Proteostasis,also known as protein homeostasis,is a tightly regulated cellular quality control process that ensures the balance of protein synthesis,folding,posttranslational modifications,and degradation.Maintaining ...Proteostasis,also known as protein homeostasis,is a tightly regulated cellular quality control process that ensures the balance of protein synthesis,folding,posttranslational modifications,and degradation.Maintaining proteostasis is vital for cellular function,organismal health,and longevity.The disru ption of proteostasis can lead to a range of detrimental effects,including accelerated aging,compromised cellular function,and even cell death,manifesting in numerous human diseases(Hipp et al.,2019).展开更多
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
Deep learning methods,particularly exemplified by AlphaFold2,have revolutionized the field of protein structure prediction-an achievement recognized by the 2024 Nobel Prize in Chemistry awarded to its core developers....Deep learning methods,particularly exemplified by AlphaFold2,have revolutionized the field of protein structure prediction-an achievement recognized by the 2024 Nobel Prize in Chemistry awarded to its core developers.Despite this remarkable achievement,the broader protein folding problem is far from solved.Key challenges—each representing opportunities for future breakthroughs—include single-sequence structure prediction,modeling protein dynamics,accurately predicting multimeric complexes,and effectively incorporating experimental constraints.Here we review recent progress in these key frontiers and share our perspective on future directions.展开更多
Background Individuals with prediabetes or diabetes face elevated dementia risk,yet robust prediction tools and mechanistic insights remain limited.Aims This study aimed to develop and validate a proteinbased risk sco...Background Individuals with prediabetes or diabetes face elevated dementia risk,yet robust prediction tools and mechanistic insights remain limited.Aims This study aimed to develop and validate a proteinbased risk score for dementia prediction in this high-risk population while elucidating underlying biological pathways and therapeutic targets.Methods Utilising data from 10 433 UK Biobank participants with prediabetes or diabetes and proteomic profiling(2911 plasma proteins measured),we developed a dementia protein risk score in a training set(n=6514)and validated it in testing(n=2790) and external cohorts(n=1129).Results In the training set,23 out of 2911 proteins were selected.In the testing set,compared with the basic model(age and sex,C-index:0.78;95% confidence interval [CI]0.74-0.82),the dementia protein risk score(C-index:0.84;95% CI 0.81-0.88) significantly improved the performance in predicting incident dementia(C-index increase:0.06;95% CI 0.02-0.12),while cardiovascular risk factors,ageing and dementia incidence risk factors(C-index:0.80;95% Cl0.76-0.83) and apolipoprotein E(APOE;age and sex included,C-index:0.81;95% CI 0.77-0.85) had no significant improvement.Six key proteins(glial fibrillary acidic protein [GFAP],neurofilament light polypeptide[NEFL],Brevican core protein [BCAN],protein MENT[MENT],APOE and growth/differentiation factor 15[GDF15]) captured the most predictive power.Pathway analyses implicated extracellular matrix remodelling and cholesterol metabolism,whereas Mendelian randomisation identified causal roles for APOE,haematopoietic prostaglandin D synthase(HPGDS),BAG family molecular chaperone regulator 3(BAG3) and GDF15.Nine proteins were prioritised as druggable targets,including HPGDS,with existing Food and Drug Administration-approved drugs.Conclusions This study establishes a highly accurate protein-based risk score for dementia prediction(including 6-23 proteins) in individuals with prediabetes or diabetes,uncovering actionable biological pathways and therapeutic targets.The findings enable precision risk stratification and accelerate translational opportunities for dementia prevention in this population.展开更多
Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in...Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.展开更多
BACKGROUND Patients with hepatocellular carcinoma(HCC)beyond the Milan criteria or with portal vein tumor thrombosis are often excluded from the transplant list owing to aggressive biology and recurrence risk.While hi...BACKGROUND Patients with hepatocellular carcinoma(HCC)beyond the Milan criteria or with portal vein tumor thrombosis are often excluded from the transplant list owing to aggressive biology and recurrence risk.While high alpha-fetoprotein(AFP)signals aggressiveness,the behavior of normal AFP HCC with elevated protein induced by vitamin K absence/antagonist-Ⅱ(PIVKA-Ⅱ)is less defined.AIM To assess the prognostic value of PIVKA-Ⅱin normal AFP HCC.METHODS Retrospective cohort of 113 patients with normal AFP and normal or elevated PIVKA-Ⅱ.“Aggressive”tumors were defined as beyond Milan and/or portal vein tumor thrombosis(n=63);others were non-aggressive(n=50).Receiver operating characteristic curve analysis identified PIVKA-Ⅱcut-offs.RESULTS This study included 78 men and 35 women;mean age 58.4±11.1 years;62.8%with decompensated cirrhosis.PIVKA-Ⅱwas higher in aggressive tumors:Median 2785 mAU/mL(interquartile range:222-8152)vs 239 mAU/mL(interquartile range:55-727),P400 mAU/mL was strongly associated with aggressive tumor phenotype(adjusted odds ratio=5.16,P=0.001).All the 29 patients with≥4000 mAU/mL were in the aggressive group(PPV:1.0).All thresholds were dataset-derived.CONCLUSION In normal AFP HCC,PIVKA-Ⅱdiscriminates aggressive biology.A cut-off of 1609.5 mAU/mL balances sensitivity and specificity;400 mAU/mL favors sensitivity;≥4000 mAU/mL delineates an ultra-high-risk subgroup.Findings support the incorporation of PIVKA-Ⅱinto risk stratification.展开更多
Novel insights into complex biological processes very often critically depend on the establishment of new potent read-out tools and improved protocols.A lot has been learned over the past four decades on physiological...Novel insights into complex biological processes very often critically depend on the establishment of new potent read-out tools and improved protocols.A lot has been learned over the past four decades on physiological functions and,importantly,disease-related roles of the prion protein(PrP),a relatively broadly expressed membrane-anchored glycoprotein with high levels in several cell types of the nervous and immune system and with well-established key roles in different progressive and fatal neurodegenerative protein misfolding diseases(proteopathies).展开更多
Following translation,newly synthesized proteins must navigate a turbulent free energy landscape that threatens to trap them in misfolded or nonfunctional conformation.To reach their native states,many proteins are as...Following translation,newly synthesized proteins must navigate a turbulent free energy landscape that threatens to trap them in misfolded or nonfunctional conformation.To reach their native states,many proteins are assisted by molecular chaperones that transiently facilitate folding and assembly without being part of the final structure.One such molecular scaffold is the heat shock protein 70(HSP70) chaperone family,which acts in concert with Bcl-2-associated athanogene(BAG) co-chaperones to regulate a wide array of clients(Figure 1).展开更多
Highlights·A TaPRR95-A haplotype reduces flowering time and increases grain yield in wheat.·Protein-protein interaction between TaPRR95-A and TaCOL16-D modulates the TaFT1-mediated flowering pathway.·A ...Highlights·A TaPRR95-A haplotype reduces flowering time and increases grain yield in wheat.·Protein-protein interaction between TaPRR95-A and TaCOL16-D modulates the TaFT1-mediated flowering pathway.·A validated functional marker enables rapid identification of the target haplotype and provides a practical tool for markerassisted selection in wheat breeding.As a staple cereal crop cultivated worldwide,common wheat(Triticum aestivum L.)accounts for approximately 35%of global dietary energy requirements(Sharma and Sharma 2025).However,agricultural yields are currently under significant pressure due to the combined impacts of anthropogenic climate change and geopolitical conflicts(Ortiz-Bobea et al.2021;Hultgren et al.2025),which threatens global food security.These challenges necessitate the urgent development of molecular breeding approaches to improve wheat production sustainably.展开更多
In this study,digested soybean protein(dspr)and peptides(dspe)were found to have different effects on the adhesion ability of Limosilactobacillus reuteri DSM17938 and HT-29 cells.Results found that dspr and dspe could...In this study,digested soybean protein(dspr)and peptides(dspe)were found to have different effects on the adhesion ability of Limosilactobacillus reuteri DSM17938 and HT-29 cells.Results found that dspr and dspe could increase L.reuteri adhesion ability by affecting their auto-aggregation and hydrophobicity during their stationary phase.The moonlighting protein may play a dominant role affected by dspe in the adhesion process of L.reuteri from stationary phase.Moreover,dspr and dspe also enhanced the adhesion ability of HT-29cells to L.reuteri DSM17938,and they might play different role at different stages of adhesion.dspr mainly promoted the expression of adhesion-related genes before L.reuteri adhesion.dspe increased them after the adhesion of L.reuteri from log phase and dspr mainly enhanced their expression after stationary phase L.reuteri adhesion.Soybean protein and peptides may therefore be considered as a potential effective modulator of L.reuteri adhesion to intestinal tract.展开更多
This study investigated the protective effect of ferulic acid(FA) on the digestibility of oxidized beef myofibrillar protein(MP).MP were treated with varying concentrations of FA(20,40,and 80 μmol/g pro) and then exp...This study investigated the protective effect of ferulic acid(FA) on the digestibility of oxidized beef myofibrillar protein(MP).MP were treated with varying concentrations of FA(20,40,and 80 μmol/g pro) and then exposed to oxidation.The results showed that FA inhibited carbonyl in a dose-dependent manner.Fluorescence spectroscopy and molecular docking studies revealed FA was bonded to MP via hydrophobic interactions and hydrogen bonds.Sodium dodecyl sulfate polyacrylamide gel electrophoresis and transmission electron microscope analysis indicated that FA mitigated the aggregation of oxidized MP.Peptidomic analysis showed FA protected 34.24% peptides recover from oxidation loss,and theses recovered peptide were mainly distributed in hydrophobic regions and lysine sites.In vitro digestion showed FA remarkably improved digestibility of oxidized MP(P < 0.05),with 80 μmol/g pro FA mitigating 67.85% loss in digestibility.Overall,FA effectively preserved the release of peptides by inhibiting hydrophobic aggregation and oxidation of lysine residues,thereby alleviating the decrease in digestibility of oxidized MP.展开更多
BACKGROUND Tropomyosin 3(TPM3)has been implicated in the progression of several cancers;however,its specific role and underlying molecular mechanisms in gastric cancer(GC)remain unclear.The current research aimed to i...BACKGROUND Tropomyosin 3(TPM3)has been implicated in the progression of several cancers;however,its specific role and underlying molecular mechanisms in gastric cancer(GC)remain unclear.The current research aimed to investigate the role of TPM3 in the onset and advancement of GC,along with the related molecular pathways.AIM To investigate TPM3’s role in enhancing GC malignancy and elucidates the underlying molecular mechanisms.METHODS TPM3 expression in GC tissues was evaluated using bioinformatics analysis.Protein expression levels were determined using western blotting,and mRNA levels were measured through quantitative real-time PCR.Cellular functional assays,including cell counting kit-8 assay,5-ethynyl-2-deoxyuridine incorporation,colony formation,wound-healing,and transwell migration/invasion,were conducted to assess the effects of TPM3 and tyrosine 3-monooxygenaseryptophan 5-monooxygenase activation protein gamma(YWHAG)on GC cell proliferation,migration,invasion,and metastatic potential.Cell cycle progression and apoptosis were analyzed using flow cytometry.A subcutaneous xenograft model in nude mice was employed to assess the tumorigenic potential of GC cells,while a tail vein injection model was used to evaluate their invasive and metastatic potential in vivo.RESULTS TPM3 was significantly upregulated in GC tissues and cells,and its high expression correlated with poor patient prognosis.Silencing TPM3 markedly inhibited GC cell proliferation,invasion,and metastasis while promoting apoptosis.TPM3 interacted with YWHAG,and TPM3 knockdown reduced YWHAG expression.Notably,the inhibitory effects of TPM3 silencing on GC progression were partially reversed by overexpressing YWHAG,confirming YWHAG as a key downstream effector.Furthermore,TPM3 knockdown suppressed activation of the mitogen-activated protein kinase pathway in a YWHAG-dependent manner.In vivo experiments demonstrated that increased TPM3 expression significantly promoted GC tumor growth and metastasis,whereas silencing YWHAG effectively attenuated this effect.CONCLUSION TPM3 promotes GC progression by regulating YWHAG and activating the mitogen-activated protein kinase signaling pathway.These findings identify the TPM3/YWHAG axis as a potential therapeutic target for GC intervention.展开更多
Alzheimer’s disease(AD)and other tauopathies are characterized by the accumulation of misfolded tau protein,which forms toxic oligomers that contribute to synaptic dysfunction and neuronal loss.Here,we briefly discus...Alzheimer’s disease(AD)and other tauopathies are characterized by the accumulation of misfolded tau protein,which forms toxic oligomers that contribute to synaptic dysfunction and neuronal loss.Here,we briefly discuss recent findings indicating that the cellular prion protein(PrPC)plays a critical role in mediating the synaptotoxic effects of tau oligomers(TauOs),offering new insights into disease pathogenesis and potential therapeutic strategies.展开更多
Cholelithiasis represents a common clinical condition within the digestive tract and continues to pose a substantial global health challenge,largely due to its high rate of recurrence and a scarcity of effective non-s...Cholelithiasis represents a common clinical condition within the digestive tract and continues to pose a substantial global health challenge,largely due to its high rate of recurrence and a scarcity of effective non-surgical interventions.Although protein succinylation has been widely characterized as a post-translational modification,its implications in cholelithiasis pathogenesis had remained poorly defined.A groundbreaking study by Wang et al demonstrates that lysine acetyltransferase 2A-mediated succinylation of adenosine monophosphate-activated protein kinase suppresses cholelithiasis.This work not only provides novel mechanistic insights into cholelithiasis but also establishes succinylation as a promising therapeutic target,thereby addressing a critical knowledge gap in the field.展开更多
Post-translational modification(PTM)of proteins is a crucial regulatory mechanism in plant cells,enabling rapid and purposeful regulation of their functions.Modified proteins play various roles in signaling pathways,i...Post-translational modification(PTM)of proteins is a crucial regulatory mechanism in plant cells,enabling rapid and purposeful regulation of their functions.Modified proteins play various roles in signaling pathways,including plant growth and development,plant metabolism,and the response to adversity stress.In recent years,there has been an increase in the number of studies focusing on plant PTM maps and functional analysis.Here we aim to review the PTM types in plants,especially in horticultural plants and tropical crops,the interactions between and among PTMs,and more importantly,the underlying pathways and functions.Additionally,the potential application of PTMs in breeding is briefly discussed.This paper focuses on plant PTMs and provides a foundation for further investigation into the functions and regulatory mechanisms of PTMs in plant proteins as well as for crop improvement.展开更多
Background This study was conducted to investigate the impact of varying degrees of heat stress on milk protein synthesis in dairy cows using comprehensive analyses of metabolomics and proteomics.Eighteen dairy cows w...Background This study was conducted to investigate the impact of varying degrees of heat stress on milk protein synthesis in dairy cows using comprehensive analyses of metabolomics and proteomics.Eighteen dairy cows were subjected to no heat stress(No-HS),mild heat stress(Mild-HS),and moderate heat stress(Mod-HS).Blood and milk samples were collected to determine the content and composition of amino acids(AA),and milk samples were used for metabolomic and proteomic analyses.Results Milk protein yield was significantly lower under Mild-HS and Mod-HS than No-HS(P<0.001).During Mild-HS,no significant difference was found in total AA concentration in both arterial(P=0.545)and venous blood(P=0.057),but arterial AA supply to the mammary gland significantly increased(P=0.045)when compared with No-HS.Under Mod-HS,the supply(P<0.001)and uptake(P=0.001)of total AA in the mammary gland decreased significantly,affecting the availability of precursors necessary for milk protein synthesis.Milk metabolomic analysis revealed that Mod-HS significantly impacted nucleotide metabolism,energy metabolism,and protein synthesis processes including translation,folding,and transport.Milk proteomic analysis showed significant downregulation of ribosomal and heat shock proteins which are crucial for protein synthesis and folding.Conclusions These findings suggest that heat stress disrupts AA utilization and energy metabolism in the mammary gland,leading to the reduced efficiency in milk protein synthesis and lowered milk protein yield.This study offers valuable insights into the metabolic and proteomic changes in dairy cows under heat stress,highlighting potential strategies to mitigate the adverse effects of heat stress on dairy production and milk quality.展开更多
α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively dete...α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively determined.The expression of low-density lipoprotein receptor–related protein 1,which is abundantly expressed in neurons and considered to be a multifunctional endocytic receptor,is elevated in the neurons of patients with Parkinson's disease.However,whether there is a direct link between low-density lipoprotein receptor–related protein 1 andα-synuclein aggregation and propagation in Parkinson's disease remains unclear.Here,we established animal models of Parkinson's disease by inoculating monkeys and mice withα-synuclein pre-formed fibrils and observed elevated low-density lipoprotein receptor–related protein 1 levels in the striatum and substantia nigra,accompanied by dopaminergic neuron loss and increasedα-synuclein levels.However,low-density lipoprotein receptor–related protein 1 knockdown efficiently rescued dopaminergic neurodegeneration and inhibited the increase inα-synuclein levels in the nigrostriatal system.In HEK293A cells overexpressingα-synuclein fragments,low-density lipoprotein receptor–related protein 1 levels were upregulated only when the N-terminus ofα-synuclein was present,whereas anα-synuclein fragment lacking the N-terminus did not lead to low-density lipoprotein receptor–related protein 1 upregulation.Furthermore,the N-terminus ofα-synuclein was found to be rich in lysine residues,and blocking lysine residues in PC12 cells treated withα-synuclein pre-formed fibrils effectively reduced the elevated low-density lipoprotein receptor–related protein 1 andα-synuclein levels.These findings indicate that low-density lipoprotein receptor–related protein 1 regulates pathological transmission ofα-synuclein from the striatum to the substantia nigra in the nigrostriatal system via lysine residues in theα-synuclein N-terminus.展开更多
Oat milk has gained widespread consumer acceptance for its creamy texture,β-glucan content,and environmental sustainability.However,its relatively low protein content(typically 2-3 g/serving)presents a nutritional li...Oat milk has gained widespread consumer acceptance for its creamy texture,β-glucan content,and environmental sustainability.However,its relatively low protein content(typically 2-3 g/serving)presents a nutritional limitation,largely due to poor protein solubility.This study investigated how processing conditions influence protein content and functional stability in oat-based systems by applying two treatments:(1)α-amylase enzymatic hydrolysis,and(2)pH-shifting(from pH 7 to 12 and back)with mild heating(50℃for 10 or 30 min).Oat protein solutions were formulated from two sources:oat flour(OF)and oat protein isolate(OPI).Results suggests that α-amylase pretreatment effectively reduced starch-driven viscosity in OF,facilitating better sample handling and centrifugation.Following pH-shifting and heat treatment,both OF and OPI solutions showed significantly improved protein solubility,with protein content increased from 2.0 to~6.5 g/serving.These changes were accompanied by reduced precipitation,smaller particle sizes,and more negative zeta potential values,indicating enhanced colloidal stability.SDS-PAGE analysis revealed the presence of low-molecular-weight protein fractions,supporting increased solubilization.Fluorescence microscopy confirmed the formation of smaller,more uniformly dispersed particles in treated samples compared to controls.However,noticeable darkening or browning occurred under high-pH heating,indicating potential challenges in color control.The findings provide useful information for future industrial applications and product innovation in the plant-based beverage sector.展开更多
Since its discovery,porcine epidemic diarrhea virus(PEDV)has significantly affected the agricultural economy worldwide.The available commercialized coronavirus vaccines cannot adequately control emerging strains.There...Since its discovery,porcine epidemic diarrhea virus(PEDV)has significantly affected the agricultural economy worldwide.The available commercialized coronavirus vaccines cannot adequately control emerging strains.Therefore,investigating the correlation between viruses and antiviral host factors is necessary.In this study,we showed that zinc finger protein 219(ZNF219)was upregulated by viral nonstructural protein 12(nsp12)upon PEDV challenge.Moreover,ZNF219 inhibited the replication of PEDV through selective autophagic degradation of the PEDV S2 protein.ZNF219 recruited TRAF6,the ubiquitin E3 ligase,to ubiquitinate the PEDV S2 protein.After recognition,the ubiquitinated PEDV S2 protein was delivered to autolysosomes via the cargo receptor p62 for degradation by autophagy,thus inhibiting the proliferation of PEDV.To summarize,after sensing PEDV infection by recognizing the viral nsp12 protein,host cells upregulated the intracellular expression of ZNF219,which degraded the viral S2 protein by activating autophagy,thus suppressing viral replication.Our study revealed a novel antiviral mechanism involving ZNF219 and provided a novel target for preventing and treating PEDV.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
基金supported by a grant of the Korea Dementia Research Project through the Korea Dementia Research Center (RS-2022-KH126506 to JSL)the ABC-based Regenerative BioTherapeutics(ABC project) grant (RS-2024-00426031 to JSL)NRF Grant (2022R1A2C3013138 to HR,RS-2024-00449723 to JGL) funded by the Korea government (the Ministry of Health&Welfare,Ministry of Science and ICT,Ministry of Education)
摘要Proteostasis,also known as protein homeostasis,is a tightly regulated cellular quality control process that ensures the balance of protein synthesis,folding,posttranslational modifications,and degradation.Maintaining proteostasis is vital for cellular function,organismal health,and longevity.The disru ption of proteostasis can lead to a range of detrimental effects,including accelerated aging,compromised cellular function,and even cell death,manifesting in numerous human diseases(Hipp et al.,2019).
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
摘要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Postdoctoral Fellowship Program and China Postdoctoral Science Foundation,Grant/Award Numbers:BX20240212,2025M783122Fundamental Research Funds for the Central UniversitiesNational Natural Science Foundation of China,Grant/Award Numbers:NSFC T2225007,T2222012,32430063,62501364,T25B2009。
摘要Deep learning methods,particularly exemplified by AlphaFold2,have revolutionized the field of protein structure prediction-an achievement recognized by the 2024 Nobel Prize in Chemistry awarded to its core developers.Despite this remarkable achievement,the broader protein folding problem is far from solved.Key challenges—each representing opportunities for future breakthroughs—include single-sequence structure prediction,modeling protein dynamics,accurately predicting multimeric complexes,and effectively incorporating experimental constraints.Here we review recent progress in these key frontiers and share our perspective on future directions.
基金supported by the National Key Research and Development Program of China (Grant Nos.2022YFC2009600,2022YFC2009605 and 2021YFC2500200)National Natural Science Foundation of China (Grant No.82570914 and 82330020)+3 种基金President Foundation of Nanfang Hospital,Southern Medical University (Grant No.2024B029)Key Technologies R&D Program of Guangdong Province (Grant No.2023B1111030004)Guangdong Provincial Clinical Research Center for Kidney Disease (Grant No.2020B1111170013)the Program of Introducing Talents of Discipline to Universities,111 Plan (Grant No.D18005)
摘要Background Individuals with prediabetes or diabetes face elevated dementia risk,yet robust prediction tools and mechanistic insights remain limited.Aims This study aimed to develop and validate a proteinbased risk score for dementia prediction in this high-risk population while elucidating underlying biological pathways and therapeutic targets.Methods Utilising data from 10 433 UK Biobank participants with prediabetes or diabetes and proteomic profiling(2911 plasma proteins measured),we developed a dementia protein risk score in a training set(n=6514)and validated it in testing(n=2790) and external cohorts(n=1129).Results In the training set,23 out of 2911 proteins were selected.In the testing set,compared with the basic model(age and sex,C-index:0.78;95% confidence interval [CI]0.74-0.82),the dementia protein risk score(C-index:0.84;95% CI 0.81-0.88) significantly improved the performance in predicting incident dementia(C-index increase:0.06;95% CI 0.02-0.12),while cardiovascular risk factors,ageing and dementia incidence risk factors(C-index:0.80;95% Cl0.76-0.83) and apolipoprotein E(APOE;age and sex included,C-index:0.81;95% CI 0.77-0.85) had no significant improvement.Six key proteins(glial fibrillary acidic protein [GFAP],neurofilament light polypeptide[NEFL],Brevican core protein [BCAN],protein MENT[MENT],APOE and growth/differentiation factor 15[GDF15]) captured the most predictive power.Pathway analyses implicated extracellular matrix remodelling and cholesterol metabolism,whereas Mendelian randomisation identified causal roles for APOE,haematopoietic prostaglandin D synthase(HPGDS),BAG family molecular chaperone regulator 3(BAG3) and GDF15.Nine proteins were prioritised as druggable targets,including HPGDS,with existing Food and Drug Administration-approved drugs.Conclusions This study establishes a highly accurate protein-based risk score for dementia prediction(including 6-23 proteins) in individuals with prediabetes or diabetes,uncovering actionable biological pathways and therapeutic targets.The findings enable precision risk stratification and accelerate translational opportunities for dementia prevention in this population.
基金supported by the National Natural Science Foundation of China,Nos.82371310(to YJ),82271306(to JP)the Sichuan Science and Technology Support Program,Nos.2023YFH0069(to JP),2023NSFSC0028(to YJ),2023NSFSC1559(to YJ),2022YFS0615(to JP),2022NSFSC1421(to JP)+1 种基金Scientific Research Project of Sichuan Provincial Health Commission,No.23LCYJ040(to YJ)Youth Foundation of Southwestern Medical University and Southwest Medical University Project,Nos.2020ZRQNA038(to JP),2021ZKZD013(to JP),2021LZXNYD-P01(to YJ),2023QN014(to JP).
摘要Neuronal cell death is a common outcome of multiple pathophysiological processes and a key factor in neurological dysfunction after subarachnoid hemorrhage.Neuronal ferroptosis in particular plays an important role in early brain injury.Bromodomain-containing protein 4,a member of the bromo and extraterminal domain family of proteins,participated in multiple cell death pathways,but the mechanisms by which it regulates ferroptosis remain unclear.The primary aim of this study was to investigate how bromodomain-containing protein 4 affects neuronal ferroptosis following subarachnoid hemorrhage in vivo and in vitro.Our findings revealed that endogenous bromodomain-containing protein 4 co-localized with neurons,and its expression was decreased 48 hours after subarachnoid hemorrhage of the cerebral cortex in vivo.In addition,ferroptosis-related pathways were activated in vivo and in vitro after subarachnoid hemorrhage.Targeted inhibition of bromodomain-containing protein 4 in neurons increased lipid peroxidation and intracellular ferrous iron accumulation via ferritinophagy and ultimately led to neuronal ferroptosis.Using cleavage under targets and tagmentation analysis,we found that bromodomain-containing protein 4 enrichment in the Raf-1 promoter region decreased following oxyhemoglobin stimulation in vitro.Furthermore,treating bromodomain-containing protein 4-knockdown HT-22 cell lines with GW5074,a Raf-1 inhibitor,exacerbated neuronal ferroptosis by suppressing the Raf-1/ERK1/2 signaling pathway.Moreover,targeted inhibition of neuronal bromodomain-containing protein 4 exacerbated early and long-term neurological function deficits after subarachnoid hemorrhage.Our findings suggest that bromodomain-containing protein 4 may have neuroprotective effects after subarachnoid hemorrhage,and that inhibiting ferroptosis could help treat subarachnoid hemorrhage.
摘要BACKGROUND Patients with hepatocellular carcinoma(HCC)beyond the Milan criteria or with portal vein tumor thrombosis are often excluded from the transplant list owing to aggressive biology and recurrence risk.While high alpha-fetoprotein(AFP)signals aggressiveness,the behavior of normal AFP HCC with elevated protein induced by vitamin K absence/antagonist-Ⅱ(PIVKA-Ⅱ)is less defined.AIM To assess the prognostic value of PIVKA-Ⅱin normal AFP HCC.METHODS Retrospective cohort of 113 patients with normal AFP and normal or elevated PIVKA-Ⅱ.“Aggressive”tumors were defined as beyond Milan and/or portal vein tumor thrombosis(n=63);others were non-aggressive(n=50).Receiver operating characteristic curve analysis identified PIVKA-Ⅱcut-offs.RESULTS This study included 78 men and 35 women;mean age 58.4±11.1 years;62.8%with decompensated cirrhosis.PIVKA-Ⅱwas higher in aggressive tumors:Median 2785 mAU/mL(interquartile range:222-8152)vs 239 mAU/mL(interquartile range:55-727),P400 mAU/mL was strongly associated with aggressive tumor phenotype(adjusted odds ratio=5.16,P=0.001).All the 29 patients with≥4000 mAU/mL were in the aggressive group(PPV:1.0).All thresholds were dataset-derived.CONCLUSION In normal AFP HCC,PIVKA-Ⅱdiscriminates aggressive biology.A cut-off of 1609.5 mAU/mL balances sensitivity and specificity;400 mAU/mL favors sensitivity;≥4000 mAU/mL delineates an ultra-high-risk subgroup.Findings support the incorporation of PIVKA-Ⅱinto risk stratification.
基金supported by the CJD Foundation,USA,the Alzheimer Forschung Initiative(AFI)e.V.,Germany,and Werner-Otto-Stiftung,Germany(all to HCA),ChinaScholarship Council(grant#202108080249 to FS)Deutsche Forschungsgemeinschaft(DFG)CRC877“Proteolysis as a regulatory event in pathophysiology”(project A12 to MG),Slovene Research and InnovationAgency(grant number P4-0176 to VCS).
摘要Novel insights into complex biological processes very often critically depend on the establishment of new potent read-out tools and improved protocols.A lot has been learned over the past four decades on physiological functions and,importantly,disease-related roles of the prion protein(PrP),a relatively broadly expressed membrane-anchored glycoprotein with high levels in several cell types of the nervous and immune system and with well-established key roles in different progressive and fatal neurodegenerative protein misfolding diseases(proteopathies).
基金supported by NIH grant,No.R01AG073121 (to GVWJ)。
摘要Following translation,newly synthesized proteins must navigate a turbulent free energy landscape that threatens to trap them in misfolded or nonfunctional conformation.To reach their native states,many proteins are assisted by molecular chaperones that transiently facilitate folding and assembly without being part of the final structure.One such molecular scaffold is the heat shock protein 70(HSP70) chaperone family,which acts in concert with Bcl-2-associated athanogene(BAG) co-chaperones to regulate a wide array of clients(Figure 1).
基金supported by the Key R&D Program of Shandong Province,China(2023LZGC022)the Shandong Provincial Natural Science Foundation,China(ZR2023QC103)the National Natural Science Foundation of China(U23A20181)。
摘要Highlights·A TaPRR95-A haplotype reduces flowering time and increases grain yield in wheat.·Protein-protein interaction between TaPRR95-A and TaCOL16-D modulates the TaFT1-mediated flowering pathway.·A validated functional marker enables rapid identification of the target haplotype and provides a practical tool for markerassisted selection in wheat breeding.As a staple cereal crop cultivated worldwide,common wheat(Triticum aestivum L.)accounts for approximately 35%of global dietary energy requirements(Sharma and Sharma 2025).However,agricultural yields are currently under significant pressure due to the combined impacts of anthropogenic climate change and geopolitical conflicts(Ortiz-Bobea et al.2021;Hultgren et al.2025),which threatens global food security.These challenges necessitate the urgent development of molecular breeding approaches to improve wheat production sustainably.
基金supported by the National Key Research and Development Program of China(2021YFD2100402)the fund of Cultivation Project of Double First-Class Disciplines of Food Science and Engineering,Beijing Technology&Business University(BTBUYXTD202207).
摘要In this study,digested soybean protein(dspr)and peptides(dspe)were found to have different effects on the adhesion ability of Limosilactobacillus reuteri DSM17938 and HT-29 cells.Results found that dspr and dspe could increase L.reuteri adhesion ability by affecting their auto-aggregation and hydrophobicity during their stationary phase.The moonlighting protein may play a dominant role affected by dspe in the adhesion process of L.reuteri from stationary phase.Moreover,dspr and dspe also enhanced the adhesion ability of HT-29cells to L.reuteri DSM17938,and they might play different role at different stages of adhesion.dspr mainly promoted the expression of adhesion-related genes before L.reuteri adhesion.dspe increased them after the adhesion of L.reuteri from log phase and dspr mainly enhanced their expression after stationary phase L.reuteri adhesion.Soybean protein and peptides may therefore be considered as a potential effective modulator of L.reuteri adhesion to intestinal tract.
基金supported by the earmarked fund for China Agriculture Research System of MOF and MARA(CARS-35)Doctoral Research Initiation Fee Grant Program,Guangdong Ocean University(060302042315)。
摘要This study investigated the protective effect of ferulic acid(FA) on the digestibility of oxidized beef myofibrillar protein(MP).MP were treated with varying concentrations of FA(20,40,and 80 μmol/g pro) and then exposed to oxidation.The results showed that FA inhibited carbonyl in a dose-dependent manner.Fluorescence spectroscopy and molecular docking studies revealed FA was bonded to MP via hydrophobic interactions and hydrogen bonds.Sodium dodecyl sulfate polyacrylamide gel electrophoresis and transmission electron microscope analysis indicated that FA mitigated the aggregation of oxidized MP.Peptidomic analysis showed FA protected 34.24% peptides recover from oxidation loss,and theses recovered peptide were mainly distributed in hydrophobic regions and lysine sites.In vitro digestion showed FA remarkably improved digestibility of oxidized MP(P < 0.05),with 80 μmol/g pro FA mitigating 67.85% loss in digestibility.Overall,FA effectively preserved the release of peptides by inhibiting hydrophobic aggregation and oxidation of lysine residues,thereby alleviating the decrease in digestibility of oxidized MP.
基金Supported by National Natural Science Foundation of China,No.82573536 and No.82360591Science and Technology Plan of Jiangxi Provincial Health and Wellness Committee,No.202510043.
摘要BACKGROUND Tropomyosin 3(TPM3)has been implicated in the progression of several cancers;however,its specific role and underlying molecular mechanisms in gastric cancer(GC)remain unclear.The current research aimed to investigate the role of TPM3 in the onset and advancement of GC,along with the related molecular pathways.AIM To investigate TPM3’s role in enhancing GC malignancy and elucidates the underlying molecular mechanisms.METHODS TPM3 expression in GC tissues was evaluated using bioinformatics analysis.Protein expression levels were determined using western blotting,and mRNA levels were measured through quantitative real-time PCR.Cellular functional assays,including cell counting kit-8 assay,5-ethynyl-2-deoxyuridine incorporation,colony formation,wound-healing,and transwell migration/invasion,were conducted to assess the effects of TPM3 and tyrosine 3-monooxygenaseryptophan 5-monooxygenase activation protein gamma(YWHAG)on GC cell proliferation,migration,invasion,and metastatic potential.Cell cycle progression and apoptosis were analyzed using flow cytometry.A subcutaneous xenograft model in nude mice was employed to assess the tumorigenic potential of GC cells,while a tail vein injection model was used to evaluate their invasive and metastatic potential in vivo.RESULTS TPM3 was significantly upregulated in GC tissues and cells,and its high expression correlated with poor patient prognosis.Silencing TPM3 markedly inhibited GC cell proliferation,invasion,and metastasis while promoting apoptosis.TPM3 interacted with YWHAG,and TPM3 knockdown reduced YWHAG expression.Notably,the inhibitory effects of TPM3 silencing on GC progression were partially reversed by overexpressing YWHAG,confirming YWHAG as a key downstream effector.Furthermore,TPM3 knockdown suppressed activation of the mitogen-activated protein kinase pathway in a YWHAG-dependent manner.In vivo experiments demonstrated that increased TPM3 expression significantly promoted GC tumor growth and metastasis,whereas silencing YWHAG effectively attenuated this effect.CONCLUSION TPM3 promotes GC progression by regulating YWHAG and activating the mitogen-activated protein kinase signaling pathway.These findings identify the TPM3/YWHAG axis as a potential therapeutic target for GC intervention.
基金supported by the Italian Ministry of Health grant RF-2021-12372337(to GF and CB).
摘要Alzheimer’s disease(AD)and other tauopathies are characterized by the accumulation of misfolded tau protein,which forms toxic oligomers that contribute to synaptic dysfunction and neuronal loss.Here,we briefly discuss recent findings indicating that the cellular prion protein(PrPC)plays a critical role in mediating the synaptotoxic effects of tau oligomers(TauOs),offering new insights into disease pathogenesis and potential therapeutic strategies.
摘要Cholelithiasis represents a common clinical condition within the digestive tract and continues to pose a substantial global health challenge,largely due to its high rate of recurrence and a scarcity of effective non-surgical interventions.Although protein succinylation has been widely characterized as a post-translational modification,its implications in cholelithiasis pathogenesis had remained poorly defined.A groundbreaking study by Wang et al demonstrates that lysine acetyltransferase 2A-mediated succinylation of adenosine monophosphate-activated protein kinase suppresses cholelithiasis.This work not only provides novel mechanistic insights into cholelithiasis but also establishes succinylation as a promising therapeutic target,thereby addressing a critical knowledge gap in the field.
基金supported by the National Natural Science Foundation of China(Grant Nos.32301873 and 32460497)Chinese Academy of Tropical Agricultural Sciences for Science and Technology Innovation Team of National Tropical Agricultural Science Center(Grant No.CATASCXTD202402)+4 种基金Project of National Key Laboratory for Tropical Crop Breeding(Grant Nos.NKLTCBCXTD24,NKLTCB-HZ04 and NKLTCB-RC202401)Special Projects for the Central-guided Local Science and Technology Development(Grant No.2022L3086)Central Public-interest Scientific Institution Basal Research Fund(Grant Nos.1630052024003 and 1630052024020)China Agriculture Research System of MOF and MARA(Grant No.CARS-17)Special Fund for Science and Technology Innovation of Fujian Agriculture and Forestry University(Grant No.KFB23183A)。
摘要Post-translational modification(PTM)of proteins is a crucial regulatory mechanism in plant cells,enabling rapid and purposeful regulation of their functions.Modified proteins play various roles in signaling pathways,including plant growth and development,plant metabolism,and the response to adversity stress.In recent years,there has been an increase in the number of studies focusing on plant PTM maps and functional analysis.Here we aim to review the PTM types in plants,especially in horticultural plants and tropical crops,the interactions between and among PTMs,and more importantly,the underlying pathways and functions.Additionally,the potential application of PTMs in breeding is briefly discussed.This paper focuses on plant PTMs and provides a foundation for further investigation into the functions and regulatory mechanisms of PTMs in plant proteins as well as for crop improvement.
基金funded by grants from the National Nature Science Foundation(Grant number:U23A20231)。
摘要Background This study was conducted to investigate the impact of varying degrees of heat stress on milk protein synthesis in dairy cows using comprehensive analyses of metabolomics and proteomics.Eighteen dairy cows were subjected to no heat stress(No-HS),mild heat stress(Mild-HS),and moderate heat stress(Mod-HS).Blood and milk samples were collected to determine the content and composition of amino acids(AA),and milk samples were used for metabolomic and proteomic analyses.Results Milk protein yield was significantly lower under Mild-HS and Mod-HS than No-HS(P<0.001).During Mild-HS,no significant difference was found in total AA concentration in both arterial(P=0.545)and venous blood(P=0.057),but arterial AA supply to the mammary gland significantly increased(P=0.045)when compared with No-HS.Under Mod-HS,the supply(P<0.001)and uptake(P=0.001)of total AA in the mammary gland decreased significantly,affecting the availability of precursors necessary for milk protein synthesis.Milk metabolomic analysis revealed that Mod-HS significantly impacted nucleotide metabolism,energy metabolism,and protein synthesis processes including translation,folding,and transport.Milk proteomic analysis showed significant downregulation of ribosomal and heat shock proteins which are crucial for protein synthesis and folding.Conclusions These findings suggest that heat stress disrupts AA utilization and energy metabolism in the mammary gland,leading to the reduced efficiency in milk protein synthesis and lowered milk protein yield.This study offers valuable insights into the metabolic and proteomic changes in dairy cows under heat stress,highlighting potential strategies to mitigate the adverse effects of heat stress on dairy production and milk quality.
基金supported by the Natural Science Foundation of Guangxi Zhuang Automomous Region,Nos.2019GXNSFDA245015(to MC),2022GXNSFBA035654(to HL)the National Natural Science Foundation of China,Nos.82360241(to MC),82304876(to HL)+1 种基金Scientific Research and Technology Development Project of Guilin City,Nos.20220139-3(to MC),20210218-5(to HL)Guangxi Medical and Health Key Discipline Construction Project(to QL)。
摘要α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively determined.The expression of low-density lipoprotein receptor–related protein 1,which is abundantly expressed in neurons and considered to be a multifunctional endocytic receptor,is elevated in the neurons of patients with Parkinson's disease.However,whether there is a direct link between low-density lipoprotein receptor–related protein 1 andα-synuclein aggregation and propagation in Parkinson's disease remains unclear.Here,we established animal models of Parkinson's disease by inoculating monkeys and mice withα-synuclein pre-formed fibrils and observed elevated low-density lipoprotein receptor–related protein 1 levels in the striatum and substantia nigra,accompanied by dopaminergic neuron loss and increasedα-synuclein levels.However,low-density lipoprotein receptor–related protein 1 knockdown efficiently rescued dopaminergic neurodegeneration and inhibited the increase inα-synuclein levels in the nigrostriatal system.In HEK293A cells overexpressingα-synuclein fragments,low-density lipoprotein receptor–related protein 1 levels were upregulated only when the N-terminus ofα-synuclein was present,whereas anα-synuclein fragment lacking the N-terminus did not lead to low-density lipoprotein receptor–related protein 1 upregulation.Furthermore,the N-terminus ofα-synuclein was found to be rich in lysine residues,and blocking lysine residues in PC12 cells treated withα-synuclein pre-formed fibrils effectively reduced the elevated low-density lipoprotein receptor–related protein 1 andα-synuclein levels.These findings indicate that low-density lipoprotein receptor–related protein 1 regulates pathological transmission ofα-synuclein from the striatum to the substantia nigra in the nigrostriatal system via lysine residues in theα-synuclein N-terminus.
基金supported by the USDA National Institute of Food and Agriculture,Hatch project 7009323.
摘要Oat milk has gained widespread consumer acceptance for its creamy texture,β-glucan content,and environmental sustainability.However,its relatively low protein content(typically 2-3 g/serving)presents a nutritional limitation,largely due to poor protein solubility.This study investigated how processing conditions influence protein content and functional stability in oat-based systems by applying two treatments:(1)α-amylase enzymatic hydrolysis,and(2)pH-shifting(from pH 7 to 12 and back)with mild heating(50℃for 10 or 30 min).Oat protein solutions were formulated from two sources:oat flour(OF)and oat protein isolate(OPI).Results suggests that α-amylase pretreatment effectively reduced starch-driven viscosity in OF,facilitating better sample handling and centrifugation.Following pH-shifting and heat treatment,both OF and OPI solutions showed significantly improved protein solubility,with protein content increased from 2.0 to~6.5 g/serving.These changes were accompanied by reduced precipitation,smaller particle sizes,and more negative zeta potential values,indicating enhanced colloidal stability.SDS-PAGE analysis revealed the presence of low-molecular-weight protein fractions,supporting increased solubilization.Fluorescence microscopy confirmed the formation of smaller,more uniformly dispersed particles in treated samples compared to controls.However,noticeable darkening or browning occurred under high-pH heating,indicating potential challenges in color control.The findings provide useful information for future industrial applications and product innovation in the plant-based beverage sector.
基金supported by the National Key Research and Development Programs of China(No.2023YFD1801300)the National Natural Science Foundation of China(No.32272999 and 32102665)the Natural Science Foundation of Shanghai(No.23ZR1476900).
摘要Since its discovery,porcine epidemic diarrhea virus(PEDV)has significantly affected the agricultural economy worldwide.The available commercialized coronavirus vaccines cannot adequately control emerging strains.Therefore,investigating the correlation between viruses and antiviral host factors is necessary.In this study,we showed that zinc finger protein 219(ZNF219)was upregulated by viral nonstructural protein 12(nsp12)upon PEDV challenge.Moreover,ZNF219 inhibited the replication of PEDV through selective autophagic degradation of the PEDV S2 protein.ZNF219 recruited TRAF6,the ubiquitin E3 ligase,to ubiquitinate the PEDV S2 protein.After recognition,the ubiquitinated PEDV S2 protein was delivered to autolysosomes via the cargo receptor p62 for degradation by autophagy,thus inhibiting the proliferation of PEDV.To summarize,after sensing PEDV infection by recognizing the viral nsp12 protein,host cells upregulated the intracellular expression of ZNF219,which degraded the viral S2 protein by activating autophagy,thus suppressing viral replication.Our study revealed a novel antiviral mechanism involving ZNF219 and provided a novel target for preventing and treating PEDV.
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).
摘要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.