Tear fluid,also referred to as tears or tear film,is an important biological fluid that plays a key role in maintaining ocular surface health and immune homeostasis.Recent studies have found that tear fluid not only p...Tear fluid,also referred to as tears or tear film,is an important biological fluid that plays a key role in maintaining ocular surface health and immune homeostasis.Recent studies have found that tear fluid not only participates in the occurrence and development of ocular diseases,but also exerts profound effects in the immune pathological mechanisms of systemic diseases,breaking through the inherent understanding previously held by the scientific community.Immune cells in tear fluid(such as T cells,neutrophils,natural killer cells,macrophages),cytokines,and immunoglobulins can specifically participate in autoimmune diseases(such as Sjögren’s syndrome,rheumatoid arthritis,systemic lupus erythematosus,multiple sclerosis,Graves’ophthalmopathy)and systemic diseases(such as Alzheimer’s disease,diabetes mellitus,graft-versus-host disease).The dynamic changes in tear fluid components can reflect systemic immune homeostasis imbalance.Tear fluid biomarkers,such as exosomal microRNA(miR)-204,miR-200b-5p,and the protein markerβ2-microglobulin,have shown great potential in early disease screening,diagnostic stratification,and therapeutic target discovery.Tear fluid immune component analysis may provide innovative diagnostic tools and therapeutic targets for systemic diseases.Future research should focus on promoting the standardization and clinical transformation of tear fluid testing technologies and their clinical application.展开更多
In a series of experiments,Phelps et al.1provided novel data linking moderate-to-vigorous physical activity (MVPA),gut microbiota composition changes and the release of the short chain fatty acid (SCFA) formate,and en...In a series of experiments,Phelps et al.1provided novel data linking moderate-to-vigorous physical activity (MVPA),gut microbiota composition changes and the release of the short chain fatty acid (SCFA) formate,and enhanced antitumor immunity via the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in cytotoxic CD8+T cells.These data support the growing awareness that the clinical benefits of MVPA are achieved at least in part through enhanced immunity with support from the gut microbiome.展开更多
Probiotics can regulate the body’s immune system through both non-specific and specific immunity,thereby regulating host health.In terms of non-specific immune regulation,probiotics can activate the intrinsic immune ...Probiotics can regulate the body’s immune system through both non-specific and specific immunity,thereby regulating host health.In terms of non-specific immune regulation,probiotics can activate the intrinsic immune system,regulate the mucosal barrier function,and play an immune role by influencing the activity of intrinsic immune cells such as macrophages,dendritic cells and natural killer cells,as well as their differentiation and maturation;in terms of specific immune regulation,probiotics play a role in regulating the immunoglobulin level and the maturation of B cells.Probiotics can also regulate T-cell differentiation according to the condition of the body,thus regulating specific immunity.Many studies have focused on the role of probiotics in metabolism and nutrition,and the mechanisms involved in the immunomodulatory role of probiotics have only been partially described.This review summarises the role of common probiotics such as Lactobacillus plantarum and Lactobacillus rhamnosus in immunomodulation as well as their mechanisms,describing the currently known mechanisms of immunomodulation by probiotics in improving the host immune system.A deeper understanding of probiotics and their specific mechanisms of action will facilitate the use of probiotics for immunomodulation in clinical medicine,functional foods,and other areas.This will also contribute to the development and research of engineered probiotics,next-generation probiotics,and other new functional probiotics with immunomodulatory effects.展开更多
Amyotrophic lateral sclerosis is characterized by the progressive loss of motor neurons.Early-stage axonal dysfunction,rather than central nervous system injury,plays a key role in the disease process.However,the mole...Amyotrophic lateral sclerosis is characterized by the progressive loss of motor neurons.Early-stage axonal dysfunction,rather than central nervous system injury,plays a key role in the disease process.However,the molecular mechanisms underlying this dysfunction remain unclear.To investigate the relationship between peripheral immune dysregulation and axonal dysfunction in amyotrophic lateral sclerosis,we recruited 372 patients within the first 12 months of sporadic amyotrophic lateral sclerosis onset between January 2018 and May 2024.We collected peripheral immune markers at baseline,including total leukocytes,lymphocytes,monocytes,neutrophils,basophils,eosinophils,and platelets.We also calculated four derived ratios:neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,lymphocyte-to-monocyte ratio,and systemic immune inflammation index.Multivariate analysis,adjusted for confounding factors,revealed that higher counts of total leukocytes and neutrophils,as well as higher neutrophil-related ratios,including the neutrophil to lymphocyte ratio and the systemic immune inflammation index,were significantly correlated with higher compound muscle action potential scores.Stratified analyses revealed that these associations varied by age and sex.Furthermore,mediation analysis demonstrated that axonal dysfunction plays a significant role in the relationship between immune markers and disease progression.These findings emphasize the critical role that peripheral immune dysregulation plays in amyotrophic lateral sclerosis progression by mediating peripheral nerve injury,particularly in the early stages of the disease.This study highlights the importance of the peripheral nervous system in the early stages of amyotrophic lateral sclerosis and provides new insights into disease mechanisms and potential therapeutic targets.展开更多
Objective:Clinical use of stimulator of interferon genes(STING)agonists has challenges due to poor responsiveness and variable efficacy.Therefore,identifying tumor types that are sensitive to these agents and clarifyi...Objective:Clinical use of stimulator of interferon genes(STING)agonists has challenges due to poor responsiveness and variable efficacy.Therefore,identifying tumor types that are sensitive to these agents and clarifying the underlying mechanisms are essential.Methods:In vitro screening was performed to identify tumor types that are sensitive to STING agonists.The non-nucleotide agonist,SR-717,and the macrocyclic agonist,E7766,were compared for efficacy.Complementary in vivo and in vitro studies,including gene-knockout models,HMGN2-knockout Neuro-2A and CT-2A cells apoptosis assays,and murine tumor models,were then performed.These experiments focused on the mechanism by which SR-717 mediates antitumor effects and emphasized the role of STING signaling-induced high-mobility group nucleosome-binding protein 2(HMGN2).In addition,the potential of HMGN2 as a prognostic biomarker was assessed.Results:Neuroblastomas and glioblastomas,two nervous system tumors,were shown to be sensitive to STING agonists.SR-717 exhibited greater antitumor efficacy compared to E7766.Mechanistic studies indicated that STING agonists promote apoptosis through activation of the intrinsic STING-signal transducer and activator of transcription 1(STAT1)-HMGN2 axis within tumor cells.Ectopic expression of HMGN2 in melanoma cells,which naturally lack HMGN2,led to significant apoptosis.Furthermore,analysis of The Cancer Genome Atlas and Gene Expression Omnibus databases revealed positive correlation between elevated HMGN2 expression and patient survival,supporting the utility of HMGN2 as a prognostic biomarker.Conclusions:This study clarified the mechanism underlying the potent antitumor activity of SR-717 in nervous system tumors through activation of the STING-STAT1-HMGN2 signaling pathway and demonstrated that SR-717 has superior efficacy compared to E7766.In addition,HMGN2 was shown to exhibit translational potential as a prognostic biomarker for patient survival.展开更多
Varicella,a highly contagious respiratory infection caused by the varicella-zoster virus(VZV),predominantly affects children and is characterized by symptoms such as low-grade fever and vesicular rash[1,2].In China,va...Varicella,a highly contagious respiratory infection caused by the varicella-zoster virus(VZV),predominantly affects children and is characterized by symptoms such as low-grade fever and vesicular rash[1,2].In China,varicella remains prevalent,with a steady increase in incidence,peaking at 70.14 cases per 100,000 individuals in 2019[3].Although the number of reported outbreaks and cases from 2020 to 2022 was lower than those from 2006 to 2012 and 2013 to 2019,varicella continues to pose a significant public health challenge[3].展开更多
SalicS1 is a genetically encoded,ratiometric FRET biosensor that brings salicylic acid(SA)research to the same real-time imaging standard long available for ABA and GA.Built through a modular Golden Gate platform and ...SalicS1 is a genetically encoded,ratiometric FRET biosensor that brings salicylic acid(SA)research to the same real-time imaging standard long available for ABA and GA.Built through a modular Golden Gate platform and informed by NPR-NIMIN structural biology,SalicS1 achieves SA specificity,tunable affinity,reversibility,and non-perturbing expression in Arabidopsis.Using this sensor,pathogen infection,non-adapted fungal challenge,and aphid feeding are shown to elicit spatially propagating SA surges rather than purely local accumulation,revealing a tissue-level organization of immune signaling that bulk assays could not resolve.SalicS1 therefore provides a broadly deployable tool for dissecting the geometry,timing,and genotype dependence of SA-mediated plant defense.展开更多
Background The objective of this study was to investigate the impacts of different dietary soybean meal(SBM)levels on jejunal immunity in nursery pigs at different days post-weaning.Methods Forty-eight pigs(6.2±0...Background The objective of this study was to investigate the impacts of different dietary soybean meal(SBM)levels on jejunal immunity in nursery pigs at different days post-weaning.Methods Forty-eight pigs(6.2±0.3 kg),weaned at 21 days of age,were assigned to 2 dietary treatments(n=12)in a randomized complete block design and fed for 20 or 42 d in 3 phases(10,10,and 22 d,respectively).The dietary treatments consisted of low and high SBM diets.On d 20 and 42,jejunal mucosa and tissue samples were collected.Treatments were arranged in 2×2 factors with dietary SBM levels(low and high SBM diets)and days post-weaning(20 d and 42 d post-weaning).Results Pigs fed high SBM diets had greater(P<0.05)relative abundance(RA)of jejunal Prevotella,tended to have greater(P=0.091)jejunal IgA,had greater(P<0.05)crypt depth,and tended to have lower(P=0.064)villus height to crypt depth ratio(VH:CD)than pigs fed low SBM diets.Pigs at 20 d post-weaning had greater(P<0.05)RA of jejunal Lactobacillus and had greater(P<0.05)jejunal IL-8 and protein carbonyl than pigs at 42 d post-weaning.Pigs at 20 d post-weaning tended to have greater(P=0.090)jejunal IgG,tended to have lower(P=0.059)jejunal IgA,and had greater(P<0.05)proportion(%)of Ki-67+cells in the jejunal crypt than pigs at 42 d post-weaning.Conclusion Pigs fed high SBM diets showed greater RA of Staphylococcus,a greater immune response,and a decreased VH:CD in the jejunum than pigs fed low SBM diets.Pigs at 20 d post-weaning were more susceptible to jejunal inflammation and intestinal damage than pigs at 42 d post-weaning,but the negative impacts of high SBM diets on jejunal inflammation and intestinal damage were consistent compared to low SBM diets at 20 d and 42 d post-weaning.展开更多
Objectives:Immunotherapy based on immune checkpoint blockade(ICB)has become a key treatment for melanoma.However,the increasing number of cases of melanoma resistant to immunotherapy highlights the need to develop met...Objectives:Immunotherapy based on immune checkpoint blockade(ICB)has become a key treatment for melanoma.However,the increasing number of cases of melanoma resistant to immunotherapy highlights the need to develop methods to overcome this resistance.This study aims to collect the most recent information on melanoma immunotherapy,discuss potential strategies to overcome resistance to immunotherapy,and identify areas that require further analysis.Methods:To achieve this goal,scientific publications from 2021-2024 available in PubMed and Google Scholar databases were analyzed.The databases were searched using the following terms:“melanoma”,“immunotherapy”,“Immune Checkpoint Blockade”,and“immunoresistance”.Results:The results of preclinical and early-stage clinical research indicate the potential application of tank-binding kinase 1(TBK-1),fecal microbiota transplant(FMT),Toll-like Receptor 9(TLR9),lipid nanoparticles(LNPs)containing a stimulator of an interferon gene agonist(STING),BRAF inhibitors,Lymphocyte Activation Gene(LAG-3),T-Cell Immunoglobulin and ITIM Domain(TIGIT),and oncolytic viruses(OVs)as potential methods to enhance melanoma sensitivity to ICB.Discussion:To optimize immunotherapy,further research is needed to determine the detailed mechanisms of action,safety profiles,tolerability,and precise patient selection criteria for methods capable of overcoming melanoma’s immunoresistance.展开更多
Background:While the treatment of metastatic renal cell carcinoma(mRCC)is evolving due to immune checkpoint inhibitors(ICIs),optimal strategies for later lines of therapy have yet to be defined.The combination of lenv...Background:While the treatment of metastatic renal cell carcinoma(mRCC)is evolving due to immune checkpoint inhibitors(ICIs),optimal strategies for later lines of therapy have yet to be defined.The combination of lenvatinib and everolimus represents a viable option,and the present review aimed to summarize its activity,effectiveness,and safety.Methods:A systematic review of the literature was conducted using PubMed,targeting studies published between 2018 and 2025.Eligible studies included English-language prospective and retrospective trials reporting survival outcomes in mRCC patients treated with lenvatinib and everolimus after at least one ICI-containing regimen.Results:Nine studies met the inclusion criteria,encompassing a total of 441 patients.The lenvatinib and everolimus combination was primarily used in the third and subsequent lines of therapy.Median overall survival ranged from 7.5 to 24.5 months,while median progression-free survival was more consistent,between 6.1 and 6.7 months,except for one study reporting 12.9 months.Objective response rates varied widely(14.0%–55.7%).Adverse events of grade≥3 did not exceed the expected rate,with diarrhoea and proteinuria as the most reported events.Dose reductions and treatment discontinuations due to toxicity occurred but were generally lower than in prior pivotal trials.Conclusions:Real-world evidence suggests that lenvatinib and everolimus represent an effective and safe option after ICI failure in mRCC patients.Nevertheless,the lack of randomized phase III trials and the heterogeneity of existing studies highlight the need for more robust prospective research to guide post-ICI therapeutic strategies.展开更多
Few studies have investigated alterations in the immune cell microenvironment of the dorsal root ganglia following spinal cord injury and whether these modifications facilitate axonal regeneration.In this study,we use...Few studies have investigated alterations in the immune cell microenvironment of the dorsal root ganglia following spinal cord injury and whether these modifications facilitate axonal regeneration.In this study,we used a single-cell RNA sequencing dataset to create a comprehensive profile of the diverse cell types in the dorsal root ganglia and spinal cord of a mid-thoracic contusion injury model in cynomolgus monkeys.Cell communication analysis indicated that specific signaling events among various dorsal root ganglia cell types occur in response to spinal cord injury.Single-cell analysis using dimensionality reduction clustering identified distinct molecular signatures for nine cell types,including macrophage subpopulations,and differential gene expression profiles between dorsal root ganglia cells and spinal cord cells following spinal cord injury.The macrophage subpopulations were categorized into 11 clusters(MC0-MC10)based on differentially expressed genes,with the top 10 genes being ABCA6,RBMS3,EBF1,LAMA4,ANTXR2,LAMA2,SOX5,FOXP2,GHR,and APOD.MC0,MC1,and MC2 constituted the predominant macrophage populations.MC4,MC6,and MC9 were nearly absent in the spinal cord,but exhibited significant increases in the dorsal root ganglia post-spinal cord injury.Notably,these subpopulations possess a strong capacity for regulating axonal regeneration.The developmental progression of dorsal root ganglia macrophages after spinal cord injury was elucidated using cell trajectory and pseudo-time analyses.Genes such as EBF1(MC6 and MC9 marker),RBMS3(MC6 and MC9 marker),and ABCA6(MC6 marker)showed high expression levels in the critical pathways of macrophage function.Through ligand-receptor pair analysis,we determined that the effects of macrophages on microglia are predominantly mediated through interaction pairs(e.g.,SPP1-CD44,LAMC1-CD44,and FN1-CD44),potentially facilitating specific cellular communications within the immune microenvironment.The single-cell RNA sequencing dataset used in this study represents the first comprehensive transcriptional analysis of the dorsal root ganglia after spinal cord injury in cynomolgus monkeys,encompassing nearly all cell types within the dorsal root ganglia region.Using this dataset,we evaluated diverse subtypes of macrophages in the post-spinal cord injury dorsal root ganglia area and examined the signaling pathways that facilitate interactions among immune response-related macrophages in the dorsal root ganglia.Findings from this study provide a theoretical basis for understanding how the immune microenvironment influences the regenerative capacity of dorsal root ganglia neurons after spinal cord injury and offer novel insights into the complex processes underlying the pathobiology of spinal cord injury.展开更多
Plants deploy a two-layered immune system:pathogen-associated molecular pattern(PAMP)-triggered immunity(PTl)and effector-triggered immunity(ETI).While PTI is initiated by cell surface receptors,ETI relies on intracel...Plants deploy a two-layered immune system:pathogen-associated molecular pattern(PAMP)-triggered immunity(PTl)and effector-triggered immunity(ETI).While PTI is initiated by cell surface receptors,ETI relies on intracellular NLR receptors that recognize pathogen effectors(Jones et al.,2024).The nucleoporin CONSTITUTIVE EXPRESSER OF PATHOGENESIS-RELATED GENES 5(CPR5)is a key negative regulator of ETI.CPR5 integrates nuclear transport,cell cycle control,and RNA processing to suppress immune signaling(Wang et al.,2014;Gu et al.,2016;Peng et al.,2022).Recent work revealed that CPR5 also modulates immunity through another nucleoporin,GUANYLATE-BINDING PROTEIN-LIKE 3(GBPL3),which interaCtS with PWWP-DOMAIN INTERACTOR OF POLYCOMBS1(PWO1),a key component of the chromatin-associated methyltransferase POLYCOMB REPRESSIVE COMPLEX 2(PRC2)(Reimann et al.,2023;Pan et al.,2025).These findings suggest unexplored roles for chromatin remodeling in the CPR5-mediated immunity.展开更多
Early life stress correlates with a higher prevalence of neurological disorders,including autism,attention-deficit/hyperactivity disorder,schizophrenia,depression,and Parkinson's disease.These conditions,primarily...Early life stress correlates with a higher prevalence of neurological disorders,including autism,attention-deficit/hyperactivity disorder,schizophrenia,depression,and Parkinson's disease.These conditions,primarily involving abnormal development and damage of the dopaminergic system,pose significant public health challenges.Microglia,as the primary immune cells in the brain,are crucial in regulating neuronal circuit development and survival.From the embryonic stage to adulthood,microglia exhibit stage-specific gene expression profiles,transcriptome characteristics,and functional phenotypes,enhancing the susceptibility to early life stress.However,the role of microglia in mediating dopaminergic system disorders under early life stress conditions remains poorly understood.This review presents an up-to-date overview of preclinical studies elucidating the impact of early life stress on microglia,leading to dopaminergic system disorders,along with the underlying mechanisms and therapeutic potential for neurodegenerative and neurodevelopmental conditions.Impaired microglial activity damages dopaminergic neurons by diminishing neurotrophic support(e.g.,insulin-like growth factor-1)and hinders dopaminergic axon growth through defective phagocytosis and synaptic pruning.Furthermore,blunted microglial immunoreactivity suppresses striatal dopaminergic circuit development and reduces neuronal transmission.Furthermore,inflammation and oxidative stress induced by activated microglia can directly damage dopaminergic neurons,inhibiting dopamine synthesis,reuptake,and receptor activity.Enhanced microglial phagocytosis inhibits dopamine axon extension.These long-lasting effects of microglial perturbations may be driven by early life stress–induced epigenetic reprogramming of microglia.Indirectly,early life stress may influence microglial function through various pathways,such as astrocytic activation,the hypothalamic–pituitary–adrenal axis,the gut–brain axis,and maternal immune signaling.Finally,various therapeutic strategies and molecular mechanisms for targeting microglia to restore the dopaminergic system were summarized and discussed.These strategies include classical antidepressants and antipsychotics,antibiotics and anti-inflammatory agents,and herbal-derived medicine.Further investigations combining pharmacological interventions and genetic strategies are essential to elucidate the causal role of microglial phenotypic and functional perturbations in the dopaminergic system disrupted by early life stress.展开更多
The present study was conducted to determine effects of different forms of yeast （Saccharomyces cerevisiae, strain Y200007） on the growth performance, intestinal development, and systemic immunity in early-weaned pi...The present study was conducted to determine effects of different forms of yeast （Saccharomyces cerevisiae, strain Y200007） on the growth performance, intestinal development, and systemic immunity in early-weaned piglets. A total of 96 piglets （14-d old, initial average body weight of 4.5 kg） were assigned to 4 dietary treatments： （1） basa diet without yeast （Control）; （2） basal diet supplemented with 3.00 g/kg live yeast （LY）; （3） basal diet supplemented with 2.66 g/kg heat-killed whole yeast （HKY）; and （4） basal diet supplemented with 3.00 g/kg superfine yeast powders （SFY）. Diets and water were provided ad libitum to the piglets during 3-week experiment. Growth performance of piglets was measured weekly. Samples of blood and small intestine were collected at days 7 and 21 of experiment. Dietary supplementation with LY and SFY improved G：F of piglets at days ]-21 of the experiment （P 〈 0.05） compared to Control group. Serum concentrations of growth hormone （GH）, triiodothyronine （T3）, tetraiodothyronine （T4）, and insulin growth factor 1 （iGF-1） in piglets at day 21 of the experiment were higher when fed diets supplemented with LY and SFY than those in Control group （P 〈 0.05）. Compared to Control group, contents of serum urea nitrogen of piglets were reduced by the 3 yeast-supplemented diets （P 〈 0.05）. Diets supplemented with LY increased villus height and villus-to-crypt ratio in duodenum and jejunum of piglets （P 〈 0.05） compared to other two groups at day 7 of the experiment. Feeding diets supplemented with LY and SFY increased （P 〈 0.05） serum concentrations of IgA, IL-2, and IL-6 levels in piglets compared to Control. The CD4＋/CD8＋ ratio and proliferation of T-lymphocytes in piglets fed diets supplemented with LY were increased compared to that of Control group at day 7 of the experiment （P 〈 0.05）. In conclusion, dietary supplementation with both LY and SFY enhanced feed conversion, small intestinal development, and systemic immunity in early-weaned piglets, with better improvement in feed conversion by dietary supplementation with LY, while dietary supplementation with SFY was more effective in increasing systemic immune functions in early-weaned piglets.展开更多
BACKGROUND Mesenchymal stem cells(MSCs)have been reported to possess immune regulatory effects in innate and adaptive immune reactions.MSCs can mediate intercellular communications by releasing extracellular vesicles(...BACKGROUND Mesenchymal stem cells(MSCs)have been reported to possess immune regulatory effects in innate and adaptive immune reactions.MSCs can mediate intercellular communications by releasing extracellular vesicles(EVs),which deliver functional molecules to targeted cells.MSC derived EVs(MSC-EVs)confer altering effects on many immune cells,including T lymphocytes,B lymphocytes,natural killer cells,dendritic cells,and macrophages.A large number of studies have suggested that MSC-EVs participate in regulating autoimmunity related diseases.This characteristic of MSC-EVs makes them be potential biomarkers for the diagnosis and treatment of autoimmunity related diseases.AIM To verify the potential of MSC-EVs for molecular targeted therapy of autoimmunity related diseases.METHODS Literature search was conducted in PubMed to retrieve the articles published between 2010 and 2020 in the English language.The keywords,such as“MSCs,”“EVs,”“exosome,”“autoimmunity,”“tumor immunity,”and“transplantation immunity,”and Boolean operator“AND”and“NOT”coalesced admirably to be used for searching studies on the specific molecular mechanisms of MSC-EVs in many immune cell types and many autoimmunity related diseases.Studies that did not investigate the molecular mechanisms of MSC-EVs in the occurrence and development of autoimmune diseases were excluded.RESULTS A total of 96 articles were chosen for final reference lists.After analyzing those publications,we found that it had been well documented that MSC-EVs have the ability to induce multiple immune cells,like T lymphocytes,B lymphocytes,natural killer cells,dendritic cells,and macrophages,to regulate immune responses in innate immunity and adaptive immunity.Many validated EVsdelivered molecules have been identified as key biomarkers,such as proteins,lipids,and nucleotides.Some EVs-encapsulated functional molecules can serve as promising therapeutic targets particularly for autoimmune disease.CONCLUSION MSC-EVs play an equally important part in the differentiation,activation,and proliferation of immune cells,and they may become potential biomarkers for diagnosis and treatment of autoimmunity related diseases.展开更多
In this paper,the security problem for the multi-access edge computing(MEC)network is researched,and an intelligent immunity-based security defense system is proposed to identify the unauthorized mobile users and to p...In this paper,the security problem for the multi-access edge computing(MEC)network is researched,and an intelligent immunity-based security defense system is proposed to identify the unauthorized mobile users and to protect the security of whole system.In the proposed security defense system,the security is protected by the intelligent immunity through three functions,identification function,learning function,and regulation function,respectively.Meanwhile,a three process-based intelligent algorithm is proposed for the intelligent immunity system.Numerical simulations are given to prove the effeteness of the proposed approach.展开更多
Severe Acute Respiratory Syndrome （SARS） is a deadly infectious disease caused by SARS Coronavirus （SARS-CoV）. Inactivated SARS-CoV has been explored as a vaccine against SARS-CoV. However, safe and potent adjuvan...Severe Acute Respiratory Syndrome （SARS） is a deadly infectious disease caused by SARS Coronavirus （SARS-CoV）. Inactivated SARS-CoV has been explored as a vaccine against SARS-CoV. However, safe and potent adjuvants, especially with more efficient and economical needle-free vaccination are alw needed more urgently in a pandemic. The development of a safe and effective mucosal adjuvant and vaccine ays for prevention of emergent infectious diseases such as SARS will be an important advancement. PIKA, a stabilized derivative of Poly （I：C）, was previously reported to be safe and potent as adjuvant in mouse models. In the present study, we demonstrated that the intraperitoneal and intranasal co-administration of inactivated SARS-CoV vaccine together with this improved Poly （I：C） derivative induced strong anti-SARS-CoV mucosal and systemic humoral immune responses with neutralizing activity against pseudotyped virus. Although intraperitoneal immunization of inactivated SARS-CoV vaccine alone could induce a certain level of neutralizing activity in serum as well as in mucosal sites, co-administration of inactivated SARS-CoV vaccine with PIKA as adjuvant could induce a much higher neutralizing activity. When intranasal immunization was used, PIKA was obligatorily for inducing neutralizing activity in serum as well as in mucosal sites and was correlated with both mucosal IgA and mucosal IgG response. Overall, PIKA could be a good mucosal adjuvant candidate for inactivated SARS-CoV vaccine for use in possible future pandemic.展开更多
Background:There is a great demand for antibiotic alternatives to maintain animal health and productivity.The objective of this experiment was to determine the efficacy of dietary supplementation of a blood group A6 t...Background:There is a great demand for antibiotic alternatives to maintain animal health and productivity.The objective of this experiment was to determine the efficacy of dietary supplementation of a blood group A6 type 1antigen oligosaccharides-based polymer(Coligo)on growth performance,diarrhea severity,intestinal health,and systemic immunity of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli(ETEC),when compared with antibiotics.Results:Pigs in antibiotic carbadox or Coligo treatment groups had greater(P<0.05)body weight on d 5 or d 11post-inoculation(PI)than pigs in the control group,respectively.Supplementation of antibiotics or Coligo enhanced(P<0.05)feed efficiency from d 0 to 5 PI and reduced(P<0.05)frequency of diarrhea throughout the experiment,compared with pigs in the control group.Supplementation of antibiotics reduced(P<0.05)fecalβ-hemolytic coliforms on d 2,5,and 8 PI.Pigs in antibiotics or Coligo groups had reduced(P<0.05)neutrophil counts and serum haptoglobin concentration compared to pigs in the control group on d 2 and 5 PI.Pigs in Coligo had reduced(P<0.05)total coliforms in mesenteric lymph nodes on d 5 and 11 PI,whereas pigs in antibiotics or Coligo groups had reduced(P<0.05)total coliforms in spleen on d 11 PI compared with pigs in the control group.On d 5 PI,pigs in the Coligo group had greater(P<0.05)gene expression of ZO1 in jejunal mucosa,but less(P<0.05)m RNA expression of IL1B,IL6,and TNF in ileal mucosa,in comparison with pigs in the control group.Supplementation of antibiotics enhanced(P<0.05)the gene expression of OCLN in jejunal mucosa but decreased(P<0.05)IL1B and IL6 gene expression in ileal mucosa,compared with the control.On d 11 PI,supplementation of antibiotics or Coligo up-regulated(P<0.05)gene expression of CLDN1 in jejunal mucosa,but Coligo reduced(P<0.05)IL6 gene expression in ileal mucosa compared to pigs in the control group.Conclusions:Supplementation of Coligo improved growth performance,alleviated diarrhea severity,and enhanced gut health in weaned pigs infected with ETEC F18 in a manner similar to in-feed antibiotics.展开更多
Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain met...Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.展开更多
The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous syst...The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.展开更多
基金supported by the Medical Scientific Research Foundation of Guangdong Province,China(A2023423)。
文摘Tear fluid,also referred to as tears or tear film,is an important biological fluid that plays a key role in maintaining ocular surface health and immune homeostasis.Recent studies have found that tear fluid not only participates in the occurrence and development of ocular diseases,but also exerts profound effects in the immune pathological mechanisms of systemic diseases,breaking through the inherent understanding previously held by the scientific community.Immune cells in tear fluid(such as T cells,neutrophils,natural killer cells,macrophages),cytokines,and immunoglobulins can specifically participate in autoimmune diseases(such as Sjögren’s syndrome,rheumatoid arthritis,systemic lupus erythematosus,multiple sclerosis,Graves’ophthalmopathy)and systemic diseases(such as Alzheimer’s disease,diabetes mellitus,graft-versus-host disease).The dynamic changes in tear fluid components can reflect systemic immune homeostasis imbalance.Tear fluid biomarkers,such as exosomal microRNA(miR)-204,miR-200b-5p,and the protein markerβ2-microglobulin,have shown great potential in early disease screening,diagnostic stratification,and therapeutic target discovery.Tear fluid immune component analysis may provide innovative diagnostic tools and therapeutic targets for systemic diseases.Future research should focus on promoting the standardization and clinical transformation of tear fluid testing technologies and their clinical application.
文摘In a series of experiments,Phelps et al.1provided novel data linking moderate-to-vigorous physical activity (MVPA),gut microbiota composition changes and the release of the short chain fatty acid (SCFA) formate,and enhanced antitumor immunity via the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway in cytotoxic CD8+T cells.These data support the growing awareness that the clinical benefits of MVPA are achieved at least in part through enhanced immunity with support from the gut microbiome.
基金funded by Ausnutria-kabrita Research Fund(RS2022-14).
文摘Probiotics can regulate the body’s immune system through both non-specific and specific immunity,thereby regulating host health.In terms of non-specific immune regulation,probiotics can activate the intrinsic immune system,regulate the mucosal barrier function,and play an immune role by influencing the activity of intrinsic immune cells such as macrophages,dendritic cells and natural killer cells,as well as their differentiation and maturation;in terms of specific immune regulation,probiotics play a role in regulating the immunoglobulin level and the maturation of B cells.Probiotics can also regulate T-cell differentiation according to the condition of the body,thus regulating specific immunity.Many studies have focused on the role of probiotics in metabolism and nutrition,and the mechanisms involved in the immunomodulatory role of probiotics have only been partially described.This review summarises the role of common probiotics such as Lactobacillus plantarum and Lactobacillus rhamnosus in immunomodulation as well as their mechanisms,describing the currently known mechanisms of immunomodulation by probiotics in improving the host immune system.A deeper understanding of probiotics and their specific mechanisms of action will facilitate the use of probiotics for immunomodulation in clinical medicine,functional foods,and other areas.This will also contribute to the development and research of engineered probiotics,next-generation probiotics,and other new functional probiotics with immunomodulatory effects.
基金Natural Science Foundation of Beijing,No.7244428(to WZ)Peking University Medicine Sailing Program for Young Scholars’Scientific and Technological Innovation,No.BMU2023YFJHPY034(to WZ)+1 种基金the National Natural Science Foundation of China,Nos.81873784(to DF),82071426(to DF)Clinical Cohort Construction Program of Peking University Third Hospital,Nos.BYSYDL2019002(to DF)and BYSYZD2021004(to DF).
文摘Amyotrophic lateral sclerosis is characterized by the progressive loss of motor neurons.Early-stage axonal dysfunction,rather than central nervous system injury,plays a key role in the disease process.However,the molecular mechanisms underlying this dysfunction remain unclear.To investigate the relationship between peripheral immune dysregulation and axonal dysfunction in amyotrophic lateral sclerosis,we recruited 372 patients within the first 12 months of sporadic amyotrophic lateral sclerosis onset between January 2018 and May 2024.We collected peripheral immune markers at baseline,including total leukocytes,lymphocytes,monocytes,neutrophils,basophils,eosinophils,and platelets.We also calculated four derived ratios:neutrophil-to-lymphocyte ratio,platelet-to-lymphocyte ratio,lymphocyte-to-monocyte ratio,and systemic immune inflammation index.Multivariate analysis,adjusted for confounding factors,revealed that higher counts of total leukocytes and neutrophils,as well as higher neutrophil-related ratios,including the neutrophil to lymphocyte ratio and the systemic immune inflammation index,were significantly correlated with higher compound muscle action potential scores.Stratified analyses revealed that these associations varied by age and sex.Furthermore,mediation analysis demonstrated that axonal dysfunction plays a significant role in the relationship between immune markers and disease progression.These findings emphasize the critical role that peripheral immune dysregulation plays in amyotrophic lateral sclerosis progression by mediating peripheral nerve injury,particularly in the early stages of the disease.This study highlights the importance of the peripheral nervous system in the early stages of amyotrophic lateral sclerosis and provides new insights into disease mechanisms and potential therapeutic targets.
文摘Objective:Clinical use of stimulator of interferon genes(STING)agonists has challenges due to poor responsiveness and variable efficacy.Therefore,identifying tumor types that are sensitive to these agents and clarifying the underlying mechanisms are essential.Methods:In vitro screening was performed to identify tumor types that are sensitive to STING agonists.The non-nucleotide agonist,SR-717,and the macrocyclic agonist,E7766,were compared for efficacy.Complementary in vivo and in vitro studies,including gene-knockout models,HMGN2-knockout Neuro-2A and CT-2A cells apoptosis assays,and murine tumor models,were then performed.These experiments focused on the mechanism by which SR-717 mediates antitumor effects and emphasized the role of STING signaling-induced high-mobility group nucleosome-binding protein 2(HMGN2).In addition,the potential of HMGN2 as a prognostic biomarker was assessed.Results:Neuroblastomas and glioblastomas,two nervous system tumors,were shown to be sensitive to STING agonists.SR-717 exhibited greater antitumor efficacy compared to E7766.Mechanistic studies indicated that STING agonists promote apoptosis through activation of the intrinsic STING-signal transducer and activator of transcription 1(STAT1)-HMGN2 axis within tumor cells.Ectopic expression of HMGN2 in melanoma cells,which naturally lack HMGN2,led to significant apoptosis.Furthermore,analysis of The Cancer Genome Atlas and Gene Expression Omnibus databases revealed positive correlation between elevated HMGN2 expression and patient survival,supporting the utility of HMGN2 as a prognostic biomarker.Conclusions:This study clarified the mechanism underlying the potent antitumor activity of SR-717 in nervous system tumors through activation of the STING-STAT1-HMGN2 signaling pathway and demonstrated that SR-717 has superior efficacy compared to E7766.In addition,HMGN2 was shown to exhibit translational potential as a prognostic biomarker for patient survival.
文摘Varicella,a highly contagious respiratory infection caused by the varicella-zoster virus(VZV),predominantly affects children and is characterized by symptoms such as low-grade fever and vesicular rash[1,2].In China,varicella remains prevalent,with a steady increase in incidence,peaking at 70.14 cases per 100,000 individuals in 2019[3].Although the number of reported outbreaks and cases from 2020 to 2022 was lower than those from 2006 to 2012 and 2013 to 2019,varicella continues to pose a significant public health challenge[3].
基金supported by the Anhui Province Tongxin Science and Technology Innovation Project(202523b11020014)the Anhui Province Higher Education Quality Engineering Program(2024fwxx003).
文摘SalicS1 is a genetically encoded,ratiometric FRET biosensor that brings salicylic acid(SA)research to the same real-time imaging standard long available for ABA and GA.Built through a modular Golden Gate platform and informed by NPR-NIMIN structural biology,SalicS1 achieves SA specificity,tunable affinity,reversibility,and non-perturbing expression in Arabidopsis.Using this sensor,pathogen infection,non-adapted fungal challenge,and aphid feeding are shown to elicit spatially propagating SA surges rather than purely local accumulation,revealing a tissue-level organization of immune signaling that bulk assays could not resolve.SalicS1 therefore provides a broadly deployable tool for dissecting the geometry,timing,and genotype dependence of SA-mediated plant defense.
文摘Background The objective of this study was to investigate the impacts of different dietary soybean meal(SBM)levels on jejunal immunity in nursery pigs at different days post-weaning.Methods Forty-eight pigs(6.2±0.3 kg),weaned at 21 days of age,were assigned to 2 dietary treatments(n=12)in a randomized complete block design and fed for 20 or 42 d in 3 phases(10,10,and 22 d,respectively).The dietary treatments consisted of low and high SBM diets.On d 20 and 42,jejunal mucosa and tissue samples were collected.Treatments were arranged in 2×2 factors with dietary SBM levels(low and high SBM diets)and days post-weaning(20 d and 42 d post-weaning).Results Pigs fed high SBM diets had greater(P<0.05)relative abundance(RA)of jejunal Prevotella,tended to have greater(P=0.091)jejunal IgA,had greater(P<0.05)crypt depth,and tended to have lower(P=0.064)villus height to crypt depth ratio(VH:CD)than pigs fed low SBM diets.Pigs at 20 d post-weaning had greater(P<0.05)RA of jejunal Lactobacillus and had greater(P<0.05)jejunal IL-8 and protein carbonyl than pigs at 42 d post-weaning.Pigs at 20 d post-weaning tended to have greater(P=0.090)jejunal IgG,tended to have lower(P=0.059)jejunal IgA,and had greater(P<0.05)proportion(%)of Ki-67+cells in the jejunal crypt than pigs at 42 d post-weaning.Conclusion Pigs fed high SBM diets showed greater RA of Staphylococcus,a greater immune response,and a decreased VH:CD in the jejunum than pigs fed low SBM diets.Pigs at 20 d post-weaning were more susceptible to jejunal inflammation and intestinal damage than pigs at 42 d post-weaning,but the negative impacts of high SBM diets on jejunal inflammation and intestinal damage were consistent compared to low SBM diets at 20 d and 42 d post-weaning.
文摘Objectives:Immunotherapy based on immune checkpoint blockade(ICB)has become a key treatment for melanoma.However,the increasing number of cases of melanoma resistant to immunotherapy highlights the need to develop methods to overcome this resistance.This study aims to collect the most recent information on melanoma immunotherapy,discuss potential strategies to overcome resistance to immunotherapy,and identify areas that require further analysis.Methods:To achieve this goal,scientific publications from 2021-2024 available in PubMed and Google Scholar databases were analyzed.The databases were searched using the following terms:“melanoma”,“immunotherapy”,“Immune Checkpoint Blockade”,and“immunoresistance”.Results:The results of preclinical and early-stage clinical research indicate the potential application of tank-binding kinase 1(TBK-1),fecal microbiota transplant(FMT),Toll-like Receptor 9(TLR9),lipid nanoparticles(LNPs)containing a stimulator of an interferon gene agonist(STING),BRAF inhibitors,Lymphocyte Activation Gene(LAG-3),T-Cell Immunoglobulin and ITIM Domain(TIGIT),and oncolytic viruses(OVs)as potential methods to enhance melanoma sensitivity to ICB.Discussion:To optimize immunotherapy,further research is needed to determine the detailed mechanisms of action,safety profiles,tolerability,and precise patient selection criteria for methods capable of overcoming melanoma’s immunoresistance.
文摘Background:While the treatment of metastatic renal cell carcinoma(mRCC)is evolving due to immune checkpoint inhibitors(ICIs),optimal strategies for later lines of therapy have yet to be defined.The combination of lenvatinib and everolimus represents a viable option,and the present review aimed to summarize its activity,effectiveness,and safety.Methods:A systematic review of the literature was conducted using PubMed,targeting studies published between 2018 and 2025.Eligible studies included English-language prospective and retrospective trials reporting survival outcomes in mRCC patients treated with lenvatinib and everolimus after at least one ICI-containing regimen.Results:Nine studies met the inclusion criteria,encompassing a total of 441 patients.The lenvatinib and everolimus combination was primarily used in the third and subsequent lines of therapy.Median overall survival ranged from 7.5 to 24.5 months,while median progression-free survival was more consistent,between 6.1 and 6.7 months,except for one study reporting 12.9 months.Objective response rates varied widely(14.0%–55.7%).Adverse events of grade≥3 did not exceed the expected rate,with diarrhoea and proteinuria as the most reported events.Dose reductions and treatment discontinuations due to toxicity occurred but were generally lower than in prior pivotal trials.Conclusions:Real-world evidence suggests that lenvatinib and everolimus represent an effective and safe option after ICI failure in mRCC patients.Nevertheless,the lack of randomized phase III trials and the heterogeneity of existing studies highlight the need for more robust prospective research to guide post-ICI therapeutic strategies.
基金supported by the Tianjin Key Medical Discipline(Specialty)Construct Project,No.TJYXZDXK-027A(to SF)the National Key Research andDevelopment Project of Stem Cell and Transformation Research,No.2019YFA0112100(to SF)+2 种基金Tianjin Natural Science Foundation’s Youth Project for DiverseInvestments,No.21JCQNJC01300(to BF)the National Natural Science Foundation of China(Youth Program),No.82102563(to BF)Tianjin Major Science andTechnology Special Projects and Engineering Projects,No.21ZXJBSY00080(to YR).
文摘Few studies have investigated alterations in the immune cell microenvironment of the dorsal root ganglia following spinal cord injury and whether these modifications facilitate axonal regeneration.In this study,we used a single-cell RNA sequencing dataset to create a comprehensive profile of the diverse cell types in the dorsal root ganglia and spinal cord of a mid-thoracic contusion injury model in cynomolgus monkeys.Cell communication analysis indicated that specific signaling events among various dorsal root ganglia cell types occur in response to spinal cord injury.Single-cell analysis using dimensionality reduction clustering identified distinct molecular signatures for nine cell types,including macrophage subpopulations,and differential gene expression profiles between dorsal root ganglia cells and spinal cord cells following spinal cord injury.The macrophage subpopulations were categorized into 11 clusters(MC0-MC10)based on differentially expressed genes,with the top 10 genes being ABCA6,RBMS3,EBF1,LAMA4,ANTXR2,LAMA2,SOX5,FOXP2,GHR,and APOD.MC0,MC1,and MC2 constituted the predominant macrophage populations.MC4,MC6,and MC9 were nearly absent in the spinal cord,but exhibited significant increases in the dorsal root ganglia post-spinal cord injury.Notably,these subpopulations possess a strong capacity for regulating axonal regeneration.The developmental progression of dorsal root ganglia macrophages after spinal cord injury was elucidated using cell trajectory and pseudo-time analyses.Genes such as EBF1(MC6 and MC9 marker),RBMS3(MC6 and MC9 marker),and ABCA6(MC6 marker)showed high expression levels in the critical pathways of macrophage function.Through ligand-receptor pair analysis,we determined that the effects of macrophages on microglia are predominantly mediated through interaction pairs(e.g.,SPP1-CD44,LAMC1-CD44,and FN1-CD44),potentially facilitating specific cellular communications within the immune microenvironment.The single-cell RNA sequencing dataset used in this study represents the first comprehensive transcriptional analysis of the dorsal root ganglia after spinal cord injury in cynomolgus monkeys,encompassing nearly all cell types within the dorsal root ganglia region.Using this dataset,we evaluated diverse subtypes of macrophages in the post-spinal cord injury dorsal root ganglia area and examined the signaling pathways that facilitate interactions among immune response-related macrophages in the dorsal root ganglia.Findings from this study provide a theoretical basis for understanding how the immune microenvironment influences the regenerative capacity of dorsal root ganglia neurons after spinal cord injury and offer novel insights into the complex processes underlying the pathobiology of spinal cord injury.
基金supported by grants from the National Natural Science Foundation of China(32270290)the Shanghai Engineering Research Center of Plant Germplasm Resources(17DZ2252700).
文摘Plants deploy a two-layered immune system:pathogen-associated molecular pattern(PAMP)-triggered immunity(PTl)and effector-triggered immunity(ETI).While PTI is initiated by cell surface receptors,ETI relies on intracellular NLR receptors that recognize pathogen effectors(Jones et al.,2024).The nucleoporin CONSTITUTIVE EXPRESSER OF PATHOGENESIS-RELATED GENES 5(CPR5)is a key negative regulator of ETI.CPR5 integrates nuclear transport,cell cycle control,and RNA processing to suppress immune signaling(Wang et al.,2014;Gu et al.,2016;Peng et al.,2022).Recent work revealed that CPR5 also modulates immunity through another nucleoporin,GUANYLATE-BINDING PROTEIN-LIKE 3(GBPL3),which interaCtS with PWWP-DOMAIN INTERACTOR OF POLYCOMBS1(PWO1),a key component of the chromatin-associated methyltransferase POLYCOMB REPRESSIVE COMPLEX 2(PRC2)(Reimann et al.,2023;Pan et al.,2025).These findings suggest unexplored roles for chromatin remodeling in the CPR5-mediated immunity.
基金supported by the National Natural Science Foundation of China,Nos.82304990(to NY),81973748(to JC),82174278(to JC)the National Key R&D Program of China,No.2023YFE0209500(to JC)+4 种基金China Postdoctoral Science Foundation,No.2023M732380(to NY)Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine,No.202102010014(to JC)Huang Zhendong Research Fund for Traditional Chinese Medicine of Jinan University,No.201911(to JC)National Innovation and Entrepreneurship Training Program for Undergraduates in China,No.202310559128(to NY and QM)Innovation and Entrepreneurship Training Program for Undergraduates at Jinan University,Nos.CX24380,CX24381(both to NY and QM)。
文摘Early life stress correlates with a higher prevalence of neurological disorders,including autism,attention-deficit/hyperactivity disorder,schizophrenia,depression,and Parkinson's disease.These conditions,primarily involving abnormal development and damage of the dopaminergic system,pose significant public health challenges.Microglia,as the primary immune cells in the brain,are crucial in regulating neuronal circuit development and survival.From the embryonic stage to adulthood,microglia exhibit stage-specific gene expression profiles,transcriptome characteristics,and functional phenotypes,enhancing the susceptibility to early life stress.However,the role of microglia in mediating dopaminergic system disorders under early life stress conditions remains poorly understood.This review presents an up-to-date overview of preclinical studies elucidating the impact of early life stress on microglia,leading to dopaminergic system disorders,along with the underlying mechanisms and therapeutic potential for neurodegenerative and neurodevelopmental conditions.Impaired microglial activity damages dopaminergic neurons by diminishing neurotrophic support(e.g.,insulin-like growth factor-1)and hinders dopaminergic axon growth through defective phagocytosis and synaptic pruning.Furthermore,blunted microglial immunoreactivity suppresses striatal dopaminergic circuit development and reduces neuronal transmission.Furthermore,inflammation and oxidative stress induced by activated microglia can directly damage dopaminergic neurons,inhibiting dopamine synthesis,reuptake,and receptor activity.Enhanced microglial phagocytosis inhibits dopamine axon extension.These long-lasting effects of microglial perturbations may be driven by early life stress–induced epigenetic reprogramming of microglia.Indirectly,early life stress may influence microglial function through various pathways,such as astrocytic activation,the hypothalamic–pituitary–adrenal axis,the gut–brain axis,and maternal immune signaling.Finally,various therapeutic strategies and molecular mechanisms for targeting microglia to restore the dopaminergic system were summarized and discussed.These strategies include classical antidepressants and antipsychotics,antibiotics and anti-inflammatory agents,and herbal-derived medicine.Further investigations combining pharmacological interventions and genetic strategies are essential to elucidate the causal role of microglial phenotypic and functional perturbations in the dopaminergic system disrupted by early life stress.
基金financially supported by grants from China Agriculture Research System(CARS-36)the Special Fund for Agro-scientific Research in the Public Interest(No.201403047)+1 种基金National Basic Research Program of China(2013CB127301 and 2013CB127304)Presidential Foundation of Guangdong Academy of Agricultural Sciences(201312)
文摘The present study was conducted to determine effects of different forms of yeast （Saccharomyces cerevisiae, strain Y200007） on the growth performance, intestinal development, and systemic immunity in early-weaned piglets. A total of 96 piglets （14-d old, initial average body weight of 4.5 kg） were assigned to 4 dietary treatments： （1） basa diet without yeast （Control）; （2） basal diet supplemented with 3.00 g/kg live yeast （LY）; （3） basal diet supplemented with 2.66 g/kg heat-killed whole yeast （HKY）; and （4） basal diet supplemented with 3.00 g/kg superfine yeast powders （SFY）. Diets and water were provided ad libitum to the piglets during 3-week experiment. Growth performance of piglets was measured weekly. Samples of blood and small intestine were collected at days 7 and 21 of experiment. Dietary supplementation with LY and SFY improved G：F of piglets at days ]-21 of the experiment （P 〈 0.05） compared to Control group. Serum concentrations of growth hormone （GH）, triiodothyronine （T3）, tetraiodothyronine （T4）, and insulin growth factor 1 （iGF-1） in piglets at day 21 of the experiment were higher when fed diets supplemented with LY and SFY than those in Control group （P 〈 0.05）. Compared to Control group, contents of serum urea nitrogen of piglets were reduced by the 3 yeast-supplemented diets （P 〈 0.05）. Diets supplemented with LY increased villus height and villus-to-crypt ratio in duodenum and jejunum of piglets （P 〈 0.05） compared to other two groups at day 7 of the experiment. Feeding diets supplemented with LY and SFY increased （P 〈 0.05） serum concentrations of IgA, IL-2, and IL-6 levels in piglets compared to Control. The CD4＋/CD8＋ ratio and proliferation of T-lymphocytes in piglets fed diets supplemented with LY were increased compared to that of Control group at day 7 of the experiment （P 〈 0.05）. In conclusion, dietary supplementation with both LY and SFY enhanced feed conversion, small intestinal development, and systemic immunity in early-weaned piglets, with better improvement in feed conversion by dietary supplementation with LY, while dietary supplementation with SFY was more effective in increasing systemic immune functions in early-weaned piglets.
文摘BACKGROUND Mesenchymal stem cells(MSCs)have been reported to possess immune regulatory effects in innate and adaptive immune reactions.MSCs can mediate intercellular communications by releasing extracellular vesicles(EVs),which deliver functional molecules to targeted cells.MSC derived EVs(MSC-EVs)confer altering effects on many immune cells,including T lymphocytes,B lymphocytes,natural killer cells,dendritic cells,and macrophages.A large number of studies have suggested that MSC-EVs participate in regulating autoimmunity related diseases.This characteristic of MSC-EVs makes them be potential biomarkers for the diagnosis and treatment of autoimmunity related diseases.AIM To verify the potential of MSC-EVs for molecular targeted therapy of autoimmunity related diseases.METHODS Literature search was conducted in PubMed to retrieve the articles published between 2010 and 2020 in the English language.The keywords,such as“MSCs,”“EVs,”“exosome,”“autoimmunity,”“tumor immunity,”and“transplantation immunity,”and Boolean operator“AND”and“NOT”coalesced admirably to be used for searching studies on the specific molecular mechanisms of MSC-EVs in many immune cell types and many autoimmunity related diseases.Studies that did not investigate the molecular mechanisms of MSC-EVs in the occurrence and development of autoimmune diseases were excluded.RESULTS A total of 96 articles were chosen for final reference lists.After analyzing those publications,we found that it had been well documented that MSC-EVs have the ability to induce multiple immune cells,like T lymphocytes,B lymphocytes,natural killer cells,dendritic cells,and macrophages,to regulate immune responses in innate immunity and adaptive immunity.Many validated EVsdelivered molecules have been identified as key biomarkers,such as proteins,lipids,and nucleotides.Some EVs-encapsulated functional molecules can serve as promising therapeutic targets particularly for autoimmune disease.CONCLUSION MSC-EVs play an equally important part in the differentiation,activation,and proliferation of immune cells,and they may become potential biomarkers for diagnosis and treatment of autoimmunity related diseases.
基金This work was supported by National Natural Science Foundation of China(No.61971026)the Fundamental Research Funds for the Central Universities(No.FRF-TP-18-008A3).
文摘In this paper,the security problem for the multi-access edge computing(MEC)network is researched,and an intelligent immunity-based security defense system is proposed to identify the unauthorized mobile users and to protect the security of whole system.In the proposed security defense system,the security is protected by the intelligent immunity through three functions,identification function,learning function,and regulation function,respectively.Meanwhile,a three process-based intelligent algorithm is proposed for the intelligent immunity system.Numerical simulations are given to prove the effeteness of the proposed approach.
基金supported by the National Natural Science Foundation of China (30670097)National Basic Research Program of China (973 Program) (2005CB522903)+1 种基金National Key R&D Program (2007BAI28B04)National S&T Major Project on Major Infectious Diseases (2008ZX10001-010)from the Ministry of Science and Technology of the People’s Republic of China
文摘Severe Acute Respiratory Syndrome （SARS） is a deadly infectious disease caused by SARS Coronavirus （SARS-CoV）. Inactivated SARS-CoV has been explored as a vaccine against SARS-CoV. However, safe and potent adjuvants, especially with more efficient and economical needle-free vaccination are alw needed more urgently in a pandemic. The development of a safe and effective mucosal adjuvant and vaccine ays for prevention of emergent infectious diseases such as SARS will be an important advancement. PIKA, a stabilized derivative of Poly （I：C）, was previously reported to be safe and potent as adjuvant in mouse models. In the present study, we demonstrated that the intraperitoneal and intranasal co-administration of inactivated SARS-CoV vaccine together with this improved Poly （I：C） derivative induced strong anti-SARS-CoV mucosal and systemic humoral immune responses with neutralizing activity against pseudotyped virus. Although intraperitoneal immunization of inactivated SARS-CoV vaccine alone could induce a certain level of neutralizing activity in serum as well as in mucosal sites, co-administration of inactivated SARS-CoV vaccine with PIKA as adjuvant could induce a much higher neutralizing activity. When intranasal immunization was used, PIKA was obligatorily for inducing neutralizing activity in serum as well as in mucosal sites and was correlated with both mucosal IgA and mucosal IgG response. Overall, PIKA could be a good mucosal adjuvant candidate for inactivated SARS-CoV vaccine for use in possible future pandemic.
基金supported by Pancosma SAGenevaSwitzerland and the United States Department of Agriculture(USDA)National Institute of Food and Agriculture(NIFA),multistate projects W4002 and NC1202。
文摘Background:There is a great demand for antibiotic alternatives to maintain animal health and productivity.The objective of this experiment was to determine the efficacy of dietary supplementation of a blood group A6 type 1antigen oligosaccharides-based polymer(Coligo)on growth performance,diarrhea severity,intestinal health,and systemic immunity of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli(ETEC),when compared with antibiotics.Results:Pigs in antibiotic carbadox or Coligo treatment groups had greater(P<0.05)body weight on d 5 or d 11post-inoculation(PI)than pigs in the control group,respectively.Supplementation of antibiotics or Coligo enhanced(P<0.05)feed efficiency from d 0 to 5 PI and reduced(P<0.05)frequency of diarrhea throughout the experiment,compared with pigs in the control group.Supplementation of antibiotics reduced(P<0.05)fecalβ-hemolytic coliforms on d 2,5,and 8 PI.Pigs in antibiotics or Coligo groups had reduced(P<0.05)neutrophil counts and serum haptoglobin concentration compared to pigs in the control group on d 2 and 5 PI.Pigs in Coligo had reduced(P<0.05)total coliforms in mesenteric lymph nodes on d 5 and 11 PI,whereas pigs in antibiotics or Coligo groups had reduced(P<0.05)total coliforms in spleen on d 11 PI compared with pigs in the control group.On d 5 PI,pigs in the Coligo group had greater(P<0.05)gene expression of ZO1 in jejunal mucosa,but less(P<0.05)m RNA expression of IL1B,IL6,and TNF in ileal mucosa,in comparison with pigs in the control group.Supplementation of antibiotics enhanced(P<0.05)the gene expression of OCLN in jejunal mucosa but decreased(P<0.05)IL1B and IL6 gene expression in ileal mucosa,compared with the control.On d 11 PI,supplementation of antibiotics or Coligo up-regulated(P<0.05)gene expression of CLDN1 in jejunal mucosa,but Coligo reduced(P<0.05)IL6 gene expression in ileal mucosa compared to pigs in the control group.Conclusions:Supplementation of Coligo improved growth performance,alleviated diarrhea severity,and enhanced gut health in weaned pigs infected with ETEC F18 in a manner similar to in-feed antibiotics.
基金supported by the National Natural Science Foundation of China, No.82274616the Key Laboratory Project for General Universities in Guangdong Province, No.2019KSYS005Guangdong Province Science and Technology Plan International Cooperation Project, No.2020A0505100052 (all to QW)。
文摘Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.
文摘The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.
