Rice(Oryza sativa)is a staple food for more than half of the world's population and a critical crop for global agriculture.Understanding the regulatory mechanisms that control gene expression in the rice genome is...Rice(Oryza sativa)is a staple food for more than half of the world's population and a critical crop for global agriculture.Understanding the regulatory mechanisms that control gene expression in the rice genome is fundamental for advancing agricultural productivity and food security.In mechanism,cis-regulatory elements(including promoters,enhancers,silencers,and insulators)are key DNA sequences whose activities determine the spatial and temporal expression patterns of nearby genes(Yocca and Edger,2022;Schmitz et al.,2022).展开更多
Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are ne...Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.展开更多
Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report...Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.展开更多
Kang et al.published a research article on the treatment of ischemic stroke using engineered Treg cells(Kang et al.,Prog Biochem Biophys,2025,52(4):946-956.DOI:10.16476/j.pibb.2025.0019).Their study mainly explores th...Kang et al.published a research article on the treatment of ischemic stroke using engineered Treg cells(Kang et al.,Prog Biochem Biophys,2025,52(4):946-956.DOI:10.16476/j.pibb.2025.0019).Their study mainly explores the immunoregulatory role of regulatory T(Treg)cells in ischemic stroke,providing an innovative therapeutic strategy.Neuroinflammation is a major driver of secondary injury after stroke.Existing treatments focus on vascular recanalization while neglecting immune regulation.Their study proposes to modulate neuroinflammation through in vitro-induced Treg cells,offering a novel approach distinct from traditional thrombolysis and endovascular interventions.展开更多
Fruit trees face various adverse environmental factors,such as extreme hydrothermal changes,soil salinization and low precipitation,leading to different types of stress.High temperature is one of the main factors affe...Fruit trees face various adverse environmental factors,such as extreme hydrothermal changes,soil salinization and low precipitation,leading to different types of stress.High temperature is one of the main factors affecting the growth of fruit trees,and an appropriate ambient temperature is a necessary condition for the normal growth and development of fruit trees.Since the 20th century,due to the intensification of the greenhouse effect and global warming,there has been a significant increase in the occurrence and duration of extreme hot weather in summer has been occurring frequently and for longer durations.Thus,the growth and production of fruit trees are affected by severe hightemperature stress.Therefore,this paper primarily summarized the impacts of high-temperature stress on fruit growth and development,flowering,fruiting,fruit setting and quality.It also discussed the physiological and biochemical responses of fruit trees to high-temperature stress,research progress on the molecular mechanisms and signal transduction pathways underlying fruit tree resistance to heat or high temperature,and research on the investigation of relevant metabolites of fruit trees under stress conditions.The future research directions were discussed,and prospects and potential difficulties were proposed to serve a reference for further investigation on the high-temperature tolerance of fruit trees.展开更多
Background:Many studies have examined the role of genes,proteins,andmicroribonucleic acids(miRNAs)in colorectal cancer(CRC).However,these studies did not establish the regulatory relationships among multi-omics,and on...Background:Many studies have examined the role of genes,proteins,andmicroribonucleic acids(miRNAs)in colorectal cancer(CRC).However,these studies did not establish the regulatory relationships among multi-omics,and only a few have investigated the key genes involved in the transition from colorectal adenoma to CRC.In this study,we established regulatory networks of target gene-miRNA-transcription factors(TFs)to elucidate the pathogenesis of CRC.Methods:Data from 70 patients with CRC were obtained from the Gene Expression Omnibus database.Bioinformatics analyses were used to identify the hub genes involved in the colorectal adenoma-carcinoma sequence.We conducted prognostic evaluations,analyzed gene co-expression patterns,assessed immune cell infiltration,and performed Mendelian randomization.A gene-miRNA-TF network was constructed and further analyzed.Results:Periostin(POSTN),thrombospondin 2(THBS2),collagen alpha-2 type I(COL1A2),and other molecules were found to interact and play key roles in the colorectal adenoma-carcinoma sequence.The 3 genes-11 miRNAs-6 TFs regulatory network we constructed was involved in this process through various pathways and interactions with immune cells.Several molecules in this network affected the final prognosis of patients with CRC.THBS2 showed a causal genetic relationship with neutrophils(p=0.035,odds ratio=1.020[95% confidence interval=1.001-1.039]).Therefore,bleomycin and other drugs may potentially improve the prognosis of patients with CRC.Conclusions:The 3 genes-11 miRNAs-6 TFs regulatory network may provide valuable insights into the pathogenesis of CRC.Additionally,some of these molecules may affect patient prognosis,serving as biomarkers or therapeutic targets.THBS2 may promote neutrophil infiltration into CRC tissues by increasing neutrophil levels in the blood.展开更多
Toxin–antitoxin(TA)systems,which are prevalent in bacteria and archaea,play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation.Despite the extensive characterization o...Toxin–antitoxin(TA)systems,which are prevalent in bacteria and archaea,play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation.Despite the extensive characterization of numerous TA systems in various bacteria,the investigation of these systems within Streptococcus suis is still limited.Here,we systematically analyzed the type Ⅱ TA systems of 95 S.suis genomes available in the GenBank database using TAfinder.A total of 612 putative type Ⅱ TA systems were retrieved and classified into 10 categories by phylogenetic analysis.Notably,an elevated occurrence of these TA systems was observed among the important prevalent serotypes 2,4,5,9,14,Chz,NCL1,and NCL3 strains.The following study identified the activities of TA systems using 2 strategies and confirmed the regulatory effect of HigBA on the type Ⅶ secretion system in S.suis by measuringβ-galactosidase activity and transcriptional changes.Moreover,we unveiled a hitherto uncharacterized,highly prevalent novel TA system,with the composition of antitoxin–toxin–antitoxin(SS-ATA),which regulates the downstream two-component signaling system.Altogether,this study systematically analyzed the type Ⅱ TA systems within S.suis,highlighting the widespread distribution of Hig BA and SS-ATA as important regulatory elements in S.suis.展开更多
Intercropping has been widely used in arid and semi-arid regions because of its high yield,stable productivity,and efficient utilization of resources.However,in recent years,the high yield of traditional intercropping...Intercropping has been widely used in arid and semi-arid regions because of its high yield,stable productivity,and efficient utilization of resources.However,in recent years,the high yield of traditional intercropping is mainly attributed to the large amount of purchased resources such as water and fertilizer,plastic film,and mechanical power.These lead to a decline in cultivated land quality and exacerbate intercrops'premature root and canopy senescence.So,the application of traditional intercropping faces major challenges in crop production.This paper analyzes the manifestations,occurrence mechanisms,and agronomic regulatory pathways of crop senescence.The physiological and ecological characteristics of intercropping to delay root and canopy senescence of crops are reviewed in this paper.The main agronomic regulatory pathways of intercropping to delay root and canopy senescence of crops are based on above-and blow-ground interactions,including collocation of crop varieties,spatial arrangement,water and fertilizer management,and tillage and mulch practices.Future research fields of intercropping to delay root and canopy senescence should focus on the aspects of selecting and breeding special varieties,application of molecular biology techniques,and developing or applying models to predict and evaluate the root and canopy senescence process of intercrops.Comprehensive analysis and evaluation of different research results could provide a basis for enhancing intercropping delay root and canopy senescence through adopting innovative technologies for regulating the physio-ecological characteristics of intercrops.This would support developing and adopting high-yield,efficient,and sustainable intercropping systems in arid and semi-arid areas with high population density,limited land,and abundant light and heat resources.展开更多
Overview of root system architecture.The plant root system is a highly dynamic and multifunctional organ system composed of primary roots,lateral roots,adventitious roots,and root hairs.Based on topological morphology...Overview of root system architecture.The plant root system is a highly dynamic and multifunctional organ system composed of primary roots,lateral roots,adventitious roots,and root hairs.Based on topological morphology,root systems can be classified as taproot systems or fibrous root systems.Root system architecture(RSA)refers to the spatial distribution and extension patterns of roots within soil,encompassing characteristics such as root length,branching angle,density,and spatial arrangement.RSA not only determines the plant’s capacity to acquire water and nutrients but also influences other root functions,playing a decisive role in overall plant health.展开更多
Through in-depth analysis of recent domestic research,this review elaborates on the mechanisms of garlic polysaccharides in regulating poultry gut microbiota balance,strengthening intestinal barrier function,and enhan...Through in-depth analysis of recent domestic research,this review elaborates on the mechanisms of garlic polysaccharides in regulating poultry gut microbiota balance,strengthening intestinal barrier function,and enhancing intestinal immunity.It also discusses their practical application effects in poultry farming,existing problems,and future research directions,aiming to provide comprehensive and in-depth theoretical support for promoting the widespread application of garlic polysaccharides in healthy poultry farming.展开更多
Cell cultured meat has been extensively studied as an environmentally friendly,energy-saving and more effective technology.However,there are many technical bottlenecks,especially the regulatory mechanism and manufactu...Cell cultured meat has been extensively studied as an environmentally friendly,energy-saving and more effective technology.However,there are many technical bottlenecks,especially the regulatory mechanism and manufacturing method of in vitro myogenesis.Based on an edible modified silk protein scaffold,with 3D culturing,in situ differentiated and transcriptome analysis,this study describes novel scaffolds and fabrication methods for cell cultured meat.The results showed that the effective space and utilization efficiency for cell culture of the scaffold is 26–1000 that of the traditional culture dish;it could form a tissue-like structure.Transcriptomics revealed the regulatory pathways and key factors of different cycles.It clarifies that the multi-cycle process of myoblast myogenesis in vitro is different from the single feedback regulation in vivo.More importantly,a novel scaffold-based cell cultured meat manufacturing method was developed,further develop a new tissue culture solution that is different from existing cell culture meat production.For manufacturing processes,it provides a new cell culture meat technology system,provides a theoretical basis for the regulation of cell proliferation and muscle growth,and lays the technical foundation for in situ tissue culture of cell cultured meat in vitro.展开更多
Primordial germ cells(PGCs)are the precursors of germline that are specified at the embryonic stage.Recent studies reveal that humans employ different mechanisms for PGC specification compared with model organisms suc...Primordial germ cells(PGCs)are the precursors of germline that are specified at the embryonic stage.Recent studies reveal that humans employ different mechanisms for PGC specification compared with model organisms such as mice.Moreover,the specific regulatory machinery remains largely unexplored,mainly due to the inaccessible nature of this complex biological process in humans.Here,we curate and integrate multi-omics data,including 581 RNA-seq,54 ATAC-seq,45 ChIP-seq,and 69 single-cell RNA-seq samples from different stages of human PGC development to recapitulate the precisely controlled and stepwise process,presenting an atlas in the human PGC database(hPGCdb).With these uniformly processed data and integrated analyses,we characterize the potential key transcription factors and regulatory networks governing human germ cell fate.We validate the important roles of some of the key factors in germ cell development by CRISPRi knockdown.We also identify the soma-germline interaction network and discover the involvement of SDC2 and LAMA4 for PGC development,as well as soma-derived NOTCH2 signaling for germ cell differentiation.Taken together,we have built a database for human PGCs(http://43.131.248.15:6882)and demonstrate that hPGCdb enables the identification of the missing pieces of mechanisms governing germline development,including both intrinsic and extrinsic regulatory programs.展开更多
BACKGROUND Liver hepatocellular carcinoma(LIHC)is a highly aggressive cancer with poor prognosis due to its complex tumor microenvironment(TME)and immune evasion.Regulatory T cells(Tregs)play a critical role in tumor ...BACKGROUND Liver hepatocellular carcinoma(LIHC)is a highly aggressive cancer with poor prognosis due to its complex tumor microenvironment(TME)and immune evasion.Regulatory T cells(Tregs)play a critical role in tumor progression.Suppressor of cytokine signaling 2(SOCS2),a key immune regulator,may modulate Treg activity and impact LIHC growth and metastasis.AIM To explore how the SOCS2 affects Treg activity in LIHC and its impact on tumor growth and metastasis.METHODS LIHC transcriptome data from The Cancer Genome Atlas database were analyzed using Gene Set Enrichment Analysis,Estimation of Stromal and Immune Cells in Malignant Tumors Using Expression Data,and Cell-Type Identification by Estimating Relative Subsets of RNA Transcripts to evaluate immune pathways and Treg infiltration.Key prognostic genes were identified using Weighted Gene Coexpression Network Analysis and machine learning.In vitro,co-culture experiments,migration assays,apoptosis detection,and enzyme-linked immunosorbent assay were conducted.In vivo,tumor growth,metastasis,and apoptosis were assessed using subcutaneous and lung metastasis mouse models with hematoxylin and eosin staining,Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling,and immunohistochemistry analyses.RESULTS SOCS2 overexpression inhibited Treg cell activity,reducing LIHC cell migration and invasion while increasing apoptosis.In vivo,SOCS2 suppressed tumor growth and metastasis,confirming its therapeutic potential.CONCLUSION SOCS2 modulates CD4+T function in the TME,contributing to LIHC progression.Targeting SOCS2 presents a potential therapeutic strategy for treating LIHC.展开更多
The intestinal immune system maintains tolerance to harmless food proteins and gut microbiota through peripherally derived RORγt+Tregs(pTregs),which prevent food intolerance and inflammatory bowel disease.Recent stud...The intestinal immune system maintains tolerance to harmless food proteins and gut microbiota through peripherally derived RORγt+Tregs(pTregs),which prevent food intolerance and inflammatory bowel disease.Recent studies suggested that RORγt+antigen-presenting cells(APCs),which encompass rare dendritic cell(DC)subsets and type 3 innate lymphoid cells(ILC3s),are key to pTreg induction.Here,we developed a mouse with reduced RORγt+APCs by deleting a specific cis-regulatory element of Rorc encoding RORγt.Single-cell RNA sequencing and flow cytometry analyses confirmed the depletion of a RORγt+DC subset and ILC3s.These mice showed a secondary reduction in pTregs,impaired tolerance to oral antigens,and an increase in T helper(Th)2 cells.Conversely,ILC3-deficient mice showed no pTregs or Th2 cell abnormalities.Lineage tracing revealed that RORγt+DCs share a lymphoid origin with ILC3s,consistent with their similar phenotypic traits.These findings highlight the role of lymphoid RORγt+DCs in maintaining intestinal immune balance and preventing conditions like food allergies.展开更多
As living conditions improve and diagnostic capabilities advance,the incidence of tumors has increased,with cancer becoming a leading cause of death worldwide.Surgery,chemotherapy,and radiotherapy are the most common ...As living conditions improve and diagnostic capabilities advance,the incidence of tumors has increased,with cancer becoming a leading cause of death worldwide.Surgery,chemotherapy,and radiotherapy are the most common treatments.Despite advances in treatment options,chemotherapy remains a routine first-line treatment for most tumors.Due to the continuous and extensive use of chemotherapy drugs,tumor resistance often develops,becoming a significant cause of treatment failure and poor prognosis.Recent research has increasingly focused on how long stranded noncoding RNAs(LncRNAs)influence the development of malignant tumors and drug resistance by regulating gene expression and other biological mechanisms during cell growth.Studies have demonstrated that variations in lncRNA expression levels,influenced by both interpatient variability and intratumoral genetic and epigenetic differences,are closely linked to tumor drug resistance.Therefore,this review advocates using lncRNA as a framework to investigate the regulation of genes associated with drug resistance,proposing lncRNA-targeted therapeutic strategies to potentially increase the efficacy of chemotherapy,improve patient outcomes,and guide future research directions.展开更多
Extracellular vesicles(EVs)have emerged as a promising technology for diagnostic and therapeutic applications in clinical settings over the past decade.However,their advancement is hindered by complex technological an...Extracellular vesicles(EVs)have emerged as a promising technology for diagnostic and therapeutic applications in clinical settings over the past decade.However,their advancement is hindered by complex technological and regulatory challenges.This review outlines key considerations in the manufacturing process,quality management,and nonclinical evaluation relevant to EV-based drug development.Furthermore,we summarize and compare technical regulatory requirements across major countries to help clarify the regulatory principles governing EV products.Our analysis reveals an ongoing international debate regarding the regulatory review of EVs.Nevertheless,adopting a risk-based classification framework that categorizes EV products as advanced therapeutic drugs is a rational approach.Critical challenges include the development of standardized production protocols,a clearer understanding of therapeutic mechanisms,and resolving complex regulatory issues.展开更多
AIM:To investigate the expression of interferon regulatory factors(IRFs)in peripheral blood mononuclear cells(PBMCs)of patients with Sjögren’s syndrome-related dry eye(SSDE)and to explore their correlation with ...AIM:To investigate the expression of interferon regulatory factors(IRFs)in peripheral blood mononuclear cells(PBMCs)of patients with Sjögren’s syndrome-related dry eye(SSDE)and to explore their correlation with clinical features,dendritic cell activation,and serological indicators.METHODS:A total of 53 SSDE patients and 62 non-Sjögren’s syndrome dry eye(NSSDE)patients were enrolled.Demographic and clinical data were collected,and comprehensive ophthalmic examinations were performed,including the ocular surface disease index(OSDI)questionnaires,Schirmer I test(SIT),tear break-up time(TBUT),corneal fluorescein staining score(CFS),and in vivo confocal microscopy(IVCM).PBMCs were isolated,and IRFs expression levels were analyzed using Western blotting(WB)and quantitative real-time polymerase chain reaction(qRT-PCR).Serological indicators,including antinuclear antibodies(ANA)and anti-Ro60,anti-Ro52,and anti-La autoantibodies,were detected.Statistical analyses evaluated correlations between IRFs expression and clinical parameters.RESULTS:Compared to NSSDE,the relative mRNA and protein expression of the IRF-8 was significantly upregulated in patients with SSDE(P<0.001),whereas no significant differences were observed in IRF-1,IRF-3,IRF-5,and IRF-7(P=0.12,P=0.10,P=0.66,P=0.96).Correlation analysis revealed that IRF-8 expression was positively associated with CFS and OSDI scores(r=0.57,r=0.38,both P<0.05).Moreover,IRF-8 expression correlated with corneal dendritic cell(DC)density and size,and the number of dendrites(r=0.43,r=0.40,r=0.65,all P<0.05).IRF-8 expression was significantly elevated in patients positive for anti-Ro60,anti-Ro52 and anti-La autoantibodies(P<0.05).CONCLUSION:In SSDE,IRF-8 is upregulated and associated with clinical features,DC activation,and serological indicators.These findings suggest that IRF-8 plays a critical role in SSDE pathogenesis and may serve as a potential therapeutic target for diagnosis and treatment.展开更多
Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects ...Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.展开更多
Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early mar...Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early interventions.There is evidence that regulatory T cells(Tregs)are involved in the development of atherosclerosis.Therefore,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated signatures.Methods:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking medication.Ultrasound of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed.Additionally,tests were conducted to assess blood lipids and determine glucose levels.Immunophenotyping of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow cytometry.Participants were categorized according to atherosclerotic plaque status.Linear and logistic regression models were used to analyze associations between parameters.Results:SAP was detected in a total of 29 participants.The participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and mTregs(OR=1.05(95%CI:1.021.10))as independent risk factors for SAP.Stepwise linear regression could reveal an association of peak oxygen uptake(β=0.441),low-density lipoprotein(LDL)(β=0.096),and SAP(β=6.733)with mTregs and LDL(β=0.104)with rTregs.Conclusion:While at an early stage of SAP,the total proportion of Tregs gives no indication of vascular changes,this is indicated by a shift in the Treg subgroups.Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators.This could be used to initiate lifestyle-based preventive measures at an early stage,which may have a protective effect against disease progression.展开更多
基金supported by the National Natural Science Foundation of China(32070656)。
文摘Rice(Oryza sativa)is a staple food for more than half of the world's population and a critical crop for global agriculture.Understanding the regulatory mechanisms that control gene expression in the rice genome is fundamental for advancing agricultural productivity and food security.In mechanism,cis-regulatory elements(including promoters,enhancers,silencers,and insulators)are key DNA sequences whose activities determine the spatial and temporal expression patterns of nearby genes(Yocca and Edger,2022;Schmitz et al.,2022).
基金supported by the Natural Science Foundation of Fujian Province,No.2021J02035(to WX).
文摘Regulated cell death is a form of cell death that is actively controlled by biomolecules.Several studies have shown that regulated cell death plays a key role after spinal cord injury.Pyroptosis and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal cords.Autophagy,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord injury.This injury triggers not only cell death but also cellular survival responses.Multiple signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and autophagy.Therefore,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord injury.Our analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord injury.Moreover,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.
基金supported by the National Natural Science Foundation of China,Nos.82171429,81771384a grant from Wuxi Municipal Health Commission,No.1286010241190480(all to YS)。
文摘Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.
文摘Kang et al.published a research article on the treatment of ischemic stroke using engineered Treg cells(Kang et al.,Prog Biochem Biophys,2025,52(4):946-956.DOI:10.16476/j.pibb.2025.0019).Their study mainly explores the immunoregulatory role of regulatory T(Treg)cells in ischemic stroke,providing an innovative therapeutic strategy.Neuroinflammation is a major driver of secondary injury after stroke.Existing treatments focus on vascular recanalization while neglecting immune regulation.Their study proposes to modulate neuroinflammation through in vitro-induced Treg cells,offering a novel approach distinct from traditional thrombolysis and endovascular interventions.
基金supported by the“JBGS”Project of Seed Industry Revitalization in Jiangsu Province[Grant No.JBGS(2021)021]the Earmarked Fund for Jiangsu Agricultural Industry Technology System[Grant No.JATS(2022)510]。
文摘Fruit trees face various adverse environmental factors,such as extreme hydrothermal changes,soil salinization and low precipitation,leading to different types of stress.High temperature is one of the main factors affecting the growth of fruit trees,and an appropriate ambient temperature is a necessary condition for the normal growth and development of fruit trees.Since the 20th century,due to the intensification of the greenhouse effect and global warming,there has been a significant increase in the occurrence and duration of extreme hot weather in summer has been occurring frequently and for longer durations.Thus,the growth and production of fruit trees are affected by severe hightemperature stress.Therefore,this paper primarily summarized the impacts of high-temperature stress on fruit growth and development,flowering,fruiting,fruit setting and quality.It also discussed the physiological and biochemical responses of fruit trees to high-temperature stress,research progress on the molecular mechanisms and signal transduction pathways underlying fruit tree resistance to heat or high temperature,and research on the investigation of relevant metabolites of fruit trees under stress conditions.The future research directions were discussed,and prospects and potential difficulties were proposed to serve a reference for further investigation on the high-temperature tolerance of fruit trees.
文摘Background:Many studies have examined the role of genes,proteins,andmicroribonucleic acids(miRNAs)in colorectal cancer(CRC).However,these studies did not establish the regulatory relationships among multi-omics,and only a few have investigated the key genes involved in the transition from colorectal adenoma to CRC.In this study,we established regulatory networks of target gene-miRNA-transcription factors(TFs)to elucidate the pathogenesis of CRC.Methods:Data from 70 patients with CRC were obtained from the Gene Expression Omnibus database.Bioinformatics analyses were used to identify the hub genes involved in the colorectal adenoma-carcinoma sequence.We conducted prognostic evaluations,analyzed gene co-expression patterns,assessed immune cell infiltration,and performed Mendelian randomization.A gene-miRNA-TF network was constructed and further analyzed.Results:Periostin(POSTN),thrombospondin 2(THBS2),collagen alpha-2 type I(COL1A2),and other molecules were found to interact and play key roles in the colorectal adenoma-carcinoma sequence.The 3 genes-11 miRNAs-6 TFs regulatory network we constructed was involved in this process through various pathways and interactions with immune cells.Several molecules in this network affected the final prognosis of patients with CRC.THBS2 showed a causal genetic relationship with neutrophils(p=0.035,odds ratio=1.020[95% confidence interval=1.001-1.039]).Therefore,bleomycin and other drugs may potentially improve the prognosis of patients with CRC.Conclusions:The 3 genes-11 miRNAs-6 TFs regulatory network may provide valuable insights into the pathogenesis of CRC.Additionally,some of these molecules may affect patient prognosis,serving as biomarkers or therapeutic targets.THBS2 may promote neutrophil infiltration into CRC tissues by increasing neutrophil levels in the blood.
基金supported by the National Key Research and Development Program of China(2022YFD1800904)the National Natural Science Foundation of China(31972650 and 32102673)+1 种基金the Postgraduate Research&Practice Innovation Program of Jiangsu Province,China(KYCX22_0780)the China Postdoctoral Science Foundation(2020M682297)。
文摘Toxin–antitoxin(TA)systems,which are prevalent in bacteria and archaea,play diverse roles in bacterial physiology and have been proposed to be significant in stress adaptation.Despite the extensive characterization of numerous TA systems in various bacteria,the investigation of these systems within Streptococcus suis is still limited.Here,we systematically analyzed the type Ⅱ TA systems of 95 S.suis genomes available in the GenBank database using TAfinder.A total of 612 putative type Ⅱ TA systems were retrieved and classified into 10 categories by phylogenetic analysis.Notably,an elevated occurrence of these TA systems was observed among the important prevalent serotypes 2,4,5,9,14,Chz,NCL1,and NCL3 strains.The following study identified the activities of TA systems using 2 strategies and confirmed the regulatory effect of HigBA on the type Ⅶ secretion system in S.suis by measuringβ-galactosidase activity and transcriptional changes.Moreover,we unveiled a hitherto uncharacterized,highly prevalent novel TA system,with the composition of antitoxin–toxin–antitoxin(SS-ATA),which regulates the downstream two-component signaling system.Altogether,this study systematically analyzed the type Ⅱ TA systems within S.suis,highlighting the widespread distribution of Hig BA and SS-ATA as important regulatory elements in S.suis.
基金supported by the National Natural Science Foundation of China(32101857 and U21A20218)the China Agricultural University Corresponding Support Research Joint Fund(GSAU-DKZY-2024-001)+1 种基金the Science and Technology Program in Gansu Province,China(24ZDNA008and23JRRA1407)the Fuxi Young Talents Fund of Gansu Agricultural University,China(Gaufx-03Y10).
文摘Intercropping has been widely used in arid and semi-arid regions because of its high yield,stable productivity,and efficient utilization of resources.However,in recent years,the high yield of traditional intercropping is mainly attributed to the large amount of purchased resources such as water and fertilizer,plastic film,and mechanical power.These lead to a decline in cultivated land quality and exacerbate intercrops'premature root and canopy senescence.So,the application of traditional intercropping faces major challenges in crop production.This paper analyzes the manifestations,occurrence mechanisms,and agronomic regulatory pathways of crop senescence.The physiological and ecological characteristics of intercropping to delay root and canopy senescence of crops are reviewed in this paper.The main agronomic regulatory pathways of intercropping to delay root and canopy senescence of crops are based on above-and blow-ground interactions,including collocation of crop varieties,spatial arrangement,water and fertilizer management,and tillage and mulch practices.Future research fields of intercropping to delay root and canopy senescence should focus on the aspects of selecting and breeding special varieties,application of molecular biology techniques,and developing or applying models to predict and evaluate the root and canopy senescence process of intercrops.Comprehensive analysis and evaluation of different research results could provide a basis for enhancing intercropping delay root and canopy senescence through adopting innovative technologies for regulating the physio-ecological characteristics of intercrops.This would support developing and adopting high-yield,efficient,and sustainable intercropping systems in arid and semi-arid areas with high population density,limited land,and abundant light and heat resources.
文摘Overview of root system architecture.The plant root system is a highly dynamic and multifunctional organ system composed of primary roots,lateral roots,adventitious roots,and root hairs.Based on topological morphology,root systems can be classified as taproot systems or fibrous root systems.Root system architecture(RSA)refers to the spatial distribution and extension patterns of roots within soil,encompassing characteristics such as root length,branching angle,density,and spatial arrangement.RSA not only determines the plant’s capacity to acquire water and nutrients but also influences other root functions,playing a decisive role in overall plant health.
文摘Through in-depth analysis of recent domestic research,this review elaborates on the mechanisms of garlic polysaccharides in regulating poultry gut microbiota balance,strengthening intestinal barrier function,and enhancing intestinal immunity.It also discusses their practical application effects in poultry farming,existing problems,and future research directions,aiming to provide comprehensive and in-depth theoretical support for promoting the widespread application of garlic polysaccharides in healthy poultry farming.
基金funded under the National key research and development plan(2021YFC2101404)Chinese Academy of Engineering Strategic Research and Consulting Project(2023-XZ-79,2022-30-19).
文摘Cell cultured meat has been extensively studied as an environmentally friendly,energy-saving and more effective technology.However,there are many technical bottlenecks,especially the regulatory mechanism and manufacturing method of in vitro myogenesis.Based on an edible modified silk protein scaffold,with 3D culturing,in situ differentiated and transcriptome analysis,this study describes novel scaffolds and fabrication methods for cell cultured meat.The results showed that the effective space and utilization efficiency for cell culture of the scaffold is 26–1000 that of the traditional culture dish;it could form a tissue-like structure.Transcriptomics revealed the regulatory pathways and key factors of different cycles.It clarifies that the multi-cycle process of myoblast myogenesis in vitro is different from the single feedback regulation in vivo.More importantly,a novel scaffold-based cell cultured meat manufacturing method was developed,further develop a new tissue culture solution that is different from existing cell culture meat production.For manufacturing processes,it provides a new cell culture meat technology system,provides a theoretical basis for the regulation of cell proliferation and muscle growth,and lays the technical foundation for in situ tissue culture of cell cultured meat in vitro.
基金supported by the National Natural Science Foundation of China awarded to D.C.(32270835)Zhejiang Natural Science Foundation awarded to D.C.(Z22C129553)Dr.Li Dak Sum&Yip Yio Chin Development Fund for Regenerative Medicine,Zhejiang University,awarded to D.C.
文摘Primordial germ cells(PGCs)are the precursors of germline that are specified at the embryonic stage.Recent studies reveal that humans employ different mechanisms for PGC specification compared with model organisms such as mice.Moreover,the specific regulatory machinery remains largely unexplored,mainly due to the inaccessible nature of this complex biological process in humans.Here,we curate and integrate multi-omics data,including 581 RNA-seq,54 ATAC-seq,45 ChIP-seq,and 69 single-cell RNA-seq samples from different stages of human PGC development to recapitulate the precisely controlled and stepwise process,presenting an atlas in the human PGC database(hPGCdb).With these uniformly processed data and integrated analyses,we characterize the potential key transcription factors and regulatory networks governing human germ cell fate.We validate the important roles of some of the key factors in germ cell development by CRISPRi knockdown.We also identify the soma-germline interaction network and discover the involvement of SDC2 and LAMA4 for PGC development,as well as soma-derived NOTCH2 signaling for germ cell differentiation.Taken together,we have built a database for human PGCs(http://43.131.248.15:6882)and demonstrate that hPGCdb enables the identification of the missing pieces of mechanisms governing germline development,including both intrinsic and extrinsic regulatory programs.
基金Supported by Wu Jieping Medical Foundation,No.320.6750.2021-06-30Guangdong Basic and Applied Basic Research Foundation,No.2019A1515110120National Natural Science Foundation of China,No.82002974。
文摘BACKGROUND Liver hepatocellular carcinoma(LIHC)is a highly aggressive cancer with poor prognosis due to its complex tumor microenvironment(TME)and immune evasion.Regulatory T cells(Tregs)play a critical role in tumor progression.Suppressor of cytokine signaling 2(SOCS2),a key immune regulator,may modulate Treg activity and impact LIHC growth and metastasis.AIM To explore how the SOCS2 affects Treg activity in LIHC and its impact on tumor growth and metastasis.METHODS LIHC transcriptome data from The Cancer Genome Atlas database were analyzed using Gene Set Enrichment Analysis,Estimation of Stromal and Immune Cells in Malignant Tumors Using Expression Data,and Cell-Type Identification by Estimating Relative Subsets of RNA Transcripts to evaluate immune pathways and Treg infiltration.Key prognostic genes were identified using Weighted Gene Coexpression Network Analysis and machine learning.In vitro,co-culture experiments,migration assays,apoptosis detection,and enzyme-linked immunosorbent assay were conducted.In vivo,tumor growth,metastasis,and apoptosis were assessed using subcutaneous and lung metastasis mouse models with hematoxylin and eosin staining,Terminal Deoxynucleotidyl Transferase dUTP Nick End Labeling,and immunohistochemistry analyses.RESULTS SOCS2 overexpression inhibited Treg cell activity,reducing LIHC cell migration and invasion while increasing apoptosis.In vivo,SOCS2 suppressed tumor growth and metastasis,confirming its therapeutic potential.CONCLUSION SOCS2 modulates CD4+T function in the TME,contributing to LIHC progression.Targeting SOCS2 presents a potential therapeutic strategy for treating LIHC.
文摘The intestinal immune system maintains tolerance to harmless food proteins and gut microbiota through peripherally derived RORγt+Tregs(pTregs),which prevent food intolerance and inflammatory bowel disease.Recent studies suggested that RORγt+antigen-presenting cells(APCs),which encompass rare dendritic cell(DC)subsets and type 3 innate lymphoid cells(ILC3s),are key to pTreg induction.Here,we developed a mouse with reduced RORγt+APCs by deleting a specific cis-regulatory element of Rorc encoding RORγt.Single-cell RNA sequencing and flow cytometry analyses confirmed the depletion of a RORγt+DC subset and ILC3s.These mice showed a secondary reduction in pTregs,impaired tolerance to oral antigens,and an increase in T helper(Th)2 cells.Conversely,ILC3-deficient mice showed no pTregs or Th2 cell abnormalities.Lineage tracing revealed that RORγt+DCs share a lymphoid origin with ILC3s,consistent with their similar phenotypic traits.These findings highlight the role of lymphoid RORγt+DCs in maintaining intestinal immune balance and preventing conditions like food allergies.
基金supported by the grant of the Medicine and Health Care Science and Technology Development Plan Projects Foundation of Shandong Province(No.202301060260).
文摘As living conditions improve and diagnostic capabilities advance,the incidence of tumors has increased,with cancer becoming a leading cause of death worldwide.Surgery,chemotherapy,and radiotherapy are the most common treatments.Despite advances in treatment options,chemotherapy remains a routine first-line treatment for most tumors.Due to the continuous and extensive use of chemotherapy drugs,tumor resistance often develops,becoming a significant cause of treatment failure and poor prognosis.Recent research has increasingly focused on how long stranded noncoding RNAs(LncRNAs)influence the development of malignant tumors and drug resistance by regulating gene expression and other biological mechanisms during cell growth.Studies have demonstrated that variations in lncRNA expression levels,influenced by both interpatient variability and intratumoral genetic and epigenetic differences,are closely linked to tumor drug resistance.Therefore,this review advocates using lncRNA as a framework to investigate the regulation of genes associated with drug resistance,proposing lncRNA-targeted therapeutic strategies to potentially increase the efficacy of chemotherapy,improve patient outcomes,and guide future research directions.
基金supported by Zhongshan Major Science and Technology Project(2022A1004).
文摘Extracellular vesicles(EVs)have emerged as a promising technology for diagnostic and therapeutic applications in clinical settings over the past decade.However,their advancement is hindered by complex technological and regulatory challenges.This review outlines key considerations in the manufacturing process,quality management,and nonclinical evaluation relevant to EV-based drug development.Furthermore,we summarize and compare technical regulatory requirements across major countries to help clarify the regulatory principles governing EV products.Our analysis reveals an ongoing international debate regarding the regulatory review of EVs.Nevertheless,adopting a risk-based classification framework that categorizes EV products as advanced therapeutic drugs is a rational approach.Critical challenges include the development of standardized production protocols,a clearer understanding of therapeutic mechanisms,and resolving complex regulatory issues.
基金Supported by National Natural Science Foundation of China(No.82471046)the Joint Medical Research Project of Chongqing Health Commission and Science and Technology Bureau(No.2023GDRC004)the Program for Youth Innovation in Future Medicine of Chongqing Medical University(No.W0185).
文摘AIM:To investigate the expression of interferon regulatory factors(IRFs)in peripheral blood mononuclear cells(PBMCs)of patients with Sjögren’s syndrome-related dry eye(SSDE)and to explore their correlation with clinical features,dendritic cell activation,and serological indicators.METHODS:A total of 53 SSDE patients and 62 non-Sjögren’s syndrome dry eye(NSSDE)patients were enrolled.Demographic and clinical data were collected,and comprehensive ophthalmic examinations were performed,including the ocular surface disease index(OSDI)questionnaires,Schirmer I test(SIT),tear break-up time(TBUT),corneal fluorescein staining score(CFS),and in vivo confocal microscopy(IVCM).PBMCs were isolated,and IRFs expression levels were analyzed using Western blotting(WB)and quantitative real-time polymerase chain reaction(qRT-PCR).Serological indicators,including antinuclear antibodies(ANA)and anti-Ro60,anti-Ro52,and anti-La autoantibodies,were detected.Statistical analyses evaluated correlations between IRFs expression and clinical parameters.RESULTS:Compared to NSSDE,the relative mRNA and protein expression of the IRF-8 was significantly upregulated in patients with SSDE(P<0.001),whereas no significant differences were observed in IRF-1,IRF-3,IRF-5,and IRF-7(P=0.12,P=0.10,P=0.66,P=0.96).Correlation analysis revealed that IRF-8 expression was positively associated with CFS and OSDI scores(r=0.57,r=0.38,both P<0.05).Moreover,IRF-8 expression correlated with corneal dendritic cell(DC)density and size,and the number of dendrites(r=0.43,r=0.40,r=0.65,all P<0.05).IRF-8 expression was significantly elevated in patients positive for anti-Ro60,anti-Ro52 and anti-La autoantibodies(P<0.05).CONCLUSION:In SSDE,IRF-8 is upregulated and associated with clinical features,DC activation,and serological indicators.These findings suggest that IRF-8 plays a critical role in SSDE pathogenesis and may serve as a potential therapeutic target for diagnosis and treatment.
基金supported by the National Key Research and Development Program of China(Grant No.2019YFC1605000)National Natural Science Foundation of China(Grant No.31871806)the Beijing Livestock Industry Innovation Team(BAIC05-2023)。
文摘Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.
基金funded by the Central Hessen Research Campus,Flexi Fund,Project No.20121_1_1.
文摘Background:Atherosclerosis forms the pathological basis for the development of cardiovascular disease.Since pathological processes initially develop without clinically relevant symptoms,the identification of early markers in the subclinical stage plays an important role for initiating early interventions.There is evidence that regulatory T cells(Tregs)are involved in the development of atherosclerosis.Therefore,the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques(SAP).In addition,various lifestyle and risk factors,such as cardiorespiratory fitness,were investigated as associated signatures.Methods:A cross-sectional study was performed in 79 participants(male:n=50;age=63.6±3.7 years;body mass index=24.9±3.1 kg/m2;mean±SD)who had no previous diagnosis of chronic disease and were not taking medication.Ultrasound of the carotids to identify SAP,cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed.Additionally,tests were conducted to assess blood lipids and determine glucose levels.Immunophenotyping of Tregs and their subtypes(resting(rTregs)and effector/memory(mTregs))was performed by 8-chanel flow cytometry.Participants were categorized according to atherosclerotic plaque status.Linear and logistic regression models were used to analyze associations between parameters.Results:SAP was detected in a total of 29 participants.The participants with plaque were older(64.8±3.6 years vs.62.9±3.5 years)and had higher peripheral systolic blood pressure(133.8±14.7 mmHg vs.125.8±10.9 mmHg).The participants with SAP were characterized by a lower percentage of rTregs(28.8%±10.7%vs.34.6%±10.7%)and a higher percentage of mTregs(40.3%±14.7%vs.30.0%±11.9%).Multiple logistic regression identified age(odds ratio(OR)=1.20(95%confidence interval(95%CI):1.011.42))and mTregs(OR=1.05(95%CI:1.021.10))as independent risk factors for SAP.Stepwise linear regression could reveal an association of peak oxygen uptake(β=0.441),low-density lipoprotein(LDL)(β=0.096),and SAP(β=6.733)with mTregs and LDL(β=0.104)with rTregs.Conclusion:While at an early stage of SAP,the total proportion of Tregs gives no indication of vascular changes,this is indicated by a shift in the Treg subgroups.Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators.This could be used to initiate lifestyle-based preventive measures at an early stage,which may have a protective effect against disease progression.
