CR Dhan 310(CRD310),a biofortified rice variety,contains a significantly higher level of grain protein compared with its recurrent parent Naveen(NV),as well as most adapted high-yielding rice varieties in India.Althou...CR Dhan 310(CRD310),a biofortified rice variety,contains a significantly higher level of grain protein compared with its recurrent parent Naveen(NV),as well as most adapted high-yielding rice varieties in India.Although a limited investigation depicted that CRD310 contained higher levels of glutelin and some essential amino acids,detailed biochemical,molecular,and cellular mechanisms remain to be studied.As one of the means to identify the proteins and understand the underlying mechanism of higher proteins accumulation in grains of CRD310,the comparative proteomics was undertaken on grains of CRD310 and NV at the yellow ripening stage.展开更多
Peptides play important roles in chemistry,medicinal chemistry and life science,due to their high efficiency and specificity,unusual biological and therapeutic properties.As naturally occurring peptides often face wit...Peptides play important roles in chemistry,medicinal chemistry and life science,due to their high efficiency and specificity,unusual biological and therapeutic properties.As naturally occurring peptides often face with their intrinsic limitations including metabolic instability and low membrane permeability,the strategies for synthesizing unnatural amino acids and peptides are explored.Among the methods for modifying amino acids and peptides,chemo-and site-selective approaches are preferred because of the ability to fine-tuning structural features.Recently,transition metal-catalyzed Csingle bondH activation has been employed for the functionalization of amino acids and peptides.Through domino Csingle bondH activation/annulation,a series of structurally complex and diverse amino acids and peptides is constructed.This review highlights recent advances in the synthesis of unnatural amino acids and peptides via transition metal-catalyzed Csingle bondH activation/annulation.展开更多
Two-dimensional nanofluidic membranes have garnered considerable interest due to their potential for cost-effective osmotic energy harvesting.One promising approach to enhancing ion conductivity and selectivity is the...Two-dimensional nanofluidic membranes have garnered considerable interest due to their potential for cost-effective osmotic energy harvesting.One promising approach to enhancing ion conductivity and selectivity is the incorporation of vip additives.However,the traditional host-vip configuration can undermine the structural integrity of nanochannels owing to the inconsistent size and shape of these additives.Drawing inspiration from the intricate design of biological protein channels,which utilize small amino acid molecules as vips,we have addressed this issue by incorporating glycine,a common amino acid,into a vermiculite membrane using a simple vacuum-assisted infiltration method.The resulting vermiculite-glycine membrane demonstrates 1.8 times greater ionic conductivity and twice the power density compared to pure vermiculite membranes.Analysis based on glycine content,coupled with spectroscopic examination,reveals that ion conductivity is linked to the distribution of glycine molecules across three specific sites within the membrane.This suggests that glycine molecules—whether confined in voids,adsorbed onto nanochannel surfaces,or intercalated within multilayered vermiculite nanoparticles—enhance nanofluidic ion transport by modulating surface and space charge density,as well as strengthening hydrogen bonding,electrostatic interactions,and steric effects.This work reveals the specific interactions between amino acids and vermiculite,offering a novel path for advancing nanofluidic composite membranes and highlighting critical considerations for the proposed strategy.展开更多
Chiral amino acids(AAs)serve as essential building blocks of proteins and play vital physiological roles in living organisms.To achieve accurate,rapid,and high-throughput analysis of chiral AAs,this work proposed a me...Chiral amino acids(AAs)serve as essential building blocks of proteins and play vital physiological roles in living organisms.To achieve accurate,rapid,and high-throughput analysis of chiral AAs,this work proposed a methylbenzyl isocyanate(MBIC)derivatization strategy coupled with ultra-high performance liquid chromatography-mass spectrometry or trapped ion mobility spectrometry-mass spectrometry.The integration of a chiral carbon atom with a rigid urea-based structure can significantly enhance the separation of chiral MBIC-labeled AA enantiomers.This phenomenon can be attributed to the labeled l-AAs allow the carboxyl group to form intramolecular hydrogen bonds with the amino group in the rigid urea-based structure,whereas labeled d-AAs are unable to form such bonds.The method based on MBIC derivatization coupled with ultra-performance liquid chromatography-tandem mass spectrometry achieved simultaneous separation of 19 pairs of chiral AAs using only a C18 column within 30 min,enabling quantitatively detect twelve types of chiral AAs in the serum of healthy humans and Parkinson's patients.The distribution of twenty-four chiral AAs is observed in mouse brain using MBIC labeling-based matrix-assisted laser desorption/ionization-trapped ion mobility spectrometry-mass spectrometry imaging without prior separation.Our work elucidates the principles governing the separation of chiral AAs using derivatization methods,providing valuable guidance for the separation of chiral compounds.展开更多
Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensiv...Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensively explores how cancer cells rewire BCAA metabolism to enhance proliferation,survival,and therapy resistance.Tumors manipulate BCAA uptake and catabolism via high expression of transporters like L-type amino acid transporter 1(LAT1)and enzymes including branched chain amino acid transaminase 1(BCAT1),branched chain amino acid transaminase 2(BCAT2),branched-chain alpha-keto acid dehydrogenase(BCKDH),and branched chain alpha-keto acid dehydrogenase kinase(BCKDK).These alterations sustain energy production,biosynthesis,redox homeostasis,and oncogenic signaling(especially mammalian target of rapamycin complex 1[mTORC1]).Crucially,tumor-driven BCAA depletion also shapes an immunosuppressive microenvironment,impairing anti-tumor immunity by limiting essential nutrients for T cells and natural killer(NK)cells.Innovative therapeutic strategies targeting BCAA pathways—ranging from selective small-molecule inhibitors(e.g.,LAT1 and BCAT1/2)to dietary modulation—have shown promising preclinical and early clinical efficacy,highlighting their potential to exploit metabolic vulnerabilities in cancer cells while bolstering immune responses.By integrating multi-omics data and precision targeting approaches,this review underscores the translational significance of BCAA metabolic reprogramming,positioning it as a novel frontier in cancer treatment.展开更多
Skeletal muscle accounts for approximately 40%of body mass and 50%–75%of whole-body protein,playing a central role in meat production and quality.Efficient protein synthesis in skeletal muscle relies on an adequate s...Skeletal muscle accounts for approximately 40%of body mass and 50%–75%of whole-body protein,playing a central role in meat production and quality.Efficient protein synthesis in skeletal muscle relies on an adequate supply of nutrient substrates and a balanced amino acid profile.Branched-chain amino acids(BCAA),including leucine(Leu),isoleucine(Ile),and valine(Val),are the most abundant essential amino acids in skeletal muscle and contribute to both protein synthesis and oxidative energy production.Additionally,BCAA function as signaling molecules that regulate gene expression and protein phosphorylation cascades,which significantly influence physiological processes,such as protein synthesis and degradation,glucose and lipid metabolism,and cell apoptosis and autophagy.These processes are primarily mediated through the PI3K/AKT/AMPK/mTOR signaling pathways.This review summarizes BCAA transporters and catabolic metabolism,their role as signaling molecules in regulating protein metabolism and glucose and lipid equilibrium,and applications in animal production.These findings offer both theoretical insights and practical guidelines for the precise regulation of feed efficiency and production performance through tailored dietary BCAA supplementations.展开更多
The detection of amino acid enantiomers holds significant importance in biomedical,chemical,food,and other fields.Traditional chiral recognition methods using fluorescent probes primarily rely on fluorescence intensit...The detection of amino acid enantiomers holds significant importance in biomedical,chemical,food,and other fields.Traditional chiral recognition methods using fluorescent probes primarily rely on fluorescence intensity changes,which can compromise accuracy and repeatability.In this study,we report a novel fluorescent probe(R)-Z1 that achieves effective enantioselective recognition of chiral amino acids in water by altering emission wavelengths(>60 nm).This water-soluble probe(R)-Z1 exhibits cyan or yellow-green luminescence upon interaction with amino acid enantiomers,enabling reliable chiral detection of 14 natural amino acids.It also allows for the determination of enantiomeric excess through monitoring changes in luminescent color.Additionally,a logic operation with two inputs and three outputs was constructed based on these optical properties.Notably,amino acid enantiomers were successfully detected via dual-channel analysis at both the food and cellular levels.This study provides a new dynamic luminescence-based tool for the accurate sensing and detection of amino acid enantiomers.展开更多
Post-exercise whey protein isolate(WPI)supplement is beneficial for skeletal muscle recovery due to the stimulation of branched chain amino acids(BCAAs).This implies us that intake slow digestion rate of protein to su...Post-exercise whey protein isolate(WPI)supplement is beneficial for skeletal muscle recovery due to the stimulation of branched chain amino acids(BCAAs).This implies us that intake slow digestion rate of protein to sustain BCAAs releasing rate may facilitate muscle protein synthesis.To examine this hypothesis,we conducted a series of protein supplements including modified slow-digesting whey(SDW),whey,hydrolyzed whey and casein,orally to mice undergoing endurance running.Our results showed that the SDW gavage constant supplied BCAAs in the serum of mice within 6 h and significantly enhanced(P<0.01)endurance exercise capacity,compared to other groups.In addition,the SDW supplementation increased the crosssectional area of mice gastrocnemius fibers,as well as their muscle and liver glycogen content.It also increased the testosterone/cortisol ratio in serum and interleukin-6(IL-6)levels in muscle,while it decreased the tumor necrosis factor-alpha(TNF-α)levels and oxidative stress in muscle.Moreover,it may activate mechanistic target of rapamycin signaling by upregulating mRNA(bcat-1 and pgc-1α)expression.Thus,our findings illustrate that prolonged BCAAs supply duration promotes mice endurance running capacity and skeletal muscle growth,contributing to the advancement of sports nutrition practices.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
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
Chiral N-substituted amino amides and esters are ubiquitous scaffolds in pesticides and pharmaceutical chemicals,but their asymmetric synthesis remains challenging especially for those with multiple chiral centers.In ...Chiral N-substituted amino amides and esters are ubiquitous scaffolds in pesticides and pharmaceutical chemicals,but their asymmetric synthesis remains challenging especially for those with multiple chiral centers.In this study,IR104 from Streptomyces aureocirculatus was identified from 157 wild-type imine reductases for the synthesis of(S)-2-((R)-2-oxo-4-propylpyrrolidin-1-yl)butanamide(antiepileptic drug Brivaracetam)via dynamic kinetic resolution reductive amination from ethyl 3-formylhexanoate and(S)-2-aminobutylamide with high diastereoselectivity.To further improve the catalytic efficiency of IR104,its mutant D191E/L195I/E253S/M258A(M3)was identified by saturation mutagenesis and iterative combinatorial mutagenesis,which exhibited a 102-fold increase in the catalytic efficiency relative to that of wild-type enzyme and high diastereoselectivity(98:2 d.r.).Crystal structural analysis and molecular dynamics simulations provided some insights into the molecular basis for the improved activity of the mutant enzyme.The imine reductase identified in this study could accept chiral amino amides/esters as amino donors for the dynamic kinetic resolution reductive amination of racemicα-substituted aldehydo-esters,expanding the substrate scope of imine reductases in the dynamic kinetic resolution-reductive amination.Finally,IR104-M3 was successfully used for the preparation of Brivaracetam at gram scale.Using this mutant,various N-substituted amino amides/esters with two chiral centers were also synthesized with up to 99:1 d.r.and 96%yields and subsequently converted intoγ-andδ-lactams,providing an efficient protocol for the synthesis of these important compounds via enzymatic dynamic kinetic resolution-reductive amination from simple building blocks.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 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
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
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
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
Cp_(2)TiCl_(2) as a Lewis acid precursor and nicotinic acid as a ligand have been used synergistically for the one-pot synthesis of 2-(N-substituted amino)-1,4-naphthoquinones.This method establishes a general strateg...Cp_(2)TiCl_(2) as a Lewis acid precursor and nicotinic acid as a ligand have been used synergistically for the one-pot synthesis of 2-(N-substituted amino)-1,4-naphthoquinones.This method establishes a general strategy for the functionalization and conversion of C-H bonds of 1,4-naphthoquinones into C-N bonds,providing an effective route to synthesize 2-(N-substituted amino)-1,4-naphthoquinone with high yield under mild conditions.Additionally,the synergistic catalytic mechanism was investigated by 1H NMR titration experiments and LC-MS analysis,with experimental results sufficiently and consistently supporting the proposed mechanism of the catalytic cycle.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
The long fermentation period constitutes a crucial process for enhancing the quality of base liquor in the production of Chinese strong-flavor Baijiu.In the present study,a comprehensive metaproteomic analysis of ferm...The long fermentation period constitutes a crucial process for enhancing the quality of base liquor in the production of Chinese strong-flavor Baijiu.In the present study,a comprehensive metaproteomic analysis of fermented grains in the long fermentation period led to the identification of 44 plant proteins and 1460 microbial proteins.Following 12 days of fermentation,bacterial proteins exhibited a rapid surge,constituting the predominant components of fermented grains proteins,ranging from 64.64 to 81.28%.The differential proteins were predominantly associated with carbohydrate metabolism,energy metabolism,and amino acid metabolism.Among these,days 18 to 220 were dominated by differential protein in the protein hydrolase system and amino acid metabolic of the bacteria.Pathway analysis delineated the potential metabolic pathways through which cysteine,tyrosine,proline,isoleucine,among others,could be metabolized to yield pyruvic acid,acetyl-CoA,ultimately leading to the production of acetic acid,butyric acid,and hexanoic acid.Furthermore,phenylalanine underwent metabolism,resulting in the production of phenylacetaldehyde,phenylacetic acid,and phenylacetic acid ethyl ester.With the extension of fermentation time,lactic acid underwent conversion to pyruvic acid,contributing to the generation of other acids,while aldehydes were converted to alcohols and acids.展开更多
This study examined four species of Scylla genus(S.paramamosain,S.olivacea,S.serrata,and S.tranquebarica)morphologically and molecularly.Morphologically,distinct frontal lobe spine shapes and colorations were observed...This study examined four species of Scylla genus(S.paramamosain,S.olivacea,S.serrata,and S.tranquebarica)morphologically and molecularly.Morphologically,distinct frontal lobe spine shapes and colorations were observed.Using HRM genotyping with CSN9 primers,we identified clear species-specific melting curve distinctions.The Tm values of S.serrata,S.paramamosain,S.tranquebarica and S.olivacea are 79.55℃,80.12℃,78.12℃ and 82.04℃,respectively.Sequencing data validated these results,revealing 28 SNPs and 9 haplotypes.Amino acid analysis showed arginine dominance in S.paramamosain,which was 40.64 mg g^(-1),and a TFAA range of 135.70-149.65 mg g^(-1).A total of 26 fatty acids were identified,while S.paramamosain showed the highest concentration(P<0.05).EPA was a major component(16.17%-23.26%),while S.paramamosain exhibited the highest levels.Principal component analysis and cluster analysis highlighted distinct species groupings based on amino acid and fatty acid profiles.These findings provide comprehensive insights into Scylla species'morphological,molecular,and biochemical diversities.展开更多
基金supported by the director of Indian Council of Agricultural Research and International Rice Research Institute (ICAR-CRRI), Cuttack, Indiathe coordinator of the ICAR-sponsored project ‘C-reactive protein (CRP) in Biofortification in Selected Crops’, India
文摘CR Dhan 310(CRD310),a biofortified rice variety,contains a significantly higher level of grain protein compared with its recurrent parent Naveen(NV),as well as most adapted high-yielding rice varieties in India.Although a limited investigation depicted that CRD310 contained higher levels of glutelin and some essential amino acids,detailed biochemical,molecular,and cellular mechanisms remain to be studied.As one of the means to identify the proteins and understand the underlying mechanism of higher proteins accumulation in grains of CRD310,the comparative proteomics was undertaken on grains of CRD310 and NV at the yellow ripening stage.
基金supported by the Natural Science Foundation of Jiangsu Province(No.BK20220409)the National Natural Science Foundation of China(No.22401153)+2 种基金the FWO[Fund for Scientific Research-Flanders(Belgium)]for financial support(recipient Erik V.Van der Eycken)the Research Council of the KU Leuven(recipient Erik V.Van der Eycken)the support of the"RUDN University Strategic Academic Leadership Program"(recipient Erik V.Van der Eycken).
文摘Peptides play important roles in chemistry,medicinal chemistry and life science,due to their high efficiency and specificity,unusual biological and therapeutic properties.As naturally occurring peptides often face with their intrinsic limitations including metabolic instability and low membrane permeability,the strategies for synthesizing unnatural amino acids and peptides are explored.Among the methods for modifying amino acids and peptides,chemo-and site-selective approaches are preferred because of the ability to fine-tuning structural features.Recently,transition metal-catalyzed Csingle bondH activation has been employed for the functionalization of amino acids and peptides.Through domino Csingle bondH activation/annulation,a series of structurally complex and diverse amino acids and peptides is constructed.This review highlights recent advances in the synthesis of unnatural amino acids and peptides via transition metal-catalyzed Csingle bondH activation/annulation.
基金supported by the National Natural Science Foundation of China(Grant No.22479097)the Shanghai Science and Technology Committee(Grant Nos.23ZR1433000)the National High-Level Talent Program for Young Scholars,the Start-up Fund(F.S.)from Shanghai Jiao Tong University,China.We also acknowledge the SJTU Instrument Analysis Centre for the measurements.
文摘Two-dimensional nanofluidic membranes have garnered considerable interest due to their potential for cost-effective osmotic energy harvesting.One promising approach to enhancing ion conductivity and selectivity is the incorporation of vip additives.However,the traditional host-vip configuration can undermine the structural integrity of nanochannels owing to the inconsistent size and shape of these additives.Drawing inspiration from the intricate design of biological protein channels,which utilize small amino acid molecules as vips,we have addressed this issue by incorporating glycine,a common amino acid,into a vermiculite membrane using a simple vacuum-assisted infiltration method.The resulting vermiculite-glycine membrane demonstrates 1.8 times greater ionic conductivity and twice the power density compared to pure vermiculite membranes.Analysis based on glycine content,coupled with spectroscopic examination,reveals that ion conductivity is linked to the distribution of glycine molecules across three specific sites within the membrane.This suggests that glycine molecules—whether confined in voids,adsorbed onto nanochannel surfaces,or intercalated within multilayered vermiculite nanoparticles—enhance nanofluidic ion transport by modulating surface and space charge density,as well as strengthening hydrogen bonding,electrostatic interactions,and steric effects.This work reveals the specific interactions between amino acids and vermiculite,offering a novel path for advancing nanofluidic composite membranes and highlighting critical considerations for the proposed strategy.
基金supported by the National Natural Science Foundation of China(Nos.22404023,22274021,and 22036001).
文摘Chiral amino acids(AAs)serve as essential building blocks of proteins and play vital physiological roles in living organisms.To achieve accurate,rapid,and high-throughput analysis of chiral AAs,this work proposed a methylbenzyl isocyanate(MBIC)derivatization strategy coupled with ultra-high performance liquid chromatography-mass spectrometry or trapped ion mobility spectrometry-mass spectrometry.The integration of a chiral carbon atom with a rigid urea-based structure can significantly enhance the separation of chiral MBIC-labeled AA enantiomers.This phenomenon can be attributed to the labeled l-AAs allow the carboxyl group to form intramolecular hydrogen bonds with the amino group in the rigid urea-based structure,whereas labeled d-AAs are unable to form such bonds.The method based on MBIC derivatization coupled with ultra-performance liquid chromatography-tandem mass spectrometry achieved simultaneous separation of 19 pairs of chiral AAs using only a C18 column within 30 min,enabling quantitatively detect twelve types of chiral AAs in the serum of healthy humans and Parkinson's patients.The distribution of twenty-four chiral AAs is observed in mouse brain using MBIC labeling-based matrix-assisted laser desorption/ionization-trapped ion mobility spectrometry-mass spectrometry imaging without prior separation.Our work elucidates the principles governing the separation of chiral AAs using derivatization methods,providing valuable guidance for the separation of chiral compounds.
基金supported by a grant from the Dalian Science and Technology Innovation Fund Program(No.2024JJ13PT070)United Foundation for Dalian Institute of Chemical Physics,Chinese Academy of Sciences and the Second Hospital of Dalian Medical University(No.DMU-2&DICP UN202410)Dalian Life and Health Field Guidance Program Project(No.2024ZDJH01PT084).
文摘Metabolic reprogramming involving branched-chain amino acids(BCAAs)—leucine,isoleucine,and valine—is increasingly recognized as pivotal in cancer progression,metastasis,and immune modulation.This review comprehensively explores how cancer cells rewire BCAA metabolism to enhance proliferation,survival,and therapy resistance.Tumors manipulate BCAA uptake and catabolism via high expression of transporters like L-type amino acid transporter 1(LAT1)and enzymes including branched chain amino acid transaminase 1(BCAT1),branched chain amino acid transaminase 2(BCAT2),branched-chain alpha-keto acid dehydrogenase(BCKDH),and branched chain alpha-keto acid dehydrogenase kinase(BCKDK).These alterations sustain energy production,biosynthesis,redox homeostasis,and oncogenic signaling(especially mammalian target of rapamycin complex 1[mTORC1]).Crucially,tumor-driven BCAA depletion also shapes an immunosuppressive microenvironment,impairing anti-tumor immunity by limiting essential nutrients for T cells and natural killer(NK)cells.Innovative therapeutic strategies targeting BCAA pathways—ranging from selective small-molecule inhibitors(e.g.,LAT1 and BCAT1/2)to dietary modulation—have shown promising preclinical and early clinical efficacy,highlighting their potential to exploit metabolic vulnerabilities in cancer cells while bolstering immune responses.By integrating multi-omics data and precision targeting approaches,this review underscores the translational significance of BCAA metabolic reprogramming,positioning it as a novel frontier in cancer treatment.
基金partly funded by National Key R&D Program of China(2023YFD1301405)the 2115 Talent Development Program of China Agricultural University。
文摘Skeletal muscle accounts for approximately 40%of body mass and 50%–75%of whole-body protein,playing a central role in meat production and quality.Efficient protein synthesis in skeletal muscle relies on an adequate supply of nutrient substrates and a balanced amino acid profile.Branched-chain amino acids(BCAA),including leucine(Leu),isoleucine(Ile),and valine(Val),are the most abundant essential amino acids in skeletal muscle and contribute to both protein synthesis and oxidative energy production.Additionally,BCAA function as signaling molecules that regulate gene expression and protein phosphorylation cascades,which significantly influence physiological processes,such as protein synthesis and degradation,glucose and lipid metabolism,and cell apoptosis and autophagy.These processes are primarily mediated through the PI3K/AKT/AMPK/mTOR signaling pathways.This review summarizes BCAA transporters and catabolic metabolism,their role as signaling molecules in regulating protein metabolism and glucose and lipid equilibrium,and applications in animal production.These findings offer both theoretical insights and practical guidelines for the precise regulation of feed efficiency and production performance through tailored dietary BCAA supplementations.
基金the financial support from the National Natural Science Foundation of China(Nos.22377097,22307036,22074114)Natural Science Foundation of Hubei Province of China(Nos.2020CFB623,2021CFB556)Engineering Research Center of Phosphorus Resources Development and Utilization of Ministry of Education(No.LCX202305)。
文摘The detection of amino acid enantiomers holds significant importance in biomedical,chemical,food,and other fields.Traditional chiral recognition methods using fluorescent probes primarily rely on fluorescence intensity changes,which can compromise accuracy and repeatability.In this study,we report a novel fluorescent probe(R)-Z1 that achieves effective enantioselective recognition of chiral amino acids in water by altering emission wavelengths(>60 nm).This water-soluble probe(R)-Z1 exhibits cyan or yellow-green luminescence upon interaction with amino acid enantiomers,enabling reliable chiral detection of 14 natural amino acids.It also allows for the determination of enantiomeric excess through monitoring changes in luminescent color.Additionally,a logic operation with two inputs and three outputs was constructed based on these optical properties.Notably,amino acid enantiomers were successfully detected via dual-channel analysis at both the food and cellular levels.This study provides a new dynamic luminescence-based tool for the accurate sensing and detection of amino acid enantiomers.
基金financially supported by the Fundamental Research Funds for the Central Universities(JUSRP622014)Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province,Jiangnan University(2022-3-2)National Key Research and Development Program of China(2022YFF1100300).
文摘Post-exercise whey protein isolate(WPI)supplement is beneficial for skeletal muscle recovery due to the stimulation of branched chain amino acids(BCAAs).This implies us that intake slow digestion rate of protein to sustain BCAAs releasing rate may facilitate muscle protein synthesis.To examine this hypothesis,we conducted a series of protein supplements including modified slow-digesting whey(SDW),whey,hydrolyzed whey and casein,orally to mice undergoing endurance running.Our results showed that the SDW gavage constant supplied BCAAs in the serum of mice within 6 h and significantly enhanced(P<0.01)endurance exercise capacity,compared to other groups.In addition,the SDW supplementation increased the crosssectional area of mice gastrocnemius fibers,as well as their muscle and liver glycogen content.It also increased the testosterone/cortisol ratio in serum and interleukin-6(IL-6)levels in muscle,while it decreased the tumor necrosis factor-alpha(TNF-α)levels and oxidative stress in muscle.Moreover,it may activate mechanistic target of rapamycin signaling by upregulating mRNA(bcat-1 and pgc-1α)expression.Thus,our findings illustrate that prolonged BCAAs supply duration promotes mice endurance running capacity and skeletal muscle growth,contributing to the advancement of sports nutrition practices.
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.
文摘Chiral N-substituted amino amides and esters are ubiquitous scaffolds in pesticides and pharmaceutical chemicals,but their asymmetric synthesis remains challenging especially for those with multiple chiral centers.In this study,IR104 from Streptomyces aureocirculatus was identified from 157 wild-type imine reductases for the synthesis of(S)-2-((R)-2-oxo-4-propylpyrrolidin-1-yl)butanamide(antiepileptic drug Brivaracetam)via dynamic kinetic resolution reductive amination from ethyl 3-formylhexanoate and(S)-2-aminobutylamide with high diastereoselectivity.To further improve the catalytic efficiency of IR104,its mutant D191E/L195I/E253S/M258A(M3)was identified by saturation mutagenesis and iterative combinatorial mutagenesis,which exhibited a 102-fold increase in the catalytic efficiency relative to that of wild-type enzyme and high diastereoselectivity(98:2 d.r.).Crystal structural analysis and molecular dynamics simulations provided some insights into the molecular basis for the improved activity of the mutant enzyme.The imine reductase identified in this study could accept chiral amino amides/esters as amino donors for the dynamic kinetic resolution reductive amination of racemicα-substituted aldehydo-esters,expanding the substrate scope of imine reductases in the dynamic kinetic resolution-reductive amination.Finally,IR104-M3 was successfully used for the preparation of Brivaracetam at gram scale.Using this mutant,various N-substituted amino amides/esters with two chiral centers were also synthesized with up to 99:1 d.r.and 96%yields and subsequently converted intoγ-andδ-lactams,providing an efficient protocol for the synthesis of these important compounds via enzymatic dynamic kinetic resolution-reductive amination from simple building blocks.
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 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 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 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2024 Special Talent Introduction Projects of Key R&D Program of Ningxia Hui Autonomous Region(2024BEH04049)the 2024 Guyuan City Innovation-Driven Achievement Transformation Project(2024BGTYF01-47)2025 Ningxia Natural Science Foundation Program(2025AAC030624).
文摘Cp_(2)TiCl_(2) as a Lewis acid precursor and nicotinic acid as a ligand have been used synergistically for the one-pot synthesis of 2-(N-substituted amino)-1,4-naphthoquinones.This method establishes a general strategy for the functionalization and conversion of C-H bonds of 1,4-naphthoquinones into C-N bonds,providing an effective route to synthesize 2-(N-substituted amino)-1,4-naphthoquinone with high yield under mild conditions.Additionally,the synergistic catalytic mechanism was investigated by 1H NMR titration experiments and LC-MS analysis,with experimental results sufficiently and consistently supporting the proposed mechanism of the catalytic cycle.
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financially supported by the National Natural Science Foundation of China(22138004)National Treasure Ecological Research Synergetic Innovation Center.
文摘The long fermentation period constitutes a crucial process for enhancing the quality of base liquor in the production of Chinese strong-flavor Baijiu.In the present study,a comprehensive metaproteomic analysis of fermented grains in the long fermentation period led to the identification of 44 plant proteins and 1460 microbial proteins.Following 12 days of fermentation,bacterial proteins exhibited a rapid surge,constituting the predominant components of fermented grains proteins,ranging from 64.64 to 81.28%.The differential proteins were predominantly associated with carbohydrate metabolism,energy metabolism,and amino acid metabolism.Among these,days 18 to 220 were dominated by differential protein in the protein hydrolase system and amino acid metabolic of the bacteria.Pathway analysis delineated the potential metabolic pathways through which cysteine,tyrosine,proline,isoleucine,among others,could be metabolized to yield pyruvic acid,acetyl-CoA,ultimately leading to the production of acetic acid,butyric acid,and hexanoic acid.Furthermore,phenylalanine underwent metabolism,resulting in the production of phenylacetaldehyde,phenylacetic acid,and phenylacetic acid ethyl ester.With the extension of fermentation time,lactic acid underwent conversion to pyruvic acid,contributing to the generation of other acids,while aldehydes were converted to alcohols and acids.
基金funded by the Key Scientific and Technological Grant of Zhejiang(No.2021C02069-6)the Earmarked Fund(No.CARS-48)K.C.Wong Magana Fund in Ningbo University。
文摘This study examined four species of Scylla genus(S.paramamosain,S.olivacea,S.serrata,and S.tranquebarica)morphologically and molecularly.Morphologically,distinct frontal lobe spine shapes and colorations were observed.Using HRM genotyping with CSN9 primers,we identified clear species-specific melting curve distinctions.The Tm values of S.serrata,S.paramamosain,S.tranquebarica and S.olivacea are 79.55℃,80.12℃,78.12℃ and 82.04℃,respectively.Sequencing data validated these results,revealing 28 SNPs and 9 haplotypes.Amino acid analysis showed arginine dominance in S.paramamosain,which was 40.64 mg g^(-1),and a TFAA range of 135.70-149.65 mg g^(-1).A total of 26 fatty acids were identified,while S.paramamosain showed the highest concentration(P<0.05).EPA was a major component(16.17%-23.26%),while S.paramamosain exhibited the highest levels.Principal component analysis and cluster analysis highlighted distinct species groupings based on amino acid and fatty acid profiles.These findings provide comprehensive insights into Scylla species'morphological,molecular,and biochemical diversities.
