Biological sex is increasingly recognized as a crucial factor in evaluating the translational value of preclinical spinal cord injury(SCI)studies.The rising incidence of SCI in females challenges the historical preced...Biological sex is increasingly recognized as a crucial factor in evaluating the translational value of preclinical spinal cord injury(SCI)studies.The rising incidence of SCI in females challenges the historical precedent of SCI being a male-dominated condition.In contrast,most basic science researchers utilize single-sex studies to minimize complications associated with bladder care in males(Stewart et al.,2020).The findings of our recent publication identify sexually dimorphic immune responses to SCI in both mice and pigs(Kumari et al.,2025).Here,we will highlight these findings and discuss the impact of sex on SCI inflammation and recovery.展开更多
The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions l...The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions like calf diarrhea is an emerging area of research nowadays because of increased concerns regarding antimicrobial resistance(AMR)and drug residues in animal products.Probiotics reduce the incidence of calf diarrhea by increasing the gut microbiota diversity and richness with more commensal bacteria such as Lactobacillus and Bifidobacterium that produce antimicrobial compounds,as well as modulating the immune response by increasing cytokines,Interleukin-2(IL-2),IL-4,IL-6,IL-10,and reducing tumor necrosis factor-α(TNF-α),by increasing production of antibodies,especially immunoglobulin E(Ig E),also Ig G,differentiating naive Th lymphocytes(Tho)into Th1,hence stimulate innate immunity and prime the adaptive immune response.Specific probiotic strains of bacteria and yeast(Saccharomyces cerevisiae)derived probiotics maintain the integrity of the intestinal barrier.In this review,data are being organized to address the role of probiotics in treating calf diarrhea by modulating gut microbiota and stimulating an immune response against notorious pathogens,to present animal and veterinary scientists and nutritionists with a new concept to treat infectious diseases from the perspective of the gut microbiota,increasing animal health,performance,and welfare.In conclusion,health status and gut microbiome are strongly interlinked.Research data indicated a significant reduction in the incidence of diarrhea after probiotic administration.If interrelations between probiotics and existing gut microbiota are explored more quantitatively,novel antibiotic substitutes can emerge in the future.展开更多
The emergence of novel phytopathogens and the accelerated spread of plant diseases to new regions,driven by global climate change,constitute significant threats to agricultural resources.Rice,a major tropical staple c...The emergence of novel phytopathogens and the accelerated spread of plant diseases to new regions,driven by global climate change,constitute significant threats to agricultural resources.Rice,a major tropical staple crucial for global food security,possesses six transcription factor superfamilies-AP2/ERF,bHLH,bZIP,MYB,NAC,and WRKY-that function in innate immunity against pathogens.We review their biological functions and regulatory mechanisms in rice immunity.展开更多
Accumulating evidence indicates that antibiotic exposure may lead to impaired vaccine responses1-4;however,the mechanisms underlying this association remain poorly understood.Here we prospectively followed 191 healthy...Accumulating evidence indicates that antibiotic exposure may lead to impaired vaccine responses1-4;however,the mechanisms underlying this association remain poorly understood.Here we prospectively followed 191 healthy,vaginally born,term infants from birth to 15 months,using a systems vaccinology approach to assess the effects of antibiotic exposure on immune responses to vaccination.Exposure to direct neonatal but not intrapartum antibiotics was associated with significantly lower antibody titres against various polysaccharides in the 13-valent pneumococcal conjugate vaccine and the Haemophilus influenzae type b polyribosylribitol phosphate and diphtheria toxoid antigens in the combined 6-in-1 Infanrix Hexa vaccine at 7 months of age.Blood from infants exposed to neonatal antibiotics had an inflammatory transcriptional profile before vaccination;in addition,faecal metagenomics showed reduced abundance of Bifidobacterium species in these infants at the time of vaccination,which was correlated with reduced vaccine antibody titres 6 months later.In preclinical models,responses to the 13-valent pneumococcal conjugate vaccine were strongly dependent on an intact microbiota but could be restored in germ-free mice by administering a consortium of Bifidobacterium species or a probiotic already widely used in neonatal units.Our data suggest that microbiota-targeted interventions could mitigate the detrimental effects of early-life antibiotics on vaccine immunogenicity.展开更多
Low-dose radiation therapy has emerged as a promising modality for cancer treatment because of its ability to stimulate antitumor immune responses while minimizing damage to healthy tissues.However,the significant het...Low-dose radiation therapy has emerged as a promising modality for cancer treatment because of its ability to stimulate antitumor immune responses while minimizing damage to healthy tissues.However,the significant heterogeneity in immune responses among patients complicates its clinical application,hindering outcome prediction and treatment personalization.Artificial intelligence(AI)offers a transformative solution by integrating multidimensional data such as immunomics,radiomics,and clinical features to decode complex immune pa-tterns and predict individual therapeutic outcomes.This editorial explored the potential of AI to address immune response heterogeneity in low-dose radiation therapy and proposed an AI-driven framework for precision immunotherapy.While promising,challenges,including data standardization,model interpre-tability,and clinical validation,must be overcome to ensure successful integration into oncological practice.展开更多
BACKGROUND Radiotherapy(RT)is a cornerstone of cancer treatment.Compared with conven-tional high-dose radiation,low-dose radiation(LDR)causes less damage to normal tissues while potentially modulating immune responses...BACKGROUND Radiotherapy(RT)is a cornerstone of cancer treatment.Compared with conven-tional high-dose radiation,low-dose radiation(LDR)causes less damage to normal tissues while potentially modulating immune responses and inhibiting tumor growth.LDR stimulates both innate and adaptive immunity,enhancing the activity of natural killer cells,dendritic cells,and T cells.However,the me-chanisms underlying the effects of LDR on the immune system remain unclear.AIM To explore the history,research hotspots,and emerging trends in immune response to LDR literature over the past two decades.METHODS Publications on immune responses to LDR were retrieved from the Web of Science Core Collection.Bibliometric tools,including CiteSpace and HistCite,were used to identify historical features,active topics,and emerging trends in this field.RESULTS Analysis of 1244 publications over the past two decades revealed a significant surge in research on immune responses to LDR,particularly in the last decade.Key journals such as INR J Radiat Biol,Cancers,and Radiat Res published pivotal studies.Citation networks identified key studies by authors like Twyman-Saint Victor C(2015)and Vanpouille-Box C(2017).Keyword analysis revealed hotspots such as ipilimumab,stereotactic body RT,and targeted therapy,possibly identifying future research directions.Temporal variations in keyword clusters and alluvial flow maps illustrate the evolution of research themes over time.CONCLUSION This bibliometric analysis provides valuable insights into the evolution of studies on responses to LDR,highlights research trends,and identifies emerging areas for further investigation.展开更多
Small RNAs(sRNAs)are a class of molecules capable of perceiving environmental changes and exerting posttranscriptional regulation over target gene expression,thereby influencing bacterial virulence and host immune res...Small RNAs(sRNAs)are a class of molecules capable of perceiving environmental changes and exerting posttranscriptional regulation over target gene expression,thereby influencing bacterial virulence and host immune responses.Pseudomonas plecoglossicida is a pathogenic bacterium that poses a significant threat to aquatic animal health.However,the regulatory mechanisms of sRNAs in P.plecoglossicida remain unclear.This study focused on sRNA113,previously identified as a potential regulator of the fliP gene,a key component of the lateral flagellar type III secretion system.To investigate the effects of sRNA113on P.plecoglossicida virulence,as well as its role in regulating pathogenic processes and host immune responses,mutant strains lacking this sRNA were generated and analyzed.Deletion of sRNA113 resulted in the up-regulation of lateral flagellar type III secretion system-related genes in P.plecoglossicida,which enhanced bacterial swarming motility,biofilm formation,and chemotaxis ability in vitro.In vivo infection experiments with pearl gentian grouper revealed that sRNA113 deletion enhanced the pathogenicity of P.plecoglossicida.This heightened virulence was attributed to the up-regulation of genes associated with the lateral flagellar type III secretion system,resulting in higher bacterial loads within host tissues.This amplification of pathogenic activity intensified tissue damage,disrupted immune responses,and impaired the ability of the host to clear infection,ultimately leading to mortality.These findings underscore the critical role of sRNA113 in regulating the virulence of P.plecoglossicida and its interaction with host immune defenses.This study provides a foundation for further exploration of sRNAmediated mechanisms in bacterial pathogenesis and hostpathogen interactions,contributing to a deeper understanding of virulence regulation and immune evasion in aquatic pathogens.展开更多
Infants exhibit diminished susceptibility to external infections,a phenomenon closely linked to the pervasive presence of the bifidobacterial community within their intestinal tract.Nonetheless,a significant knowledge...Infants exhibit diminished susceptibility to external infections,a phenomenon closely linked to the pervasive presence of the bifidobacterial community within their intestinal tract.Nonetheless,a significant knowledge gap remains concerning the distinct species of bifidobacteria initiating anti-infection immune responses during the early developmental stages.In this study,the impact of early intervention with Bifidobacterium bifidum,Bifidobacterium breve,and Bifidobacterium longum on neonatal rats infected with Salmonella enterica serovar Typhimurium SL1344 were compared.The study encompasses various immunity levels,including gut immunity,central immunity(thymus),peripheral immunity(spleen),and brain immunity.Following Salmonella infection,significant alterations in neonatal rats were observed in growth and developmental levels,immune markers,cytokine levels,balance of T lymphocyte subpopulations,intestinal barrier function,and blood-brain barrier integrity.Compared with B.breve and B.longum,B.bifidum demonstrated more pronounced efficacy in regulating these physiological processes.By conducting multi-level analyses of gut microbiota,bifidobacterial community,colonic content metabolomics,and serum metabolomics,the significance of B.bifidum’s role is underscored,and the immune-enhancing function of messenger metabolites is unveiled.Among these metabolites,γ-L-glutamyl-L-glutamic acid and orotic acid were found to be shared by all 3 species,while hippuric acid and 1a,1b-dihomo prostaglandin F2αwere unique to B.bifidum,and DL-arginine was specific to B.longum.Overall,this study has provided novel insights into the intervention and immunomodulation by Bifidobacterium in early-life infections,emphasizing the significant role of B.bifidum.展开更多
Brucellosis,a zoonotic disease caused by Brucella infection,poses a major threat to both global health and livestock productivity.Although reproductive impairment is well established,the molecular mechanisms driving t...Brucellosis,a zoonotic disease caused by Brucella infection,poses a major threat to both global health and livestock productivity.Although reproductive impairment is well established,the molecular mechanisms driving testicular immunopathology remain poorly understood.In this study,single-cell RNA sequencing was used to delineate transcriptional changes in goat testicular tissues under physiological and Brucella-infected conditions,revealing dynamic immunological remodeling of the testicular microenvironment.Infection induced marked shifts in T cell and macrophage phenotypes,with T cells exhibiting pronounced hyperactivation linked to CD45-mediated signaling cascades.Thioredoxin-interacting protein(TXNIP),a gene strongly up-regulated in response to infection,emerged as a potential immunotherapeutic target.Intercellular communication networks were significantly disrupted in infected testes,with CD39-and JAM-dependent signaling pathways implicated in the erosion of immune privilege.Regulon analysis further identified GATA3,IRF5,SEMA4A,and HCLS1 as transcriptional regulators associated with T cells and macrophages in infected testes.These findings provide novel insights into the molecular mechanisms driving testicular immunopathology during Brucella infection and highlight candidate targets for immunomodulatory intervention in disease control and livestock reproductive health.展开更多
Superior neutral or cationic dinuclear gold(Ⅰ)N-heterocyclic carbene(NHC)complexes with antitumor and tumor microenvironment regulation functions were developed by introducing an additional gold atom.The novel cation...Superior neutral or cationic dinuclear gold(Ⅰ)N-heterocyclic carbene(NHC)complexes with antitumor and tumor microenvironment regulation functions were developed by introducing an additional gold atom.The novel cationic dinuclear gold(Ⅰ)complex 4a(BF5-Au)with bis-NHC ligands exhibited potent anti-liver cancer capacity in vitro and in vivo.The Hyper7 sensor was first used to analyze the sites of reactive oxygen species(ROS)generation by BF5-Au,showing that ROS were preferably generated in mitochondria and endoplasmic reticulum.Mechanism studies showed that BF5-Au could induce immunogenic cell death(ICD)via ROS-driven endoplasmic reticulum stress(ERS).However,targeting a single type of immune cell seems insufficient to reverse the immunosuppressive circumstances.Further investigation indicated that BF5-Au could enhance antitumor immune responses by inducing ferroptosis and polarizing macrophages to M1-like types.Overall,BF5-Au could inhibit tumor growth and remodel the tumor microenvironment via ROS-driven ERS and ferroptosis,which is expected to be a promising chemoimmunotherapy for cancer treatment.展开更多
Metal-based antimicrobial materials have been extensively studied and applied over decades.While these materials are notably characterized by their superior antibacterial performance and low propensity to induce drug ...Metal-based antimicrobial materials have been extensively studied and applied over decades.While these materials are notably characterized by their superior antibacterial performance and low propensity to induce drug resistance,critical limitations such as inherent cytotoxicity,poor solubility,and instability in aqueous solution remain significant challenges requiring systematic optimization.In this study,we synthesized water-soluble molecular iron-oxo clusters(MIC)with excellent biosafety and stability of aqueous solution.Our findings demonstrate that MIC exhibits marked therapeutic efficacy in cecal ligation and puncture induced sepsis models,a critical validation given sepsis'etiology as a life-threatening infection mediated systemic inflammatory syndrome.MIC combats bacteria by enhancing humoral immune responsiveness.MIC significantly improved the survival rate,reduced bacterial burden,stabilized body temperature,and modulated cytokine profiles in mice with sepsis.Further investigations revealed that MIC promotes B cells proliferation and oxidative phosphorylation,and mitigates mitochondrial damage and apoptosis in B cells,suggesting its role in modulating cellular metabolism.RNA sequencing analysis demonstrated that MIC exerts its effects by influencing key pathways involved in humoral immunity,inflammatory responses,and metabolic adaptation.These findings establish MIC as a novel therapeutic agent for regulating immune responses in sepsis,providing innovative strategies to improve recovery from this life-threatening condition.展开更多
Over one-third of 700,000 military personnel who served in the first Gulf War(GW)suffer from an assortment of symptoms,including cognitive and memory problems,musculoskeletal pain,gastrointestinal discomfort,fatigue,a...Over one-third of 700,000 military personnel who served in the first Gulf War(GW)suffer from an assortment of symptoms,including cognitive and memory problems,musculoskeletal pain,gastrointestinal discomfort,fatigue,and respiratory issues[1,2].The precise etiology of Gulf War illness(GWI)is unclear.However,epidemiological and preclinical studies imply that exposures to the prophylactic drug pyridostigmine bromide,insecticides,pesticides,smoke from oil well fires,and interaction between these exposures and war-related stress underlie this illness[2].As per the Kansas case definition,GWI is a chronic multi-symptom illness displaying one moderately severe and/or multiple symptoms of any severity in at least 3 of 6 symptom domains(fatigue,pain,neurological/cognitive/mood,skin,gastrointestinal,respiratory)[1,2].While the exact pathophysiological changes underlying GWI have not been identified,alterations in immune regulation and dysregulation of the redox balance have been observed in GWI,resulting in chronic systemic inflammation and neuroinflammation[2].展开更多
Hemorrhagic stroke,the second leading cause of stroke,is a severe medical emergency that often leads to severe disability or death;however,the causal relationship between antibody-mediated immune responses and hemorrh...Hemorrhagic stroke,the second leading cause of stroke,is a severe medical emergency that often leads to severe disability or death;however,the causal relationship between antibody-mediated immune responses and hemorrhagic stroke remains unknown.This study aimed to investigate the potential causal relationship between antibody-mediated immune responses to infectious agents and hemorrhagic stroke using the two-sample Mendelian randomization(MR)method.Comprehensive analyses were conducted using publicly available data from genome-wide association study(GWAS),which involved the whole genomes of 9724 European participants and 46 antibody measurement phenotypes,and summary statistics from the FinnGen dataset R12(including intracerebral hemorrhage and subarachnoid hemorrhage)were used.The causal relationship between the aforementioned immune responses and hemorrhagic stroke was analyzed using inverse-variance weighting,MR-Egger regression,weighted median,weighted mode,simple mode,and MR-pleiotropy residual sum and outlier(MR-PRESSO),while various sensitivity analyses were performed to assess heterogeneity and pleiotropy in the study findings.Results showed that human herpes virus 7(HHV-7)U14 antibody levels(OR:0.877,95%CI:0.797-0.964,P=0.007)exerted a protective effect against hemorrhagic stroke,and Chlamydia trachomatis(CT)tarp-D F2 antibody levels(OR:0.937,95%CI:0.885-0.992,P=0.025)had a potential protective effect;additionally,Epstein-Barr virus(EBV)ZEBRA antibody levels(OR:1.062,95%CI:1.012-1.114,P=0.014),human herpesvirus 6(HHV-6)p101k antibody levels(OR:1.054,95%CI:1.002-1.108,P=0.042),and cytomegalovirus(CMV)pp150 antibody levels(OR:1.086,95%CI:1.002-1.176,P=0.045)were potential risk factors for the disease.No significant pleiotropy or heterogeneity was observed in any of the MR analyses.Collectively,these findings confirmed a significant causal relationship between antibody-mediated immune responses and hemorrhagic stroke,and this study contributed to a deeper understanding of the potential mechanisms underlying hemorrhagic stroke onset.展开更多
Acute myeloid leukemia(AML)is a common and aggressive blood cancer characterized by the abnormal growth of primitive bone marrow cells.Genetic mutations prevent normal differentiation into blood components.Potential c...Acute myeloid leukemia(AML)is a common and aggressive blood cancer characterized by the abnormal growth of primitive bone marrow cells.Genetic mutations prevent normal differentiation into blood components.Potential causes include environmental factors,radiation,and viral infections.Research on AML is essential for enhancing our understanding of the disease,facilitating the development of effective treatments,and improving early diagnostic methods to ultimately increase patient survival rates and quality of life.This study focused on the T-cell immune response and T-cell immunotherapy in AML.We collected CD8+T cells,CD4+T cells,Natural killer T(NKT)cells,and γδT cells among the T cells and analyzed the roles that they play in AML.Long-term disease control in AML requires a variety of immunotherapies,including T-cell receptor-engineered T cells(TCR-T),chimeric antigen receptor T-cell therapy(CAR-T),and T-cell immune checkpoint inhibitors.We discuss these treatments and try to find better treatments for AML in the future.展开更多
Viral reproductive tract infections(VRTIs)are a significant global health concern with severe consequences,including infertility,chronic pelvic pain,and increased risk of HIV transmission.Complex interplay between pat...Viral reproductive tract infections(VRTIs)are a significant global health concern with severe consequences,including infertility,chronic pelvic pain,and increased risk of HIV transmission.Complex interplay between pathogens and the host immune system plays a critical role in the pathogenesis and treatment of VRTIs.This review aims to provide a comprehensive overview of the multifaceted roles of the immune system in both contributing to and combating VRTIs.The review will also address the consequent perturbations in immune homeostasis and the implications for disease manifestation and progression.The interrelation between systemic immunity and local immune responses is discussed,providing insights into the challenges and breakthroughs in managing these infections.By providing a comprehensive overview of the mechanisms,implications,and therapeutic strategies associated with viral reproductive tract infections and immune dysfunction,this review also informs future research and clinical practice in this important area of reproductive health.展开更多
This study investigates the role of Interleukin 17(IL-17)in exacerbating periapical lesions caused by Porphyromonas gingivalis(Pg)lipopolysaccharides(LPS)in the context of metabolic disease and its potential impact on...This study investigates the role of Interleukin 17(IL-17)in exacerbating periapical lesions caused by Porphyromonas gingivalis(Pg)lipopolysaccharides(LPS)in the context of metabolic disease and its potential impact on glucose tolerance.Researchers developed a unique mouse model where mice were monocolonized with Pg to induce periapical lesions.After 1 month,they were fed a highfat diet(HFD)for 2 months to simulate metabolic disease and oral microbiota dysbiosis.To explore the role of LPS from Pg,wildtype(WT)mice were challenged with purified LPS from Porphyromonas gingivalis,as well as with LPS-depleted and non-depleted Pg bacteria;IL-17 knockout(KO)mice were also included to assess the role of IL-17 signaling.The impact on bone lysis,periapical injury,glucose intolerance,and immune response was assessed.Results showed that in WT mice,the presence of LPS significantly worsened bone lysis,Th17 cell recruitment,and periapical injury.IL-17 KO mice exhibited reduced bone loss,glucose intolerance,and immune cell infiltration.Additionally,inflammatory markers in adipose tissue were lower in IL-17 KO mice,despite increased dysbiosis.The findings suggest that IL-17 plays a critical role in amplifying Pg-induced periapical lesions and systemic metabolic disturbances.Targeting IL-17 recruitment could offer a novel approach to improving glycemic control and reducing type 2 diabetes(T2D)risk in individuals with periapical disease.展开更多
[Objective] The aim of this study was to investigate the effects of mycotoxin from moldy maize on immune response of piglets.[Method] ELISA method was used to determine the content of Aflatoxin B1 and ochratoxin A in ...[Objective] The aim of this study was to investigate the effects of mycotoxin from moldy maize on immune response of piglets.[Method] ELISA method was used to determine the content of Aflatoxin B1 and ochratoxin A in maize; after the piglets were fed with the moldy maize,the corresponding antibody titers in the serums of piglets were measured.[Result] Antibody levels of tested group were obvious lower than that of the control,while the histological section of immune organs also suggested that mycotoxin could significantly inhibit the immune response of piglets.[Conclusion] Mycotoxin in maize had important effects on the internal organs and immune response of piglets.展开更多
[ Objective] The research aimed to explore effects of an immunological stress on immune response in different breeds of piglets ( Lulai pig, Laiwu pig and Yorkshire pig). [Method] All the 12 weaning pigs (Lulai pig...[ Objective] The research aimed to explore effects of an immunological stress on immune response in different breeds of piglets ( Lulai pig, Laiwu pig and Yorkshire pig). [Method] All the 12 weaning pigs (Lulai pig, Laiwu pig and Yorkshire pig) weighing (12.6 ±0.5) kg were used in a 2 x3 factorial design. The main factors consisted of immunological challenge ( LPS or saline) and breeds ( Lulai pig, Laiwu pig and Yorkshire pig). On Day 1, six piglets of each breed were injected with LPS at the usage of 200 μg/kg BW or an equivalent amount of sterile saline, and in jected classical swine fever vaccine at the same time. Blood sample were collected on Day 2, 7 and 14 post injection to analyze the blood lympho cyte proliferation. The levels of antibodies against classical swine fever were tested on Day 1 prior to injection and on Day 7 and 14 post injection. [ Result] On Day 2 after injection, the lymphocyte transformation rate of piglets injected with LPS were significantly (P〈O. 01 ) increased compared with piglets injected with saline. The lymphocyte transformation rate of Laiwu piglets was significant higher than that of Yorkshire piglets ( P 〈 0.05). Effects of immunological stress on the level of antibodies against classical swine fever were not significantly different among different breeds of pig lets. [ Conclusion] LPS can effectively stimulate cellular immunity response in different breeds of piglets, and the immune response ability is different among various breeds of piglets.展开更多
Immunotherapy for Alzheimer's disease (AD) is effective in improving cognitive function in transgenic mouse models of AD. Because the AN1792 [beta-amyloid (Aβ) 1-42] vaccine was halted because of T cell mediated...Immunotherapy for Alzheimer's disease (AD) is effective in improving cognitive function in transgenic mouse models of AD. Because the AN1792 [beta-amyloid (Aβ) 1-42] vaccine was halted because of T cell mediated meningoencephalitis, many scientists are searching for a nove) vaccine to avoid the T cell mediated immune response caused by the Aβ1-42. Importantly, the time when the immunization is begun can influence the immune effect. In this study, an adenovirus vaccine was constructed containing 10 x Aβ3-10 repeats and gene adjuvant CpG DNA. Transgenic AD mice were immunized intranasally for 3 months. After 10 × Aβ3-10 vaccine immunization, high titers of anti-Aβ42 IgG1 predominant antibodies were induced. In spatial learning ability and probe tests, the 10 × Aβ3-10 immunized mice showed significantly improved memories compared to control mice. The 10 × Aβ3-10 vaccine resulted in a robust Th2 dominant humoral immune response and reduced learning deficits in AD mice. In addition, the 10 × Aβ3-10 vaccine might be more efficient if administered before Aβ aggregation at an early stage in the AD mouse brain. Thus, the adenovirus vector encoding 10 × Aβ-10 is a promising vaccine for AD.展开更多
Polyfluoroalkyl substances(PFAS)have emerged as persistent environmental contaminants because of their chemical stability,degradation-resistance and bioaccumulation potential.However,current studies mainly focus on th...Polyfluoroalkyl substances(PFAS)have emerged as persistent environmental contaminants because of their chemical stability,degradation-resistance and bioaccumulation potential.However,current studies mainly focus on the toxicity of single PFAS such as perfluorooctanoic acid(PFOA)and perfluorobutanoic acid(PFBA),the knowledge of their combined effects is relatively limited.In this study,we explored the immune response of the gut in large yellow croaker(Larimichthys crocea)under the combined stress of PFOA and PFBA.Histologicalanalyses revealed that the combined effect induced intestinal vacuolization and decreased the length of intestinal villi.And it significantly activated pro-inflammatory pathways with marked upregulation of tnfα,il1β,il6 and myd88 expressions,particularly after 14 days of exposure.Gut microbiota analysis revealed substantial dysbiosis,including 1)reduced alpha diversity,2)increased abundance of potential pathogenic taxa(Proteobacteria and Spirochaetota),and 3)depletion of beneficial Firmicutes.PICRUSt-based functional prediction indicated temporal metabolic shifts,with upregulation of DNA repair pathways at day 3 and enhanced bacterial motility protein activity at days 7 and 14 of post-exposure.The Pearson correlation analysis further indicated that these immune genes had significant positive correlations with Vibrio and Brevinema,and negative correlations with Streptococcus.Our present study will provide novel insights into the microbiome-mediated immunomodulation in the larger yellow croaker exposed to combined PFAS,which will be helpful for healthy farming of economically important marine species.展开更多
基金supported by University of Kentucky-SCoBIRC Endowed Chair#5Craig H.Neilsen 1173493 and NIH RF1NS135504(to JCG).
文摘Biological sex is increasingly recognized as a crucial factor in evaluating the translational value of preclinical spinal cord injury(SCI)studies.The rising incidence of SCI in females challenges the historical precedent of SCI being a male-dominated condition.In contrast,most basic science researchers utilize single-sex studies to minimize complications associated with bladder care in males(Stewart et al.,2020).The findings of our recent publication identify sexually dimorphic immune responses to SCI in both mice and pigs(Kumari et al.,2025).Here,we will highlight these findings and discuss the impact of sex on SCI inflammation and recovery.
基金financial support from the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation(GZC20230718)。
文摘The interplay between gut microbiota and host health has attracted significant interest in the animal science community.Maintaining gut microbiota homeostasis by supplementing probiotics to treat clinical conditions like calf diarrhea is an emerging area of research nowadays because of increased concerns regarding antimicrobial resistance(AMR)and drug residues in animal products.Probiotics reduce the incidence of calf diarrhea by increasing the gut microbiota diversity and richness with more commensal bacteria such as Lactobacillus and Bifidobacterium that produce antimicrobial compounds,as well as modulating the immune response by increasing cytokines,Interleukin-2(IL-2),IL-4,IL-6,IL-10,and reducing tumor necrosis factor-α(TNF-α),by increasing production of antibodies,especially immunoglobulin E(Ig E),also Ig G,differentiating naive Th lymphocytes(Tho)into Th1,hence stimulate innate immunity and prime the adaptive immune response.Specific probiotic strains of bacteria and yeast(Saccharomyces cerevisiae)derived probiotics maintain the integrity of the intestinal barrier.In this review,data are being organized to address the role of probiotics in treating calf diarrhea by modulating gut microbiota and stimulating an immune response against notorious pathogens,to present animal and veterinary scientists and nutritionists with a new concept to treat infectious diseases from the perspective of the gut microbiota,increasing animal health,performance,and welfare.In conclusion,health status and gut microbiome are strongly interlinked.Research data indicated a significant reduction in the incidence of diarrhea after probiotic administration.If interrelations between probiotics and existing gut microbiota are explored more quantitatively,novel antibiotic substitutes can emerge in the future.
基金supported by Research Program for Agricultural Science and Technology Development,Republic of Korea(PJ01570601)the Fellowship Program(PJ01661001)of the National Institute of Agricultural Sciences,Republic of KoreaRural Development Administration,Republic of Korea.
文摘The emergence of novel phytopathogens and the accelerated spread of plant diseases to new regions,driven by global climate change,constitute significant threats to agricultural resources.Rice,a major tropical staple crucial for global food security,possesses six transcription factor superfamilies-AP2/ERF,bHLH,bZIP,MYB,NAC,and WRKY-that function in innate immunity against pathogens.We review their biological functions and regulatory mechanisms in rice immunity.
文摘Accumulating evidence indicates that antibiotic exposure may lead to impaired vaccine responses1-4;however,the mechanisms underlying this association remain poorly understood.Here we prospectively followed 191 healthy,vaginally born,term infants from birth to 15 months,using a systems vaccinology approach to assess the effects of antibiotic exposure on immune responses to vaccination.Exposure to direct neonatal but not intrapartum antibiotics was associated with significantly lower antibody titres against various polysaccharides in the 13-valent pneumococcal conjugate vaccine and the Haemophilus influenzae type b polyribosylribitol phosphate and diphtheria toxoid antigens in the combined 6-in-1 Infanrix Hexa vaccine at 7 months of age.Blood from infants exposed to neonatal antibiotics had an inflammatory transcriptional profile before vaccination;in addition,faecal metagenomics showed reduced abundance of Bifidobacterium species in these infants at the time of vaccination,which was correlated with reduced vaccine antibody titres 6 months later.In preclinical models,responses to the 13-valent pneumococcal conjugate vaccine were strongly dependent on an intact microbiota but could be restored in germ-free mice by administering a consortium of Bifidobacterium species or a probiotic already widely used in neonatal units.Our data suggest that microbiota-targeted interventions could mitigate the detrimental effects of early-life antibiotics on vaccine immunogenicity.
文摘Low-dose radiation therapy has emerged as a promising modality for cancer treatment because of its ability to stimulate antitumor immune responses while minimizing damage to healthy tissues.However,the significant heterogeneity in immune responses among patients complicates its clinical application,hindering outcome prediction and treatment personalization.Artificial intelligence(AI)offers a transformative solution by integrating multidimensional data such as immunomics,radiomics,and clinical features to decode complex immune pa-tterns and predict individual therapeutic outcomes.This editorial explored the potential of AI to address immune response heterogeneity in low-dose radiation therapy and proposed an AI-driven framework for precision immunotherapy.While promising,challenges,including data standardization,model interpre-tability,and clinical validation,must be overcome to ensure successful integration into oncological practice.
文摘BACKGROUND Radiotherapy(RT)is a cornerstone of cancer treatment.Compared with conven-tional high-dose radiation,low-dose radiation(LDR)causes less damage to normal tissues while potentially modulating immune responses and inhibiting tumor growth.LDR stimulates both innate and adaptive immunity,enhancing the activity of natural killer cells,dendritic cells,and T cells.However,the me-chanisms underlying the effects of LDR on the immune system remain unclear.AIM To explore the history,research hotspots,and emerging trends in immune response to LDR literature over the past two decades.METHODS Publications on immune responses to LDR were retrieved from the Web of Science Core Collection.Bibliometric tools,including CiteSpace and HistCite,were used to identify historical features,active topics,and emerging trends in this field.RESULTS Analysis of 1244 publications over the past two decades revealed a significant surge in research on immune responses to LDR,particularly in the last decade.Key journals such as INR J Radiat Biol,Cancers,and Radiat Res published pivotal studies.Citation networks identified key studies by authors like Twyman-Saint Victor C(2015)and Vanpouille-Box C(2017).Keyword analysis revealed hotspots such as ipilimumab,stereotactic body RT,and targeted therapy,possibly identifying future research directions.Temporal variations in keyword clusters and alluvial flow maps illustrate the evolution of research themes over time.CONCLUSION This bibliometric analysis provides valuable insights into the evolution of studies on responses to LDR,highlights research trends,and identifies emerging areas for further investigation.
基金supported by the National Natural Science Foundation of China (32373181)National Key Research and Development Program (2023YFD2400700)+2 种基金Science and Technology Plan Project of Fujian Province (2022L3059)High-quality Development of Marine and Fishery Industry Special Fund Project of Fujian Province (FJHYF-L-2023-5)Open Fund of Fujian Province Key Laboratory of Special Aquatic Formula Feed (TMKJZ2302)。
文摘Small RNAs(sRNAs)are a class of molecules capable of perceiving environmental changes and exerting posttranscriptional regulation over target gene expression,thereby influencing bacterial virulence and host immune responses.Pseudomonas plecoglossicida is a pathogenic bacterium that poses a significant threat to aquatic animal health.However,the regulatory mechanisms of sRNAs in P.plecoglossicida remain unclear.This study focused on sRNA113,previously identified as a potential regulator of the fliP gene,a key component of the lateral flagellar type III secretion system.To investigate the effects of sRNA113on P.plecoglossicida virulence,as well as its role in regulating pathogenic processes and host immune responses,mutant strains lacking this sRNA were generated and analyzed.Deletion of sRNA113 resulted in the up-regulation of lateral flagellar type III secretion system-related genes in P.plecoglossicida,which enhanced bacterial swarming motility,biofilm formation,and chemotaxis ability in vitro.In vivo infection experiments with pearl gentian grouper revealed that sRNA113 deletion enhanced the pathogenicity of P.plecoglossicida.This heightened virulence was attributed to the up-regulation of genes associated with the lateral flagellar type III secretion system,resulting in higher bacterial loads within host tissues.This amplification of pathogenic activity intensified tissue damage,disrupted immune responses,and impaired the ability of the host to clear infection,ultimately leading to mortality.These findings underscore the critical role of sRNA113 in regulating the virulence of P.plecoglossicida and its interaction with host immune defenses.This study provides a foundation for further exploration of sRNAmediated mechanisms in bacterial pathogenesis and hostpathogen interactions,contributing to a deeper understanding of virulence regulation and immune evasion in aquatic pathogens.
基金supported by the National Natural Science Foundation of China(32272332,31972052,32021005,31820103010)the Fundamental Research Funds for the Central Universities(JUSRP622020,JUSRP22006,JUSRP51501)the Program of Collaborative Innovation Centre of Food Safety and Quality Control in Jiangsu Province,Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX22_2391).
文摘Infants exhibit diminished susceptibility to external infections,a phenomenon closely linked to the pervasive presence of the bifidobacterial community within their intestinal tract.Nonetheless,a significant knowledge gap remains concerning the distinct species of bifidobacteria initiating anti-infection immune responses during the early developmental stages.In this study,the impact of early intervention with Bifidobacterium bifidum,Bifidobacterium breve,and Bifidobacterium longum on neonatal rats infected with Salmonella enterica serovar Typhimurium SL1344 were compared.The study encompasses various immunity levels,including gut immunity,central immunity(thymus),peripheral immunity(spleen),and brain immunity.Following Salmonella infection,significant alterations in neonatal rats were observed in growth and developmental levels,immune markers,cytokine levels,balance of T lymphocyte subpopulations,intestinal barrier function,and blood-brain barrier integrity.Compared with B.breve and B.longum,B.bifidum demonstrated more pronounced efficacy in regulating these physiological processes.By conducting multi-level analyses of gut microbiota,bifidobacterial community,colonic content metabolomics,and serum metabolomics,the significance of B.bifidum’s role is underscored,and the immune-enhancing function of messenger metabolites is unveiled.Among these metabolites,γ-L-glutamyl-L-glutamic acid and orotic acid were found to be shared by all 3 species,while hippuric acid and 1a,1b-dihomo prostaglandin F2αwere unique to B.bifidum,and DL-arginine was specific to B.longum.Overall,this study has provided novel insights into the intervention and immunomodulation by Bifidobacterium in early-life infections,emphasizing the significant role of B.bifidum.
基金supported by the National Key Research and Development Program of China (2023YFF1000904,2022YFD1302201)National Natural Science Foundation of China(32372970, U24A20438)+2 种基金Key Technologies Demonstration of Animal Husbandry in Shaanxi Province (2025NYGG005, 2024NYGG005)Inner Mongolia Autonomous Region Open Competition Projects(2022JBGS0025)Open Fund Project of the National Key Laboratory of Veterinary Public Health and Safety (2025SKLVPHS08)。
文摘Brucellosis,a zoonotic disease caused by Brucella infection,poses a major threat to both global health and livestock productivity.Although reproductive impairment is well established,the molecular mechanisms driving testicular immunopathology remain poorly understood.In this study,single-cell RNA sequencing was used to delineate transcriptional changes in goat testicular tissues under physiological and Brucella-infected conditions,revealing dynamic immunological remodeling of the testicular microenvironment.Infection induced marked shifts in T cell and macrophage phenotypes,with T cells exhibiting pronounced hyperactivation linked to CD45-mediated signaling cascades.Thioredoxin-interacting protein(TXNIP),a gene strongly up-regulated in response to infection,emerged as a potential immunotherapeutic target.Intercellular communication networks were significantly disrupted in infected testes,with CD39-and JAM-dependent signaling pathways implicated in the erosion of immune privilege.Regulon analysis further identified GATA3,IRF5,SEMA4A,and HCLS1 as transcriptional regulators associated with T cells and macrophages in infected testes.These findings provide novel insights into the molecular mechanisms driving testicular immunopathology during Brucella infection and highlight candidate targets for immunomodulatory intervention in disease control and livestock reproductive health.
基金supported by the National Natural Science Foundation of China(No.82173684)the Priority Academic Program Development of Jiangsu Higher Education Institutions(Integration of Chinese and Western Medicine),High level key discipline construction project of the National Administration of Traditional Chinese Medicine-Resource Chemistry of Chinese Medicinal Materials(No.zyyzdxk-2023083)+1 种基金the Key R&D Program of Jiangsu Province(No.BE2023840)Yunnan Provincial Science and Technology Talent and Platform Program(No.202405AF140031)。
文摘Superior neutral or cationic dinuclear gold(Ⅰ)N-heterocyclic carbene(NHC)complexes with antitumor and tumor microenvironment regulation functions were developed by introducing an additional gold atom.The novel cationic dinuclear gold(Ⅰ)complex 4a(BF5-Au)with bis-NHC ligands exhibited potent anti-liver cancer capacity in vitro and in vivo.The Hyper7 sensor was first used to analyze the sites of reactive oxygen species(ROS)generation by BF5-Au,showing that ROS were preferably generated in mitochondria and endoplasmic reticulum.Mechanism studies showed that BF5-Au could induce immunogenic cell death(ICD)via ROS-driven endoplasmic reticulum stress(ERS).However,targeting a single type of immune cell seems insufficient to reverse the immunosuppressive circumstances.Further investigation indicated that BF5-Au could enhance antitumor immune responses by inducing ferroptosis and polarizing macrophages to M1-like types.Overall,BF5-Au could inhibit tumor growth and remodel the tumor microenvironment via ROS-driven ERS and ferroptosis,which is expected to be a promising chemoimmunotherapy for cancer treatment.
基金the generous supported by the National Key R&D Program of China(No.2023YFC2413100)the National Natural Science Foundation of China(Nos.22322102,21871042 and 21471028)+1 种基金the Fundamental Research Funds for the Central Universities-Excellent Youth Team Program(No.2412023YQ001)the Natural Science Foundation of Jilin Province(Nos.YDZJ202401550ZYTS,20200201083JC)。
文摘Metal-based antimicrobial materials have been extensively studied and applied over decades.While these materials are notably characterized by their superior antibacterial performance and low propensity to induce drug resistance,critical limitations such as inherent cytotoxicity,poor solubility,and instability in aqueous solution remain significant challenges requiring systematic optimization.In this study,we synthesized water-soluble molecular iron-oxo clusters(MIC)with excellent biosafety and stability of aqueous solution.Our findings demonstrate that MIC exhibits marked therapeutic efficacy in cecal ligation and puncture induced sepsis models,a critical validation given sepsis'etiology as a life-threatening infection mediated systemic inflammatory syndrome.MIC combats bacteria by enhancing humoral immune responsiveness.MIC significantly improved the survival rate,reduced bacterial burden,stabilized body temperature,and modulated cytokine profiles in mice with sepsis.Further investigations revealed that MIC promotes B cells proliferation and oxidative phosphorylation,and mitigates mitochondrial damage and apoptosis in B cells,suggesting its role in modulating cellular metabolism.RNA sequencing analysis demonstrated that MIC exerts its effects by influencing key pathways involved in humoral immunity,inflammatory responses,and metabolic adaptation.These findings establish MIC as a novel therapeutic agent for regulating immune responses in sepsis,providing innovative strategies to improve recovery from this life-threatening condition.
基金Department of Defense(W81XWH-17-1-0447 and W81XWH1910548 to AKS)Texas A&M University School of Medicine。
文摘Over one-third of 700,000 military personnel who served in the first Gulf War(GW)suffer from an assortment of symptoms,including cognitive and memory problems,musculoskeletal pain,gastrointestinal discomfort,fatigue,and respiratory issues[1,2].The precise etiology of Gulf War illness(GWI)is unclear.However,epidemiological and preclinical studies imply that exposures to the prophylactic drug pyridostigmine bromide,insecticides,pesticides,smoke from oil well fires,and interaction between these exposures and war-related stress underlie this illness[2].As per the Kansas case definition,GWI is a chronic multi-symptom illness displaying one moderately severe and/or multiple symptoms of any severity in at least 3 of 6 symptom domains(fatigue,pain,neurological/cognitive/mood,skin,gastrointestinal,respiratory)[1,2].While the exact pathophysiological changes underlying GWI have not been identified,alterations in immune regulation and dysregulation of the redox balance have been observed in GWI,resulting in chronic systemic inflammation and neuroinflammation[2].
基金Supported by the National Natural Science Foundations of China(82271340,82071368)。
文摘Hemorrhagic stroke,the second leading cause of stroke,is a severe medical emergency that often leads to severe disability or death;however,the causal relationship between antibody-mediated immune responses and hemorrhagic stroke remains unknown.This study aimed to investigate the potential causal relationship between antibody-mediated immune responses to infectious agents and hemorrhagic stroke using the two-sample Mendelian randomization(MR)method.Comprehensive analyses were conducted using publicly available data from genome-wide association study(GWAS),which involved the whole genomes of 9724 European participants and 46 antibody measurement phenotypes,and summary statistics from the FinnGen dataset R12(including intracerebral hemorrhage and subarachnoid hemorrhage)were used.The causal relationship between the aforementioned immune responses and hemorrhagic stroke was analyzed using inverse-variance weighting,MR-Egger regression,weighted median,weighted mode,simple mode,and MR-pleiotropy residual sum and outlier(MR-PRESSO),while various sensitivity analyses were performed to assess heterogeneity and pleiotropy in the study findings.Results showed that human herpes virus 7(HHV-7)U14 antibody levels(OR:0.877,95%CI:0.797-0.964,P=0.007)exerted a protective effect against hemorrhagic stroke,and Chlamydia trachomatis(CT)tarp-D F2 antibody levels(OR:0.937,95%CI:0.885-0.992,P=0.025)had a potential protective effect;additionally,Epstein-Barr virus(EBV)ZEBRA antibody levels(OR:1.062,95%CI:1.012-1.114,P=0.014),human herpesvirus 6(HHV-6)p101k antibody levels(OR:1.054,95%CI:1.002-1.108,P=0.042),and cytomegalovirus(CMV)pp150 antibody levels(OR:1.086,95%CI:1.002-1.176,P=0.045)were potential risk factors for the disease.No significant pleiotropy or heterogeneity was observed in any of the MR analyses.Collectively,these findings confirmed a significant causal relationship between antibody-mediated immune responses and hemorrhagic stroke,and this study contributed to a deeper understanding of the potential mechanisms underlying hemorrhagic stroke onset.
文摘Acute myeloid leukemia(AML)is a common and aggressive blood cancer characterized by the abnormal growth of primitive bone marrow cells.Genetic mutations prevent normal differentiation into blood components.Potential causes include environmental factors,radiation,and viral infections.Research on AML is essential for enhancing our understanding of the disease,facilitating the development of effective treatments,and improving early diagnostic methods to ultimately increase patient survival rates and quality of life.This study focused on the T-cell immune response and T-cell immunotherapy in AML.We collected CD8+T cells,CD4+T cells,Natural killer T(NKT)cells,and γδT cells among the T cells and analyzed the roles that they play in AML.Long-term disease control in AML requires a variety of immunotherapies,including T-cell receptor-engineered T cells(TCR-T),chimeric antigen receptor T-cell therapy(CAR-T),and T-cell immune checkpoint inhibitors.We discuss these treatments and try to find better treatments for AML in the future.
基金supported by the Universiti Malaya ArtScience Fellowship Grant(UMG004-2024IAS)UM Community Engagement Grant 2023(Project RUU002-23KS).
文摘Viral reproductive tract infections(VRTIs)are a significant global health concern with severe consequences,including infertility,chronic pelvic pain,and increased risk of HIV transmission.Complex interplay between pathogens and the host immune system plays a critical role in the pathogenesis and treatment of VRTIs.This review aims to provide a comprehensive overview of the multifaceted roles of the immune system in both contributing to and combating VRTIs.The review will also address the consequent perturbations in immune homeostasis and the implications for disease manifestation and progression.The interrelation between systemic immunity and local immune responses is discussed,providing insights into the challenges and breakthroughs in managing these infections.By providing a comprehensive overview of the mechanisms,implications,and therapeutic strategies associated with viral reproductive tract infections and immune dysfunction,this review also informs future research and clinical practice in this important area of reproductive health.
基金supported by the Paul Calas Award from the French Society of Endodontics(SFE)。
文摘This study investigates the role of Interleukin 17(IL-17)in exacerbating periapical lesions caused by Porphyromonas gingivalis(Pg)lipopolysaccharides(LPS)in the context of metabolic disease and its potential impact on glucose tolerance.Researchers developed a unique mouse model where mice were monocolonized with Pg to induce periapical lesions.After 1 month,they were fed a highfat diet(HFD)for 2 months to simulate metabolic disease and oral microbiota dysbiosis.To explore the role of LPS from Pg,wildtype(WT)mice were challenged with purified LPS from Porphyromonas gingivalis,as well as with LPS-depleted and non-depleted Pg bacteria;IL-17 knockout(KO)mice were also included to assess the role of IL-17 signaling.The impact on bone lysis,periapical injury,glucose intolerance,and immune response was assessed.Results showed that in WT mice,the presence of LPS significantly worsened bone lysis,Th17 cell recruitment,and periapical injury.IL-17 KO mice exhibited reduced bone loss,glucose intolerance,and immune cell infiltration.Additionally,inflammatory markers in adipose tissue were lower in IL-17 KO mice,despite increased dysbiosis.The findings suggest that IL-17 plays a critical role in amplifying Pg-induced periapical lesions and systemic metabolic disturbances.Targeting IL-17 recruitment could offer a novel approach to improving glycemic control and reducing type 2 diabetes(T2D)risk in individuals with periapical disease.
文摘[Objective] The aim of this study was to investigate the effects of mycotoxin from moldy maize on immune response of piglets.[Method] ELISA method was used to determine the content of Aflatoxin B1 and ochratoxin A in maize; after the piglets were fed with the moldy maize,the corresponding antibody titers in the serums of piglets were measured.[Result] Antibody levels of tested group were obvious lower than that of the control,while the histological section of immune organs also suggested that mycotoxin could significantly inhibit the immune response of piglets.[Conclusion] Mycotoxin in maize had important effects on the internal organs and immune response of piglets.
文摘[ Objective] The research aimed to explore effects of an immunological stress on immune response in different breeds of piglets ( Lulai pig, Laiwu pig and Yorkshire pig). [Method] All the 12 weaning pigs (Lulai pig, Laiwu pig and Yorkshire pig) weighing (12.6 ±0.5) kg were used in a 2 x3 factorial design. The main factors consisted of immunological challenge ( LPS or saline) and breeds ( Lulai pig, Laiwu pig and Yorkshire pig). On Day 1, six piglets of each breed were injected with LPS at the usage of 200 μg/kg BW or an equivalent amount of sterile saline, and in jected classical swine fever vaccine at the same time. Blood sample were collected on Day 2, 7 and 14 post injection to analyze the blood lympho cyte proliferation. The levels of antibodies against classical swine fever were tested on Day 1 prior to injection and on Day 7 and 14 post injection. [ Result] On Day 2 after injection, the lymphocyte transformation rate of piglets injected with LPS were significantly (P〈O. 01 ) increased compared with piglets injected with saline. The lymphocyte transformation rate of Laiwu piglets was significant higher than that of Yorkshire piglets ( P 〈 0.05). Effects of immunological stress on the level of antibodies against classical swine fever were not significantly different among different breeds of pig lets. [ Conclusion] LPS can effectively stimulate cellular immunity response in different breeds of piglets, and the immune response ability is different among various breeds of piglets.
基金the National Natural Science Foundation of China, No. 30471927
文摘Immunotherapy for Alzheimer's disease (AD) is effective in improving cognitive function in transgenic mouse models of AD. Because the AN1792 [beta-amyloid (Aβ) 1-42] vaccine was halted because of T cell mediated meningoencephalitis, many scientists are searching for a nove) vaccine to avoid the T cell mediated immune response caused by the Aβ1-42. Importantly, the time when the immunization is begun can influence the immune effect. In this study, an adenovirus vaccine was constructed containing 10 x Aβ3-10 repeats and gene adjuvant CpG DNA. Transgenic AD mice were immunized intranasally for 3 months. After 10 × Aβ3-10 vaccine immunization, high titers of anti-Aβ42 IgG1 predominant antibodies were induced. In spatial learning ability and probe tests, the 10 × Aβ3-10 immunized mice showed significantly improved memories compared to control mice. The 10 × Aβ3-10 vaccine resulted in a robust Th2 dominant humoral immune response and reduced learning deficits in AD mice. In addition, the 10 × Aβ3-10 vaccine might be more efficient if administered before Aβ aggregation at an early stage in the AD mouse brain. Thus, the adenovirus vector encoding 10 × Aβ-10 is a promising vaccine for AD.
基金supported by the Ningbo Natural Science Foundation(Youth Foundation,No.2024J449)the Scientific Research Foundation for Introduced Talents of Ningbo University(Nos.ZX2022000602 and ZX2024000043)。
文摘Polyfluoroalkyl substances(PFAS)have emerged as persistent environmental contaminants because of their chemical stability,degradation-resistance and bioaccumulation potential.However,current studies mainly focus on the toxicity of single PFAS such as perfluorooctanoic acid(PFOA)and perfluorobutanoic acid(PFBA),the knowledge of their combined effects is relatively limited.In this study,we explored the immune response of the gut in large yellow croaker(Larimichthys crocea)under the combined stress of PFOA and PFBA.Histologicalanalyses revealed that the combined effect induced intestinal vacuolization and decreased the length of intestinal villi.And it significantly activated pro-inflammatory pathways with marked upregulation of tnfα,il1β,il6 and myd88 expressions,particularly after 14 days of exposure.Gut microbiota analysis revealed substantial dysbiosis,including 1)reduced alpha diversity,2)increased abundance of potential pathogenic taxa(Proteobacteria and Spirochaetota),and 3)depletion of beneficial Firmicutes.PICRUSt-based functional prediction indicated temporal metabolic shifts,with upregulation of DNA repair pathways at day 3 and enhanced bacterial motility protein activity at days 7 and 14 of post-exposure.The Pearson correlation analysis further indicated that these immune genes had significant positive correlations with Vibrio and Brevinema,and negative correlations with Streptococcus.Our present study will provide novel insights into the microbiome-mediated immunomodulation in the larger yellow croaker exposed to combined PFAS,which will be helpful for healthy farming of economically important marine species.