Brain endothelial cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway in aging and neurodegeneration

The cyclic GMP-AMP synthase(cGAS)-stimulator of interferon genes(STING)signaling pathway has emerged as a key mediator of neuroinflammation.While current studies primarily attribute its effects to neurons and glial cells,emerging research suggests that cGAS-STING signaling may play a critical role in cerebral vasculature,particularly in brain endothelial cells.Therefore,studying the role 7of inflammation caused by the cGAS-STING pathway in brain endothelial cells could provide a more comprehensive understanding of neuroinflammatory disease and new avenues for therapeutic interventions.Here,we review the multifaceted role of global cGAS-STING signaling in various neurological and neuroinflammatory diseases and the potential contribution of cGAS-STING in brain endothelial cells.

The cGAS-STING-interferon regulatory factor 7 pathway regulates neuroinflammation in Parkinson's disease

Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.

Science Letters:Transient expression of chicken alpha interferon gene in lettuce

We investigated the possibility of producing chicken alpha interferon （ChlFN-α） in transgenic plants. The cDNA encoding ChlFN-α was introduced into lettuce （Lactuca sativa L.） plants by using an agro-infiltration transient expression system. The ChlFN-a gene was correctly transcribed and translated in the lettuce plants according to RT-PCR and ELISA assays. Recombinant protein exhibited antiviral activity in vitro by inhibition of vesicular stomatitis virus （VSV） replication on chicken embryonic fibroblast （CEF）. The results demonstrate that biologically active avian cytokine with potential pharmaceutical applications could be expressed in transgenic lettuce plants and that it is possible to generate interferon protein in forage plants for preventing infectious diseases of poultry.

Chicken Embryo Inhibition Test of Recombinant Freeze-drying Chicken Interferon against Newcastle Disease Virus( NDV) F_(48)E_(10)

The paper was to study the inhibitory effect of recombinant freeze-drying chicken interferon against Newcastle disease virus （NDV） F48E10. Nine-day-old chicken embryos were inoculated with recombinant freeze-drying chicken interferon via allaotoic sack, while 10-day-old chicken embryos were inoculated with NDV F48E10, and in vivo protective efficacy of interferon on chichen embryos was studied. The results showed that the recombinant freeze-drying chicken interferon at the dose of 1.28 mg/embryo reached the protection ratio of 90% on chicken embryo infected by F48E10.

Interferon-γ acts as a regulator in the trade-off between phagocytosis and production performance in dwarf chickens

Background: Interferon-γ(IFN-γ) is critical for innate and adaptive immunity against viral and bacterial infections. IFN-γ reportedly affects the phagocytic ability of monocytes and macrophages as well as regulates pituitary function in humans and mice. The present study analyzed the impact of IFN-γ on monocyte and macrophage phagocytosis, production performance, and pituitary function in vivo and in vitro(in dwarf chickens). IFN-γ was injected into dwarf chickens through a vein, and then, the laying rate, average egg weight, and levels of follicle-stimulating hormone(FSH) and IFN-γ were measured in treatment and control groups. For the in vitro experiment, the pituitary tissues were supplemented with IFN-γ, and the m RNA expression levels of follicle-stimulating hormone beta subunit(FSH-β), interferon gamma receptor 1(IFNGR1),and interferon gamma receptor 2(IFNGR2) in the pituitary were assessed.Results: Monocyte and macrophage phagocytosis product(PP) was decreased by IFN-γ treatment in a dose-dependent manner in vitro. In the in vivo experiment, the level of IFN-γ in the treatment group was higher than that in the control group at 7 d(P < 0.05), 14 d(P < 0.01), and 21 d(P < 0.01) post-injection.Compared with the control group, monocyte and macrophage PP was lower in the treatment group after injection(P < 0.01). The laying rate was higher in the treatment group than in the control group at 2 and3 wk post-injection(P < 0.05). There was a significant difference between the treatment and control groups in the levels of FSH at 1, 3, 7, and 14 d post-injection(P < 0.01). In the in vitro experiment, increased m RNA expression levels of FSH-β, IFNGR1, and IFNGR2 were observed in the treatment group after stimulation with100 U/m L IFN-γ for 24 h compared to those in the control group(P < 0.05).Conclusions: IFN-γ inhibited the phagocytosis of monocytes and macrophages; up-regulated the m RNA expression levels of the FSH-β, IFNGR1, and IFNGR2; enhanced the secretion of FSH; and improved the laying rate. IFN-γ might be an important regulator in the trade-off between the immune effect and production performance in dwarf chickens.

Genome-wide investigation to assess copy number variants in the Italian local chicken population

Background Copy number variants(CNV)hold significant functional and evolutionary importance.Numerous ongoing CNV studies aim to elucidate the etiology of human diseases and gain insights into the population structure of livestock.High-density chips have enabled the detection of CNV with increased resolution,leading to the identification of even small CNV.This study aimed to identify CNV in local Italian chicken breeds and investigate their distribution across the genome.Results Copy number variants were mainly distributed across the first six chromosomes and primarily associated with loss type CNV.The majority of CNV in the investigated breeds were of types 0 and 1,and the minimum length of CNV was significantly larger than that reported in previous studies.Interestingly,a high proportion of the length of chromosome 16 was covered by copy number variation regions(CNVR),with the major histocompatibility complex being the likely cause.Among the genes identified within CNVR,only those present in at least five animals across breeds(n=95)were discussed to reduce the focus on redundant CNV.Some of these genes have been associated to functional traits in chickens.Notably,several CNVR on different chromosomes harbor genes related to muscle development,tissue-specific biological processes,heat stress resistance,and immune response.Quantitative trait loci(QTL)were also analyzed to investigate potential overlapping with the identified CNVR:54 out of the 95 gene-containing regions overlapped with 428 QTL associated to body weight and size,carcass characteristics,egg production,egg components,fat deposition,and feed intake.Conclusions The genomic phenomena reported in this study that can cause changes in the distribution of CNV within the genome over time and the comparison of these differences in CNVR of the local chicken breeds could help in preserving these genetic resources.

High expression circRALGPS2 in atretic follicle induces chicken granulosa cell apoptosis and autophagy via encoding a new protein

Background The reproductive performance of chickens mainly depends on the development of follicles.Abnor-mal follicle development can lead to decreased reproductive performance and even ovarian disease among chick-ens.Chicken is the only non-human animal with a high incidence of spontaneous ovarian cancer.In recent years,the involvement of circRNAs in follicle development and atresia regulation has been confirmed.Results In the present study,we used healthy and atretic chicken follicles for circRNA RNC-seq.The results showed differential expression of circRALGPS2.It was then confirmed that circRALGPS2 can translate into a protein,named cir-cRALGPS2-212aa,which has IRES activity.Next,we found that circRALGPS2-212aa promotes apoptosis and autophagy in chicken granulosa cells by forming a complex with PARP1 and HMGB1.Conclusions Our results revealed that circRALGPS2 can regulate chicken granulosa cell apoptosis and autophagy through the circRALGPS2-212aa/PARP1/HMGB1 axis.

Investigation on taste characteristics and sensory perception of soft-boiled chicken during oral processing based on electronic tongue and electronic nose

The sensory perception of food is a dynamic process,which is closely related to the release of flavor substances during oral processing.It’s not only affected by the food material,but also subjected to the individual oral environment.To explore the oral processing characteristics of soft-boiled chicken,the sensory properties,texture,particle size,viscosity,characteristic values of electronic nose and tongue of different chicken samples were investigated.The correlation analysis showed that the physical characteristics especially the cohesiveness,springiness,resilience of the sample determined oral processing behavior.The addition of chicken skin played a role in lubrication during oral processing.The particle size of the bolus was heightened at the early stage,and the fluidity was enhanced in the end,which reduced the chewing time to the swallowing point and raised the aromatic compounds signal of electronic nose.But the effect of chicken skin on chicken thigh with relatively high fat content,was opposite in electronic nose,which had a certain masking effect on the perception of umami and sweet taste.In conclusion,fat played a critical role in chicken oral processing and chicken thigh had obvious advantages in comprehensive evaluation of soft-boiled chicken,which was more popular among people.

Transcriptome-based analysis of key signaling pathways affecting the formation of primordial germ cell in chickens

Bone morphogenetic protein 4(BMP4)can induce the formation of chicken primordial germ cells(PGCs)in vitro;however,its regulatory mechanism in poultry remains unknown.This study aimed to use RNA-seq to analyze PGCs in chicken embryos and iPGCs induced by BMP4 in vitro,clarify the internal regulatory factors of PGCs,analyze the mechanism of the formation of PGCs,and lay a theoretical foundation for the further optimization of PGCs induction systems.Embryonic stem cells(ESCs),PGCs and iPGCs induced by BMP4 in vitro were collected.The transcriptional maps of the three cell types were studied using RNA-seq.The results showed 6,142 genes differentially expressed between PGCs and iPGCs,of which 2,728 were upregulated in iPGCs and 3,414 were downregulated in iPGCs.Compared to that in ESCs,BMP4 was significantly upregulated in PGCs and iPGCs.KEGG results showed that both the TGF-βand Wnt signaling pathways were activated during the formation of PGCs in vitro and in vivo,and the activation was more significant during iPGCs induced by BMP4.The expression of Nodal,an inhibitory factor of TGF-βsignaling,was significantly decreased in PGCs and iPGCs,but was not expressed in iPGCs,which further supports our conclusion.Additionally,the Lysosome and PI3K-AKT signaling pathways were significantly enriched in PGCs and iPGCs,respectively.Further,transmission electron microscopy(TEM)results showed that the number of autolysosomes was significantly higher after the addition of BMP4,which is consistent with the KEGG results.Furthermore,the number of PGCs was significantly reduced after ATG14 was interfered in vivo and in vitro.In conclusion,this study screened out the key signaling pathways during the formation of PGCs,aiming to provide help for enriching the mechanism network regulating PGCs formation in chicken and laying a theoretical foundation for further improving the efficiency of inducing PGCs in vitro.

Large‑scale transcriptomic and genomic analyses reveal a novel functional gene SERPINB6 for chicken carcass traits

Background Carcass traits are crucial indicators of meat production efficiency.However,the molecular regulatory mechanisms associated with these traits remain unclear.Results In this study,we conducted comprehensive transcriptomic and genomic analyses on 399 Tiannong partridge chickens to identify key genes and variants associated with carcass traits and to elucidate the underlying regulatory mechanisms.Based on association analyses with the elastic net(EN)model,we identified 12 candidate genes(AMY1A,AP3B2,CEBPG,EEF2,EIF4EBP1,FGFR1,FOXD3,GOLM1,LOC107052698,PABPC1,SERPINB6 and TBC1D16)for 4 carcass-related traits,namely live weight,dressed weight,eviscerated weight,and breast muscle weight.SERPINB6 was identified as the only overlapping gene by 3 analyses,EN model analysis,weighted gene co-expression network analysis and differential expression analysis.Cell-level experiments confirmed that SERPINB6 promotes the proliferation of chicken DF1 cells and primary myoblasts.Further expression genome-wide association study and association analysis indicated that rs317934171 is the critical site that enhances SERPINB6 expression.Furthermore,a dual-luciferase reporter assay proved that gga-miR-1615 targets the 3′UTR of SERPINB6.Conclusions Collectively,our findings reveal that SERPINB6 serves as a novel gene for chicken carcass traits by promoting fibroblast and myoblast proliferation.Additionally,the downstream variant rs317934171 regulates SERPINB6 expression.These results identify a new target gene and molecular marker for the molecular mechanisms of chicken carcass traits.

Gut microbial metabolite targets HDAC3-FOXK1-interferon axis in fibroblast-like synoviocytes to ameliorate rheumatoid arthritis

Rheumatoid arthritis(RA)is an autoimmune disease.Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility.However,accumulating evidence demonstrates that genetics also shape the gut microbiota.It is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis(CIA),while the others are resistant to CIA.Here,we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice.C57BL/6J mice and healthy human individuals have enriched B.fragilis than DBA/1J mice and RA patients.Transplantation of B.fragilis prevents CIA in DBA/1J mice.We identify that B.fragilis mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of propionate.Fibroblast-like synoviocytes(FLSs)in RA are activated to undergo tumor-like transformation.Propionate disrupts HDAC3-FOXK1 interaction to increase acetylation of FOXK1,resulting in reduced FOXK1 stability,blocked interferon signaling and deactivation of RA-FLSs.We treat CIA mice with propionate and show that propionate attenuates CIA.Moreover,a combination of propionate with anti-TNF etanercept synergistically relieves CIA.These results suggest that B.fragilis or propionate could be an alternative or complementary approach to the current therapies.

Retinol is involved in the intestinal regeneration and strengthens the intestinal barrier during refeeding in broiler chickens

Fasting is typically used before feeding metabolizable energy assessment in broilers.Previous studies have shown that fasting cause atrophy of the intestinal villus.Whether fasting affects intestinal permeability during refeeding by altering barrier function and nutrient absorption is of concern.Here,23-d-old broilers were randomly assigned to 5 treatments,fasted for 0,12,24,36,and 48 h,respectively,and then refed for 2 d,to study the impact of different duration of fasting on the intestinal regeneration and barrier function during refeeding.Results showed that the intestinal morphology in fasted birds was recovered in 2 d of refeeding at most.As fasting durations increased,enterocytes per intestinal villus were linearly and quadratically increased(both P<0.05),whereas goblet cells per intestinal villus was linearly decreased(both P<0.05).Besides,the mRNA level of lysozyme was linearly decreased as fasting durations increased during refeeding(both P<0.05),while quadratically increased mucin 2 was observed only after 1 d of refeeding(P<0.05).Linear increase effects were observed for claudin 2 and zonula occludens-1with increased fasting durations after 1 d of refeeding(all P<0.05),and linear and quadratical effects were observed for claudin 2 at 2 d of refeeding(both P<0.05).Besides,we found that intestinal permeability to creatinine,4 and 70 kD dextran were linearly and quadratically decreased with increased fasting durations at 6 h and 1 d of refeeding(all P<0.05).Furthermore,jejunum proteomic from birds refed for 6 h showed that birds fasted for 36 h showed increased antimicrobial peptides and upregulated retinol metabolism when compared to the nonfasted birds(P<0.05).Further study showed that retinyl ester catabolism was inhibited during fasting and enhanced during refeeding.Results of intestinal organoid culture showed that retinol benefits the cell proliferation and enterocyte differentiation.In conclusion,the intestinal permeability to small and large molecules was decreased during refeeding by strengthening the intestinal barrier function,and the activated retinol metabolism during refeeding is involved in the intestinal regeneration and strengthens the intestinal barrier.

A novel live attenuated vaccine candidate protects chickens against subtype B avian metapneumovirus

Avian metapneumovirus(aMPV) is a highly contagious pathogen that causes acute upper respiratory tract diseases in chickens and turkeys, resulting in serious economic losses. Subtype B aMPV has recently become the dominant epidemic strain in China. We developed an attenuated aMPV subtype B strain by serial passaging in Vero cells and evaluated its safety and efficacy as a vaccine candidate. The safety test showed that after the 30th passage, the LN16-A strain was fully attenuated, as clinical signs of infection and histological lesions were absent after inoculation.The LN16-A strain did not revert to a virulent strain after five serial passages in chickens. The genomic sequence of LN16-A differed from that of the parent wild-type LN16(wtLN16) strain and had nine amino acid mutations. In chickens, a single immunization with LN16-A induced robust humoral and cellular immune responses, including the abundant production of neutralizing antibodies, CD4^(+) T lymphocytes, and the Th1(IFN-γ) and Th2(IL-4 and IL-6)cytokines. We also confirmed that LN16-A provided 100% protection against subtype B aMPV and significantly reduced viral shedding and turbinate inflammation. Our findings suggest that the LN16-A strain is a promising live attenuated vaccine candidate that can prevent infection with subtype B aMPV.

Endoplasmic reticulum stress improved chicken tenderness,promoted apoptosis and autophagy during postmortem ageing

In this study,endoplasmic reticulum(ER)stress inducer tunicamycin(TM)and inhibitor 4-phenylbutyric acid(4-PBA)were used to treat postmortem chicken breast muscle to investigate changes in tenderness and effects on apoptosis and autophagy during 5 days ageing.TM-induced ER stress reduced shear force,enhanced myofibril fragmentation index(MFI),disrupted myofibril structure,increased desmin degradation,and activatedμ-calpain and caspase-12.In addition,TM-induced ER stress increased the expression of Bax,Bim,and cytochrome c,and decreased the expression of Bcl-x L.Furthermore,TM-induced ER stress improved the conversion of LC3I to LC3II,raised the expression of Beclin-1,and decreased the expression of p62,PI3K,and m TOR.The opposite results were observed after 4-PBA treatment.These results suggested that ER stress could improve chicken tenderness,promote apoptosis and autophagy during chicken postmortem ageing.

Expression level of interferon-stimulated genes PKR,OAS1,MX1,and ISG15 in peripheral blood mononuclear cells of COVID-19 patients:A retrospective study

Objective:To explore expression level of interferon-stimulated genes PKR,OAS1,MX1,and ISG15 in peripheral blood mononuclear cells of COVID-19 patients.Methods:In this study,changes in the expression of four interferon-stimulated genes(ISGs),including PKR,OAS1,MX1,and ISG15,in peripheral blood mononuclear cells of 45 COVID-19 patients with different severities were evaluated by real-time PCR method.Results:OAS1,MX1,PKR,and ISG15 were differently expressed in COVID-19 patients with different severity.The results showed that the expression of OAS1,MX1,PKR,and ISG15 genes was significantly(P=0.001)lower in severe patients.Conclusions:Weak and defective IFN response and subsequent disruption of ISGs may be associated with COVID-19 severity.

Significant genomic introgression from grey junglefowl(Gallus sonneratii)to domestic chickens(Gallus gallus domesticus)

Background Chicken is one of the most numerous and widely distributed species around the world,and many studies support the multiple ancestral origins of domestic chickens.The research regarding the yellow skin phenotype in domestic chickens(regulated by BCO2)likely originating from the grey junglefowl serves as crucial evidence for demonstrating the multiple origins of chickens.However,beyond the BCO2 gene region,much remains unknown about the introgression from the grey junglefowl into domestic chickens.Therefore,in this study,based on wholegenome data of 149 samples including 4 species of wild junglefowls and 13 local domestic chicken breeds,we explored the introgression events from the grey junglefowl to domestic chickens.Results We successfully detected introgression regions besides BCO2,including two associated with growth trait(IGFBP2 and TKT),one associated with angiogenesis(TIMP3)and two members of the heat shock protein family(HSPB2 and CRYAB).Our findings suggest that the introgression from the grey junglefowl may impact the growth performance of chickens.Furthermore,we revealed introgression events from grey junglefowl at the BCO2 region in multiple domestic chicken breeds,indicating a phenomenon where the yellow skin phenotype likely underwent strong selection and was retained.Additionally,our haplotype analysis shed light on BCO2 introgression event from different sources of grey junglefowl into domestic chickens,possibly suggesting multiple genetic flows between the grey junglefowl and domestic chickens.Conclusions In summary,our findings provide evidences of the grey junglefowl contributing to the genetic diversity of domestic chickens,laying the foundation for a deeper understanding of the genetic composition within domestic chickens,and offering new perspectives on the impact of introgression on domestic chickens.

Asymmetric expression of CA2 and CA13 linked to calcification in the bilateral mandibular condyles cause crossed beaks in chickens

Crossed beak is a complex mode of inheritance with prevalence ranging from 0.2 to 7.4% in at least 12 chicken strains worldwide.To reveal the intrinsic factors causing crossed beaks,genes expression patterns in bilateral mandibular condyle between affected and normal birds were characterized by RNA sequencing analysis in the present studies.Crossed beak was induced by short length of unilateral mandibular ramus,and a total of 110differentially expressed genes were up-or down-regulated in the affected(short)mandibular condyle side as compared to the normal side.Carbonic anhydrase 2(CA2)and Carbonic anhydrase 13(CA13)were enriched in the carbonate dehydratase activity,and high-expressed in mandibular condyle and osteoblasts(P<0.05).However,both were low-expressed in short mandibular condyle side of affected birds(P<0.05).The carbonate dehydratase inhibitor experiments confirmed that there is positive association between the calcification and carbonic anhydrase isoenzymes.Quantitative analysis with cetylpyridinium chloride showed a decrease in calcification when the cells were transfected with an anti-CA13 shRNA.Our research suggested that CA2 and CA13 are down-calcified in shortside mandibular condyle,and caused mandibular ramus to grow slowly.CA2 and CA13 have the critical role in crossed beaks by regulating calcification of mandibular condyle.

Proteo-transcriptomic profiles reveal key regulatory pathways and functions of LDHA in the ovulation of domestic chickens(Gallus gallus)

Background In poultry, the smooth transition of follicles from the preovulatory-to-postovulatory phase impacts egg production in hens and can benefit the poultry industry. However, the regulatory mechanism underlying follicular ovulation in avians is a complex biological process that remains unclear.Results Critical biochemical events involved in ovulation in domestic chickens(Gallus gallus) were evaluated by transcriptomics, proteomics, and in vitro assays. Comparative transcriptome analyses of the largest preovulatory follicle(F1) and postovulatory follicle(POF1) in continuous laying(CL) and intermittent laying(IL) chickens indicated the greatest difference between CL_F1 and IL_F1, with 950 differentially expressed genes(DEGs), and the smallest difference between CL_POF1 and IL_POF1, with 14 DEGs. Additionally, data-independent acquisition proteomics revealed 252 differentially abundant proteins between CL_F1 and IL_F1. Perivitelline membrane synthesis, steroid biosynthesis, lysosomes, and oxidative phosphorylation were identified as pivotal pathways contributing to ovulation regulation. In particular, the regulation of zona pellucida sperm-binding protein 3, plasminogen activator, cathepsin A, and lactate dehydrogenase A(LDHA) was shown to be essential for ovulation. Furthermore, the inhibition of LDHA decreased cell viability and promoted apoptosis of ovarian follicles in vitro.Conclusions This study reveals several important biochemical events involved in the process of ovulation, as well as crucial role of LDHA. These findings improve our understanding of ovulation and its regulatory mechanisms in avian species.

Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86.Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer.Results In total,143 patients were enrolled(NH group,n=49;NA group,n=47;P group,n=47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001.Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Layer chicken microbiota:a comprehensive analysis of spatial and temporal dynamics across all major gut sections

Background The gut microbiota influences chicken health,welfare,and productivity.A diverse and balanced microbiota has been associated with improved growth,efficient feed utilisation,a well-developed immune system,disease resistance,and stress tolerance in chickens.Previous studies on chicken gut microbiota have predominantly focused on broiler chickens and have usually been limited to one or two sections of the digestive system,under con-trolled research environments,and often sampled at a single time point.To extend these studies,this investigation examined the microbiota of commercially raised layer chickens across all major gut sections of the digestive system and with regular sampling from rearing to the end of production at 80 weeks.The aim was to build a detailed picture of microbiota development across the entire digestive system of layer chickens and study spatial and temporal dynamics.Results The taxonomic composition of gut microbiota differed significantly between birds in the rearing and pro-duction stages,indicating a shift after laying onset.Similar microbiota compositions were observed between proven-triculus and gizzard,as well as between jejunum and ileum,likely due to their anatomical proximity.Lactobacil-lus dominated the upper gut in pullets and the lower gut in older birds.The oesophagus had a high proportion of Proteobacteria,including opportunistic pathogens such as Gallibacterium.Relative abundance of Gallibacterium increased after peak production in multiple gut sections.Aeriscardovia was enriched in the late-lay phase compared to younger birds in multiple gut sections.Age influenced microbial richness and diversity in different organs.The upper gut showed decreased diversity over time,possibly influenced by dietary changes,while the lower gut,specifi-cally cecum and colon,displayed increased richness as birds matured.However,age-related changes were inconsist-ent across all organs,suggesting the influence of organ-specific factors in microbiota maturation.Conclusion Addressing a gap in previous research,this study explored the microbiota across all major gut sections and tracked their dynamics from rearing to the end of the production cycle in commercially raised layer chickens.This study provides a comprehensive understanding of microbiota structure and development which help to develop targeted strategies to optimise gut health and overall productivity in poultry production.