Mango(Mangifera indica L.)is one of the main economic crops in Hainan,China,prized for its distinctive flavor and high nutritional value.It is also rich in health-promoting antioxidants such as vitamin C and flavonoid...Mango(Mangifera indica L.)is one of the main economic crops in Hainan,China,prized for its distinctive flavor and high nutritional value.It is also rich in health-promoting antioxidants such as vitamin C and flavonoids.Enhanced ultraviolet-B(UV—B)radiation,a growing global environmental concern,alters plant antioxidant systems,with increased flavonoid accumulation as a common adaptive response.However,its effects on mango fruit remain largely unexplored.To investigate the antioxidant responses of mango to enhanced UV-B radiation and identify key responsive flavonoid compounds and regulatory genes,we exposed‘Tainong 1’mango fruits growing under natural light to 96 kJ·m^(-2)·d^(-1)of UV-B radiation to simulate high UV-B conditions.Treated fruits were smaller in size and had a pulp of a more intense yellow colour.Further,malondialdehyde content in treated fruits was higher during the phase of rapid fruit enlargement.Additionally,treated fruits showed increased sugar-acid ratios,total phenol,total flavonoid,carotenoid,and ascorbic acid contents.Furthermore,they showed significantly enhanced antioxidant activity,as measured by the FRAP,ABTS,and DPPH assays.Extensive targeted metabolomic-analysis identified flavonoids as the largest category of compounds differentially expressed in treated and control groups.Quantitative metabolomics of flavonoids identified hyperoside,quercimeritrin,and(-)-catechin gallate as the key flavonoid metabolites responsive to UV-B treatment.Transcriptome analysis revealed an enrichment of the flavonoid biosynthesis pathway,with most associated differentially expressed genes showing upregulation.Furthermore,qRT-PCR analysis confirmed that the expression of the genes MiCHS7,MiCHI1,MiCHI2,MiFLS,MiF3H2,and MiF3H3 correlated with changes in key flavonoid metabolites.Indeed,correlation analysis indicated that MiCHS7,MiCHI1,MiFLS,and MiF3H3 are potential key genes involved in flavonoid accumulation under UV-B treatment.Thus,our study provides a theoretical basis for breeding for new resilient varieties and developing UV-B-resistant mango cultivation techniques.展开更多
Background: Cancer-associated fibroblasts (CAFs) play critical roles in tumor progression and immunosuppression;however, their contribution to the functional classification and personalized treatment of gastric cancer...Background: Cancer-associated fibroblasts (CAFs) play critical roles in tumor progression and immunosuppression;however, their contribution to the functional classification and personalized treatment of gastric cancerremains poorly defined. This study aimed to identify effective therapeutic targets to facilitate individualized treatmentstrategies for patients with gastric cancer. Methods: Single-cell and bulk transcriptomic analyses were integrated tocharacterize gastric cancer fibroblasts. “Seurat”, “Slingshot”, and “CellChat” were used for dimensionality reduction,trajectory inference, and cell-cell communication analyses, respectively. Key metastasis-associated fibroblast moduleswere identified using High-dimensional weighted gene co-expression network analysis (hdWGCNA) to construct aprognostic model, which was further evaluated for immune infiltration, therapeutic response, and mutational features.The expression and function of the core gene tripeptidyl peptidase 1 (TPP1) were validated through immunoblotting, PCR, and functional assays. Results: Eight fibroblast subpopulations associated with gastric cancer metastasisexhibited distinct differentiation trajectories and transcriptional heterogeneity. Prognostic analysis indicated thatmetastasis-associated fibroblasts correlated with poor clinical outcomes. The high-risk subgroup showed markedimmunosuppression, resistance to immunotherapy, and reduced mutational burden, with tumor progression-relatedpathways significantly enriched in this group. In vitro experiments further confirmed that TPP1 knockdown suppressedgastric cancer cell metastasis, invasion, and clonogenic capacity while inducing apoptosis. Conclusion: This studycharacterized the heterogeneity of gastric cancer-associated fibroblasts using single-cell transcriptomic analysis andestablished a prognostic model based on metastasis-related fibroblast markers. The model demonstrated strongpredictive performance for patient prognosis, immune landscape, and immunotherapy response. Furthermore, thefindings highlighted the pivotal role of TPP1 in gastric cancer progression and its potential as a therapeutic target.展开更多
Background:Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations,such as firefighting,law enforcement,mili...Background:Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations,such as firefighting,law enforcement,military,and sports.A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work environment.Methods:To study regulatory processes in intense physical activity simulating real-life conditions,we performed a multi-omics analysis of 3 biofluids(blood plasma,urine,and saliva)collected from 11 wildland firefighters before and after a 45 min,intense exercise regimen.Omics profiles post-vs.pre-exercise were compared by Student’s t-test followed by pathway analysis and comparison between the different omics modalities.Results:Our multi-omics analysis identified and quantified 3835 proteins,730 lipids and 182 metabolites combining the 3 different types of samples.The blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy demands.The urine analysis showed a strong,concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites,reabsorption of nutrients and maintenance of fluid balance.In saliva,we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides.A systematic literature review identified 6 papers that support an altered susceptibility to respiratory infection.Conclusions:This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility,suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.展开更多
Objective:Triple-negative breast cancer(TNBC)is a highly aggressive subtype that lacks targeted therapies,leading to a poorer prognosis.However,some patients achieve long-term recurrence-free survival(RFS),offering va...Objective:Triple-negative breast cancer(TNBC)is a highly aggressive subtype that lacks targeted therapies,leading to a poorer prognosis.However,some patients achieve long-term recurrence-free survival(RFS),offering valuable insights into tumor biology and potential treatment strategies.Methods:We conducted a comprehensive multi-omics analysis of 132 patients with American Joint Committee on Cancer(AJCC)stage III TNBC,comprising 36 long-term survivors(RFS≥8 years),62 moderate-term survivors(RFS:3-8 years),and 34 short-term survivors(RFS<3 years).Analyses investigated clinicopathological factors,whole-exome sequencing,germline mutations,copy number alterations(CNAs),RNA sequences,and metabolomic profiles.Results:Long-term survivors exhibited fewer metastatic regional lymph nodes,along with tumors showing reduced stromal fibrosis and lower Ki67 index.Molecularly,these tumors exhibited multiple alterations in genes related to homologous recombination repair,with higher frequencies of germline mutations and somatic CNAs.Additionally,tumors from long-term survivors demonstrated significant downregulation of the RTK-RAS signaling pathway.Metabolomic profiling revealed decreased levels of lipids and carbohydrate,particularly those involved in glycerophospholipid,fructose,and mannose metabolism,in long-term survival group.Multivariate Cox analysis identified fibrosis[hazard ratio(HR):12.70,95%confidence interval(95%CI):2.19-73.54,P=0.005]and RAC1copy number loss/deletion(HR:0.22,95%CI:0.06-0.83,P=0.026)as independent predictors of RFS.Higher fructose/mannose metabolism was associated with worse overall survival(HR:1.30,95%CI:1.01-1.68,P=0.045).Our findings emphasize the association between biological determinants and prolonged survival in patients with TNBC.Conclusions:Our study systematically identified the key molecular and metabolic features associated with prolonged survival in AJCC stage III TNBC,suggesting potential therapeutic targets to improve patient outcomes.展开更多
Dissolved oxygen(DO)is an important indicator of aquaculture,and its accurate forecasting can effectively improve the quality of aquatic products.In this paper,a new DO hybrid forecasting model is proposed that includ...Dissolved oxygen(DO)is an important indicator of aquaculture,and its accurate forecasting can effectively improve the quality of aquatic products.In this paper,a new DO hybrid forecasting model is proposed that includes three stages:multi-factor analysis,adaptive decomposition,and an optimizationbased ensemble.First,considering the complex factors affecting DO,the grey relational(GR)degree method is used to screen out the environmental factors most closely related to DO.The consideration of multiple factors makes model fusion more effective.Second,the series of DO,water temperature,salinity,and oxygen saturation are decomposed adaptively into sub-series by means of the empirical wavelet transform(EWT)method.Then,five benchmark models are utilized to forecast the sub-series of EWT decomposition.The ensemble weights of these five sub-forecasting models are calculated by particle swarm optimization and gravitational search algorithm(PSOGSA).Finally,a multi-factor ensemble model for DO is obtained by weighted allocation.The performance of the proposed model is verified by timeseries data collected by the pacific islands ocean observing system(PacIOOS)from the WQB04 station at Hilo.The evaluation indicators involved in the experiment include the Nash–Sutcliffe efficiency(NSE),Kling–Gupta efficiency(KGE),mean absolute percent error(MAPE),standard deviation of error(SDE),and coefficient of determination(R^(2)).Example analysis demonstrates that:①The proposed model can obtain excellent DO forecasting results;②the proposed model is superior to other comparison models;and③the forecasting model can be used to analyze the trend of DO and enable managers to make better management decisions.展开更多
Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been s...Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been shown to play an important role in AML leukemogenesis and progression.In the current study,we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas(TCGA)based on differential gene expression analysis and univariable Cox proportional hazards regression analysis.By using multi-model analysis,including Adaptive LASSO regression,LASSO regression,and Elastic Net,we constructed a 9-CSMs prognostic model for risk stratification of the AML patients.The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels.Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients.The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores.Notably,single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance.Furthermore,PI3K inhibitors were identified as potential treatments for these high-risk patients.In conclusion,we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.展开更多
Autoimmune liver disease overlap syndrome(OS)is a rare and clinically significant condition that has received limited attention in microbiome research.In their recent study,Wang et al combined 16S rRNA sequencing with...Autoimmune liver disease overlap syndrome(OS)is a rare and clinically significant condition that has received limited attention in microbiome research.In their recent study,Wang et al combined 16S rRNA sequencing with untargeted metabolomics to characterize the gut-liver axis in OS,identifying shared features of dysbiosis in autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC),and unique signatures,including enrichment of Klebsiella and Escherichia and depletion of aromatic amino acids.In this letter,we critically appraise these findings,emphasizing that OS should be considered a distinct immunometabolic phenotype rather than a simple mixture of AIH and PBC.We discuss the potential mechanistic relevance of the Fusicatenibacter-tyrosine relationship,highlight the clinical implications of integrating microbiota-metabolite analyses,and outline the limitations that future studies must address.展开更多
Traditional global sensitivity analysis(GSA)neglects the epistemic uncertainties associated with the probabilistic characteristics(i.e.type of distribution type and its parameters)of input rock properties emanating du...Traditional global sensitivity analysis(GSA)neglects the epistemic uncertainties associated with the probabilistic characteristics(i.e.type of distribution type and its parameters)of input rock properties emanating due to the small size of datasets while mapping the relative importance of properties to the model response.This paper proposes an augmented Bayesian multi-model inference(BMMI)coupled with GSA methodology(BMMI-GSA)to address this issue by estimating the imprecision in the momentindependent sensitivity indices of rock structures arising from the small size of input data.The methodology employs BMMI to quantify the epistemic uncertainties associated with model type and parameters of input properties.The estimated uncertainties are propagated in estimating imprecision in moment-independent Borgonovo’s indices by employing a reweighting approach on candidate probabilistic models.The proposed methodology is showcased for a rock slope prone to stress-controlled failure in the Himalayan region of India.The proposed methodology was superior to the conventional GSA(neglects all epistemic uncertainties)and Bayesian coupled GSA(B-GSA)(neglects model uncertainty)due to its capability to incorporate the uncertainties in both model type and parameters of properties.Imprecise Borgonovo’s indices estimated via proposed methodology provide the confidence intervals of the sensitivity indices instead of their fixed-point estimates,which makes the user more informed in the data collection efforts.Analyses performed with the varying sample sizes suggested that the uncertainties in sensitivity indices reduce significantly with the increasing sample sizes.The accurate importance ranking of properties was only possible via samples of large sizes.Further,the impact of the prior knowledge in terms of prior ranges and distributions was significant;hence,any related assumption should be made carefully.展开更多
Parkinson' s disease(PD) is a progressive neurodegenerative disorder affecting movement,with no treatments currently available to halt or slow its progression.Therefore,the development of new anti-PD drugs is urge...Parkinson' s disease(PD) is a progressive neurodegenerative disorder affecting movement,with no treatments currently available to halt or slow its progression.Therefore,the development of new anti-PD drugs is urgently needed.As a kind of medicine and food homologous plant,Cistanches Herba has a promising future for the treatment of PD.In this study,a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mouse model was used to detect Cistanches Herba' s anti-PD effects via histopathology and molecular biology.Simultaneously,the effect of Cistanches Herba on the "gut microbiota-barrier axis" was assessed through gut microbiota and intestinal barrier function in mice.Finally,transcriptomics analysis was conducted to further verify the results.As a result,37 differential metabolites and 16 microbial genera were screened and tentatively identified.Thirty-two metabolites and sixteen microbial genera were simultaneously altered with opposing trends in variation after MPTP and Cistanches Herba treatments.We built a framework for predicting targets and hostmicrobe interaction mechanisms,as well as identifying alternative treatment for PD,which should be validated further for clinical application.In conclusion,Cistanches Herba exerts a protective effect against the development of PD by manipulating the structural feature of intestinal flora to influence the host metabolites.展开更多
Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of mul...Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of multi-omics data from The Cancer Genome Atlas colorectal adenocarcinoma cohort(TCGA-COADREAD),accessed through cBioPortal,to develop machine learning models for predicting progression-free survival(PFS)following immunotherapy.The dataset included clinical variables,genomic alterations in Kirsten Rat Sarcoma Viral Oncogene Homolog(KRAS),B-Raf Proto-Oncogene(BRAF),and Neuroblastoma RAS Viral Oncogene Homolog(NRAS),microsatellite instability(MSI)status,tumor mutation burden(TMB),and expression of immune checkpoint genes.Kaplan–Meier analysis showed that KRAS mutations were significantly associated with reduced PFS,while BRAF and NRAS mutations had no significant impact.MSI-high tumors exhibited elevated TMB and increased immune checkpoint expression,reflecting their immunologically active phenotype.We developed both survival and classification models,with the Extra Trees classifier achieving the best performance(accuracy=0.86,precision=0.67,recall=0.70,F1-score=0.68,AUC=0.84).These findings highlight the potential of combining genomic and immune biomarkers with machine learning to improve patient stratification and guide personalized immunotherapy decisions.An interactive web application was also developed to enable clinicians to input patient-specific molecular and clinical data and visualize individualized PFS predictions,supporting timely,data-driven treatment planning.展开更多
This study focused on elucidating the lignocellulose degradation mechanism of Pholiota adiposa strain YAHS,aiming to provide theoretical basis and microbial resources for straw biorefining.Using the aniline blue-guaia...This study focused on elucidating the lignocellulose degradation mechanism of Pholiota adiposa strain YAHS,aiming to provide theoretical basis and microbial resources for straw biorefining.Using the aniline blue-guaiacol plate screening method,11 fungal strains were isolated from the Loess Plateau of northern Shaanxi.The highly efficient degrading strain P.adiposa YAHS was identified through DNS-based enzyme activity assays for cellulase and ligninase,combined with ITS sequence analysis.Whole-genome sequencing was performed using a hybrid approach integrating Illumina NovaSeq and Nanopore MinION platforms.Transcriptome-wide differential gene expression analysis was conducted via DESeq2,and untargeted metabolomics was carried out using UPLC-QTOF-MS.Multi-omics data were integrated to dissect the degradation pathways.Results showed that the genome of P.adiposa YAHS is 55.2 Mb in size,encoding 719 carbohydrate-active enzymes(CAZymes),with glycoside hydrolases(GHs)accounting for 37.4%.Multi-omics analysis revealed that this strain degrades lignocellulose into carbohydrates such as monosaccharides,oligosaccharides,and sugar alcohols through key enzymatic genes(e.g.,exoglucanase,β-glucosidase,β-xylosidase,β-mannanase,monooxygenase)and metabolic pathways(e.g.,sucrose/starch metabolism,fructose/mannose metabolism,anthranilate degradation).We preliminarily elucidated the lignocellulose degradation mechanism of fungi in the genus Pholiota through integrated multi-omics analysis,revealed the critical roles of key cellulolytic enzymes in this process,and provided important microbial resources and theoretical support for the development of novel biorefining technologies.展开更多
The carotenoid-producing strain Rhodosporidium toruloides NP11 and its mutant strain A1-15 were cultivated under salt stress using chemostat cultivation.A multi-omics approach revealed distinct mechanisms between NP11...The carotenoid-producing strain Rhodosporidium toruloides NP11 and its mutant strain A1-15 were cultivated under salt stress using chemostat cultivation.A multi-omics approach revealed distinct mechanisms between NP11 and A1-15 under stress conditions.Salt stress significantly reduced carotenoid production in NP11 but increased it in A1-15,with torularhodin being the predominant carotenoid in A1-15.NP11 exhibited enhanced lipid synthesis under salt stress,suggesting this as its primary adaptive response.In A1-15,reactive oxygen species(ROS)pressure upregulated the CRTI and CRTY genes,with a more pronounced upregulation of CRTI,likely contributing to increased torularhodin production.Additionally,upregulation of the COX7A gene in both strains may support energy demands and mitigate oxidative stress.Notably,this study is the first to mention and explore COX7A in research related to R.toruloides.展开更多
Exploring the tolerance mechanisms of microorganisms to ferulic acid(FA),is pivotal for engineering robust cell factories to produce high-value products from lignocellulosic feedstocks.However,high concentrations of F...Exploring the tolerance mechanisms of microorganisms to ferulic acid(FA),is pivotal for engineering robust cell factories to produce high-value products from lignocellulosic feedstocks.However,high concentrations of FA restrict substrate loading and carbon source conversion efficiency,which has emerged as a critical bottleneck hampering the industrialization of lignin refining.Thus,it is urgent to analyze the FA tolerance mechanism in E.coli.In this study,E.coli was used as the model organism,and high-tolerance strain was screened through integrating transcriptomic and metabolomic analysis.Transcriptomic analysis revealed that under high FA concentrations,the strain activated global regulatory networks and repressed non-essential metabolic pathways.Metabolomic analysis indicated that glycine metabolism was enriched under high FA concentrations to enhance antioxidant capacity,and the detection of FA derivatives demonstrated that E.coli actively converts FA into less toxic compounds for self-detoxification.Combined multi-omics analysis revealed that the co-overexpression of recN,soxS,and yhiM endows E.coli with tolerance to 2 g/L FA.This study provides a theoretical basis and critical targets for engineering FA tolerance in E.coli,laying a foundation for improving the conversion efficiency of strains in complex lignin hydrolysates.This study not only clarifies the FA tolerance mechanism of E.coli but also provides a modified strain for the food-grade biotransformation of FA into high-value food additives,supporting the sustainable utilization of food industry waste.展开更多
Bifidobacterium faces major challenges in the gastrointestinal tract,including inactivation under acidic conditions and insufficient targeted release.In this study,three novel heterologous dual-protein complex systems...Bifidobacterium faces major challenges in the gastrointestinal tract,including inactivation under acidic conditions and insufficient targeted release.In this study,three novel heterologous dual-protein complex systems were constructed by lactoferrin(LF)withα-lactalbumin(ALA),β-lactoglobulin(BLG),casein(CN).Subsequently,sodium alginate(SA)-cross-linked gel microcapsules loaded with these dual-protein complexes and B.animalis F1-7.The optimal preparation conditions for the dual-protein were as follows:ALA/LF=1.5,50℃;BLG/LF=2,50℃;CN/LF=0.5,25℃.Incorporation of SA and endogenous emulsification method enabled efficient encapsulation of B.animalis F1-7,achieving encapsulation efficiency exceeding 90%.B.animalis F1-7@SA-(LF-ALA/BLG/CN)exhibited strong acid resistance,favorable intestinal responsiveness,and significantly improved microbial viability.The microcapsules enhanced gastric acid tolerance primarily through a spatial barrier effect,while the incorporation of dual-protein components contributed to matrix structural reinforcement and digestion-responsive release behavior.This integrated“physical protection-structural modulation”strategy also conferred excellent 28-day storage stability.In vitro experiments by mice/human feces,combined with 16S rRNA and metabolomics analysis,revealed that the composite microcapsules effectively regulated the structure of the microbial community and altered metabolite profiles(e.g.,pathways involved in nitrogen metabolism).Overall,this study provided reproducible preparation parameters and a theoretical basis for SA-based dual-protein composite encapsulation delivery systems,and offered a promising strategy to address the coordinated chal-lenges of activity,controlled release,and storage stability of sensitive food bioactive microorganisms or nutrients.展开更多
Tibetan Qula,a traditional fermented food processed from yak milk,is valued for its high nutritional content and distinctive flavor,but the vast territory of Xizang often results in quality heterogeneity.To identify t...Tibetan Qula,a traditional fermented food processed from yak milk,is valued for its high nutritional content and distinctive flavor,but the vast territory of Xizang often results in quality heterogeneity.To identify the core microorganisms with metabolic activities in Qula,we conducted a comprehensive investigation of 10 samples from 7 regions of Xizang using integrated multi-omics techniques and multivariate statistical analysis.All samples were higher in protein content(36.43-60.25%),acidity(86.72-216.52°T)and lactic acid bacteria count(3.69-6.14 logCFU/g),while lower in fat(2.40-11.35%)and moisture contents(5.84-12.02%).High-throughput sequencing showed significant differences in microbial diversity and community composition among samples,but Lactococcus,Lactobacillus,Leuconostoc,Acetobacter,Penicillium and Aspergillus were core microorganisms due to their high abundance and wide distribution.Notably,they also played an important role in maintaining community interactions,especially Acetobacter.Of the 60 volatiles detected by GC-MS,23 compounds such as hexanal,heptanal,butanoic acid,hexanoic acid and ethyl octanoate were identified as the dominant flavors.In contrast,the 62 non-volatiles obtained from metabolomics were primarily composed of carbohydrates,organic acids,fatty acids and amino acids,with lactose,lactic acid,palmitic acid and alanine being the most abundant metabolites in their respective categories.Correlation analysis indicated that core microorganisms were predominantly involved in the formation and transformation of metabolites,while Lactococcus,Rhodotorula and Trichothecium facilitated the accumulation of various flavors.This study provides a comprehensive analysis of the microbial and metabolic characteristics of Tibetan Qula,offering a scientific foundation for quality enhancement through biofortification technology.展开更多
BACKGROUND The complexity of the immune microenvironment has an impact on the treatment of colorectal cancer(CRC),one of the most prevalent malignancies worldwide.In this study,multi-omics and single-cell sequencing t...BACKGROUND The complexity of the immune microenvironment has an impact on the treatment of colorectal cancer(CRC),one of the most prevalent malignancies worldwide.In this study,multi-omics and single-cell sequencing techniques were used to investigate the mechanism of action of circulating and infiltrating B cells in CRC.By revealing the heterogeneity and functional differences of B cells in cancer immunity,we aim to deepen our understanding of immune regulation and provide a scientific basis for the development of more effective cancer treatment strategies.AIM To explore the role of circulating and infiltrating B cell subsets in the immune microenvironment of CRC,explore the potential driving mechanism of B cell development,analyze the interaction between B cells and other immune cells in the immune microenvironment and the functions of communication molecules,and search for possible regulatory pathways to promote the anti-tumor effects of B cells.METHODS A total of 69 paracancer(normal),tumor and peripheral blood samples were collected from 23 patients with CRC from The Cancer Genome Atlas database(https://portal.gdc.cancer.gov/).After the immune cells were sorted by multicolor flow cytometry,the single cell transcriptome and B cell receptor group library were sequenced using the 10X Genomics platform,and the data were analyzed using bioinformatics tools such as Seurat.The differences in the number and function of B cell infiltration between tumor and normal tissue,the interaction between B cell subsets and T cells and myeloid cell subsets,and the transcription factor regulatory network of B cell subsets were explored and analyzed.RESULTS Compared with normal tissue,the infiltrating number of CD20+B cell subsets in tumor tissue increased significantly.Among them,germinal center B cells(GCB)played the most prominent role,with positive clone expansion and heavy chain mutation level increasing,and the trend of differentiation into memory B cells increased.However,the number of plasma cells in the tumor microenvironment decreased significantly,and the plasma cells secreting IgA antibodies decreased most obviously.In addition,compared with the immune microenvironment of normal tissues,GCB cells in tumor tissues became more closely connected with other immune cells such as T cells,and communication molecules that positively regulate immune function were significantly enriched.CONCLUSION The role of GCB in CRC tumor microenvironment is greatly enhanced,and its affinity to tumor antigen is enhanced by its significantly increased heavy chain mutation level.Meanwhile,GCB has enhanced its association with immune cells in the microenvironment,which plays a positive anti-tumor effect.展开更多
Belimumab is an antibody targeting the cytokine B-cell activating factor(BAFF),which is crucial for B cell differentiation,and is the first molecularly targeted drug approved for systemic lupus erythematosus(SLE).The ...Belimumab is an antibody targeting the cytokine B-cell activating factor(BAFF),which is crucial for B cell differentiation,and is the first molecularly targeted drug approved for systemic lupus erythematosus(SLE).The primary endpoints have been met in clinical trials of belimumab involving patients with active SLE without severe organ complications,as well as in trials involving patients with lupus nephritis.In addition,the effects of belimumab in preventing relapses and reducing glucocorticoid use have been confirmed.Moreover,there were no significant differences in the incidences of many adverse events between the belimumab and placebo groups.Recent multiomics analyses have revealed that the cells targeted by belimumab are limited to naïve B cells and a subset of memory B cells.These findings align with the efficacy and safety profile of belimumab.An improved understanding of the mechanism of action of belimumab could support its use earlier during the treatment course or in a broader range of SLE cases.展开更多
For chromosome abnormalities(CAs),such as Down syndrome(DS),the influence of genomic variations on chromosome conformation and gene transcription remains elusive.Based on the complete genomic sequences from the parent...For chromosome abnormalities(CAs),such as Down syndrome(DS),the influence of genomic variations on chromosome conformation and gene transcription remains elusive.Based on the complete genomic sequences from the parents of a DS trisomy patient,we systematically delineated an atlas of parental-specific,haplotype-resolved single nucleotide polymorphisms(SNPs),copy number variations(CNVs),threedimensional(3D)genome architecture,and RNA expression profiles in the diencephalon of the DS patient.The integrated haplotype-resolved multi-omics analysis demonstrated that one-dimensional(1D)genomic variations including SNPs and CNVs in the DS patient are highly correlated with the alterations in the 3D genome organization and the subsequent changes in gene transcription.This correlation remains valid at the haplotype level.Moreover,we revealed the 3D genome alteration-associated dysregulation of DS-related genes,which facilitates understanding the pathogenesis of CAs.Together,our study contributes to deciphering the coding from 1D genomic variations to 3D genome architecture and the subsequent gene transcription outcomes in both health and disease.展开更多
Background Sustainable livestock production is essential for food security and environmental management. Lignocellulosic biomass can be used in animal feed, thereby reducing feed production costs and enhancing sustain...Background Sustainable livestock production is essential for food security and environmental management. Lignocellulosic biomass can be used in animal feed, thereby reducing feed production costs and enhancing sustainability. Expansin-like proteins(ELPs) play essential roles in plant cell wall degradation, yet their functions remain largely underexplored in rumen microbes. The purpose of this study was to investigate the effects of rumen microbial ELPs on lignocellulose degradation.Results This study systematically identified 396 ELPs within the rumen microbiota, uncovering remarkable diversity, particularly among anaerobic fungi. Three representative ELPs from Pecoramyces ruminantium F1(PFLoos_1, PFSWO1_1, PFSWO2_1) were selected for biochemical characterization. While PFSWO2_1 could not be expressed, PFLoos_1 and PFSWO1_1 exhibited significant synergy with cellulases. The CBM10-containing PFSWO1_1 demonstrated superior thermal stability(up to 65 ℃) and substrate affinity, increasing rice straw hydrolysis efficiency by 21.6%(reducing sugar yield) compared to cellulase alone. Structural analyses revealed that CBM10 enabled PFSWO1_1 to preferentially bind complex substrates, whereas the single-domain PFLoos_1 targeted simpler substrates. Notably, ELP pretreatment of corn stover significantly improved fermentation quality(pH and lactic acid) and nutritional value(neutral detergent fiber, acid detergent fiber, and water-soluble carbohydrates).Conclusions These findings indicate that ELPs are abundant in the rumen and play a synergistic role in lignocellulosic biomass conversion.展开更多
基金financially supported by the National Natural Science Foundation of China(Grant No.32160677)the Hainan University Mango Research System.
文摘Mango(Mangifera indica L.)is one of the main economic crops in Hainan,China,prized for its distinctive flavor and high nutritional value.It is also rich in health-promoting antioxidants such as vitamin C and flavonoids.Enhanced ultraviolet-B(UV—B)radiation,a growing global environmental concern,alters plant antioxidant systems,with increased flavonoid accumulation as a common adaptive response.However,its effects on mango fruit remain largely unexplored.To investigate the antioxidant responses of mango to enhanced UV-B radiation and identify key responsive flavonoid compounds and regulatory genes,we exposed‘Tainong 1’mango fruits growing under natural light to 96 kJ·m^(-2)·d^(-1)of UV-B radiation to simulate high UV-B conditions.Treated fruits were smaller in size and had a pulp of a more intense yellow colour.Further,malondialdehyde content in treated fruits was higher during the phase of rapid fruit enlargement.Additionally,treated fruits showed increased sugar-acid ratios,total phenol,total flavonoid,carotenoid,and ascorbic acid contents.Furthermore,they showed significantly enhanced antioxidant activity,as measured by the FRAP,ABTS,and DPPH assays.Extensive targeted metabolomic-analysis identified flavonoids as the largest category of compounds differentially expressed in treated and control groups.Quantitative metabolomics of flavonoids identified hyperoside,quercimeritrin,and(-)-catechin gallate as the key flavonoid metabolites responsive to UV-B treatment.Transcriptome analysis revealed an enrichment of the flavonoid biosynthesis pathway,with most associated differentially expressed genes showing upregulation.Furthermore,qRT-PCR analysis confirmed that the expression of the genes MiCHS7,MiCHI1,MiCHI2,MiFLS,MiF3H2,and MiF3H3 correlated with changes in key flavonoid metabolites.Indeed,correlation analysis indicated that MiCHS7,MiCHI1,MiFLS,and MiF3H3 are potential key genes involved in flavonoid accumulation under UV-B treatment.Thus,our study provides a theoretical basis for breeding for new resilient varieties and developing UV-B-resistant mango cultivation techniques.
基金funded by the Key Research and Development and Promotion Project of Henan Province(Grant No.232102310130)。
文摘Background: Cancer-associated fibroblasts (CAFs) play critical roles in tumor progression and immunosuppression;however, their contribution to the functional classification and personalized treatment of gastric cancerremains poorly defined. This study aimed to identify effective therapeutic targets to facilitate individualized treatmentstrategies for patients with gastric cancer. Methods: Single-cell and bulk transcriptomic analyses were integrated tocharacterize gastric cancer fibroblasts. “Seurat”, “Slingshot”, and “CellChat” were used for dimensionality reduction,trajectory inference, and cell-cell communication analyses, respectively. Key metastasis-associated fibroblast moduleswere identified using High-dimensional weighted gene co-expression network analysis (hdWGCNA) to construct aprognostic model, which was further evaluated for immune infiltration, therapeutic response, and mutational features.The expression and function of the core gene tripeptidyl peptidase 1 (TPP1) were validated through immunoblotting, PCR, and functional assays. Results: Eight fibroblast subpopulations associated with gastric cancer metastasisexhibited distinct differentiation trajectories and transcriptional heterogeneity. Prognostic analysis indicated thatmetastasis-associated fibroblasts correlated with poor clinical outcomes. The high-risk subgroup showed markedimmunosuppression, resistance to immunotherapy, and reduced mutational burden, with tumor progression-relatedpathways significantly enriched in this group. In vitro experiments further confirmed that TPP1 knockdown suppressedgastric cancer cell metastasis, invasion, and clonogenic capacity while inducing apoptosis. Conclusion: This studycharacterized the heterogeneity of gastric cancer-associated fibroblasts using single-cell transcriptomic analysis andestablished a prognostic model based on metastasis-related fibroblast markers. The model demonstrated strongpredictive performance for patient prognosis, immune landscape, and immunotherapy response. Furthermore, thefindings highlighted the pivotal role of TPP1 in gastric cancer progression and its potential as a therapeutic target.
基金supported by the BRAVE Agile Investment from the PNNL
文摘Background:Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations,such as firefighting,law enforcement,military,and sports.A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work environment.Methods:To study regulatory processes in intense physical activity simulating real-life conditions,we performed a multi-omics analysis of 3 biofluids(blood plasma,urine,and saliva)collected from 11 wildland firefighters before and after a 45 min,intense exercise regimen.Omics profiles post-vs.pre-exercise were compared by Student’s t-test followed by pathway analysis and comparison between the different omics modalities.Results:Our multi-omics analysis identified and quantified 3835 proteins,730 lipids and 182 metabolites combining the 3 different types of samples.The blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy demands.The urine analysis showed a strong,concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites,reabsorption of nutrients and maintenance of fluid balance.In saliva,we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides.A systematic literature review identified 6 papers that support an altered susceptibility to respiratory infection.Conclusions:This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility,suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs.
基金supported by grants from the Medical Engineering Jiont Fund of the Fudan University(No.IDH2310117)。
文摘Objective:Triple-negative breast cancer(TNBC)is a highly aggressive subtype that lacks targeted therapies,leading to a poorer prognosis.However,some patients achieve long-term recurrence-free survival(RFS),offering valuable insights into tumor biology and potential treatment strategies.Methods:We conducted a comprehensive multi-omics analysis of 132 patients with American Joint Committee on Cancer(AJCC)stage III TNBC,comprising 36 long-term survivors(RFS≥8 years),62 moderate-term survivors(RFS:3-8 years),and 34 short-term survivors(RFS<3 years).Analyses investigated clinicopathological factors,whole-exome sequencing,germline mutations,copy number alterations(CNAs),RNA sequences,and metabolomic profiles.Results:Long-term survivors exhibited fewer metastatic regional lymph nodes,along with tumors showing reduced stromal fibrosis and lower Ki67 index.Molecularly,these tumors exhibited multiple alterations in genes related to homologous recombination repair,with higher frequencies of germline mutations and somatic CNAs.Additionally,tumors from long-term survivors demonstrated significant downregulation of the RTK-RAS signaling pathway.Metabolomic profiling revealed decreased levels of lipids and carbohydrate,particularly those involved in glycerophospholipid,fructose,and mannose metabolism,in long-term survival group.Multivariate Cox analysis identified fibrosis[hazard ratio(HR):12.70,95%confidence interval(95%CI):2.19-73.54,P=0.005]and RAC1copy number loss/deletion(HR:0.22,95%CI:0.06-0.83,P=0.026)as independent predictors of RFS.Higher fructose/mannose metabolism was associated with worse overall survival(HR:1.30,95%CI:1.01-1.68,P=0.045).Our findings emphasize the association between biological determinants and prolonged survival in patients with TNBC.Conclusions:Our study systematically identified the key molecular and metabolic features associated with prolonged survival in AJCC stage III TNBC,suggesting potential therapeutic targets to improve patient outcomes.
基金the National Natural Science Foundation of China(61873283)the Changsha Science&Technology Project(KQ1707017)the innovation-driven project of the Central South University(2019CX005).
文摘Dissolved oxygen(DO)is an important indicator of aquaculture,and its accurate forecasting can effectively improve the quality of aquatic products.In this paper,a new DO hybrid forecasting model is proposed that includes three stages:multi-factor analysis,adaptive decomposition,and an optimizationbased ensemble.First,considering the complex factors affecting DO,the grey relational(GR)degree method is used to screen out the environmental factors most closely related to DO.The consideration of multiple factors makes model fusion more effective.Second,the series of DO,water temperature,salinity,and oxygen saturation are decomposed adaptively into sub-series by means of the empirical wavelet transform(EWT)method.Then,five benchmark models are utilized to forecast the sub-series of EWT decomposition.The ensemble weights of these five sub-forecasting models are calculated by particle swarm optimization and gravitational search algorithm(PSOGSA).Finally,a multi-factor ensemble model for DO is obtained by weighted allocation.The performance of the proposed model is verified by timeseries data collected by the pacific islands ocean observing system(PacIOOS)from the WQB04 station at Hilo.The evaluation indicators involved in the experiment include the Nash–Sutcliffe efficiency(NSE),Kling–Gupta efficiency(KGE),mean absolute percent error(MAPE),standard deviation of error(SDE),and coefficient of determination(R^(2)).Example analysis demonstrates that:①The proposed model can obtain excellent DO forecasting results;②the proposed model is superior to other comparison models;and③the forecasting model can be used to analyze the trend of DO and enable managers to make better management decisions.
基金supported by the National Natural Science Foundation of China(Grant Nos.32200590 to K.L.,81972358 to Q.W.,91959113 to Q.W.,and 82372897 to Q.W.)the Natural Science Foundation of Jiangsu Province(Grant No.BK20210530 to K.L.).
文摘Given the extremely high inter-patient heterogeneity of acute myeloid leukemia(AML),the identification of biomarkers for prognostic assessment and therapeutic guidance is critical.Cell surface markers(CSMs)have been shown to play an important role in AML leukemogenesis and progression.In the current study,we evaluated the prognostic potential of all human CSMs in 130 AML patients from The Cancer Genome Atlas(TCGA)based on differential gene expression analysis and univariable Cox proportional hazards regression analysis.By using multi-model analysis,including Adaptive LASSO regression,LASSO regression,and Elastic Net,we constructed a 9-CSMs prognostic model for risk stratification of the AML patients.The predictive value of the 9-CSMs risk score was further validated at the transcriptome and proteome levels.Multivariable Cox regression analysis showed that the risk score was an independent prognostic factor for the AML patients.The AML patients with high 9-CSMs risk scores had a shorter overall and event-free survival time than those with low scores.Notably,single-cell RNA-sequencing analysis indicated that patients with high 9-CSMs risk scores exhibited chemotherapy resistance.Furthermore,PI3K inhibitors were identified as potential treatments for these high-risk patients.In conclusion,we constructed a 9-CSMs prognostic model that served as an independent prognostic factor for the survival of AML patients and held the potential for guiding drug therapy.
基金Supported by the Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education,No.RS-2023-00237287.
文摘Autoimmune liver disease overlap syndrome(OS)is a rare and clinically significant condition that has received limited attention in microbiome research.In their recent study,Wang et al combined 16S rRNA sequencing with untargeted metabolomics to characterize the gut-liver axis in OS,identifying shared features of dysbiosis in autoimmune hepatitis(AIH)and primary biliary cholangitis(PBC),and unique signatures,including enrichment of Klebsiella and Escherichia and depletion of aromatic amino acids.In this letter,we critically appraise these findings,emphasizing that OS should be considered a distinct immunometabolic phenotype rather than a simple mixture of AIH and PBC.We discuss the potential mechanistic relevance of the Fusicatenibacter-tyrosine relationship,highlight the clinical implications of integrating microbiota-metabolite analyses,and outline the limitations that future studies must address.
文摘Traditional global sensitivity analysis(GSA)neglects the epistemic uncertainties associated with the probabilistic characteristics(i.e.type of distribution type and its parameters)of input rock properties emanating due to the small size of datasets while mapping the relative importance of properties to the model response.This paper proposes an augmented Bayesian multi-model inference(BMMI)coupled with GSA methodology(BMMI-GSA)to address this issue by estimating the imprecision in the momentindependent sensitivity indices of rock structures arising from the small size of input data.The methodology employs BMMI to quantify the epistemic uncertainties associated with model type and parameters of input properties.The estimated uncertainties are propagated in estimating imprecision in moment-independent Borgonovo’s indices by employing a reweighting approach on candidate probabilistic models.The proposed methodology is showcased for a rock slope prone to stress-controlled failure in the Himalayan region of India.The proposed methodology was superior to the conventional GSA(neglects all epistemic uncertainties)and Bayesian coupled GSA(B-GSA)(neglects model uncertainty)due to its capability to incorporate the uncertainties in both model type and parameters of properties.Imprecise Borgonovo’s indices estimated via proposed methodology provide the confidence intervals of the sensitivity indices instead of their fixed-point estimates,which makes the user more informed in the data collection efforts.Analyses performed with the varying sample sizes suggested that the uncertainties in sensitivity indices reduce significantly with the increasing sample sizes.The accurate importance ranking of properties was only possible via samples of large sizes.Further,the impact of the prior knowledge in terms of prior ranges and distributions was significant;hence,any related assumption should be made carefully.
基金supported by the National Natural Science Foundation of China (82204375,81903657,82003933)the Science and Technology Development Planning Project of Traditional Chinese Medicine of Jiangsu Province of China (QN202417,QN202103)+9 种基金Supporting Projects of Youth Science Foundation of National Natural Science Foundation of China (XPT82204375)333High-level Talent Development Project in Jiangsu Province ((2024)3-2394)Supporting Projects of Natural Science Foundation of Jiangsu Province (PT20240402)Research Project of Jiangsu Association of Chinese Medicine (CYTF2024021)Jiangsu Science and Technology Association Young Science and Technology Talents Lifting Project(JSTJ-2024-343)Natural Science Foundation of Nanjing University of Chinese Medicine (XZR2021046)the Nanjing Youth Talent Training Plan of TCM (ZYQ20006)NATCM's Project of High-level Construction of Key TCM DisciplinesNanjing University of Chinese Medicine Foundation Youth Project (NZY903657)the Research Project of Jiangsu Commission of Health (Z2023057)。
文摘Parkinson' s disease(PD) is a progressive neurodegenerative disorder affecting movement,with no treatments currently available to halt or slow its progression.Therefore,the development of new anti-PD drugs is urgently needed.As a kind of medicine and food homologous plant,Cistanches Herba has a promising future for the treatment of PD.In this study,a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD mouse model was used to detect Cistanches Herba' s anti-PD effects via histopathology and molecular biology.Simultaneously,the effect of Cistanches Herba on the "gut microbiota-barrier axis" was assessed through gut microbiota and intestinal barrier function in mice.Finally,transcriptomics analysis was conducted to further verify the results.As a result,37 differential metabolites and 16 microbial genera were screened and tentatively identified.Thirty-two metabolites and sixteen microbial genera were simultaneously altered with opposing trends in variation after MPTP and Cistanches Herba treatments.We built a framework for predicting targets and hostmicrobe interaction mechanisms,as well as identifying alternative treatment for PD,which should be validated further for clinical application.In conclusion,Cistanches Herba exerts a protective effect against the development of PD by manipulating the structural feature of intestinal flora to influence the host metabolites.
基金funded by the Research,Development,and Innovation Authority(RDIA)—Kingdom of Saudi Arabia(Grant No.13292-psu-2023-PSNU-R-3-1-EF-).
文摘Colorectal cancer is the third most diagnosed cancer worldwide,and immune checkpoint inhibitors have shown promising therapeutic outcomes in selected patient groups.This study performed a comprehensive analysis of multi-omics data from The Cancer Genome Atlas colorectal adenocarcinoma cohort(TCGA-COADREAD),accessed through cBioPortal,to develop machine learning models for predicting progression-free survival(PFS)following immunotherapy.The dataset included clinical variables,genomic alterations in Kirsten Rat Sarcoma Viral Oncogene Homolog(KRAS),B-Raf Proto-Oncogene(BRAF),and Neuroblastoma RAS Viral Oncogene Homolog(NRAS),microsatellite instability(MSI)status,tumor mutation burden(TMB),and expression of immune checkpoint genes.Kaplan–Meier analysis showed that KRAS mutations were significantly associated with reduced PFS,while BRAF and NRAS mutations had no significant impact.MSI-high tumors exhibited elevated TMB and increased immune checkpoint expression,reflecting their immunologically active phenotype.We developed both survival and classification models,with the Extra Trees classifier achieving the best performance(accuracy=0.86,precision=0.67,recall=0.70,F1-score=0.68,AUC=0.84).These findings highlight the potential of combining genomic and immune biomarkers with machine learning to improve patient stratification and guide personalized immunotherapy decisions.An interactive web application was also developed to enable clinicians to input patient-specific molecular and clinical data and visualize individualized PFS predictions,supporting timely,data-driven treatment planning.
文摘This study focused on elucidating the lignocellulose degradation mechanism of Pholiota adiposa strain YAHS,aiming to provide theoretical basis and microbial resources for straw biorefining.Using the aniline blue-guaiacol plate screening method,11 fungal strains were isolated from the Loess Plateau of northern Shaanxi.The highly efficient degrading strain P.adiposa YAHS was identified through DNS-based enzyme activity assays for cellulase and ligninase,combined with ITS sequence analysis.Whole-genome sequencing was performed using a hybrid approach integrating Illumina NovaSeq and Nanopore MinION platforms.Transcriptome-wide differential gene expression analysis was conducted via DESeq2,and untargeted metabolomics was carried out using UPLC-QTOF-MS.Multi-omics data were integrated to dissect the degradation pathways.Results showed that the genome of P.adiposa YAHS is 55.2 Mb in size,encoding 719 carbohydrate-active enzymes(CAZymes),with glycoside hydrolases(GHs)accounting for 37.4%.Multi-omics analysis revealed that this strain degrades lignocellulose into carbohydrates such as monosaccharides,oligosaccharides,and sugar alcohols through key enzymatic genes(e.g.,exoglucanase,β-glucosidase,β-xylosidase,β-mannanase,monooxygenase)and metabolic pathways(e.g.,sucrose/starch metabolism,fructose/mannose metabolism,anthranilate degradation).We preliminarily elucidated the lignocellulose degradation mechanism of fungi in the genus Pholiota through integrated multi-omics analysis,revealed the critical roles of key cellulolytic enzymes in this process,and provided important microbial resources and theoretical support for the development of novel biorefining technologies.
基金supported by the National Natural Science Foundation of China(31972204).
文摘The carotenoid-producing strain Rhodosporidium toruloides NP11 and its mutant strain A1-15 were cultivated under salt stress using chemostat cultivation.A multi-omics approach revealed distinct mechanisms between NP11 and A1-15 under stress conditions.Salt stress significantly reduced carotenoid production in NP11 but increased it in A1-15,with torularhodin being the predominant carotenoid in A1-15.NP11 exhibited enhanced lipid synthesis under salt stress,suggesting this as its primary adaptive response.In A1-15,reactive oxygen species(ROS)pressure upregulated the CRTI and CRTY genes,with a more pronounced upregulation of CRTI,likely contributing to increased torularhodin production.Additionally,upregulation of the COX7A gene in both strains may support energy demands and mitigate oxidative stress.Notably,this study is the first to mention and explore COX7A in research related to R.toruloides.
基金supported by Key Lab of Process Analysis and Control of Sichuan Universities(Grant No.GCFX2025003).
文摘Exploring the tolerance mechanisms of microorganisms to ferulic acid(FA),is pivotal for engineering robust cell factories to produce high-value products from lignocellulosic feedstocks.However,high concentrations of FA restrict substrate loading and carbon source conversion efficiency,which has emerged as a critical bottleneck hampering the industrialization of lignin refining.Thus,it is urgent to analyze the FA tolerance mechanism in E.coli.In this study,E.coli was used as the model organism,and high-tolerance strain was screened through integrating transcriptomic and metabolomic analysis.Transcriptomic analysis revealed that under high FA concentrations,the strain activated global regulatory networks and repressed non-essential metabolic pathways.Metabolomic analysis indicated that glycine metabolism was enriched under high FA concentrations to enhance antioxidant capacity,and the detection of FA derivatives demonstrated that E.coli actively converts FA into less toxic compounds for self-detoxification.Combined multi-omics analysis revealed that the co-overexpression of recN,soxS,and yhiM endows E.coli with tolerance to 2 g/L FA.This study provides a theoretical basis and critical targets for engineering FA tolerance in E.coli,laying a foundation for improving the conversion efficiency of strains in complex lignin hydrolysates.This study not only clarifies the FA tolerance mechanism of E.coli but also provides a modified strain for the food-grade biotransformation of FA into high-value food additives,supporting the sustainable utilization of food industry waste.
基金supported by National Key Research and Development Program of China[grant number 2024YFF1106500]Natural Science Foundation of Wuhan[grant number 2024040801020285].
文摘Bifidobacterium faces major challenges in the gastrointestinal tract,including inactivation under acidic conditions and insufficient targeted release.In this study,three novel heterologous dual-protein complex systems were constructed by lactoferrin(LF)withα-lactalbumin(ALA),β-lactoglobulin(BLG),casein(CN).Subsequently,sodium alginate(SA)-cross-linked gel microcapsules loaded with these dual-protein complexes and B.animalis F1-7.The optimal preparation conditions for the dual-protein were as follows:ALA/LF=1.5,50℃;BLG/LF=2,50℃;CN/LF=0.5,25℃.Incorporation of SA and endogenous emulsification method enabled efficient encapsulation of B.animalis F1-7,achieving encapsulation efficiency exceeding 90%.B.animalis F1-7@SA-(LF-ALA/BLG/CN)exhibited strong acid resistance,favorable intestinal responsiveness,and significantly improved microbial viability.The microcapsules enhanced gastric acid tolerance primarily through a spatial barrier effect,while the incorporation of dual-protein components contributed to matrix structural reinforcement and digestion-responsive release behavior.This integrated“physical protection-structural modulation”strategy also conferred excellent 28-day storage stability.In vitro experiments by mice/human feces,combined with 16S rRNA and metabolomics analysis,revealed that the composite microcapsules effectively regulated the structure of the microbial community and altered metabolite profiles(e.g.,pathways involved in nitrogen metabolism).Overall,this study provided reproducible preparation parameters and a theoretical basis for SA-based dual-protein composite encapsulation delivery systems,and offered a promising strategy to address the coordinated chal-lenges of activity,controlled release,and storage stability of sensitive food bioactive microorganisms or nutrients.
基金supported by Guizhou Provincial Science and Technology Projects(Qiankehe Jichu[2024]Youth 196,197)Youth Science and Technology Talent Development Project(Qianjiaoji[2024]265).
文摘Tibetan Qula,a traditional fermented food processed from yak milk,is valued for its high nutritional content and distinctive flavor,but the vast territory of Xizang often results in quality heterogeneity.To identify the core microorganisms with metabolic activities in Qula,we conducted a comprehensive investigation of 10 samples from 7 regions of Xizang using integrated multi-omics techniques and multivariate statistical analysis.All samples were higher in protein content(36.43-60.25%),acidity(86.72-216.52°T)and lactic acid bacteria count(3.69-6.14 logCFU/g),while lower in fat(2.40-11.35%)and moisture contents(5.84-12.02%).High-throughput sequencing showed significant differences in microbial diversity and community composition among samples,but Lactococcus,Lactobacillus,Leuconostoc,Acetobacter,Penicillium and Aspergillus were core microorganisms due to their high abundance and wide distribution.Notably,they also played an important role in maintaining community interactions,especially Acetobacter.Of the 60 volatiles detected by GC-MS,23 compounds such as hexanal,heptanal,butanoic acid,hexanoic acid and ethyl octanoate were identified as the dominant flavors.In contrast,the 62 non-volatiles obtained from metabolomics were primarily composed of carbohydrates,organic acids,fatty acids and amino acids,with lactose,lactic acid,palmitic acid and alanine being the most abundant metabolites in their respective categories.Correlation analysis indicated that core microorganisms were predominantly involved in the formation and transformation of metabolites,while Lactococcus,Rhodotorula and Trichothecium facilitated the accumulation of various flavors.This study provides a comprehensive analysis of the microbial and metabolic characteristics of Tibetan Qula,offering a scientific foundation for quality enhancement through biofortification technology.
文摘BACKGROUND The complexity of the immune microenvironment has an impact on the treatment of colorectal cancer(CRC),one of the most prevalent malignancies worldwide.In this study,multi-omics and single-cell sequencing techniques were used to investigate the mechanism of action of circulating and infiltrating B cells in CRC.By revealing the heterogeneity and functional differences of B cells in cancer immunity,we aim to deepen our understanding of immune regulation and provide a scientific basis for the development of more effective cancer treatment strategies.AIM To explore the role of circulating and infiltrating B cell subsets in the immune microenvironment of CRC,explore the potential driving mechanism of B cell development,analyze the interaction between B cells and other immune cells in the immune microenvironment and the functions of communication molecules,and search for possible regulatory pathways to promote the anti-tumor effects of B cells.METHODS A total of 69 paracancer(normal),tumor and peripheral blood samples were collected from 23 patients with CRC from The Cancer Genome Atlas database(https://portal.gdc.cancer.gov/).After the immune cells were sorted by multicolor flow cytometry,the single cell transcriptome and B cell receptor group library were sequenced using the 10X Genomics platform,and the data were analyzed using bioinformatics tools such as Seurat.The differences in the number and function of B cell infiltration between tumor and normal tissue,the interaction between B cell subsets and T cells and myeloid cell subsets,and the transcription factor regulatory network of B cell subsets were explored and analyzed.RESULTS Compared with normal tissue,the infiltrating number of CD20+B cell subsets in tumor tissue increased significantly.Among them,germinal center B cells(GCB)played the most prominent role,with positive clone expansion and heavy chain mutation level increasing,and the trend of differentiation into memory B cells increased.However,the number of plasma cells in the tumor microenvironment decreased significantly,and the plasma cells secreting IgA antibodies decreased most obviously.In addition,compared with the immune microenvironment of normal tissues,GCB cells in tumor tissues became more closely connected with other immune cells such as T cells,and communication molecules that positively regulate immune function were significantly enriched.CONCLUSION The role of GCB in CRC tumor microenvironment is greatly enhanced,and its affinity to tumor antigen is enhanced by its significantly increased heavy chain mutation level.Meanwhile,GCB has enhanced its association with immune cells in the microenvironment,which plays a positive anti-tumor effect.
基金supported by The Center of Innovation Program from the Japan Science and Technology Agency(JST),Grant/Award Number:JPMJCE1304 to Keishi FujioThe Ministry of Education,Culture,Sports,and the Japan Agency for Medical Research and Development(AMED),Grant/Award Numbers:JP21zf0127004,JP21tm0424221,JP22ek0410074,JP22fa627001,JP23fa627001,JP23gm1810005 to Keishi FujioJSPS Grant-in-Aid for Scientific Research(B),Grant/Award Numbers:JP19H03697,JP22H03110,JP23K24369 to Tomohisa Okamura,Chugai Pharmaceutical Co.,Ltd.,Tokyo,Japan.
文摘Belimumab is an antibody targeting the cytokine B-cell activating factor(BAFF),which is crucial for B cell differentiation,and is the first molecularly targeted drug approved for systemic lupus erythematosus(SLE).The primary endpoints have been met in clinical trials of belimumab involving patients with active SLE without severe organ complications,as well as in trials involving patients with lupus nephritis.In addition,the effects of belimumab in preventing relapses and reducing glucocorticoid use have been confirmed.Moreover,there were no significant differences in the incidences of many adverse events between the belimumab and placebo groups.Recent multiomics analyses have revealed that the cells targeted by belimumab are limited to naïve B cells and a subset of memory B cells.These findings align with the efficacy and safety profile of belimumab.An improved understanding of the mechanism of action of belimumab could support its use earlier during the treatment course or in a broader range of SLE cases.
基金supported by the National Natural Science Foundation of China(Grant Nos.32221005 to Gang Cao and 81900063 to He Long)the Natural Science Foundation of Hubei Province,China(Grant No.2022CFB180 to Zhijun Zhang).
文摘For chromosome abnormalities(CAs),such as Down syndrome(DS),the influence of genomic variations on chromosome conformation and gene transcription remains elusive.Based on the complete genomic sequences from the parents of a DS trisomy patient,we systematically delineated an atlas of parental-specific,haplotype-resolved single nucleotide polymorphisms(SNPs),copy number variations(CNVs),threedimensional(3D)genome architecture,and RNA expression profiles in the diencephalon of the DS patient.The integrated haplotype-resolved multi-omics analysis demonstrated that one-dimensional(1D)genomic variations including SNPs and CNVs in the DS patient are highly correlated with the alterations in the 3D genome organization and the subsequent changes in gene transcription.This correlation remains valid at the haplotype level.Moreover,we revealed the 3D genome alteration-associated dysregulation of DS-related genes,which facilitates understanding the pathogenesis of CAs.Together,our study contributes to deciphering the coding from 1D genomic variations to 3D genome architecture and the subsequent gene transcription outcomes in both health and disease.
基金funded by the National Natural Science Foundation of China(grant nos.32372905)。
文摘Background Sustainable livestock production is essential for food security and environmental management. Lignocellulosic biomass can be used in animal feed, thereby reducing feed production costs and enhancing sustainability. Expansin-like proteins(ELPs) play essential roles in plant cell wall degradation, yet their functions remain largely underexplored in rumen microbes. The purpose of this study was to investigate the effects of rumen microbial ELPs on lignocellulose degradation.Results This study systematically identified 396 ELPs within the rumen microbiota, uncovering remarkable diversity, particularly among anaerobic fungi. Three representative ELPs from Pecoramyces ruminantium F1(PFLoos_1, PFSWO1_1, PFSWO2_1) were selected for biochemical characterization. While PFSWO2_1 could not be expressed, PFLoos_1 and PFSWO1_1 exhibited significant synergy with cellulases. The CBM10-containing PFSWO1_1 demonstrated superior thermal stability(up to 65 ℃) and substrate affinity, increasing rice straw hydrolysis efficiency by 21.6%(reducing sugar yield) compared to cellulase alone. Structural analyses revealed that CBM10 enabled PFSWO1_1 to preferentially bind complex substrates, whereas the single-domain PFLoos_1 targeted simpler substrates. Notably, ELP pretreatment of corn stover significantly improved fermentation quality(pH and lactic acid) and nutritional value(neutral detergent fiber, acid detergent fiber, and water-soluble carbohydrates).Conclusions These findings indicate that ELPs are abundant in the rumen and play a synergistic role in lignocellulosic biomass conversion.
