased.Therefore,further research on individual BCAA is required.For untar-geted metabolomic analysis,Con(+)was selected as a normal diet(NP)while Con(-)represented a low-protein diet(LP).L&A(+)denotes a low-protein amino acid balanced diet(LPAB)and Thr(+)represents a low-protein amino acid imbalance diet(LPAI).The metabolites oxypurinol,pantothenic acid,and D-octopine in birds were significantly influ-enced by different dietary amino acid patterns.Conclusion Adjusting the amino acid profile of low-protein diets is required to achieve normal growth performance in broiler chickens fed normal-protein diets.Oxypurinol,pantothenic acid,and D-octopine have been identified as potentially sensitive biomarkers for assessing amino acid balance.