Large-scale proteomics studies can refine our understanding of health and disease and enable precision medicine.Here,we provide a detailed atlas of 2,920 plasma proteins linking to diseases(406 prevalent and 660 incid...Large-scale proteomics studies can refine our understanding of health and disease and enable precision medicine.Here,we provide a detailed atlas of 2,920 plasma proteins linking to diseases(406 prevalent and 660 incident)and 986 health-related traits in 53,026 individuals(median follow-up:14.8 years)from the UK Biobank,representing the most comprehensive proteome profiles to date.This atlas revealed 168,100 protein-disease associations and 554,488 protein-trait associations.展开更多
Large-scale proteomics studies can refine our understanding of health and disease and enable precision medicine.Here,we provide a detailed atlas of 2,920 plasma proteins linking to diseases(406 prevalent and 660 incid...Large-scale proteomics studies can refine our understanding of health and disease and enable precision medicine.Here,we provide a detailed atlas of 2,920 plasma proteins linking to diseases(406 prevalent and 660 incident)and 986 health-related traits in 53,026 individuals(median follow-up:14.8 years)from the UK Biobank,representing the most comprehensive proteome profiles to date.This atlas revealed 168,100 protein-disease associations and 554,488 protein-trait associations.Over 650 proteins were shared among at least 50 diseases,and over 1,000 showed sex and age heterogeneity.Furthermore,proteins demonstrated promising potential in disease discrimination(area under the curve[AUC]>0.80 in 183 diseases).Finally,integrating protein quantitative trait locus data determined 474 causal proteins,providing 37 drug-repurposing opportunities and 26 promising targets with favorable safety profiles.These results provide an open-access comprehensive proteome-phenome resource(https://proteome-phenome-atlas.com/)to help elucidate the biological mechanisms of diseases and accelerate the development of disease biomarkers,prediction models,and therapeutic targets.展开更多
Cryptocaryon irritans is the parasite responsible for“white spot disease”in the yellowfin seabream Acanthopagrus latus,which has caused significant losses to the aquaculture industry.This experiment investigated the...Cryptocaryon irritans is the parasite responsible for“white spot disease”in the yellowfin seabream Acanthopagrus latus,which has caused significant losses to the aquaculture industry.This experiment investigated the changes in the morphology,transcriptome,and proteome of gill tissue in yellowfin seabream infected with C.irritans,aiming to provide foundational data for further understanding the pathogenic mechanisms and control measures against this parasite.The main findings were as follows,after C.irritans infection,the structure of gill tissue in yellowfin seabream was damaged,with microvessels ruptured,some cells proliferating,and large amounts of mucus infiltrating.Transcriptome analysis revealed a total of 4299 differentially expressed genes,with 2367 up-regulated and 1932down-regulated.Further bioinformatics analysis of all differentially expressed genes identified nine immune-related genes,cox-2,mcama,tbx21,dcn,tnfb,cd74a,illb,ppib,and cd4-1 in A.latus.The reliability of the transcriptome data was validated by real time q PCR,which showed the same trend as the RNA-seq results.Proteome analysis found365 differential proteins,with 180 proteins up-regulated and 185 proteins down-regulated.Bioinformatics analysis identified three immune-related proteins,Myll,Gapdh,and Actn3b.These findings indicated that C.irritans disrupted the structure of gill tissue,impeded gas exchange and led to asphyxiation and death in affected fish.Transcriptome and proteome analyses showed that the expression of immune-related genes and proteins in yellowfin seabream,involved not only inflammatory responses and the activation and migration of immune cells but also potentially participated in tissue repair and defense regulation.These findings highlighted the complex immune regulatory network in response to C.irritans infection,offering references for prevention and control of white spot disease in yellowfin seabream.展开更多
Soil cadmium pollution has increasingly become a serious problem for crop production,which drastically attenuates plant growth and food safety.Although N6-methyladenosine(m^(6)A)methylation is crucial for plant respon...Soil cadmium pollution has increasingly become a serious problem for crop production,which drastically attenuates plant growth and food safety.Although N6-methyladenosine(m^(6)A)methylation is crucial for plant response to various stresses,the regulatory mechanism underlying m^(6)A modification during cadmium(Cd)stress remains unclear.This study investigated the physiological responses,transcriptome-wide m^(6)A methylome,and proteome changes in tomato roots exposed to 50 μmol·L^(-1)CdCl2.Excess Cd restricted plant growth,altered the antioxidant system and disrupted mineral nutrient absorption.We identified a negative correlation between m^(6)A levels and gene transcription for that 150 out of 198 differentially expressed genes(DEGs)were hypomethylated but mRNA up-regulated.Cd stress also enhanced translational efficiency,particularly for differentially abundant proteins(DAPs).Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed that differentially m^(6)A modified genes(DMGs),DEGs,and DAPs were commonly enriched in phenylpropanoid biosynthesis,glutathione metabolism,and ABC transporters,reflecting cell wall barriers,chelation,and transport of Cd,respectively.Finally,we confirmed the Cd-transport activity of eight putative metal transporters identified in DMGs,DEGs,or DAPs by yeast complementaion experiments,and pharmacologically investigated the effect of m^(6)A modification on their expression.Treatment with the m^(6)A methylation inhibitor 3-deazaneplanocin A(3-DA)reduced SlIRT1/2 expression and increased SlNRAMP3/SlZIP4 expression,while the m^(6)A demethylase inhibitor meclofenamic acid(MA)treatment decreased SlNRAMP3 expression but elevated SlIRT2 expression under Cd stress.Our findings provide novel insights into the interplay between m^(6)A modification,transcription,and translation under Cd stress and the associated plant stress response.展开更多
Background The objective was to characterize the colostrum proteome of primiparous Holstein cows in association with immunoglobulin G(IgG)content.Immediately after calving,colostrum samples were collected from 18 cows...Background The objective was to characterize the colostrum proteome of primiparous Holstein cows in association with immunoglobulin G(IgG)content.Immediately after calving,colostrum samples were collected from 18 cows to measure IgG concentration.Based on colostrum IgG content,samples were classified through cluster analysis and were identified as poor,average,and excellent quality.The proteome was assessed with quantitative shotgun proteomics;abundance data were compared among the colostrum types;enrichment analysis of metabolic processes and proteins classes was performed as well.We also tested correlations between this proteome and blood globulin level of cows and passive immunity level of calves.Results On average,428 proteins were identified per sample,which belonged mainly to cellular process,biological regulation,response to stimulus,metabolic process,and immune system process.Most abundant proteins were complement C3(Q2UVX4),alpha-S1-casein(P02662),Ig-like domain-containing protein(A0A3Q1M032),albumin(A0A140T897),polymeric immunoglobulin receptor(P81265),lactotransferrrin(P24627),and IGHG1*01(X167014).Colostrum of excellent quality had greater(P<0.05)abundance of serpin A3-7(A2I7N3),complement factorl(A0A3Q1 MIF4),lipocalin/cytosolic fatty-acid binding domain-containing protein(A0A3Q1 MRQ2),complement C3(E1B805),complement component 4 binding protein alpha(A0AAF6ZHP5),and complement component C6(F1MM86).However,colostrum of excellent quality had lower(P<0.05)abundance of HGF activator(E1BCW0),alpha-S1-casein(P02662),and xanthine dehydrogenase/oxidase(P80457).This resulted in enrichment of the biological processes predominantly for complement activation alternative pathway,complement activation,complement activation classical pathway,humoral immune response,leukocyte mediated immunity,and negative regulation of endopeptidase activity in excellent-quality colostrum.Additionally,some colostrum proteins were found to be correlated with the blood globulin level of cows and with the passive immunity level of calves(P<0.05;r≥0.57).Conclusions This study provides new insights into the bovine colostrum proteome,demonstrating associations between IgG levels and the abundance of other proteins,as well as the enrichment of metabolic processes related to innate immune response.Thus,results suggest that the colostrum proteomic profile is associated with the content of IgG.Future research should deeply explore the association of these findings with pre-calving nutrition status and blood composition of the cow,and with passive immunity transfer to the calf.展开更多
[Objective] The research aimed to establish the two-dimensional electrophoresis(2-DE)technology which was suitable for the rapeseed proteome research.[Method] Xiangyou 17 was as the material.The sample preparation m...[Objective] The research aimed to establish the two-dimensional electrophoresis(2-DE)technology which was suitable for the rapeseed proteome research.[Method] Xiangyou 17 was as the material.The sample preparation method,gel concentration and loading amount,etc.in 2-DE technology were optimized.[Result] The best extraction method of total protein of rapeseed was TCA-acetone method,and the protein spots on 2-DE map were the most.When IPG strip(pH 3-10)and 12% gel were used,and the loading amount was 250 μg,the two-dimensional electrophoresis map with the clear background,good repeatability and high protein spot resolution was obtained.[Conclusion] The research laid the foundation for carrying out the rapeseed proteomics research.展开更多
Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.Methods:Thirty-five male m...Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.Methods:Thirty-five male macaques aged 10-15 years underwent an 18-month HFD intervention.Physiological parameters(BMI,BP,hematology),liver fat fraction(evaluated by ultrasound/MRI),cardiac function(assessed by echocardiography),and histopathology(using liver biopsy)were measured before and after the intervention.Serum proteomics with KEGG/STRING analyses identified molecular mechanisms.Results:Within 6 months,HFD induced dyslipidemia(elevated TG,TCHO,HDL-C,LDL-C).After 18 months,metabolic dysfunction-associated steatohepatitis(MASH)was confirmed by histopathology in 57.14%(16/28)of macaques,diabetes(elevated FPG/HbA1c)in 17.86%(5/28),and myocardial hypertrophy(elevated LVMass/LAD)in 46.43%(13/28).Proteomics identified Bile acid-CoA:amino acid N-acyltransferase(BAAT)as a MASH hallmark protein,the level of which was inversely correlated with the degree of fibrosis.For diabetes,citrate synthase(CS)and malate dehydrogenase 1(MDH1)impaired glucose oxidation via the TCA cycle,while hexose-6-phosphate de-hydrogenase(H6PD)disrupted gluconeogenesis.Myocardial hypertrophy was associ-ated with the downregulation of SRC proto-oncogene,non-receptor tyrosine kinase(SRC),mitogen-activated protein kinase 14(MAPK14),emerin(EMD),and integrin subunit beta 1(ITGB1).Conclusions:An 18-month HFD successfully established a translational M.fascicula-ris model replicating key metabolic disorders(MASH,diabetes,cardiac hypertrophy).BAAT,CS/MDH1/H6PD,and SRC/MAPK14/EMD/ITGB1 were identified as mecha-nistic biomarkers for these conditions.展开更多
Advances in skeletal muscle omics has expanded our understanding of exercise-induced adaptations at the molecular level.Over the past 2 decades,transcriptome studies in muscle have detailed acute and chronic responses...Advances in skeletal muscle omics has expanded our understanding of exercise-induced adaptations at the molecular level.Over the past 2 decades,transcriptome studies in muscle have detailed acute and chronic responses to resistance,endurance,and concurrent exercise,focusing on variables such as training status,nutrition,age,sex,and metabolic health profile.Multi-omics approaches,such as the integration of transcriptomic and epigenetic data,along with emerging ribosomal RNA sequencing advancements,have further provided insights into how skeletal muscle adapts to exercise across the lifespan.Downstream of the transcriptome,proteomic and phosphoproteomic studies have identified novel regulators of exercise adaptations,while single-cell/nucleus and spatial sequencing technologies promise to evolve our understanding of cellular specialization and communication in and around skeletal muscle cells.This narrative review highlights(a)the historical foundations of exercise omics in skeletal muscle,(b)current research at 3 layers of the omics cascade(DNA,RNA,and protein),and(c)applications of single-cell omics and spatial sequencing technologies to study skeletal muscle adaptation to exercise.Further elaboration of muscle's global molecular footprint using multi-omics methods will help researchers and practitioners develop more effective and targeted approaches to improve skeletal muscle health as well as athletic performance.展开更多
Cognitive impairment is a particularly severe non-motor symptom of Parkinson's disease that significantly diminishes the quality of life of affected individuals.Identifying reliable biomarkers for cognitive impair...Cognitive impairment is a particularly severe non-motor symptom of Parkinson's disease that significantly diminishes the quality of life of affected individuals.Identifying reliable biomarkers for cognitive impairment in Parkinson's disease is essential for early diagnosis,prognostic assessments,and the development of targeted therapies.This review aims to summarize recent advancements in biofluid biomarkers for cognitive impairment in Parkinson's disease,focusing on the detection of specific proteins,metabolites,and other biomarkers in blood,cerebrospinal fluid,and saliva.These biomarkers can shed light on the multifaceted etiology of cognitive impairment in Parkinson's disease,which includes protein misfolding,neurodegeneration,inflammation,and oxidative stress.The integration of biofluid biomarkers with neuroimaging and clinical data can facilitate the development of predictive models to enhance early diagnosis and monitor the progression of cognitive impairment in patients with Parkinson's disease.This comprehensive approach can improve the existing understanding of the mechanisms driving cognitive decline and support the development of targeted therapeutic strategies aimed at modifying the course of cognitive impairment in Parkinson's disease.Despite the promise of these biomarkers in characterizing the mechanisms underlying cognitive decline in Parkinson's disease,further research is necessary to validate their clinical utility and establish a standardized framework for early detection and monitoring of cognitive impairment in Parkinson's disease.展开更多
AIM:To identify early biomarkers associated with glaucomatous visual field(VF)progression in patients with normal-tension glaucoma(NTG).METHODS:This study included patients were divided into two groups based on diseas...AIM:To identify early biomarkers associated with glaucomatous visual field(VF)progression in patients with normal-tension glaucoma(NTG).METHODS:This study included patients were divided into two groups based on disease progression status.Tear samples were collected for proteomic analysis.Dataindependent acquisition(DIA)mass spectrometry combined with bioinformatic analyses was performed to identify and validate potential protein biomarkers for NTG progression.Additionally,differentially expressed proteins(DEPs)were evaluated using mediating effect models and receiver operating characteristic(ROC)curve analysis.RESULTS:A total of 19 patients(20 eyes)with NTG participated in this study,including 10 patients(4 males and 6 females;10 eyes)in the progression group with mean age of 67.70±9.03y and 10 patients(4 males and 6 females;10 eyes)in the non-progression group with mean age of 68.60±7.58y.A total of 158 significantly differentially expressed proteins were detected.UniProt database annotation identified 3 upregulated proteins and 12 downregulated proteins.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that these DEPs were mainly enriched in pathways such as oocyte meiosis.Gene Ontology(GO)enrichment analysis revealed functional clusters related to cellular processes.Weighted gene coexpression network analysis(WGCNA)indicated that the core proteins were primarily involved in the neurodegenerationmultiple diseases pathway and cellular processes.Mediating effect analysis identified PRDX4(L)as a potential protein biomarker.ROC curve analysis showed that GNAI1 had the largest area under the curve(AUC=0.889).CONCLUSION:This study identifies 15 differentially expressed proteins in the tear fluid of NTG patients,including PRDX4(L).PRDX4(L)plays a key role in oxidative stress.展开更多
Backgroud Efficient communication between the embryo and the endometrium is essential for the successful establishment and maintenance of pregnancy.Uterine-derived extracellular vesicles(EVs)contribute to embryomatern...Backgroud Efficient communication between the embryo and the endometrium is essential for the successful establishment and maintenance of pregnancy.Uterine-derived extracellular vesicles(EVs)contribute to embryomaternal communication,supporting early embryonic development.This study aimed to:(i)compare the protein cargo of uterine fluid EVs(UF-EVs)from CYCLIC and PREGNANT heifers;(ii)characterize the protein profile of conditioned medium(CM)-EVs from endometrial explants cultured alone(EXPL)or co-cultured with five d 7 blastocysts(EXPL+EMB)in vitro;and(iii)compare the EV protein cargo between the in vivo and in vitro models(i.e.,EXPL vs.CYCLIC and EXPL+EMB vs.PREGNANT).Results We identified 1,459 and 1,752 proteins in the UF-EVs of CYCLIC and PREGNANT heifers,respectively.Among these,12 were exclusive to CYCLIC,and 18 were exclusive to PREGNANT.Among the 1,329 proteins identified in both groups,16 were differently abundant;ten were more abundant,and six were less abundant in UF-EVs from PREGNANT heifers.In vivo,the changes in UF-EV protein cargo induced by the presence of a blastocyst were related to inflammatory and immune responses,endometrial receptivity,and support of early embryonic development by promoting cell polarity,cell–cell adhesion,and stem cell differentiation.In vitro,we identified 1,501 proteins in the CM-EVs from EXPL,1,975 in the CM-EVs from EXPL+EMB,and 82 in the CM-EVs from EMB.Additionally,50 proteins were unique to EXPL+EMB,and another 33 were differentially abundant due to the synergistic interaction between the embryo and the endometrium.These proteins are involved in embryonic development,regulation of stem cell differentiation,establishment and maintenance of cell polarity,interferon tau(IFNT)-mediated cell signaling,endometrial receptivity,and immune modulation.Although there are qualitative and quantitative differences between in vivo and in vitro-derived EVs,UF-EVs from CYCLIC heifers compared to CM-EVs from EXPL,as well as UFEVs from PREGNANT heifers compared to CM-EVs from EXPL+EMB shared common proteins.Conclusions These findings highlight the pivotal role of EVs in embryo-maternal communication,suggesting that their protein cargo may actively contribute to the modulation of the uterine environment to support early embryonic development.Understanding these molecular interactions could provide valuable insights into the mechanisms of implantation and pregnancy establishment.展开更多
Traditional psychiatric diagnosis relies on subjective symptom assessment,lacking objective biomarkers that hinder early detection and personalized treatment.Plasma proteins and polygenic risk score(PRS),as potential ...Traditional psychiatric diagnosis relies on subjective symptom assessment,lacking objective biomarkers that hinder early detection and personalized treatment.Plasma proteins and polygenic risk score(PRS),as potential predictive tools,hold promise for advancing early diagnosis of mental disorders.This study aims to evaluate the predictive potential of proteomic features and PRS in multiple mental illnesses(depression,schizophrenia,and post-traumatic stress disorder(PTSD)).Using participant data from the UK Biobank-Pharma Proteomics Project,we screen protein associations with mental disorders through least absolute shrinkage and selection operator(LASSO)analysis and construct a Cox regression risk prediction model by integrating the PRS.Additionally,we evaluate predictive performance using 6 machine learning methods and Kaplan-Meier survival curves.Our findings reveal distinct predictive patterns across dis-orders.For depression,integrating plasma proteins with PRS significantly improves prediction beyond the clinical model(C-index=0.6322).For schizophrenia,adding plasma proteins enhances predictive performance,whereas PRS provides no significant improvement.For PTSD,neither plasma proteins nor PRS add substantial predictive value beyond clinical variables.Risk stratification analysis demonstrat that all three mental disorders models can clearly distinguish high-risk from low-risk groups(depression:HR=2.34,P<0.001;schizophrenia:HR=5.47,P<0.001;PTSD:HR=3.02,P<0.001).Al-though it shows good performance in short-term prediction,its long-term prediction ability has decreased,and it needs to be further optimized in the future.This study underscores the differential utility of biomarkers across mental disorders and provides a rationale for disorder-specific predictive modeling in precision psychiatry.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
Objective Urine is a promising biomarker source for clinical proteomics studies.Regional physiological differences are common in multi-center clinical studies.In this study,we investigate whether significant differenc...Objective Urine is a promising biomarker source for clinical proteomics studies.Regional physiological differences are common in multi-center clinical studies.In this study,we investigate whether significant differences are present in the urinary proteomes of individuals from different regions in China.Methods In this study,morning urine samples were collected from healthy urban residents in three regions of China(Haikou,Xi’an and Xining)and urinary proteins were preserved using a membrane-based method(Urimem).The urine proteomes of 27 normal samples were analyzed using LC-MS/MS and compared among three regions.Functional annotation of the differential proteins among the three areas was analyzed using the DAVID online database,and pathway enrichment of the differential urinary proteins was analyzed using KEGG.Results We identified 1898 proteins from Urimem samples using label-free proteome quantification,of which 56 urine proteins were differentially expressed among the three regions(P<0.05).Hierarchical clustering analysis showed that inter-regional differences caused less significant changes in the urine proteome than intersex differences.After gender stratification,16 differential proteins were identified in male samples and 84 differential proteins were identified in female samples.Among these differential proteins,several proteins have been previously reported as urinary disease biomarkers.Conclusions Urimem will facilitate urinary protein storage for large-scale urine sample collection.Regional differences are a confounding factor influencing the urine proteome and should be considered in future multicenter biomarker studies.展开更多
This manuscript examines the utility, utilizing the Ciphergen Protein Biosystem II, to develop a fingerprint for the diagnosis of prostate cancer. The investigators compared samples from control individuals as well as...This manuscript examines the utility, utilizing the Ciphergen Protein Biosystem II, to develop a fingerprint for the diagnosis of prostate cancer. The investigators compared samples from control individuals as well as those with prostate cancer. In doing so, they utilize several chip platforms on which to examine the resulting展开更多
AIM: To isolate and identify the biological characteristics of human colon cancer stem cells (SW1116 cells) and further study their proteome. METHODS: SW1116 cells were isolated and cultured with a serum-free medi...AIM: To isolate and identify the biological characteristics of human colon cancer stem cells (SW1116 cells) and further study their proteome. METHODS: SW1116 cells were isolated and cultured with a serum-free medium (SFM). Sphere formation was assayed to observe the formation of colon cancer stem cell spheres. SW1116 cells were inoculated into a serum-containing medium for observing their differentiation characteristics. Proliferation curve and cross-resistance of SWl116 cells to different drugs were detected by MTT. Percentage of SP cells in SW1116 cells was detected with Hoechst33342 staining. Telomerase activity in SW1116cells was checked by polymerase chain reaction (PCR)-enzyme linked immunosorbent assay. Expressions of stem cell relevant genes and proteins were detected by reverse transcription-PCR and Western blot, respectively. Total protein was isolated from SW1116 cells by two-dimensional gel electrophoresis (2-DE) and differentially expressed proteins were identified by tandem mass spectrometry (MALDI-TOF/TOF). RESULTS: The isolated SW1116 cells presented as spheroid and suspension growths in SFM with a strong self-renewal, proliferation, differentiation and drug-resistance ability. The percentage of SP cells in SW1116 cells was 38.9%. The SW1116 cells co-expressed the CD133 and CD29 proteins. The telomerase activity in SW1116 cells was increased. The expressions of different stem cell relevant genes and proteins were detected. The proteomic analysis showed that the 26 protein spots were differently expressed in SW1116 cells and 10 protein spots were identified as ubiquitin fusion- degradation l-like protein, nuclear chloride channel protein, tubulin 13, Raichu404X, stratifin, F-actin cap- ping protein α-1 subunit, eukaryotic translation elongation factor 1 delta isoform 2, hypothetical protein, glyceraldehyde-3-phosphate dehydrogenase and guanine nucleotide binding protein 13 polypeptide 2-like 1, respectively. CONCLUSION: SW1116 cells are biologically characterized by self-renewal, proliferation and differentiation, and the differently expressed proteins in SW1116 cells may be essential for isolating cancer stem cells.展开更多
Background: Early pregnancy failure has a profound impact on both human reproductive health and animal production. 2/3 pregnancy failures occur during the peri-implantation period; however, the underlying mechanism(...Background: Early pregnancy failure has a profound impact on both human reproductive health and animal production. 2/3 pregnancy failures occur during the peri-implantation period; however, the underlying mechanism(s) remains unclear. Well-organized modification of the endometrium to a receptive state is critical to establish pregnancy Aberrant endometrial modification during implantation is thought to be largely responsible for early pregnancy loss. Result: In this study, using well-managed recipient ewes that received embryo transfer as model, we compared the endometrial proteome between pregnant and non-pregnant ewes during implantation period. After embryo transfer, recipients were assigned as pregnant or non-pregnant ewes according to the presence or absence of an elongated conceptus at Day 17 of pregnancy. By comparing the endometrial proteomic profiles between pregnant and non-pregnant ewes, we identified 94 and 257 differentially expressed proteins (DEPs) in the endometrial caruncular and intercaruncular areas, respectively. Functional analysis showed that the DEPs were mainly associated with immune response, nutrient transport and utilization, as well as proteasome-mediated proteolysis. Conclusion: These analysis imply that dysfunction of these biological processes or pathways of DEP in the endometrium is highly associated with early pregnancy loss. In addition, many proteins that are essential for the establishment of pregnancy showed dysregulation in the endometrium of non-pregnant ewes. These proteins, as potential candidates, may contribute to early pregnancy loss.展开更多
Objective To identify potential serum biomarkers for distinguishing between latent tuberculosis infection(LTBI) and active tuberculosis(TB). Methods A proteome microarray containing 4,262 antigens was used for scr...Objective To identify potential serum biomarkers for distinguishing between latent tuberculosis infection(LTBI) and active tuberculosis(TB). Methods A proteome microarray containing 4,262 antigens was used for screening serum biomarkers of 40 serum samples from patients with LTBI and active TB at the systems level. The interaction network and functional classification of differentially expressed antigens were analyzed using STRING 10.0 and the TB database, respectively. Enzyme-linked immunosorbent assays(ELISA) were used to validate candidate antigens further using 279 samples. The diagnostic performances of candidate antigens were evaluated by receiver operating characteristic curve(ROC) analysis. Both antigen combination and logistic regression analysis were used to improve diagnostic ability. Results Microarray results showed that levels of 152 Mycobacterium tuberculosis(Mtb)-antigenspecific IgG were significantly higher in active TB patients than in LTBI patients(P 〈 0.05), and these differentially expressed antigens showed stronger associations with each other and were involved in various biological processes. Eleven candidate antigens were further validated using ELISA and showed consistent results in microarray analysis. ROC analysis showed that antigens Rv2031 c, Rv1408, and Rv2421 c had higher areas under the curve(AUCs) of 0.8520, 0.8152, and 0.7970, respectively. In addition, both antigen combination and logistic regression analysis improved the diagnostic ability. Conclusion Several antigens have the potential to serve as serum biomarkers for discrimination between LTBI and active TB.展开更多
To evaluate the response of alfalfa to water deficit (WD) stress, WD-induced candidates were investigated through a proteomic approach. Alfalfa seedlings were exposed to WD stress for 12 and 15 days respectively, fo...To evaluate the response of alfalfa to water deficit (WD) stress, WD-induced candidates were investigated through a proteomic approach. Alfalfa seedlings were exposed to WD stress for 12 and 15 days respectively, followed by 3 days re-watering. Water deficit increased H202 content, lipid peroxidation, DPPH (1,1-diphenyl-2-picrylhydrazyl)-radical scavenging activity, and the free proline level in alfalfa roots. Root proteins were extracted and separated by two-dimentional polyacrylamide gel electrophoresis (2-DE). A total of 49 WD-responsive proteins were identified in alfalfa roots; 25 proteins were reproducibly found to be up-regulated and 24 were down-regulated. Two proteins, namely cytosolic ascorbate peroxidase (APx2) and putative F-box protein were newly detected on 2-DE maps of WD-treated plants. We identified several proteins including agamous-like 65, albumin b-32, inward rectifying potassium channel, and auxin-independent growth promoter. The identified proteins are involved in a variety of cellular functions including calcium signaling, abacisic acid (ABA) biosynthesis, reactive oxygen species (ROS) regulation, transcription/translation, antioxidant/detoxification/stress defense, energy metabolism, signal transduction, and storage. These results indicate the potential candidates were responsible for adaptive response in alfalfa roots.展开更多
Background:Immunological stress decreases feed intake,suppresses growth and induces economic losses.However,the underlying molecular mechanism remains unclear.Label-free liquid chromatography and mass spectrometry(LC-...Background:Immunological stress decreases feed intake,suppresses growth and induces economic losses.However,the underlying molecular mechanism remains unclear.Label-free liquid chromatography and mass spectrometry(LC-MS)proteomics techniques were employed to investigate effects of immune stress on the hepatic proteome changes of Arbor Acres broilers(Gallus Gallus domesticus)challenged with Escherichia coli lipopolysaccharide(LPS).Results:Proteomic analysis indicated that 111 proteins were differentially expressed in the liver of broiler chickens from the immune stress group.Of these,28 proteins were down-regulated,and 83 proteins were up-regulated in the immune stress group.Enrichment analysis showed that immune stress upregulated the expression of hepatic proteins involved in defense function,amino acid catabolism,ion transport,wound healing,and hormone secretion.Furthermore,immune stress increased valine,leucine and isoleucine degradation pathways.Conclusion:The data suggests that growth depression of broiler chickens induced by immune stress is triggered by hepatic proteome alterations,and provides a new insight into the mechanism by which immune challenge impairs poultry production.展开更多
文摘Large-scale proteomics studies can refine our understanding of health and disease and enable precision medicine.Here,we provide a detailed atlas of 2,920 plasma proteins linking to diseases(406 prevalent and 660 incident)and 986 health-related traits in 53,026 individuals(median follow-up:14.8 years)from the UK Biobank,representing the most comprehensive proteome profiles to date.This atlas revealed 168,100 protein-disease associations and 554,488 protein-trait associations.
文摘Large-scale proteomics studies can refine our understanding of health and disease and enable precision medicine.Here,we provide a detailed atlas of 2,920 plasma proteins linking to diseases(406 prevalent and 660 incident)and 986 health-related traits in 53,026 individuals(median follow-up:14.8 years)from the UK Biobank,representing the most comprehensive proteome profiles to date.This atlas revealed 168,100 protein-disease associations and 554,488 protein-trait associations.Over 650 proteins were shared among at least 50 diseases,and over 1,000 showed sex and age heterogeneity.Furthermore,proteins demonstrated promising potential in disease discrimination(area under the curve[AUC]>0.80 in 183 diseases).Finally,integrating protein quantitative trait locus data determined 474 causal proteins,providing 37 drug-repurposing opportunities and 26 promising targets with favorable safety profiles.These results provide an open-access comprehensive proteome-phenome resource(https://proteome-phenome-atlas.com/)to help elucidate the biological mechanisms of diseases and accelerate the development of disease biomarkers,prediction models,and therapeutic targets.
基金Fujian Province Science and Technology Plan Project under contract No.2023N0011Xiamen Municipal Bureau of Marine Development Project under contract No.S24258。
文摘Cryptocaryon irritans is the parasite responsible for“white spot disease”in the yellowfin seabream Acanthopagrus latus,which has caused significant losses to the aquaculture industry.This experiment investigated the changes in the morphology,transcriptome,and proteome of gill tissue in yellowfin seabream infected with C.irritans,aiming to provide foundational data for further understanding the pathogenic mechanisms and control measures against this parasite.The main findings were as follows,after C.irritans infection,the structure of gill tissue in yellowfin seabream was damaged,with microvessels ruptured,some cells proliferating,and large amounts of mucus infiltrating.Transcriptome analysis revealed a total of 4299 differentially expressed genes,with 2367 up-regulated and 1932down-regulated.Further bioinformatics analysis of all differentially expressed genes identified nine immune-related genes,cox-2,mcama,tbx21,dcn,tnfb,cd74a,illb,ppib,and cd4-1 in A.latus.The reliability of the transcriptome data was validated by real time q PCR,which showed the same trend as the RNA-seq results.Proteome analysis found365 differential proteins,with 180 proteins up-regulated and 185 proteins down-regulated.Bioinformatics analysis identified three immune-related proteins,Myll,Gapdh,and Actn3b.These findings indicated that C.irritans disrupted the structure of gill tissue,impeded gas exchange and led to asphyxiation and death in affected fish.Transcriptome and proteome analyses showed that the expression of immune-related genes and proteins in yellowfin seabream,involved not only inflammatory responses and the activation and migration of immune cells but also potentially participated in tissue repair and defense regulation.These findings highlighted the complex immune regulatory network in response to C.irritans infection,offering references for prevention and control of white spot disease in yellowfin seabream.
基金supported by the National Natural Science Foundation of China(Grant No.32002113)the Natural Science Research Project of Jiangsu Higher Education Institutions(Grant No.19KJB210001)+7 种基金the Natural Science Foundation of Jiangsu Province(Grant No.BK20190958)the Key Research and Development Program of Zhejiang Province(Grant No.2021C02052)National Key Research and Development Program of China(Grant Nos.2018YFD1000800,2017YFE0114500)Zhejiang Provincial major Agricultural Science and Technology Projects of New Varieties Breeding(2021C02065)China Agriculture Research System of MOF and MARA(Grant No.CARS-23-G44)the Ministry of Science and Technology of the People’s Republic of China(Grant No.DL2022026004L)the National Natural Science Foundation of China(Grant No.31950410555)the Innovative Research Team(Science and Technology)in the University of Henan Province(Grant No.23IRTSTHN024).
文摘Soil cadmium pollution has increasingly become a serious problem for crop production,which drastically attenuates plant growth and food safety.Although N6-methyladenosine(m^(6)A)methylation is crucial for plant response to various stresses,the regulatory mechanism underlying m^(6)A modification during cadmium(Cd)stress remains unclear.This study investigated the physiological responses,transcriptome-wide m^(6)A methylome,and proteome changes in tomato roots exposed to 50 μmol·L^(-1)CdCl2.Excess Cd restricted plant growth,altered the antioxidant system and disrupted mineral nutrient absorption.We identified a negative correlation between m^(6)A levels and gene transcription for that 150 out of 198 differentially expressed genes(DEGs)were hypomethylated but mRNA up-regulated.Cd stress also enhanced translational efficiency,particularly for differentially abundant proteins(DAPs).Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed that differentially m^(6)A modified genes(DMGs),DEGs,and DAPs were commonly enriched in phenylpropanoid biosynthesis,glutathione metabolism,and ABC transporters,reflecting cell wall barriers,chelation,and transport of Cd,respectively.Finally,we confirmed the Cd-transport activity of eight putative metal transporters identified in DMGs,DEGs,or DAPs by yeast complementaion experiments,and pharmacologically investigated the effect of m^(6)A modification on their expression.Treatment with the m^(6)A methylation inhibitor 3-deazaneplanocin A(3-DA)reduced SlIRT1/2 expression and increased SlNRAMP3/SlZIP4 expression,while the m^(6)A demethylase inhibitor meclofenamic acid(MA)treatment decreased SlNRAMP3 expression but elevated SlIRT2 expression under Cd stress.Our findings provide novel insights into the interplay between m^(6)A modification,transcription,and translation under Cd stress and the associated plant stress response.
基金supported by Austrian Federal Ministry for Digital and Economic Affairsthe National Foundation for Research,Technology and Developmentsupported using resources of the Vet Core Facility(Mass Spectrometry)of the University of Veterinary Medicine Vienna。
文摘Background The objective was to characterize the colostrum proteome of primiparous Holstein cows in association with immunoglobulin G(IgG)content.Immediately after calving,colostrum samples were collected from 18 cows to measure IgG concentration.Based on colostrum IgG content,samples were classified through cluster analysis and were identified as poor,average,and excellent quality.The proteome was assessed with quantitative shotgun proteomics;abundance data were compared among the colostrum types;enrichment analysis of metabolic processes and proteins classes was performed as well.We also tested correlations between this proteome and blood globulin level of cows and passive immunity level of calves.Results On average,428 proteins were identified per sample,which belonged mainly to cellular process,biological regulation,response to stimulus,metabolic process,and immune system process.Most abundant proteins were complement C3(Q2UVX4),alpha-S1-casein(P02662),Ig-like domain-containing protein(A0A3Q1M032),albumin(A0A140T897),polymeric immunoglobulin receptor(P81265),lactotransferrrin(P24627),and IGHG1*01(X167014).Colostrum of excellent quality had greater(P<0.05)abundance of serpin A3-7(A2I7N3),complement factorl(A0A3Q1 MIF4),lipocalin/cytosolic fatty-acid binding domain-containing protein(A0A3Q1 MRQ2),complement C3(E1B805),complement component 4 binding protein alpha(A0AAF6ZHP5),and complement component C6(F1MM86).However,colostrum of excellent quality had lower(P<0.05)abundance of HGF activator(E1BCW0),alpha-S1-casein(P02662),and xanthine dehydrogenase/oxidase(P80457).This resulted in enrichment of the biological processes predominantly for complement activation alternative pathway,complement activation,complement activation classical pathway,humoral immune response,leukocyte mediated immunity,and negative regulation of endopeptidase activity in excellent-quality colostrum.Additionally,some colostrum proteins were found to be correlated with the blood globulin level of cows and with the passive immunity level of calves(P<0.05;r≥0.57).Conclusions This study provides new insights into the bovine colostrum proteome,demonstrating associations between IgG levels and the abundance of other proteins,as well as the enrichment of metabolic processes related to innate immune response.Thus,results suggest that the colostrum proteomic profile is associated with the content of IgG.Future research should deeply explore the association of these findings with pre-calving nutrition status and blood composition of the cow,and with passive immunity transfer to the calf.
基金Supported by National 863 Project(2010AA101503)National Science and Technology Support Planning Item(2006BAD05A12)Student Innovation Fund Item of Hefei University of Technology(XS2010100)~~
文摘[Objective] The research aimed to establish the two-dimensional electrophoresis(2-DE)technology which was suitable for the rapeseed proteome research.[Method] Xiangyou 17 was as the material.The sample preparation method,gel concentration and loading amount,etc.in 2-DE technology were optimized.[Result] The best extraction method of total protein of rapeseed was TCA-acetone method,and the protein spots on 2-DE map were the most.When IPG strip(pH 3-10)and 12% gel were used,and the loading amount was 250 μg,the two-dimensional electrophoresis map with the clear background,good repeatability and high protein spot resolution was obtained.[Conclusion] The research laid the foundation for carrying out the rapeseed proteomics research.
基金National Key Research and Development Program of China,Grant/Award Number:2021YFF0702200Science and Technology Projects in Guangzhou,Grant/Award Number:202206010084,202206010197 and 202206060002+1 种基金Guangdong S&T programme,Grant/Award Number:2009A081000002 and 2023B0303040004Technology Planning Project of Linzhi,Grant/Award Number:2023-YZ-01。
文摘Background:The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet(HFD)to mimic clinical disease progression.Methods:Thirty-five male macaques aged 10-15 years underwent an 18-month HFD intervention.Physiological parameters(BMI,BP,hematology),liver fat fraction(evaluated by ultrasound/MRI),cardiac function(assessed by echocardiography),and histopathology(using liver biopsy)were measured before and after the intervention.Serum proteomics with KEGG/STRING analyses identified molecular mechanisms.Results:Within 6 months,HFD induced dyslipidemia(elevated TG,TCHO,HDL-C,LDL-C).After 18 months,metabolic dysfunction-associated steatohepatitis(MASH)was confirmed by histopathology in 57.14%(16/28)of macaques,diabetes(elevated FPG/HbA1c)in 17.86%(5/28),and myocardial hypertrophy(elevated LVMass/LAD)in 46.43%(13/28).Proteomics identified Bile acid-CoA:amino acid N-acyltransferase(BAAT)as a MASH hallmark protein,the level of which was inversely correlated with the degree of fibrosis.For diabetes,citrate synthase(CS)and malate dehydrogenase 1(MDH1)impaired glucose oxidation via the TCA cycle,while hexose-6-phosphate de-hydrogenase(H6PD)disrupted gluconeogenesis.Myocardial hypertrophy was associ-ated with the downregulation of SRC proto-oncogene,non-receptor tyrosine kinase(SRC),mitogen-activated protein kinase 14(MAPK14),emerin(EMD),and integrin subunit beta 1(ITGB1).Conclusions:An 18-month HFD successfully established a translational M.fascicula-ris model replicating key metabolic disorders(MASH,diabetes,cardiac hypertrophy).BAAT,CS/MDH1/H6PD,and SRC/MAPK14/EMD/ITGB1 were identified as mecha-nistic biomarkers for these conditions.
基金supported by National Institutes of Health(NIH)Grants AG063944 and AG080047 to KAM.
文摘Advances in skeletal muscle omics has expanded our understanding of exercise-induced adaptations at the molecular level.Over the past 2 decades,transcriptome studies in muscle have detailed acute and chronic responses to resistance,endurance,and concurrent exercise,focusing on variables such as training status,nutrition,age,sex,and metabolic health profile.Multi-omics approaches,such as the integration of transcriptomic and epigenetic data,along with emerging ribosomal RNA sequencing advancements,have further provided insights into how skeletal muscle adapts to exercise across the lifespan.Downstream of the transcriptome,proteomic and phosphoproteomic studies have identified novel regulators of exercise adaptations,while single-cell/nucleus and spatial sequencing technologies promise to evolve our understanding of cellular specialization and communication in and around skeletal muscle cells.This narrative review highlights(a)the historical foundations of exercise omics in skeletal muscle,(b)current research at 3 layers of the omics cascade(DNA,RNA,and protein),and(c)applications of single-cell omics and spatial sequencing technologies to study skeletal muscle adaptation to exercise.Further elaboration of muscle's global molecular footprint using multi-omics methods will help researchers and practitioners develop more effective and targeted approaches to improve skeletal muscle health as well as athletic performance.
基金supported by Applied Basic Research Foundation of Yunnan Province,Nos.202301AS070045,202101AY070001-115(to XY and BL)National Natural Science Foundation of China,No.81960242(to XY)。
文摘Cognitive impairment is a particularly severe non-motor symptom of Parkinson's disease that significantly diminishes the quality of life of affected individuals.Identifying reliable biomarkers for cognitive impairment in Parkinson's disease is essential for early diagnosis,prognostic assessments,and the development of targeted therapies.This review aims to summarize recent advancements in biofluid biomarkers for cognitive impairment in Parkinson's disease,focusing on the detection of specific proteins,metabolites,and other biomarkers in blood,cerebrospinal fluid,and saliva.These biomarkers can shed light on the multifaceted etiology of cognitive impairment in Parkinson's disease,which includes protein misfolding,neurodegeneration,inflammation,and oxidative stress.The integration of biofluid biomarkers with neuroimaging and clinical data can facilitate the development of predictive models to enhance early diagnosis and monitor the progression of cognitive impairment in patients with Parkinson's disease.This comprehensive approach can improve the existing understanding of the mechanisms driving cognitive decline and support the development of targeted therapeutic strategies aimed at modifying the course of cognitive impairment in Parkinson's disease.Despite the promise of these biomarkers in characterizing the mechanisms underlying cognitive decline in Parkinson's disease,further research is necessary to validate their clinical utility and establish a standardized framework for early detection and monitoring of cognitive impairment in Parkinson's disease.
基金Supported by The Eye Hospital of Wenzhou Medical University(No.KYQD20220304)The Fifth Batch of Provincial Ten Thousand Personnel Program Outstanding Talents Funding(No.474092204)+1 种基金Innovative Talents and Teams(2024)-The Fifth Batch of Funding Funds for Scientific and Technological Innovation Leading Talents Under the Provincial Ten Thousand Personnel Program(No.4240924003G)The Key R&D Program of Zhejiang(No.2022C03112).
文摘AIM:To identify early biomarkers associated with glaucomatous visual field(VF)progression in patients with normal-tension glaucoma(NTG).METHODS:This study included patients were divided into two groups based on disease progression status.Tear samples were collected for proteomic analysis.Dataindependent acquisition(DIA)mass spectrometry combined with bioinformatic analyses was performed to identify and validate potential protein biomarkers for NTG progression.Additionally,differentially expressed proteins(DEPs)were evaluated using mediating effect models and receiver operating characteristic(ROC)curve analysis.RESULTS:A total of 19 patients(20 eyes)with NTG participated in this study,including 10 patients(4 males and 6 females;10 eyes)in the progression group with mean age of 67.70±9.03y and 10 patients(4 males and 6 females;10 eyes)in the non-progression group with mean age of 68.60±7.58y.A total of 158 significantly differentially expressed proteins were detected.UniProt database annotation identified 3 upregulated proteins and 12 downregulated proteins.Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis showed that these DEPs were mainly enriched in pathways such as oocyte meiosis.Gene Ontology(GO)enrichment analysis revealed functional clusters related to cellular processes.Weighted gene coexpression network analysis(WGCNA)indicated that the core proteins were primarily involved in the neurodegenerationmultiple diseases pathway and cellular processes.Mediating effect analysis identified PRDX4(L)as a potential protein biomarker.ROC curve analysis showed that GNAI1 had the largest area under the curve(AUC=0.889).CONCLUSION:This study identifies 15 differentially expressed proteins in the tear fluid of NTG patients,including PRDX4(L).PRDX4(L)plays a key role in oxidative stress.
基金supported by research projects:PID2019-111641RB-I00 and PID2023-149027OB-I00 funded by MCIN/AEI/10.13039/501100011033/to DR and PRE2020-094452 to RM。
文摘Backgroud Efficient communication between the embryo and the endometrium is essential for the successful establishment and maintenance of pregnancy.Uterine-derived extracellular vesicles(EVs)contribute to embryomaternal communication,supporting early embryonic development.This study aimed to:(i)compare the protein cargo of uterine fluid EVs(UF-EVs)from CYCLIC and PREGNANT heifers;(ii)characterize the protein profile of conditioned medium(CM)-EVs from endometrial explants cultured alone(EXPL)or co-cultured with five d 7 blastocysts(EXPL+EMB)in vitro;and(iii)compare the EV protein cargo between the in vivo and in vitro models(i.e.,EXPL vs.CYCLIC and EXPL+EMB vs.PREGNANT).Results We identified 1,459 and 1,752 proteins in the UF-EVs of CYCLIC and PREGNANT heifers,respectively.Among these,12 were exclusive to CYCLIC,and 18 were exclusive to PREGNANT.Among the 1,329 proteins identified in both groups,16 were differently abundant;ten were more abundant,and six were less abundant in UF-EVs from PREGNANT heifers.In vivo,the changes in UF-EV protein cargo induced by the presence of a blastocyst were related to inflammatory and immune responses,endometrial receptivity,and support of early embryonic development by promoting cell polarity,cell–cell adhesion,and stem cell differentiation.In vitro,we identified 1,501 proteins in the CM-EVs from EXPL,1,975 in the CM-EVs from EXPL+EMB,and 82 in the CM-EVs from EMB.Additionally,50 proteins were unique to EXPL+EMB,and another 33 were differentially abundant due to the synergistic interaction between the embryo and the endometrium.These proteins are involved in embryonic development,regulation of stem cell differentiation,establishment and maintenance of cell polarity,interferon tau(IFNT)-mediated cell signaling,endometrial receptivity,and immune modulation.Although there are qualitative and quantitative differences between in vivo and in vitro-derived EVs,UF-EVs from CYCLIC heifers compared to CM-EVs from EXPL,as well as UFEVs from PREGNANT heifers compared to CM-EVs from EXPL+EMB shared common proteins.Conclusions These findings highlight the pivotal role of EVs in embryo-maternal communication,suggesting that their protein cargo may actively contribute to the modulation of the uterine environment to support early embryonic development.Understanding these molecular interactions could provide valuable insights into the mechanisms of implantation and pregnancy establishment.
基金The National Natural Science Foundation of China-Regional Science“Identification of novel drug targets for lung cancer via Mendelian randomization analysis based on blood proteomics”(62362062)The 2025 Xinjiang University Excellent Graduate Innovation Project“Research on identification of therapeutic targets and predictive factors for mental disorders based on proteomics”(XJDX2025YJS151)。
文摘Traditional psychiatric diagnosis relies on subjective symptom assessment,lacking objective biomarkers that hinder early detection and personalized treatment.Plasma proteins and polygenic risk score(PRS),as potential predictive tools,hold promise for advancing early diagnosis of mental disorders.This study aims to evaluate the predictive potential of proteomic features and PRS in multiple mental illnesses(depression,schizophrenia,and post-traumatic stress disorder(PTSD)).Using participant data from the UK Biobank-Pharma Proteomics Project,we screen protein associations with mental disorders through least absolute shrinkage and selection operator(LASSO)analysis and construct a Cox regression risk prediction model by integrating the PRS.Additionally,we evaluate predictive performance using 6 machine learning methods and Kaplan-Meier survival curves.Our findings reveal distinct predictive patterns across dis-orders.For depression,integrating plasma proteins with PRS significantly improves prediction beyond the clinical model(C-index=0.6322).For schizophrenia,adding plasma proteins enhances predictive performance,whereas PRS provides no significant improvement.For PTSD,neither plasma proteins nor PRS add substantial predictive value beyond clinical variables.Risk stratification analysis demonstrat that all three mental disorders models can clearly distinguish high-risk from low-risk groups(depression:HR=2.34,P<0.001;schizophrenia:HR=5.47,P<0.001;PTSD:HR=3.02,P<0.001).Al-though it shows good performance in short-term prediction,its long-term prediction ability has decreased,and it needs to be further optimized in the future.This study underscores the differential utility of biomarkers across mental disorders and provides a rationale for disorder-specific predictive modeling in precision psychiatry.
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 Key Basic Research Program of the Ministry of Science and Technology of China(No.2013FY114100)the National Key Research and Development Program of China(No.2018YFC0910202,2016YFC1306300)+3 种基金the Beijing Natural Science Foundation(No.7172076)the Beijing Cooperative Construction Project(No.110651103)Beijing Normal University(No.11100704)Peking Union Medical College Hospital(2016-2.27)
文摘Objective Urine is a promising biomarker source for clinical proteomics studies.Regional physiological differences are common in multi-center clinical studies.In this study,we investigate whether significant differences are present in the urinary proteomes of individuals from different regions in China.Methods In this study,morning urine samples were collected from healthy urban residents in three regions of China(Haikou,Xi’an and Xining)and urinary proteins were preserved using a membrane-based method(Urimem).The urine proteomes of 27 normal samples were analyzed using LC-MS/MS and compared among three regions.Functional annotation of the differential proteins among the three areas was analyzed using the DAVID online database,and pathway enrichment of the differential urinary proteins was analyzed using KEGG.Results We identified 1898 proteins from Urimem samples using label-free proteome quantification,of which 56 urine proteins were differentially expressed among the three regions(P<0.05).Hierarchical clustering analysis showed that inter-regional differences caused less significant changes in the urine proteome than intersex differences.After gender stratification,16 differential proteins were identified in male samples and 84 differential proteins were identified in female samples.Among these differential proteins,several proteins have been previously reported as urinary disease biomarkers.Conclusions Urimem will facilitate urinary protein storage for large-scale urine sample collection.Regional differences are a confounding factor influencing the urine proteome and should be considered in future multicenter biomarker studies.
文摘This manuscript examines the utility, utilizing the Ciphergen Protein Biosystem II, to develop a fingerprint for the diagnosis of prostate cancer. The investigators compared samples from control individuals as well as those with prostate cancer. In doing so, they utilize several chip platforms on which to examine the resulting
基金Supported by Medical Guidance Project of Shanghai Science Committee (No. 10411961800)Youth Science Fund of Fudan University (No. 08FQ49)
文摘AIM: To isolate and identify the biological characteristics of human colon cancer stem cells (SW1116 cells) and further study their proteome. METHODS: SW1116 cells were isolated and cultured with a serum-free medium (SFM). Sphere formation was assayed to observe the formation of colon cancer stem cell spheres. SW1116 cells were inoculated into a serum-containing medium for observing their differentiation characteristics. Proliferation curve and cross-resistance of SWl116 cells to different drugs were detected by MTT. Percentage of SP cells in SW1116 cells was detected with Hoechst33342 staining. Telomerase activity in SW1116cells was checked by polymerase chain reaction (PCR)-enzyme linked immunosorbent assay. Expressions of stem cell relevant genes and proteins were detected by reverse transcription-PCR and Western blot, respectively. Total protein was isolated from SW1116 cells by two-dimensional gel electrophoresis (2-DE) and differentially expressed proteins were identified by tandem mass spectrometry (MALDI-TOF/TOF). RESULTS: The isolated SW1116 cells presented as spheroid and suspension growths in SFM with a strong self-renewal, proliferation, differentiation and drug-resistance ability. The percentage of SP cells in SW1116 cells was 38.9%. The SW1116 cells co-expressed the CD133 and CD29 proteins. The telomerase activity in SW1116 cells was increased. The expressions of different stem cell relevant genes and proteins were detected. The proteomic analysis showed that the 26 protein spots were differently expressed in SW1116 cells and 10 protein spots were identified as ubiquitin fusion- degradation l-like protein, nuclear chloride channel protein, tubulin 13, Raichu404X, stratifin, F-actin cap- ping protein α-1 subunit, eukaryotic translation elongation factor 1 delta isoform 2, hypothetical protein, glyceraldehyde-3-phosphate dehydrogenase and guanine nucleotide binding protein 13 polypeptide 2-like 1, respectively. CONCLUSION: SW1116 cells are biologically characterized by self-renewal, proliferation and differentiation, and the differently expressed proteins in SW1116 cells may be essential for isolating cancer stem cells.
基金supported by grants from the National High-Tech R&D Program (Nos.2011AA100303,2013AA102506)the National Key Technology R&D Program(Nos.2011BAD19B01,2011BAD19B03,2011BAD19B04)
文摘Background: Early pregnancy failure has a profound impact on both human reproductive health and animal production. 2/3 pregnancy failures occur during the peri-implantation period; however, the underlying mechanism(s) remains unclear. Well-organized modification of the endometrium to a receptive state is critical to establish pregnancy Aberrant endometrial modification during implantation is thought to be largely responsible for early pregnancy loss. Result: In this study, using well-managed recipient ewes that received embryo transfer as model, we compared the endometrial proteome between pregnant and non-pregnant ewes during implantation period. After embryo transfer, recipients were assigned as pregnant or non-pregnant ewes according to the presence or absence of an elongated conceptus at Day 17 of pregnancy. By comparing the endometrial proteomic profiles between pregnant and non-pregnant ewes, we identified 94 and 257 differentially expressed proteins (DEPs) in the endometrial caruncular and intercaruncular areas, respectively. Functional analysis showed that the DEPs were mainly associated with immune response, nutrient transport and utilization, as well as proteasome-mediated proteolysis. Conclusion: These analysis imply that dysfunction of these biological processes or pathways of DEP in the endometrium is highly associated with early pregnancy loss. In addition, many proteins that are essential for the establishment of pregnancy showed dysregulation in the endometrium of non-pregnant ewes. These proteins, as potential candidates, may contribute to early pregnancy loss.
基金supported by the Natural Science Foundation of China[No:81470091]Beijing Municipal Administration of Hospitals Ascent Plan[DFL20151501]
文摘Objective To identify potential serum biomarkers for distinguishing between latent tuberculosis infection(LTBI) and active tuberculosis(TB). Methods A proteome microarray containing 4,262 antigens was used for screening serum biomarkers of 40 serum samples from patients with LTBI and active TB at the systems level. The interaction network and functional classification of differentially expressed antigens were analyzed using STRING 10.0 and the TB database, respectively. Enzyme-linked immunosorbent assays(ELISA) were used to validate candidate antigens further using 279 samples. The diagnostic performances of candidate antigens were evaluated by receiver operating characteristic curve(ROC) analysis. Both antigen combination and logistic regression analysis were used to improve diagnostic ability. Results Microarray results showed that levels of 152 Mycobacterium tuberculosis(Mtb)-antigenspecific IgG were significantly higher in active TB patients than in LTBI patients(P 〈 0.05), and these differentially expressed antigens showed stronger associations with each other and were involved in various biological processes. Eleven candidate antigens were further validated using ELISA and showed consistent results in microarray analysis. ROC analysis showed that antigens Rv2031 c, Rv1408, and Rv2421 c had higher areas under the curve(AUCs) of 0.8520, 0.8152, and 0.7970, respectively. In addition, both antigen combination and logistic regression analysis improved the diagnostic ability. Conclusion Several antigens have the potential to serve as serum biomarkers for discrimination between LTBI and active TB.
基金supported by the National Research Foundation of Korea (NRF) Grant (NRF-2011-616-F00013)supported by post-doctoral grantsupported by the scholarship from BK21Plus program, Ministry of Education, Republic of Korea
文摘To evaluate the response of alfalfa to water deficit (WD) stress, WD-induced candidates were investigated through a proteomic approach. Alfalfa seedlings were exposed to WD stress for 12 and 15 days respectively, followed by 3 days re-watering. Water deficit increased H202 content, lipid peroxidation, DPPH (1,1-diphenyl-2-picrylhydrazyl)-radical scavenging activity, and the free proline level in alfalfa roots. Root proteins were extracted and separated by two-dimentional polyacrylamide gel electrophoresis (2-DE). A total of 49 WD-responsive proteins were identified in alfalfa roots; 25 proteins were reproducibly found to be up-regulated and 24 were down-regulated. Two proteins, namely cytosolic ascorbate peroxidase (APx2) and putative F-box protein were newly detected on 2-DE maps of WD-treated plants. We identified several proteins including agamous-like 65, albumin b-32, inward rectifying potassium channel, and auxin-independent growth promoter. The identified proteins are involved in a variety of cellular functions including calcium signaling, abacisic acid (ABA) biosynthesis, reactive oxygen species (ROS) regulation, transcription/translation, antioxidant/detoxification/stress defense, energy metabolism, signal transduction, and storage. These results indicate the potential candidates were responsible for adaptive response in alfalfa roots.
基金Sponsored by National Natural Science Foundation of China(grant no.31101731)National Key Research and Development Program of China(No.2018YFD0500600)The Agricultural Science and Technology Innovation Program(ASTIP).
文摘Background:Immunological stress decreases feed intake,suppresses growth and induces economic losses.However,the underlying molecular mechanism remains unclear.Label-free liquid chromatography and mass spectrometry(LC-MS)proteomics techniques were employed to investigate effects of immune stress on the hepatic proteome changes of Arbor Acres broilers(Gallus Gallus domesticus)challenged with Escherichia coli lipopolysaccharide(LPS).Results:Proteomic analysis indicated that 111 proteins were differentially expressed in the liver of broiler chickens from the immune stress group.Of these,28 proteins were down-regulated,and 83 proteins were up-regulated in the immune stress group.Enrichment analysis showed that immune stress upregulated the expression of hepatic proteins involved in defense function,amino acid catabolism,ion transport,wound healing,and hormone secretion.Furthermore,immune stress increased valine,leucine and isoleucine degradation pathways.Conclusion:The data suggests that growth depression of broiler chickens induced by immune stress is triggered by hepatic proteome alterations,and provides a new insight into the mechanism by which immune challenge impairs poultry production.