Diabetic nephropathy (DN) is an enduring condition that leads to inflammation and affects a substantial number of individuals with diabetes worldwide. A gradual reduction in glomerular filtration and emergence of prot...Diabetic nephropathy (DN) is an enduring condition that leads to inflammation and affects a substantial number of individuals with diabetes worldwide. A gradual reduction in glomerular filtration and emergence of proteins in the urine are typical aspects of DN, ultimately resulting in renal failure. Mounting evidence suggests that immunological and inflammatory factors are crucial for the development of DN. Therefore, the activation of innate immunity by resident renal and immune cells is critical for initiating and perpetuating inflammation. Toll-like receptors (TLRs) are an important group of receptors that identify patterns and activate immune responses and inflammation. Meanwhile, inflammatory responses in the liver, pancreatic islets, and kidneys involve inflammasomes and chemokines that generate pro-inflammatory cytokines. Moreover, the activation of the complement cascade can be triggered by glycated proteins. This review highlights recent findings elucidating how the innate immune system contributes to tissue fibrosis and organ dysfunction, ultimately leading to renal failure. This review also discusses innovative approaches that can be utilized to modulate the innate immune responses in DN for therapeutic purposes.展开更多
The basic region/leucine zipper(bZIP)transcription factors play important roles in plant development and responses to abiotic and biotic stresses.OsbZIP53 regulates resistance to Magnaporthe oryzae in rice by analyzin...The basic region/leucine zipper(bZIP)transcription factors play important roles in plant development and responses to abiotic and biotic stresses.OsbZIP53 regulates resistance to Magnaporthe oryzae in rice by analyzing APIP5-RNAi transgenic plants.To further investigate the biological functions of OsbZIP53,we generated osbzip53 mutants using CRISPR/Cas9 editing and also constructed OsbZIP53 over-expression transgenic plants.Comprehensive analysis of phenotypical,physiological,and transcriptional data showed that knocking-out OsbZIP53 not only improved disease resistance by inducing a hypersensitivity response in plants,but also regulated the immune response through the salicylic acid pathway.Specifically,disrupting OsbZIP53 increased H2O2 accumulation by promoting reactive oxygen species generation through up-regulation of several respiratory burst oxidase homologs(Osrboh genes)and weakened H2O2 degradation by directly targeting OsMYBS1.In addition,the growth of osbzip53 mutants was seriously impaired,while OsbZIP53 over-expression lines displayed a similar phenotype to the wild type,suggesting that OsbZIP53 has a balancing effect on rice immune response and growth.展开更多
The liver is the front line organ of the immune system.The liver contains the largest collection of phagocytic cells in the body that detect both pathogens that enter through the gut and endogenously produced antigens...The liver is the front line organ of the immune system.The liver contains the largest collection of phagocytic cells in the body that detect both pathogens that enter through the gut and endogenously produced antigens.This is possible by the highly developed differentiation capacity of the liver immune system between self-antigens or non-self-antigens,such as food antigens or pathogens.As an immune active organ,the liver functions as a gatekeeping barrier from the outside world,and it can create a rapid and strong immune response,under unfavorable conditions.However,the liver's assumed immune status is anti-inflammatory or immuno-tolerant.Dynamic interactions between the numerous populations of immune cells in the liver are key for maintaining the delicate balance between immune screening and immune tolerance.The anatomical structure of the liver can facilitate the preparation of lymphocytes,modulate the immune response against hepatotropic pathogens,and contribute to some of its unique immunological properties,particularly its capacity to induce antigen-specific tolerance.Since liver sinusoidal endothelial cell is fenestrated and lacks a basement membrane,circulating lymphocytes can closely contact with antigens,displayed by endothelial cells,Kupffer cells,and dendritic cells while passing through the sinusoids.Loss of immune tolerance,leading to an autoaggressive immune response in the liver,if not controlled,can lead to the induction of autoimmune or autoinflammatory diseases.This review mentions the unique features of liver immunity,and dysregulated immune responses in patients with autoimmune liver diseases who have a close association with inborn errors of immunity have also been the emphases.展开更多
The present study investigated the effect of treatment with methanolic extracts of Yin- and Yang-Chinese tonifying herbs on concanavalin A (Con A)/lipopolysaccharide (LPS)-stimulated splenocyte proliferation (adaptive...The present study investigated the effect of treatment with methanolic extracts of Yin- and Yang-Chinese tonifying herbs on concanavalin A (Con A)/lipopolysaccharide (LPS)-stimulated splenocyte proliferation (adaptive immunity) and natural killer (NK) cell activity (innate immunity) in an ex vivo mouse model. The results indicated that while treatment with most Yin herbal extracts potentiated the Con A/LPS-stimulated splenocyte proliferation, only Yang (but not Yin) herbal extracts stimulated NK cell activity. The differential effects of Yin- and Yang-Chinese tonifying herbs on innate and adaptive immunity are consistent with the Chinese medicine theory which depicts the Yin and Yang functional components of Zheng Qi (vital energy), with the Yang component being responsible for the first line of defense against invading microorganisms (i.e., innate immunity) and the Yin oner serving as a follow-up defensive response (adaptive immunity).展开更多
Background In broiler chickens,necrotic enteritis(NE)infection can reduce production performance.Tannic acid has shown great potential as a treatment of NE in broilers.However,the appropriate dosage of tannic acid in ...Background In broiler chickens,necrotic enteritis(NE)infection can reduce production performance.Tannic acid has shown great potential as a treatment of NE in broilers.However,the appropriate dosage of tannic acid in NE of broilers and the improvement effect on intestinal health are not very clear.In this study,we aimed to investigate the effects of different doses of tannic acid on the production performance,immunity,and intestinal health of broilers by constructing an NE model with C.perfringens infection and determining the appropriate dosage of tannic acid with regard to NE.Results Challenged birds showed significant reduction in body weight,villus height,and the ratio of villus height to crypt depth(P<0.05)and increase in the feed consumption gain ratio,intestinal lesion score,and crypt depth(P<0.05).The infection significantly reduced the relative Bacteroidota and Ligilactobacillus abundance(P<0.05)and increased the ratio of Firmicutes/Bacteroidota and cecal content of C.perfringens(P<0.05).Challenged birds fed diets supplemented with tannic acid showed significantly increased mRNA expression of nutrient transport carriers and intestinal barrier genes and growth performance and reduced serum zonulin and endotoxin levels(P<0.05).Addi-tion of tannic acid to the diet inhibited the inflammatory response by reducing the number of coccidia oocysts in feces and the content of C.perfringens in the cecum.Specifically,tannic acid reduced the serum levels of C reactive protein,myeloperoxidase,and specific IgY and ileal mucosal secretory immunoglobulin A levels in the ileal mucosa compared with those in the NE-infected birds.NE-infected birds fed diets supplemented with tannic acid also showed significantly increased relative Anaerocolumna,Thermoanaerobacterium,and Thermosinus abundance(P<0.05);their microbial composition and functional predictions were similar to those of the NC group.Conclusions Tannic acid in the diet alleviated NE by enhancing the intestinal barrier and absorption function.The recommended dietary tannic acid additive level is 500–750 mg/kg.Our study findings would be useful in reducing related economic losses in the broiler industry.展开更多
Mushrooms are experiencing a kind of renaissance as a part of the contemporary human diet.These valuable organisms are more than food,they fit in perfectly as a novel market group known as nutra-mycoceuticals.Immune-b...Mushrooms are experiencing a kind of renaissance as a part of the contemporary human diet.These valuable organisms are more than food,they fit in perfectly as a novel market group known as nutra-mycoceuticals.Immune-balancing mushroom dietary fibers and secondary metabolites such as polyphenols are the main focus of the healthcare industry.Wellness and cosmetic companies are increasingly using mushroom extracts rich in these ingredients.This review considers the basic molecular immunomodulatory mechanisms of action of the most commonly used mushroom dietary fibers,β-glucans.The literature data on their bioavailability,metabolic transformations,preclinical and human clinical research,and safety are discussed.Immunomodulatory mechanisms of polyphenol ingredients are also considered.These molecules present great potential in the design of the new immunity balancer formulations according to their widespread structural diversity.Finally,we draw attention to the perspectives of modern trends in mushroom nutraceutical and cosmeceutical formulations to strengthen and balance immunity.展开更多
Plants use a sophisticated immune system to perceive pathogen infection and activate immune responses in a tightly controlled manner.In barley,Hv WRKY2 acts as a repressor in barley disease resistance to the powdery m...Plants use a sophisticated immune system to perceive pathogen infection and activate immune responses in a tightly controlled manner.In barley,Hv WRKY2 acts as a repressor in barley disease resistance to the powdery mildew fungus,Blumeria graminis f.sp.hordei(Bgh).However,the molecular features of Hv WRKY2 in its DNA-binding and repressor functions,as well as its target genes,are uncharacterized.We show that the W-box binding of Hv WRKY2 requires an intact WRKY domain and an upstream sequence of~75 amino acids,and the Hv WRKY2 W-box binding activity is linked to its repressor function in disease resistance.Chromatin immunoprecipitation(ChIP)-seq analysis identified HvCEBiP,a putative chitin receptor gene,as a target gene of Hv WRKY2 in overexpressing transgenic barley plants.ChIP-qPCR and Electrophoretic Mobility Shift Assay(EMSA)verified the direct binding of Hv WRKY2 to a W-boxcontaining sequence in the HvCEBiP promoter.Hv CEBiP positively regulates resistance against Bgh in barley.Our findings suggest that Hv WRKY2 represses barley basal immunity by directly targeting pathogen-associated molecular pattern(PAMP)recognition receptor genes,suggesting that Hv CEBiP and likely chitin signaling function in barley PAMP-triggered immune responses to Bgh infection.展开更多
Bacterial wilt is a devastating disease of tomato(Solanum lycopersicum)caused by Ralstonia solanacearum that severely threatens tomato production.Group III WRKY transcription factors(TFs)are implicated in the plant re...Bacterial wilt is a devastating disease of tomato(Solanum lycopersicum)caused by Ralstonia solanacearum that severely threatens tomato production.Group III WRKY transcription factors(TFs)are implicated in the plant response to pathogen infection;however,their roles in the response of tomato to R.solanacearum infection(RSI)remain largely unexplored.Here,we report the crucial role of SlWRKY30,a group III SlWRKY TF,in the regulation of tomato response to RSI.SlWRKY30 was strongly induced by RSI.SlWRKY30 overexpression reduced tomato susceptibility to RSI,and also increased H2O2 accumulation and cell necrosis,suggesting that SlWRKY30 positively regulates tomato resistance to RSI.RNA sequencing and reverse transcription–quantitative PCR revealed that SlWRKY30 overexpression significantly upregulated pathogenesis-related protein(SlPR-STH2)genes SlPR-STH2a,SlPR-STH2b,SlPR-STH2c,and SlPR-STH2d(hereafter SlPR-STH2a/b/c/d)in tomato,and these SlPR-STH2 genes were directly targeted by SlWRKY30.Moreover,four group III WRKY proteins(SlWRKY52,SlWRKY59,SlWRKY80,and SlWRKY81)interacted with SlWRKY30,and SlWRKY81 silencing increased tomato susceptibility to RSI.Both SlWRKY30 and SlWRKY81 activated SlPR-STH2a/b/c/d expression by directly binding to their promoters.Taking these results together,SlWRKY30 and SlWRKY81 synergistically regulate resistance to RSI by activating SlPR-STH2a/b/c/d expression in tomato.Our results also highlight the potential of SlWRKY30 to improve tomato resistance to RSI via genetic manipulations.展开更多
Pepper mild mottle virus(PMMoV)is a devastating viral pathogen of pepper(Capsicum annuum)but it is unclear whether and how peppers protect against PMMoV infection.The expression of the chloroplast outer membrane prote...Pepper mild mottle virus(PMMoV)is a devastating viral pathogen of pepper(Capsicum annuum)but it is unclear whether and how peppers protect against PMMoV infection.The expression of the chloroplast outer membrane protein 24(OMP24)of C.annuum was upregulated under PMMoV infection and it interacted with PMMoV coat protein(CP).Silencing of OMP24 in either C.annuum or Nicotiana benthamiana facilitated PMMoV infection,whereas overexpression of N.benthamiana OMP24 in transgenic plants inhibited PMMoV infection.Both C.annuum OMP24(CaOMP24)and N.benthamiana OMP24(NbOMP24)localized to the chloroplast and have a moderately hydrophobic transmembrane domain that is necessary for their localization.Overexpression of CaOMP24 induced stromules,perinuclear chloroplast clustering,and accumulation of reactive oxygen species(ROS),the typical defense responses of chloroplasts transferring the retrograde signaling to the nucleus to regulate resistance genes.The expression of PR1 and PR2 was also upregulated significantly in plants overexpressing OMP24.Self-interaction of OMP24 was demonstrated and was required for OMP24-mediated plant defense.Interaction with PMMoV CP interfered with the self-interaction of OMP24 and impaired OMP24-induced stromules,perinuclear chloroplast clustering and ROS accumulation.The results demonstrate the defense function of OMP24 in pepper during viral infection and suggest a possible mechanism by which PMMoV CP modulates the plant defense to facilitate viral infection.展开更多
Prenatal programming during pregnancy sets physiological outcomes in the offspring by integrating external or internal stimuli.Accordingly,pregnancy is an important stage of physiological adaptations to the environmen...Prenatal programming during pregnancy sets physiological outcomes in the offspring by integrating external or internal stimuli.Accordingly,pregnancy is an important stage of physiological adaptations to the environment where the fetus becomes exposed and adapted to the maternal milieu.Maternal exposure to high-energy dense diets can affect motivated behavior in the offs p ring leading to addiction and impaired sociability.A high-energy dense exposure also increases the pro-inflammatory cytokines profile in plasma and brain and favors microglia activation in the offspring.While still under investigation,prenatal exposure to high-energy dense diets promotes structural abnormalities in selective brain regions regulating motivation and social behavior in the offspring.The current review addresses the role of energy-dense foods programming central and peripheral inflammatory profiles during embryonic development and its effect on motivated behavior in the offspring.We provide preclinical and clinical evidence that supports the contribution of prenatal programming in shaping immune profiles that favor structural and brain circuit disruption leading to aberrant motivated behaviors after birth.We hope this minireview encourages future research on novel insights into the mechanisms underlying maternal programming of motivated behavior by central immune networks.展开更多
Meloidogyne incognita is a devastating plant-parasitic nematode.Effectors play important roles during the stages of nematodes infection and parasitism,but their molecular functions remain largely unknown.In this study...Meloidogyne incognita is a devastating plant-parasitic nematode.Effectors play important roles during the stages of nematodes infection and parasitism,but their molecular functions remain largely unknown.In this study,we characterized a new effector,Minc03329,which contains signal peptide for secretion and a C-type lectin domain.The yeast signal sequence trap experiments indicated that the signal peptide of Minc03329 is functional.In situ hybridization showed that Minc03329 was specifically expressed in the subventral esophageal gland.Real-time qPCR confirmed that the expression level of Minc03329 transcript was significantly increased in pre-parasitic and parasitic second-stage juveniles(pre-J2s and par-J2s).Tobacco rattle virus(TRV)-mediated gene silencing of Minc03329 in host plants largely reduced the pathogenicity of nematodes.On the contrary,ectopic expression of Minc03329 in Arabidopsis thaliana significantly increased plant susceptibility to nematodes.Transient expression of Minc03329 in Nicotiana benthamiana leaves suppressed the programmed cell death triggered by the pro-apoptotic protein BAX.Moreover,the transcriptome analysis of Minc03329-transgenic Arabidopsis and wild type revealed that many defense-related genes were significantly down-regulated.Interestingly,some different expressed genes were involved in the formation of nematode feeding sites.These results revealed that Minc03329 is an important effector for M.incognita,suppressing host defense response and promoting pathogenicity.展开更多
Recombinant adenovirus serotype 5(Ad5)vector has been widely applied in vaccine development targeting infectious diseases,such as Ebola virus disease and coronavirus disease 2019(COVID-19).However,the high prevalence ...Recombinant adenovirus serotype 5(Ad5)vector has been widely applied in vaccine development targeting infectious diseases,such as Ebola virus disease and coronavirus disease 2019(COVID-19).However,the high prevalence of preexisting anti-vector immunity compromises the immunogenicity of Ad5-based vaccines.Thus,there is a substantial unmet need to minimize preexisting immunity while improving the insert-induced immunity of Ad5 vectors.Herein,we address this need by utilizing biocompatible nanoparticles to modulate Ad5–host interactions.We show that positively charged human serum albumin nanoparticles((+)HSAnp),which are capable of forming a complex with Ad5,significantly increase the transgene expression of Ad5 in both coxsackievirus–adenovirus receptor-positive and-negative cells.Furthermore,in charge-and dose-dependent manners,Ad5/(+)HSAnp complexes achieve robust(up to227-fold higher)and long-term(up to 60 days)transgene expression in the lungs of mice following intranasal instillation.Importantly,in the presence of preexisting anti-Ad5 immunity,complexed Ad5-based Ebola and COVID-19 vaccines significantly enhance antigen-specific humoral response and mucosal immunity.These findings suggest that viral aggregation and charge modification could be leveraged to engineer enhanced viral vectors for vaccines and gene therapies.展开更多
Background The tongue-rolling behaviour of cows is regarded as an outward sign of stressed animals in a low welfare status.The primary aim of this observational study was to evaluate the association between the freque...Background The tongue-rolling behaviour of cows is regarded as an outward sign of stressed animals in a low welfare status.The primary aim of this observational study was to evaluate the association between the frequency of tongue-rolling behaviour and its physiological function.The secondary aim was to explore the relationship between general activities and the frequency of tongue-rolling behaviour of cows.A total of 126 scan sampling behavioural observations were collected over 7 d on 348 Holstein cows with the same lactation stage in the same barn.The tongue-rolling frequency was defined as the number of tongue-rolling observations as a percentage to the total observations per individual cow.According to their tongue-rolling frequency,the cows were grouped into the CON(no tongue-rolling),LT(frequency 1%),MT(frequency 5%),and HT(frequency 10%)groups.Six cows from each group were randomly selected for sampling.Serum samples,rumen fluid,milk yield,and background infor-mation were collected.The general behaviour data during 72 continuous hours of dairy cows,including eating time,rumination time,food time(eating time+rumination time),and lying time,were recorded by the collar sensor.Results Cortisol(P=0.012),γ-hydroxybutyric acid(P=0.008),epinephrine(P=0.030),and dopamine(P=0.047)levels were significantly higher in tongue-rolling groups than in the CON group.Cortisol levels and tongue-rolling frequency had a moderate positive correlation(linearly r=0.363).With the increase in tongue-rolling frequency,the rumen pH decreased first and then increased(P=0.013),comparing to the CON group.HT cows had significantly less food time than CON cows(P=0.035).The frequency of tongue-rolling had a moderate negative relationship with rumination time(r=-0.384)and food time(r=-0.492).Conclusions The tongue-rolling behaviour is considered as a passive coping mechanism,as the stress response in cows with high tongue-rolling frequency increased.Food intake and rumination activities were all closely related to the occurrence of tongue-rolling behaviour.展开更多
Alzheimer’s disease(AD) is an age-related neurodegenerative disease characterized by progressive cognitive defects. The role of the central immune system dominated by microglia in the progression of AD has been exten...Alzheimer’s disease(AD) is an age-related neurodegenerative disease characterized by progressive cognitive defects. The role of the central immune system dominated by microglia in the progression of AD has been extensively investigated. However, little is known about the peripheral immune system in AD pathogenesis.Recently, with the discovery of the meningeal lymphatic vessels and glymphatic system, the roles of the acquired immunity in the maintenance of central homeostasis and neurodegenerative diseases have attracted an increasing attention. The T cells not only regulate the function of neurons, astrocytes, microglia, oligodendrocytes and brain microvascular endothelial cells, but also participate in the clearance of β-amyloid(Aβ) plaques. Apart from producing antibodies to bind Aβ peptides, the B cells affect Aβ-related cascades via a variety of antibodyindependent mechanisms. This review systemically summarizes the recent progress in understanding pathophysiological roles of the T cells and B cells in AD.展开更多
Background:Lactic acid bacteria(LAB)participating in milk fermentation naturally release and enrich the fermented dairy product with a broad range of bioactive metabolites,which has numerous roles in the intestinal he...Background:Lactic acid bacteria(LAB)participating in milk fermentation naturally release and enrich the fermented dairy product with a broad range of bioactive metabolites,which has numerous roles in the intestinal health-promot-ing of the consumer.However,information is lacking regarding the application prospect of LAB fermented milk in the animal industry.This study investigated the effects of lactic acid bacteria-fermented formula milk(LFM)on the growth performance,intestinal immunity,microbiota composition,and transcriptomic responses in weaned piglets.A total of 24 male weaned piglets were randomly divided into the control(CON)and LFM groups.Each group consisted of 6 replicates(cages)with 2 piglets per cage.Each piglet in the LFM group were supplemented with 80 mL LFM three times a day,while the CON group was treated with the same amount of drinking water.Results:LFM significantly increased the average daily gain of piglets over the entire 14 d(P<0.01)and the average daily feed intake from 7 to 14 d(P<0.05).Compared to the CON group,ileal goblet cell count,villus-crypt ratio,sIgA,and lactate concentrations in the LFM group were significantly increased(P<0.05).Transcriptomic analysis of ileal mucosa identified 487 differentially expressed genes(DEGs)between two groups.Especially,DEGs involved in the intestinal immune network for IgA production pathways,such as polymeric immunoglobulin receptor(PIGR),were significantly up-regulated(P<0.01)by LFM supplementation.Moreover,trefoil factor 2(TFF2)in the LFM group,one of the DEGs involved in the secretory function of goblet cells,was also significantly up-regulated(P<0.01).Sequenc-ing of the 16S rRNA gene of microbiota demonstrated that LFM led to selective enrichment of lactate-producing and short-chain fatty acid(SCFA)-producing bacteria in the ileum,such as an increase in the relative abundance of Entero-coccus(P=0.09)and Acetitomaculum(P<0.05).Conclusions:LFM can improve intestinal health and immune tolerance,thus enhancing the growth performance of weaned piglets.The changes in microbiota and metabolites induced by LFM might mediate the regulation of the secretory function of goblet cells.展开更多
Viral infections have led to many public health crises and pandemics in the last few centuries.Neurotropic virus infection-induced viral encephalitis(VE),especially the symptomatic inflammation of the meninges and bra...Viral infections have led to many public health crises and pandemics in the last few centuries.Neurotropic virus infection-induced viral encephalitis(VE),especially the symptomatic inflammation of the meninges and brain parenchyma,has attracted growing attention due to its high mortality and disability rates.Understanding the infectious routes of neurotropic viruses and the mechanism underlying the host immune response is critical to reduce viral spread and improve antiviral therapy outcomes.In this review,we summarize the common categories of neurotropic viruses,viral transmission routes in the body,host immune responses,and experimental animal models used for VE study to gain a deeper understanding of recent progress in the pathogenic and immunological mechanisms under neurotropic viral infection.This review should provide valuable resources and perspectives on how to cope with pandemic infections.展开更多
Background Cold regions have long autumn and winter seasons and low ambient temperatures.When pigs are unable to adjust to the cold,oxidative damage and inflammation may develop.However,the differences between cold an...Background Cold regions have long autumn and winter seasons and low ambient temperatures.When pigs are unable to adjust to the cold,oxidative damage and inflammation may develop.However,the differences between cold and non-cold adaptation regarding glucose and lipid metabolism,gut microbiota and colonic mucosal immunological features in pigs are unknown.This study revealed the glucose and lipid metabolic responses and the dual role of gut microbiota in pigs during cold and non-cold adaptation.Moreover,the regulatory effects of dietary glucose supplements on glucose and lipid metabolism and the colonic mucosal barrier were evaluated in cold-exposed pigs.Results Cold and non-cold-adapted models were established by Min and Yorkshire pigs.Our results exhibited that cold exposure induced glucose overconsumption in non-cold-adapted pig models(Yorkshire pigs),decreasing plasma glucose concentrations.In this case,cold exposure enhanced the ATGL and CPT-1αexpression to promote liver lipolysis and fatty acid oxidation.Meanwhile,the two probiotics(Collinsella and Bifidobacterium)depletion and the enrichment of two pathogens(Sutterella and Escherichia-Shigella)in colonic microbiota are not conducive to colonic mucosal immunity.However,glucagon-mediated hepatic glycogenolysis in cold-adapted pig models(Min pigs)maintained the stability of glucose homeostasis during cold exposure.It contributed to the gut microbiota(including the enrichment of the Rikenellaceae RC9 gut group,[Eubacterium]coprostanoligenes group and WCHB1-41)that favored cold-adapted metabolism.Conclusions The results of both models indicate that the gut microbiota during cold adaptation contributes to the protection of the colonic mucosa.During non-cold adaptation,cold-induced glucose overconsumption promotes thermogenesis through lipolysis,but interferes with the gut microbiome and colonic mucosal immunity.Furthermore,glucagon-mediated hepatic glycogenolysis contributes to glucose homeostasis during cold exposure.展开更多
Identification of immunity-associated leucine-rich repeat receptor-like protein kinases(LRR-RLK) is critical to elucidate the LRR-RLK mediated mechanism of plant immunity.Here,we reported the map-based cloning of a no...Identification of immunity-associated leucine-rich repeat receptor-like protein kinases(LRR-RLK) is critical to elucidate the LRR-RLK mediated mechanism of plant immunity.Here,we reported the map-based cloning of a novel rice SPOTTED-LEAF 41(Os SPL41) encoding a putative LRR-RLK protein(Os LRR-RLK41/Os SPL41) that regulated disease responses to the bacterial blight pathogen Xanthomonas oryzae pv.oryzae(Xoo).An 8-bp insertion at position 865 bp in a mutant spotted-leaf 41(spl41) allele led to the formation of purple-brown lesions on leaves.Functional complementation by the wild type allele(Os SPL41) can rescue the mutant phenotype,and the complementary lines showed similar performance to wild type in a number of agronomic,physiological and molecular indices.Os SPL41 was constitutively expressed in all tissues tested,and Os SPL41 contains a typical transmembrane domain critical for its localization to the cell membrane.The mutant exhibited an enhanced level of resistance to Xoo in companion of markedly up-regulated expression of pathogenesis-related genes such as Os PR10a,Os PAL1 and Os NPR1,while the level of salicylic acid was significantly increased in spl41.In contrast,the over-expression lines exhibited a reduced level of H_(2)O_(2) and were much susceptible to Xoo with down-regulated expression of pathogenesis-related genes.These results suggested that Os SPL41 might negatively regulate plant immunity through the salicylic acid signaling pathway in rice.展开更多
Immune checkpoint blockade(ICB)has achieved durable clinical responses and has significantly improved the overall survival of cancer patients1.Among the ICB agents,programmed death 1(PD-1)/programmed death ligand 1(PD...Immune checkpoint blockade(ICB)has achieved durable clinical responses and has significantly improved the overall survival of cancer patients1.Among the ICB agents,programmed death 1(PD-1)/programmed death ligand 1(PD-L1)antibodies are used to treat various human tumors by blocking PD-1/PD-L1 signaling.Impressive response rates with low autoimmune toxicity have been reported in 20%–30%of non-selected patients1;however,most patients fail to respond to PD-1/PD-L1 blockade or acquire resistance during therapy through unknown mechanisms1.展开更多
Cancer immunotherapy is a preferred strategy for boosting anti-tumor immunity to eliminate malignant cells and is considered a major breakthrough in the field of cancer treatment however,immunosuppressive cells in the...Cancer immunotherapy is a preferred strategy for boosting anti-tumor immunity to eliminate malignant cells and is considered a major breakthrough in the field of cancer treatment however,immunosuppressive cells in the tumor microenvironment(TME)pose a major obstacle to the efficacy of immunotherapy.Myeloid cells,such as tumor-a ssociated macrophages(TAMs)and myeloid-derived suppressor cells(MDSCs).展开更多
基金financially supported by the National Natural Science Foundation of China(Grant Nos.:82100801,81974096,81770711,81974097,and 81961138007).
文摘Diabetic nephropathy (DN) is an enduring condition that leads to inflammation and affects a substantial number of individuals with diabetes worldwide. A gradual reduction in glomerular filtration and emergence of proteins in the urine are typical aspects of DN, ultimately resulting in renal failure. Mounting evidence suggests that immunological and inflammatory factors are crucial for the development of DN. Therefore, the activation of innate immunity by resident renal and immune cells is critical for initiating and perpetuating inflammation. Toll-like receptors (TLRs) are an important group of receptors that identify patterns and activate immune responses and inflammation. Meanwhile, inflammatory responses in the liver, pancreatic islets, and kidneys involve inflammasomes and chemokines that generate pro-inflammatory cytokines. Moreover, the activation of the complement cascade can be triggered by glycated proteins. This review highlights recent findings elucidating how the innate immune system contributes to tissue fibrosis and organ dysfunction, ultimately leading to renal failure. This review also discusses innovative approaches that can be utilized to modulate the innate immune responses in DN for therapeutic purposes.
基金the Zhejiang Natural Science Foundation,China(Grant No.LY21C130004)the Key Research and Development Program of Zhejiang Province,China(Grant No.2021C02056-3)+1 种基金the Central Public-Interest Scientific Institution Basal Research Fund,China(Grant No.CPSIBRF-CNRRI-202202)the Agricultural Science and Technology Innovation Program,China(Grant No.CAASASTIP-2021-CNRRI).
文摘The basic region/leucine zipper(bZIP)transcription factors play important roles in plant development and responses to abiotic and biotic stresses.OsbZIP53 regulates resistance to Magnaporthe oryzae in rice by analyzing APIP5-RNAi transgenic plants.To further investigate the biological functions of OsbZIP53,we generated osbzip53 mutants using CRISPR/Cas9 editing and also constructed OsbZIP53 over-expression transgenic plants.Comprehensive analysis of phenotypical,physiological,and transcriptional data showed that knocking-out OsbZIP53 not only improved disease resistance by inducing a hypersensitivity response in plants,but also regulated the immune response through the salicylic acid pathway.Specifically,disrupting OsbZIP53 increased H2O2 accumulation by promoting reactive oxygen species generation through up-regulation of several respiratory burst oxidase homologs(Osrboh genes)and weakened H2O2 degradation by directly targeting OsMYBS1.In addition,the growth of osbzip53 mutants was seriously impaired,while OsbZIP53 over-expression lines displayed a similar phenotype to the wild type,suggesting that OsbZIP53 has a balancing effect on rice immune response and growth.
文摘The liver is the front line organ of the immune system.The liver contains the largest collection of phagocytic cells in the body that detect both pathogens that enter through the gut and endogenously produced antigens.This is possible by the highly developed differentiation capacity of the liver immune system between self-antigens or non-self-antigens,such as food antigens or pathogens.As an immune active organ,the liver functions as a gatekeeping barrier from the outside world,and it can create a rapid and strong immune response,under unfavorable conditions.However,the liver's assumed immune status is anti-inflammatory or immuno-tolerant.Dynamic interactions between the numerous populations of immune cells in the liver are key for maintaining the delicate balance between immune screening and immune tolerance.The anatomical structure of the liver can facilitate the preparation of lymphocytes,modulate the immune response against hepatotropic pathogens,and contribute to some of its unique immunological properties,particularly its capacity to induce antigen-specific tolerance.Since liver sinusoidal endothelial cell is fenestrated and lacks a basement membrane,circulating lymphocytes can closely contact with antigens,displayed by endothelial cells,Kupffer cells,and dendritic cells while passing through the sinusoids.Loss of immune tolerance,leading to an autoaggressive immune response in the liver,if not controlled,can lead to the induction of autoimmune or autoinflammatory diseases.This review mentions the unique features of liver immunity,and dysregulated immune responses in patients with autoimmune liver diseases who have a close association with inborn errors of immunity have also been the emphases.
文摘The present study investigated the effect of treatment with methanolic extracts of Yin- and Yang-Chinese tonifying herbs on concanavalin A (Con A)/lipopolysaccharide (LPS)-stimulated splenocyte proliferation (adaptive immunity) and natural killer (NK) cell activity (innate immunity) in an ex vivo mouse model. The results indicated that while treatment with most Yin herbal extracts potentiated the Con A/LPS-stimulated splenocyte proliferation, only Yang (but not Yin) herbal extracts stimulated NK cell activity. The differential effects of Yin- and Yang-Chinese tonifying herbs on innate and adaptive immunity are consistent with the Chinese medicine theory which depicts the Yin and Yang functional components of Zheng Qi (vital energy), with the Yang component being responsible for the first line of defense against invading microorganisms (i.e., innate immunity) and the Yin oner serving as a follow-up defensive response (adaptive immunity).
基金the China Agriculture Research System program(CARS-41-G11).
文摘Background In broiler chickens,necrotic enteritis(NE)infection can reduce production performance.Tannic acid has shown great potential as a treatment of NE in broilers.However,the appropriate dosage of tannic acid in NE of broilers and the improvement effect on intestinal health are not very clear.In this study,we aimed to investigate the effects of different doses of tannic acid on the production performance,immunity,and intestinal health of broilers by constructing an NE model with C.perfringens infection and determining the appropriate dosage of tannic acid with regard to NE.Results Challenged birds showed significant reduction in body weight,villus height,and the ratio of villus height to crypt depth(P<0.05)and increase in the feed consumption gain ratio,intestinal lesion score,and crypt depth(P<0.05).The infection significantly reduced the relative Bacteroidota and Ligilactobacillus abundance(P<0.05)and increased the ratio of Firmicutes/Bacteroidota and cecal content of C.perfringens(P<0.05).Challenged birds fed diets supplemented with tannic acid showed significantly increased mRNA expression of nutrient transport carriers and intestinal barrier genes and growth performance and reduced serum zonulin and endotoxin levels(P<0.05).Addi-tion of tannic acid to the diet inhibited the inflammatory response by reducing the number of coccidia oocysts in feces and the content of C.perfringens in the cecum.Specifically,tannic acid reduced the serum levels of C reactive protein,myeloperoxidase,and specific IgY and ileal mucosal secretory immunoglobulin A levels in the ileal mucosa compared with those in the NE-infected birds.NE-infected birds fed diets supplemented with tannic acid also showed significantly increased relative Anaerocolumna,Thermoanaerobacterium,and Thermosinus abundance(P<0.05);their microbial composition and functional predictions were similar to those of the NC group.Conclusions Tannic acid in the diet alleviated NE by enhancing the intestinal barrier and absorption function.The recommended dietary tannic acid additive level is 500–750 mg/kg.Our study findings would be useful in reducing related economic losses in the broiler industry.
基金supported by the Science Fund of the Republic of Serbia,#Grant No:7748088。
文摘Mushrooms are experiencing a kind of renaissance as a part of the contemporary human diet.These valuable organisms are more than food,they fit in perfectly as a novel market group known as nutra-mycoceuticals.Immune-balancing mushroom dietary fibers and secondary metabolites such as polyphenols are the main focus of the healthcare industry.Wellness and cosmetic companies are increasingly using mushroom extracts rich in these ingredients.This review considers the basic molecular immunomodulatory mechanisms of action of the most commonly used mushroom dietary fibers,β-glucans.The literature data on their bioavailability,metabolic transformations,preclinical and human clinical research,and safety are discussed.Immunomodulatory mechanisms of polyphenol ingredients are also considered.These molecules present great potential in the design of the new immunity balancer formulations according to their widespread structural diversity.Finally,we draw attention to the perspectives of modern trends in mushroom nutraceutical and cosmeceutical formulations to strengthen and balance immunity.
基金supported by National Key Research and Development Program of China(2018YFD1000703,2018YFD1000700)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB11020400)+3 种基金National Program on Research and Development of Transgenic Plants(2016ZX08009-003-001)Startup Fund for Advanced Talents of Lushan Botanical GardenChinese Academy of Science(2020ZWZX03 and 2020ZWZX05)the“Double Hundred and Double Thousand”Talent Project of Jiujiang City(jjsbsq2020026)。
文摘Plants use a sophisticated immune system to perceive pathogen infection and activate immune responses in a tightly controlled manner.In barley,Hv WRKY2 acts as a repressor in barley disease resistance to the powdery mildew fungus,Blumeria graminis f.sp.hordei(Bgh).However,the molecular features of Hv WRKY2 in its DNA-binding and repressor functions,as well as its target genes,are uncharacterized.We show that the W-box binding of Hv WRKY2 requires an intact WRKY domain and an upstream sequence of~75 amino acids,and the Hv WRKY2 W-box binding activity is linked to its repressor function in disease resistance.Chromatin immunoprecipitation(ChIP)-seq analysis identified HvCEBiP,a putative chitin receptor gene,as a target gene of Hv WRKY2 in overexpressing transgenic barley plants.ChIP-qPCR and Electrophoretic Mobility Shift Assay(EMSA)verified the direct binding of Hv WRKY2 to a W-boxcontaining sequence in the HvCEBiP promoter.Hv CEBiP positively regulates resistance against Bgh in barley.Our findings suggest that Hv WRKY2 represses barley basal immunity by directly targeting pathogen-associated molecular pattern(PAMP)recognition receptor genes,suggesting that Hv CEBiP and likely chitin signaling function in barley PAMP-triggered immune responses to Bgh infection.
基金This work was supported by the Guangdong Basic and Applied Basic Research Foundation(2019A1515110239)the China Postdoctoral Science Foundation(2020 M682732)the Key Project of Biology Discipline Construction of Yan’an University(301200085).
文摘Bacterial wilt is a devastating disease of tomato(Solanum lycopersicum)caused by Ralstonia solanacearum that severely threatens tomato production.Group III WRKY transcription factors(TFs)are implicated in the plant response to pathogen infection;however,their roles in the response of tomato to R.solanacearum infection(RSI)remain largely unexplored.Here,we report the crucial role of SlWRKY30,a group III SlWRKY TF,in the regulation of tomato response to RSI.SlWRKY30 was strongly induced by RSI.SlWRKY30 overexpression reduced tomato susceptibility to RSI,and also increased H2O2 accumulation and cell necrosis,suggesting that SlWRKY30 positively regulates tomato resistance to RSI.RNA sequencing and reverse transcription–quantitative PCR revealed that SlWRKY30 overexpression significantly upregulated pathogenesis-related protein(SlPR-STH2)genes SlPR-STH2a,SlPR-STH2b,SlPR-STH2c,and SlPR-STH2d(hereafter SlPR-STH2a/b/c/d)in tomato,and these SlPR-STH2 genes were directly targeted by SlWRKY30.Moreover,four group III WRKY proteins(SlWRKY52,SlWRKY59,SlWRKY80,and SlWRKY81)interacted with SlWRKY30,and SlWRKY81 silencing increased tomato susceptibility to RSI.Both SlWRKY30 and SlWRKY81 activated SlPR-STH2a/b/c/d expression by directly binding to their promoters.Taking these results together,SlWRKY30 and SlWRKY81 synergistically regulate resistance to RSI by activating SlPR-STH2a/b/c/d expression in tomato.Our results also highlight the potential of SlWRKY30 to improve tomato resistance to RSI via genetic manipulations.
基金This work was financially supported by National Key R&D Program of China(2022YFD1401200)China Agriculture Research System of MOF and MARA(CARS-24-C-04)+3 种基金National Natural Science Foundation of China(32270294)Ningbo Major Special Projects of the Plan‘Science and Technology Innovation 2025’(2021Z106)the Postdoctoral Science Foundation of Anhui Province,China(2021B558)K.C.Wong Magna Fund in Ningbo University.
文摘Pepper mild mottle virus(PMMoV)is a devastating viral pathogen of pepper(Capsicum annuum)but it is unclear whether and how peppers protect against PMMoV infection.The expression of the chloroplast outer membrane protein 24(OMP24)of C.annuum was upregulated under PMMoV infection and it interacted with PMMoV coat protein(CP).Silencing of OMP24 in either C.annuum or Nicotiana benthamiana facilitated PMMoV infection,whereas overexpression of N.benthamiana OMP24 in transgenic plants inhibited PMMoV infection.Both C.annuum OMP24(CaOMP24)and N.benthamiana OMP24(NbOMP24)localized to the chloroplast and have a moderately hydrophobic transmembrane domain that is necessary for their localization.Overexpression of CaOMP24 induced stromules,perinuclear chloroplast clustering,and accumulation of reactive oxygen species(ROS),the typical defense responses of chloroplasts transferring the retrograde signaling to the nucleus to regulate resistance genes.The expression of PR1 and PR2 was also upregulated significantly in plants overexpressing OMP24.Self-interaction of OMP24 was demonstrated and was required for OMP24-mediated plant defense.Interaction with PMMoV CP interfered with the self-interaction of OMP24 and impaired OMP24-induced stromules,perinuclear chloroplast clustering and ROS accumulation.The results demonstrate the defense function of OMP24 in pepper during viral infection and suggest a possible mechanism by which PMMoV CP modulates the plant defense to facilitate viral infection.
基金supported by the National Council of Science and Technology in Mexico(CONACYT)708452 CONACYT to LMM855559 CONACYT to GCC+1 种基金573686 CONACYT to RMRPAICYT 2021 to ACM。
文摘Prenatal programming during pregnancy sets physiological outcomes in the offspring by integrating external or internal stimuli.Accordingly,pregnancy is an important stage of physiological adaptations to the environment where the fetus becomes exposed and adapted to the maternal milieu.Maternal exposure to high-energy dense diets can affect motivated behavior in the offs p ring leading to addiction and impaired sociability.A high-energy dense exposure also increases the pro-inflammatory cytokines profile in plasma and brain and favors microglia activation in the offspring.While still under investigation,prenatal exposure to high-energy dense diets promotes structural abnormalities in selective brain regions regulating motivation and social behavior in the offspring.The current review addresses the role of energy-dense foods programming central and peripheral inflammatory profiles during embryonic development and its effect on motivated behavior in the offspring.We provide preclinical and clinical evidence that supports the contribution of prenatal programming in shaping immune profiles that favor structural and brain circuit disruption leading to aberrant motivated behaviors after birth.We hope this minireview encourages future research on novel insights into the mechanisms underlying maternal programming of motivated behavior by central immune networks.
基金funded by the National Natural Science Foundation of China(31672010 and 31871942)the Beijing Natural Science Foundation,China(6222054)+1 种基金the China Agriculture Research System(CARS-23)the Natural Science Foundation of Inner Mongolia Autonomous Region of China(2018MS03083)。
文摘Meloidogyne incognita is a devastating plant-parasitic nematode.Effectors play important roles during the stages of nematodes infection and parasitism,but their molecular functions remain largely unknown.In this study,we characterized a new effector,Minc03329,which contains signal peptide for secretion and a C-type lectin domain.The yeast signal sequence trap experiments indicated that the signal peptide of Minc03329 is functional.In situ hybridization showed that Minc03329 was specifically expressed in the subventral esophageal gland.Real-time qPCR confirmed that the expression level of Minc03329 transcript was significantly increased in pre-parasitic and parasitic second-stage juveniles(pre-J2s and par-J2s).Tobacco rattle virus(TRV)-mediated gene silencing of Minc03329 in host plants largely reduced the pathogenicity of nematodes.On the contrary,ectopic expression of Minc03329 in Arabidopsis thaliana significantly increased plant susceptibility to nematodes.Transient expression of Minc03329 in Nicotiana benthamiana leaves suppressed the programmed cell death triggered by the pro-apoptotic protein BAX.Moreover,the transcriptome analysis of Minc03329-transgenic Arabidopsis and wild type revealed that many defense-related genes were significantly down-regulated.Interestingly,some different expressed genes were involved in the formation of nematode feeding sites.These results revealed that Minc03329 is an important effector for M.incognita,suppressing host defense response and promoting pathogenicity.
基金supported in part by the grant from National Natural Science Foundation of China(82171818,81703048,82041019,and 82101919)the grant from Defense Industrial Technology Development Program of China(JCKY2020802B001)Beijing Municipal Science and Technology Commission(Z201100005420024)。
文摘Recombinant adenovirus serotype 5(Ad5)vector has been widely applied in vaccine development targeting infectious diseases,such as Ebola virus disease and coronavirus disease 2019(COVID-19).However,the high prevalence of preexisting anti-vector immunity compromises the immunogenicity of Ad5-based vaccines.Thus,there is a substantial unmet need to minimize preexisting immunity while improving the insert-induced immunity of Ad5 vectors.Herein,we address this need by utilizing biocompatible nanoparticles to modulate Ad5–host interactions.We show that positively charged human serum albumin nanoparticles((+)HSAnp),which are capable of forming a complex with Ad5,significantly increase the transgene expression of Ad5 in both coxsackievirus–adenovirus receptor-positive and-negative cells.Furthermore,in charge-and dose-dependent manners,Ad5/(+)HSAnp complexes achieve robust(up to227-fold higher)and long-term(up to 60 days)transgene expression in the lungs of mice following intranasal instillation.Importantly,in the presence of preexisting anti-Ad5 immunity,complexed Ad5-based Ebola and COVID-19 vaccines significantly enhance antigen-specific humoral response and mucosal immunity.These findings suggest that viral aggregation and charge modification could be leveraged to engineer enhanced viral vectors for vaccines and gene therapies.
基金the National Natural Science Foundation of China(32272926)the Agricultural Science and Technology Innovation Program(ASTIP-IAS07,Beijing,China).
文摘Background The tongue-rolling behaviour of cows is regarded as an outward sign of stressed animals in a low welfare status.The primary aim of this observational study was to evaluate the association between the frequency of tongue-rolling behaviour and its physiological function.The secondary aim was to explore the relationship between general activities and the frequency of tongue-rolling behaviour of cows.A total of 126 scan sampling behavioural observations were collected over 7 d on 348 Holstein cows with the same lactation stage in the same barn.The tongue-rolling frequency was defined as the number of tongue-rolling observations as a percentage to the total observations per individual cow.According to their tongue-rolling frequency,the cows were grouped into the CON(no tongue-rolling),LT(frequency 1%),MT(frequency 5%),and HT(frequency 10%)groups.Six cows from each group were randomly selected for sampling.Serum samples,rumen fluid,milk yield,and background infor-mation were collected.The general behaviour data during 72 continuous hours of dairy cows,including eating time,rumination time,food time(eating time+rumination time),and lying time,were recorded by the collar sensor.Results Cortisol(P=0.012),γ-hydroxybutyric acid(P=0.008),epinephrine(P=0.030),and dopamine(P=0.047)levels were significantly higher in tongue-rolling groups than in the CON group.Cortisol levels and tongue-rolling frequency had a moderate positive correlation(linearly r=0.363).With the increase in tongue-rolling frequency,the rumen pH decreased first and then increased(P=0.013),comparing to the CON group.HT cows had significantly less food time than CON cows(P=0.035).The frequency of tongue-rolling had a moderate negative relationship with rumination time(r=-0.384)and food time(r=-0.492).Conclusions The tongue-rolling behaviour is considered as a passive coping mechanism,as the stress response in cows with high tongue-rolling frequency increased.Food intake and rumination activities were all closely related to the occurrence of tongue-rolling behaviour.
基金supported by grants from the National Natural Science Foundation of China (Grants No. 82071199 and 32100674)。
文摘Alzheimer’s disease(AD) is an age-related neurodegenerative disease characterized by progressive cognitive defects. The role of the central immune system dominated by microglia in the progression of AD has been extensively investigated. However, little is known about the peripheral immune system in AD pathogenesis.Recently, with the discovery of the meningeal lymphatic vessels and glymphatic system, the roles of the acquired immunity in the maintenance of central homeostasis and neurodegenerative diseases have attracted an increasing attention. The T cells not only regulate the function of neurons, astrocytes, microglia, oligodendrocytes and brain microvascular endothelial cells, but also participate in the clearance of β-amyloid(Aβ) plaques. Apart from producing antibodies to bind Aβ peptides, the B cells affect Aβ-related cascades via a variety of antibodyindependent mechanisms. This review systemically summarizes the recent progress in understanding pathophysiological roles of the T cells and B cells in AD.
基金supported by the National Natural Science Foundation of China(31872362 and 32072688)the Agricultural Science and Technology Independent Innovation Fund Project of Jiangsu Province[CX(19)1006].
文摘Background:Lactic acid bacteria(LAB)participating in milk fermentation naturally release and enrich the fermented dairy product with a broad range of bioactive metabolites,which has numerous roles in the intestinal health-promot-ing of the consumer.However,information is lacking regarding the application prospect of LAB fermented milk in the animal industry.This study investigated the effects of lactic acid bacteria-fermented formula milk(LFM)on the growth performance,intestinal immunity,microbiota composition,and transcriptomic responses in weaned piglets.A total of 24 male weaned piglets were randomly divided into the control(CON)and LFM groups.Each group consisted of 6 replicates(cages)with 2 piglets per cage.Each piglet in the LFM group were supplemented with 80 mL LFM three times a day,while the CON group was treated with the same amount of drinking water.Results:LFM significantly increased the average daily gain of piglets over the entire 14 d(P<0.01)and the average daily feed intake from 7 to 14 d(P<0.05).Compared to the CON group,ileal goblet cell count,villus-crypt ratio,sIgA,and lactate concentrations in the LFM group were significantly increased(P<0.05).Transcriptomic analysis of ileal mucosa identified 487 differentially expressed genes(DEGs)between two groups.Especially,DEGs involved in the intestinal immune network for IgA production pathways,such as polymeric immunoglobulin receptor(PIGR),were significantly up-regulated(P<0.01)by LFM supplementation.Moreover,trefoil factor 2(TFF2)in the LFM group,one of the DEGs involved in the secretory function of goblet cells,was also significantly up-regulated(P<0.01).Sequenc-ing of the 16S rRNA gene of microbiota demonstrated that LFM led to selective enrichment of lactate-producing and short-chain fatty acid(SCFA)-producing bacteria in the ileum,such as an increase in the relative abundance of Entero-coccus(P=0.09)and Acetitomaculum(P<0.05).Conclusions:LFM can improve intestinal health and immune tolerance,thus enhancing the growth performance of weaned piglets.The changes in microbiota and metabolites induced by LFM might mediate the regulation of the secretory function of goblet cells.
基金supported by the National Natural Science Foundation of China(81825011,81930038,81961160738)Program of Shanghai Academic/Technology Research Leader(22XD1400800)Strategic Priority Research Program of the Chinese Academy of Sciences(XDB19030200)。
文摘Viral infections have led to many public health crises and pandemics in the last few centuries.Neurotropic virus infection-induced viral encephalitis(VE),especially the symptomatic inflammation of the meninges and brain parenchyma,has attracted growing attention due to its high mortality and disability rates.Understanding the infectious routes of neurotropic viruses and the mechanism underlying the host immune response is critical to reduce viral spread and improve antiviral therapy outcomes.In this review,we summarize the common categories of neurotropic viruses,viral transmission routes in the body,host immune responses,and experimental animal models used for VE study to gain a deeper understanding of recent progress in the pathogenic and immunological mechanisms under neurotropic viral infection.This review should provide valuable resources and perspectives on how to cope with pandemic infections.
基金supported by the National Key R&D Program of China(2021YFD1300403)the Major Program of Heilongjiang Province of China(2021ZX12B08-02).
文摘Background Cold regions have long autumn and winter seasons and low ambient temperatures.When pigs are unable to adjust to the cold,oxidative damage and inflammation may develop.However,the differences between cold and non-cold adaptation regarding glucose and lipid metabolism,gut microbiota and colonic mucosal immunological features in pigs are unknown.This study revealed the glucose and lipid metabolic responses and the dual role of gut microbiota in pigs during cold and non-cold adaptation.Moreover,the regulatory effects of dietary glucose supplements on glucose and lipid metabolism and the colonic mucosal barrier were evaluated in cold-exposed pigs.Results Cold and non-cold-adapted models were established by Min and Yorkshire pigs.Our results exhibited that cold exposure induced glucose overconsumption in non-cold-adapted pig models(Yorkshire pigs),decreasing plasma glucose concentrations.In this case,cold exposure enhanced the ATGL and CPT-1αexpression to promote liver lipolysis and fatty acid oxidation.Meanwhile,the two probiotics(Collinsella and Bifidobacterium)depletion and the enrichment of two pathogens(Sutterella and Escherichia-Shigella)in colonic microbiota are not conducive to colonic mucosal immunity.However,glucagon-mediated hepatic glycogenolysis in cold-adapted pig models(Min pigs)maintained the stability of glucose homeostasis during cold exposure.It contributed to the gut microbiota(including the enrichment of the Rikenellaceae RC9 gut group,[Eubacterium]coprostanoligenes group and WCHB1-41)that favored cold-adapted metabolism.Conclusions The results of both models indicate that the gut microbiota during cold adaptation contributes to the protection of the colonic mucosa.During non-cold adaptation,cold-induced glucose overconsumption promotes thermogenesis through lipolysis,but interferes with the gut microbiome and colonic mucosal immunity.Furthermore,glucagon-mediated hepatic glycogenolysis contributes to glucose homeostasis during cold exposure.
基金supported by the National Natural Science Foundation of China(Grant No.32072049)the Central Public-Interest Scientific Institution Basal Research Fund, China(Grant No.CPSIBRF-CNRRI-202203)。
文摘Identification of immunity-associated leucine-rich repeat receptor-like protein kinases(LRR-RLK) is critical to elucidate the LRR-RLK mediated mechanism of plant immunity.Here,we reported the map-based cloning of a novel rice SPOTTED-LEAF 41(Os SPL41) encoding a putative LRR-RLK protein(Os LRR-RLK41/Os SPL41) that regulated disease responses to the bacterial blight pathogen Xanthomonas oryzae pv.oryzae(Xoo).An 8-bp insertion at position 865 bp in a mutant spotted-leaf 41(spl41) allele led to the formation of purple-brown lesions on leaves.Functional complementation by the wild type allele(Os SPL41) can rescue the mutant phenotype,and the complementary lines showed similar performance to wild type in a number of agronomic,physiological and molecular indices.Os SPL41 was constitutively expressed in all tissues tested,and Os SPL41 contains a typical transmembrane domain critical for its localization to the cell membrane.The mutant exhibited an enhanced level of resistance to Xoo in companion of markedly up-regulated expression of pathogenesis-related genes such as Os PR10a,Os PAL1 and Os NPR1,while the level of salicylic acid was significantly increased in spl41.In contrast,the over-expression lines exhibited a reduced level of H_(2)O_(2) and were much susceptible to Xoo with down-regulated expression of pathogenesis-related genes.These results suggested that Os SPL41 might negatively regulate plant immunity through the salicylic acid signaling pathway in rice.
基金supported by the National Nature Science Foundation(Grant Nos.82150115,82025027,and 32000517)the National Key R&D Program of China(Grant No.2022YFA1105200).
文摘Immune checkpoint blockade(ICB)has achieved durable clinical responses and has significantly improved the overall survival of cancer patients1.Among the ICB agents,programmed death 1(PD-1)/programmed death ligand 1(PD-L1)antibodies are used to treat various human tumors by blocking PD-1/PD-L1 signaling.Impressive response rates with low autoimmune toxicity have been reported in 20%–30%of non-selected patients1;however,most patients fail to respond to PD-1/PD-L1 blockade or acquire resistance during therapy through unknown mechanisms1.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82150119 to HX.L.and Grant No.8223000771 to B.Z.)。
文摘Cancer immunotherapy is a preferred strategy for boosting anti-tumor immunity to eliminate malignant cells and is considered a major breakthrough in the field of cancer treatment however,immunosuppressive cells in the tumor microenvironment(TME)pose a major obstacle to the efficacy of immunotherapy.Myeloid cells,such as tumor-a ssociated macrophages(TAMs)and myeloid-derived suppressor cells(MDSCs).
