Small RNAs(sRNAs)are a class of molecules capable of perceiving environmental changes and exerting posttranscriptional regulation over target gene expression,thereby influencing bacterial virulence and host immune res...Small RNAs(sRNAs)are a class of molecules capable of perceiving environmental changes and exerting posttranscriptional regulation over target gene expression,thereby influencing bacterial virulence and host immune responses.Pseudomonas plecoglossicida is a pathogenic bacterium that poses a significant threat to aquatic animal health.However,the regulatory mechanisms of sRNAs in P.plecoglossicida remain unclear.This study focused on sRNA113,previously identified as a potential regulator of the fliP gene,a key component of the lateral flagellar type III secretion system.To investigate the effects of sRNA113on P.plecoglossicida virulence,as well as its role in regulating pathogenic processes and host immune responses,mutant strains lacking this sRNA were generated and analyzed.Deletion of sRNA113 resulted in the up-regulation of lateral flagellar type III secretion system-related genes in P.plecoglossicida,which enhanced bacterial swarming motility,biofilm formation,and chemotaxis ability in vitro.In vivo infection experiments with pearl gentian grouper revealed that sRNA113 deletion enhanced the pathogenicity of P.plecoglossicida.This heightened virulence was attributed to the up-regulation of genes associated with the lateral flagellar type III secretion system,resulting in higher bacterial loads within host tissues.This amplification of pathogenic activity intensified tissue damage,disrupted immune responses,and impaired the ability of the host to clear infection,ultimately leading to mortality.These findings underscore the critical role of sRNA113 in regulating the virulence of P.plecoglossicida and its interaction with host immune defenses.This study provides a foundation for further exploration of sRNAmediated mechanisms in bacterial pathogenesis and hostpathogen interactions,contributing to a deeper understanding of virulence regulation and immune evasion in aquatic pathogens.展开更多
The sugar beet cyst nematode(Heterodera schachtii) is one of the most destructive pathogens in sugar beet production, which causes serious economic losses every year. Few molecular details of effectors of H. schachtii...The sugar beet cyst nematode(Heterodera schachtii) is one of the most destructive pathogens in sugar beet production, which causes serious economic losses every year. Few molecular details of effectors of H. schachtii parasitism are known. We analyzed the genome and transcriptome data of H. schachtii and identified multiple potential predicted proteins. After filtering out predicted proteins with high homology to other plant-parasitic nematodes, we performed functional validation of the remaining effector proteins. 37 putative effectors of H. schachtii were screened based on the Nicotiana benthamiana system for identifying the effectors that inhibit plant immune response, eventually determines 13 candidate effectors could inhibit cell death caused by Bax. Among the 13 effectors, nine have the ability to inhibit GPA2/RBP1-induced cell death. All 13 effectortriggered immunity(ETI) suppressor genes were analyzed by qRT-PCR and confirmed to result in a significant downregulation of one or more defense genes during infection compared to empty vector. For in situ hybridization,13 effectors were specifically expressed and located in esophageal gland cells. These data and functional analysis set the stage for further studies on the interaction of H. schachtii with host and H. schachtii parasitic control.展开更多
Background:Dengue fever,an acute insect-borne infectious disease caused by the dengue virus(DENV),poses a great challenge to global public health.Hepatic involve-ment is the most common complication of severe dengue a...Background:Dengue fever,an acute insect-borne infectious disease caused by the dengue virus(DENV),poses a great challenge to global public health.Hepatic involve-ment is the most common complication of severe dengue and is closely related to the occurrence and development of disease.However,the features of adaptive immune responses associated with liver injury in severe dengue are not clear.Methods:We used single-cell sequencing to examine the liver tissues of mild or se-vere dengue mice model to analyze the changes in immune response of T cells in the liver after dengue virus infection,and the immune interaction between macrophages and T cells.Flow cytometry was used to detect T cells and macrophages in mouse liver and blood to verify the single-cell sequencing results.Results:Our result showed CTLs were significantly activated in the severe liver injury group but the immune function-related signal pathway was down-regulated.The rea-son may be that the excessive immune response in the severe group at the late stage of DENV infection induces the polarization of macrophages into M2 type,and the macrophages then inhibit T cell immunity through the TGF-βsignaling pathway.In ad-dition,the increased proportion of Treg cells suggested that Th17/Treg homeostasis was disrupted in the livers of severe liver injury mice.Conclusions:In this study,single-cell sequencing and flow cytometry revealed the characteristic changes of T cell immune response and the role of macrophages in the liver of severe dengue fever mice.Our study provides a better understanding of the pathogenesis of liver injury in dengue fever patients.展开更多
Background Monoglycerides have emerged as a promising alternative to conventional practices due to their biolog-ical activities,including antimicrobial properties.However,few studies have assessed the efficacy of mono...Background Monoglycerides have emerged as a promising alternative to conventional practices due to their biolog-ical activities,including antimicrobial properties.However,few studies have assessed the efficacy of monoglyceride blend on weaned pigs and their impacts on performance,immune response,and gut health using a disease chal-lenge model.Therefore,this study aimed to investigate the effects of dietary monoglycerides of short-and medium-chain fatty acids on the immunity and gut health of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli F18.Results Pigs supplemented with high-dose zinc oxide(ZNO)had greater(P<0.05)growth performance than other treatments,but no difference was observed in average daily feed intake between ZNO and monoglycerides groups during the post-challenge period.Pigs in ZNO and antibiotic groups had lower(P<0.05)severity of diarrhea than control,but the severity of diarrhea was not different between antibiotic and monoglycerides groups.Pigs fed with monoglycerides or ZNO had lower(P<0.05)serum haptoglobin on d 2 or 5 post-inoculation than control.Pigs in ZNO had greater(P<0.05)goblet cell numbers per villus,villus area and height,and villus height:crypt depth ratio(VH:CD)in duodenum on d 5 post-inoculation than pigs in other treatments.Pigs supplemented with monoglyc-erides,ZNO,or antibiotics had reduced(P<0.05)ileal crypt depth compared with control on d 5 post-inoculation,contributing to the increase(P=0.06)in VH:CD.Consistently,pigs in ZNO expressed the lowest(P<0.05)TNFa,IL6,IL10,IL12,IL1A,IL1B,and PTGS2 in ileal mucosa on d 5 post-inoculation,and no difference was observed in the expres-sion of those genes between ZNO and monoglycerides.Supplementation of ZNO and antibiotic had significant impacts on metabolic pathways in the serum compared with control,particularly on carbohydrate and amino acid metabolism,while limited impacts on serum metabolites were observed in monoglycerides group when compared with control.Conclusions The results suggest that supplementation of monoglyceride blend may enhance disease resist-ance of weaned pigs by alleviating the severity of diarrhea and mitigating intestinal and systemic inflammation,although the effectiveness may not be comparable to high-dose zinc oxide.展开更多
With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune func...With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were investigated.Results showed that REFB could improve the immune organ index,and promote the proliferation and differentiation of splenic T lymphocytes.In addition,it attenuated intestinal mucosal damage and improved intestinal cellular immunity.REFB administration also up-regulated the expression of IL-4,INF-γ,TNF-α,T-bet and GATA-3 mRNA in small intestine.Furthermore,administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus,such as Bacteroides.It also increased the production of fecal short-chain fatty acids.These indicate that REFB has the potential to improve immunity,alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice.展开更多
BACKGROUND Gastric cancer remains a leading cause of cancer-related mortality globally.Traditional open surgery for gastric cancer is often associated with significant morbidity and prolonged recovery.AIM To evaluate ...BACKGROUND Gastric cancer remains a leading cause of cancer-related mortality globally.Traditional open surgery for gastric cancer is often associated with significant morbidity and prolonged recovery.AIM To evaluate the effectiveness of laparoscopic minimally invasive surgery as an alternative to traditional open surgery for gastric cancer,focusing on its potential to reduce trauma,accelerate recovery,and achieve comparable oncological out-comes.METHODS This study retrospectively analyzed 203 patients with gastric cancer who underwent surgery at the Shanghai Health Medical College Affiliated Chongming Hospital from January 2020 to December 2023.The patients were divided into two groups:Minimally invasive surgery group(n=102),who underwent laparoscopic gastrectomy,and open surgery group(n=101),who underwent traditional open gastrectomy.We compared surgical indicators(surgical incision size,intraop-erative blood loss,surgical duration,and number of lymph nodes dissected),recovery parameters(time to first flatus,time to start eating,time to ambulation,and length of hospital stay),immune function(levels of IgA,IgG,and IgM),intestinal barrier function(levels of D-lactic acid and diamine oxidase),and stress response(levels of C-reactive protein,interleukin-6,and procalcitonin).RESULTS The minimally invasive surgery group demonstrated significantly better outcomes in terms of surgical indicators,including smaller incisions,less blood loss,shorter surgery time,and more lymph nodes dissected(P<0.05 for all).Recovery was also faster in the minimally invasive surgery group,with earlier return of bowel function,earlier initiation of diet,quicker mobilization,and shorter hospital stays(P<0.05 for all).Furthermore,patients in the minimally invasive surgery group had better preserved immune function,superior intestinal barrier function,and a less pronounced stress response postoperatively(P<0.05 for all).CONCLUSION Laparoscopic minimally invasive surgery for gastric cancer not only provides superior surgical indicators and faster recovery but also offers advantages in preserving immune function,protecting intestinal barrier function,and mitigating the stress response compared to traditional open surgery.These findings support the broader adoption of laparoscopic techniques in the management of gastric cancer.展开更多
Our previous study found that feeding with Lactobacillus plantarum Ep-M17 could effectively affect the growth performance,immune response,and gut microbiota of Penaeus vannamei.However,high temperature and pressure du...Our previous study found that feeding with Lactobacillus plantarum Ep-M17 could effectively affect the growth performance,immune response,and gut microbiota of Penaeus vannamei.However,high temperature and pressure during feed pelletizing is the main problem that can lead to a decrease in the activity of probiotics or cause their inactivation.Further investigation needs to investigate whether inactivated Ep-M17 can exert similar effects as live Ep-M17.Therefore,we evaluated the effects of inactivated L.plantarum Ep-M17 on growth performance,immune response,disease resistance,and gut microbiota in P.vannamei.Results show that adding inactivated Ep-M17 to the feed also promoted body weight gain and increased relative immune protection in shrimp.Also,histological examination revealed that the administration of inactivated Ep-M17 led to improvements in the density and distribution of microvilli in the intestines and enhancements in the abundance of B and R cells in the hepatopancreas.Additionally,the inactivated Ep-M17 supplementation resulted in increased activity levels of nutrient immune-related enzymes in both the shrimp hepatopancreas and intestines.Moreover,it stimulated the expression of Lvlec,PEN-3a,Crustin,LGBP,Lysozyme,and proPo genes in both the hepatopancreas and intestines.Furthermore,the inactivated Ep-M17 also increased bacterial diversity in the gut of shrimp and promoted the abundance of specific flora,facilitating the host organism’s metabolism and immunity to improve the disease resistance of shrimp.Therefore,supplementation of inactivated L.plantarum Ep-M17 in shrimp diets can exert similar effects as live L.plantarum Ep-M17 effectively improving growth performance,gut microbiota,immune response,and disease resistance in P.vannamei.展开更多
Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune ...Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune activation.Addressing these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS generation.This not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor rechallenge.Our in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/PDT.As such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.展开更多
The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer(CRC).However,the effect of ginsenoside Rk3(Rk3)on CRC and gut microbiota remains unclear.Therefo...The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer(CRC).However,the effect of ginsenoside Rk3(Rk3)on CRC and gut microbiota remains unclear.Therefore,the purpose of this study is to explore the potential effect of Rk3 on CRC from the perspective of gut microbiota and immune regulation.Our results reveal that treatment with Rk3 significantly suppresses the formation of colon tumors,repairs intestinal barrier damage,and regulates the gut microbiota imbalance caused by CRC,including enrichment of probiotics such as Akkermansia muciniphila and Barnesiella intestinihominis,and clearance of pathogenic Desulfovibrio.Subsequent metabolomics data demonstrate that Rk3 can modulate the metabolism of amino acids and bile acids,particularly by upregulating glutamine,which has the potential to regulate the immune response.Furthermore,we elucidate the regulatory effects of Rk3 on chemokines and inflammatory factors associated with group 3 innate lymphoid cells(ILC3s)and T helper 17(Th17)signaling pathways,which inhibits the hyperactivation of the Janus kinase-signal transducer and activator of transcription 3(JAK-STAT3)signaling pathway.These results indicate that Rk3 modulates gut microbiota,regulates ILC3s immune response,and inhibits the JAK-STAT3 signaling pathway to suppress the development of colon tumors.More importantly,the results of fecal microbiota transplantation suggest that the inhibitory effect of Rk3 on colon tumors and its regulation of ILC3 immune responses are mediated by the gut microbiota.In summary,these findings emphasize that Rk3 can be utilized as a regulator of the gut microbiota for the prevention and treatment of CRC.展开更多
Objective:To evaluate the immunological response elicited by an inactivated bacterial vector carrying the K39 antigen of Leishmania infantum,and a purified antigen.Methods:Mice were subjected to the following treatmen...Objective:To evaluate the immunological response elicited by an inactivated bacterial vector carrying the K39 antigen of Leishmania infantum,and a purified antigen.Methods:Mice were subjected to the following treatments:(1)Purified recombinant K39(rK39)protein at a 20μg dose with complete Freund’s adjuvant;(2)Inactivated Escherichia coli(BL21 DE3)carrying the K39 protein at an equivalent total protein content of 200μg;(3)Inactivated bacteria lacking the K39 protein;(4)Non-immunized control animals.Serological monitoring was performed.All groups were challenged by intraperitoneal injection of 10^(7) Leishmania infantum promastigotes.After euthanasia,the liver and spleen were collected to analyze the levels of TNF,IFN-γ,IL-12,IL-4,and IL-10.Results:Mice immunized with purified rK39 or the inactivated bacterial vector carrying the K39 antigen of Leishmania infantum showed a long-lasting immune response with high levels of polyclonal antibodies specifically recognizing the recombinant proteins.The IgG1 subclass was the predominant immunoglobulin;however,the induction of IgG2a and the profile of cytokines produced were indicative of the induction of a mixed-type response.Conclusions:The inactivated bacterial vector carrying the K39 antigen,as well as the purified antigen can induce a long-lasting immune response in immunized mice,predominantly favouring a Th2 profile response.展开更多
Background:This study aimed to assess how acupoint catgut-embedding therapy influences Th2-type immune response and the infiltration of CD4^(+)and CD8^(+)cells in DNCB-induced atopic dermatitis in BALB/c mice.It also ...Background:This study aimed to assess how acupoint catgut-embedding therapy influences Th2-type immune response and the infiltration of CD4^(+)and CD8^(+)cells in DNCB-induced atopic dermatitis in BALB/c mice.It also conducted an initial examination of the underlying molecular mechanisms.Methods:Seventy-two mice were randomly divided into four groups:normal control,DNCB-induced atopic dermatitis model(AD),AD with acupoint catgut-embedding treatment(ADA),and AD with sham-acupoint catgut-embedding treatment.After DNCB challenge to induce AD,the ADA group received acupoint catgut-embedding therapy treatment at Zusanli(ST 36)and Quchi(LI 11)acupoints every other week from day 8.Mice in the AD with sham-acupoint catgut-embedding treatment group underwent the same procedure as the ADA group but without catgut implantation.Severity was assessed using SCORAD on treatment days 1,10,and 20.On day 18,nine mice per group were euthanized,and the remaining on day 28.Histopathological changes were observed using hematoxylin-eosin and immunohistochemistry staining.TNF-α,IL-4,IL-6,and IL-13 levels were analyzed by ELISA,and GATA3 and STAT6 protein levels by western blot.Results:After 20 days of acupoint catgut-embedding therapy treatment,mice showed reduced dermatitis scores compared to DNCB-induced AD-like mice.Significant decreases occurred in serum IL-4,IL-6,IL-13,and TNF-αlevels.Skin analysis revealed marked reductions in CD4^(+)and CD8^(+)cell infiltration,as well as GATA3 and STAT6 protein levels.Conclusion:Acupoint catgut-embedding therapy may effectively alleviate atopic dermatitis by suppressing Th2 immune responses via the STAT6-GATA3 pathway and reducing CD4^(+)and CD8^(+)T cell infiltration in skin lesions.展开更多
Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflamm...Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.展开更多
Objective Venous thromboembolism is a highly prevalent condition after polytrauma,and recognized as an important factor contributing to poor prognosis.The aim of this study was to investigate the risk factors for lowe...Objective Venous thromboembolism is a highly prevalent condition after polytrauma,and recognized as an important factor contributing to poor prognosis.The aim of this study was to investigate the risk factors for lower extremity deep venous thrombosis(LEDVT)in a severely traumatized population and to evaluate their predictive value for LEDVT.Methods This was a retrospective,single-center observational study.All subjects were severely traumatized patients who were admitted to the Traumatic Intensive Care Unit from January 2021 to May 2024.Based on Doppler ultrasound findings of both lower extremities from the time of injury to 30 days post-injury,patients who developed LEDVT were enrolled in the LEDVT group,and those who did not develop LEDVT were enrolled in the NLEDVT group.Demographic,clinical,and laboratory data were collected upon admission.Multivariable logistic regression analysis was performed to identify risk factors for LEDVT.Receiver operating characteristic(ROC)curve was used to evaluate the overall fit of the final model.Results There were 56 patients enrolled in the LEDVT group and 81 patients in the NLEDVT group.Age,Aggregate Index of Systemic Inflammation(AISI),Systemic Inflammation Response Index(SIRI),ICU length of stay,and albumin were identified as independent risk factors for LEDVT(all P<0.05).The area under their ROC curves were 0.604,0.657,0.694,0.668,and 0.405,respectively.Combined model for early clinical prediction of LEDVT in severely traumatized patients by age,SIRI,AISI,and albumin resulted in an area under the ROC curve of 0.805(95%CI:0.73-0.88,SE=0.037).Conclusion The combination of age,SIRI,AISI,and albumin has a predictive value for LEDVT in severely traumatized patients.展开更多
Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain met...Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.展开更多
Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive ...Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.展开更多
Verticillium dahliae is an important soil-borne fungal pathogen that causes great yield losses in many cash crops.Effectors of this fungus are known to regulate plant immunity but the mechanism much remains unclear.A ...Verticillium dahliae is an important soil-borne fungal pathogen that causes great yield losses in many cash crops.Effectors of this fungus are known to regulate plant immunity but the mechanism much remains unclear.A glycine-rich nuclear effector,VdCE51,was able to suppress immune responses in tobacco against Botrytis cinerea and Sclerotinia sclerotiorum.This effector was a required factor for full virulence of V.dahliae,and its nuclear localization was a requisite for suppressing plant immunity.The thioredoxin GhTRXH2,identified as a positive regulator of plant immunity,was a host target of VdCE51.Our findings show a virulence regulating mechanism whereby the secreted nuclear effector VdCE51 interferes with the transcription of PR genes,and the SA signaling pathway by inhibiting the accumulation of GhTRXH2,thus suppressing plant immunity.展开更多
Background Post-weaned piglets suffer from F18+Escherichia coli(E.coli)infections resulting in post-weaning diar-rhoea or oedema disease.Frequently used management strategies,including colistin and zinc oxide,have con...Background Post-weaned piglets suffer from F18+Escherichia coli(E.coli)infections resulting in post-weaning diar-rhoea or oedema disease.Frequently used management strategies,including colistin and zinc oxide,have contrib-uted to the emergence and spread of antimicrobial resistance.Novel antimicrobials capable of directly interacting with pathogens and modulating the host immune responses are being investigated.Lactoferrin has shown promising results against porcine enterotoxigenic E.coli strains,both in vitro and in vivo.Results We investigated the influence of bovine lactoferrin(bLF)on the microbiome of healthy and infected weaned piglets.Additionally,we assessed whether bLF influenced the immune responses upon Shiga toxin-producing E.coli(STEC)infection.Therefore,2 in vivo trials were conducted:a microbiome trial and a challenge infection trial,using an F18+STEC strain.BLF did not affect theα-andβ-diversity.However,bLF groups showed a higher relative abundance(RA)for the Actinobacteria phylum and the Bifidobacterium genus in the ileal mucosa.When analysing the immune response upon infection,the STEC group exhibited a significant increase in F18-specific IgG serum levels,whereas this response was absent in the bLF group.Conclusion Taken together,the oral administration of bLF did not have a notable impact on theα-andβ-diversity of the gut microbiome in weaned piglets.Nevertheless,it did increase the RA of the Actinobacteria phylum and Bifi-dobacterium genus,which have previously been shown to play an important role in maintaining gut homeostasis.Furthermore,bLF administration during STEC infection resulted in the absence of F18-specific serum IgG responses.展开更多
Fusarium graminearum,the primary pathogenic fungus responsible for Fusarium head blight(FHB)in wheat,secretes abundant chemical compounds that interact with host plants.In this study,a secreted protein FgHrip1,isolate...Fusarium graminearum,the primary pathogenic fungus responsible for Fusarium head blight(FHB)in wheat,secretes abundant chemical compounds that interact with host plants.In this study,a secreted protein FgHrip1,isolated from the culture filtrate of F.graminearum,was found to induce typical cell death in tobacco.The FgHrip1 gene was then cloned and expressed in Escherichia coli.Further bioassay analysis showed that the recombinant FgHrip1 induced early defense induction events,such as reactive oxygen species(ROS)production,callose deposition,and up-regulation of defense-related genes in tobacco.Furthermore,FgHrip1 significantly enhanced immunity in tobacco seedlings against Pseudomonas syringae pv.tabaci 6605(Pst.6605)and tobacco mosaic virus(TMV).FgHrip1-treated wheat spikes also exhibited defense-related transcript accumulation and developed immunity against FHB infection.Whereas the expression of FgHrip1 was induced during the infection process,the deletion of the gene impaired the virulence of F.graminearum.Our results suggest that FgHrip1triggers immunity and induces disease resistance in tobacco and wheat,thereby providing new insight into strategy for biocontrol of FHB.展开更多
Parasitoids are key regulators in ecological communities and widely used as agents in biocontrol programmes.The fall armyworm,Spodoptera frugiperda,recently invaded multiple continents and caused substantial economic ...Parasitoids are key regulators in ecological communities and widely used as agents in biocontrol programmes.The fall armyworm,Spodoptera frugiperda,recently invaded multiple continents and caused substantial economic losses in agriculture.Pyemotes zhonghuajia,a newly identified mite parasitoid,has shown potential for controlling various agricultural insect pests.Therefore,this study tested the performance of P.zhonghuajia in parasitising S.frugiperda.We also investigated the sublethal effects of parasitism by P.zhonghuajia on host fitness traits,transgenerational impacts,and cellular and humoral immunity.Our result showed that the fifth-instar larvae of S.frugiperda parasitised by 40 P.zhonghuajia were all dead(i.e.,a lethal effect),while parasitism by 5 or 10 P.zhonghuajia was considered sublethal since many S.frugiperda survived to adulthood and produced offspring after mating.The sublethal influences from parasitism by P.zhonghuajia resulted in reduced pupal weight,adult emergence rate and fecundity,but increased developmental time and longevity.Parasitism at both lethal(40 mites)and sublethal(10 mites)levels impaired the cellular and humoral immunity of S.frugiperda.This study presents the first empirical evidence that mite parasitoids can negatively influence host immunity.Moreover,it provides insights into the biocontrol potential of mite parasitoids and their interactions with hosts.展开更多
Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is ...Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is limited research on the relationship between CRABP2 and immunotherapy response.This study found that negative correlations of CRABP2 and immune checkpoint markers(PD-1,PD-L1,and CTLA-4)were observed in breast invasive carcinoma(BRCA),skin cutaneous melanoma(SKCM),stomach adenocarcinoma(STAD)and testicular germ cell tumors(TGCT).In particular,in SKCM patients who were treated with PD-1 inhibitors,high levels of CRABP2 predicted poor prognosis.Additionally,CRABP2 expression was elevated in cancer-associated fibroblasts(CAFs)at the single-cell level.The expression of CRABP2 was positively correlated with markers of CAFs,such as MFAP5,PDPN,ITGA11,PDGFRα/βand THY1 in SKCM.To validate the tumor-promoting effect of CRABP2 in vivo,SKCM xenograft mice models with CRABP2 overexpression have been constructed.These models showed an increase in tumor weight and volume.Enrichment analysis indicated that CRABP2 may be involved in immunerelated pathways of SKCM,such as extracellular matrix(ECM)receptor interaction and epithelial-mesenchymal transition(EMT).The study suggests that CRABP2 may regulate immunotherapy in SKCM patients by influencing infiltration of CAFs.In conclusion,this study provides new insights into the role of CRABP2 in immunotherapy response.The findings suggest that CRABP2 may be a promising biomarker for PD-1 inhibitors in SKCM patients.Further research is needed to confirm these findings and to explore the clinical implications of CRABP2 in immunotherapy.展开更多
基金supported by the National Natural Science Foundation of China (32373181)National Key Research and Development Program (2023YFD2400700)+2 种基金Science and Technology Plan Project of Fujian Province (2022L3059)High-quality Development of Marine and Fishery Industry Special Fund Project of Fujian Province (FJHYF-L-2023-5)Open Fund of Fujian Province Key Laboratory of Special Aquatic Formula Feed (TMKJZ2302)。
文摘Small RNAs(sRNAs)are a class of molecules capable of perceiving environmental changes and exerting posttranscriptional regulation over target gene expression,thereby influencing bacterial virulence and host immune responses.Pseudomonas plecoglossicida is a pathogenic bacterium that poses a significant threat to aquatic animal health.However,the regulatory mechanisms of sRNAs in P.plecoglossicida remain unclear.This study focused on sRNA113,previously identified as a potential regulator of the fliP gene,a key component of the lateral flagellar type III secretion system.To investigate the effects of sRNA113on P.plecoglossicida virulence,as well as its role in regulating pathogenic processes and host immune responses,mutant strains lacking this sRNA were generated and analyzed.Deletion of sRNA113 resulted in the up-regulation of lateral flagellar type III secretion system-related genes in P.plecoglossicida,which enhanced bacterial swarming motility,biofilm formation,and chemotaxis ability in vitro.In vivo infection experiments with pearl gentian grouper revealed that sRNA113 deletion enhanced the pathogenicity of P.plecoglossicida.This heightened virulence was attributed to the up-regulation of genes associated with the lateral flagellar type III secretion system,resulting in higher bacterial loads within host tissues.This amplification of pathogenic activity intensified tissue damage,disrupted immune responses,and impaired the ability of the host to clear infection,ultimately leading to mortality.These findings underscore the critical role of sRNA113 in regulating the virulence of P.plecoglossicida and its interaction with host immune defenses.This study provides a foundation for further exploration of sRNAmediated mechanisms in bacterial pathogenesis and hostpathogen interactions,contributing to a deeper understanding of virulence regulation and immune evasion in aquatic pathogens.
基金supported by the Open Fund of the Key Laboratory of Integrated Pest Management on Crop in Northwestern Oasis,Ministry of Agriculture and Rural Affairsof China(KFJJ202101)the National KeyR&D Program of China(2021YFD1400100)+1 种基金the National Natural Science Foundation of China(31972247)the Tianchi Talent Introduction Program in Xinjiang Uygur Autonomous Region,China and the Science and Technology Innovation Project of the Chinese Academy of Agricultural Sciences.
文摘The sugar beet cyst nematode(Heterodera schachtii) is one of the most destructive pathogens in sugar beet production, which causes serious economic losses every year. Few molecular details of effectors of H. schachtii parasitism are known. We analyzed the genome and transcriptome data of H. schachtii and identified multiple potential predicted proteins. After filtering out predicted proteins with high homology to other plant-parasitic nematodes, we performed functional validation of the remaining effector proteins. 37 putative effectors of H. schachtii were screened based on the Nicotiana benthamiana system for identifying the effectors that inhibit plant immune response, eventually determines 13 candidate effectors could inhibit cell death caused by Bax. Among the 13 effectors, nine have the ability to inhibit GPA2/RBP1-induced cell death. All 13 effectortriggered immunity(ETI) suppressor genes were analyzed by qRT-PCR and confirmed to result in a significant downregulation of one or more defense genes during infection compared to empty vector. For in situ hybridization,13 effectors were specifically expressed and located in esophageal gland cells. These data and functional analysis set the stage for further studies on the interaction of H. schachtii with host and H. schachtii parasitic control.
基金Chinese Academy of Medical Sciences Initiative for Innovative Medicine,Grant/Award Number:2021-I2M-1-035 and 2022-I2M-1-011。
文摘Background:Dengue fever,an acute insect-borne infectious disease caused by the dengue virus(DENV),poses a great challenge to global public health.Hepatic involve-ment is the most common complication of severe dengue and is closely related to the occurrence and development of disease.However,the features of adaptive immune responses associated with liver injury in severe dengue are not clear.Methods:We used single-cell sequencing to examine the liver tissues of mild or se-vere dengue mice model to analyze the changes in immune response of T cells in the liver after dengue virus infection,and the immune interaction between macrophages and T cells.Flow cytometry was used to detect T cells and macrophages in mouse liver and blood to verify the single-cell sequencing results.Results:Our result showed CTLs were significantly activated in the severe liver injury group but the immune function-related signal pathway was down-regulated.The rea-son may be that the excessive immune response in the severe group at the late stage of DENV infection induces the polarization of macrophages into M2 type,and the macrophages then inhibit T cell immunity through the TGF-βsignaling pathway.In ad-dition,the increased proportion of Treg cells suggested that Th17/Treg homeostasis was disrupted in the livers of severe liver injury mice.Conclusions:In this study,single-cell sequencing and flow cytometry revealed the characteristic changes of T cell immune response and the role of macrophages in the liver of severe dengue fever mice.Our study provides a better understanding of the pathogenesis of liver injury in dengue fever patients.
文摘Background Monoglycerides have emerged as a promising alternative to conventional practices due to their biolog-ical activities,including antimicrobial properties.However,few studies have assessed the efficacy of monoglyceride blend on weaned pigs and their impacts on performance,immune response,and gut health using a disease chal-lenge model.Therefore,this study aimed to investigate the effects of dietary monoglycerides of short-and medium-chain fatty acids on the immunity and gut health of weaned pigs experimentally infected with an enterotoxigenic Escherichia coli F18.Results Pigs supplemented with high-dose zinc oxide(ZNO)had greater(P<0.05)growth performance than other treatments,but no difference was observed in average daily feed intake between ZNO and monoglycerides groups during the post-challenge period.Pigs in ZNO and antibiotic groups had lower(P<0.05)severity of diarrhea than control,but the severity of diarrhea was not different between antibiotic and monoglycerides groups.Pigs fed with monoglycerides or ZNO had lower(P<0.05)serum haptoglobin on d 2 or 5 post-inoculation than control.Pigs in ZNO had greater(P<0.05)goblet cell numbers per villus,villus area and height,and villus height:crypt depth ratio(VH:CD)in duodenum on d 5 post-inoculation than pigs in other treatments.Pigs supplemented with monoglyc-erides,ZNO,or antibiotics had reduced(P<0.05)ileal crypt depth compared with control on d 5 post-inoculation,contributing to the increase(P=0.06)in VH:CD.Consistently,pigs in ZNO expressed the lowest(P<0.05)TNFa,IL6,IL10,IL12,IL1A,IL1B,and PTGS2 in ileal mucosa on d 5 post-inoculation,and no difference was observed in the expres-sion of those genes between ZNO and monoglycerides.Supplementation of ZNO and antibiotic had significant impacts on metabolic pathways in the serum compared with control,particularly on carbohydrate and amino acid metabolism,while limited impacts on serum metabolites were observed in monoglycerides group when compared with control.Conclusions The results suggest that supplementation of monoglyceride blend may enhance disease resist-ance of weaned pigs by alleviating the severity of diarrhea and mitigating intestinal and systemic inflammation,although the effectiveness may not be comparable to high-dose zinc oxide.
基金The financial supports from the Key Program of the National Natural Science Foundation of China(32130082)Jiangxi High Level Talent Cultivation Project(20204BCJ24006)+1 种基金Project of State Key Laboratory of Food Science and Technology(SKLF-ZZA-201911)Central Government Guide Local Special Fund Project for Scientific and Technological Development of Jiangxi Province(20212ZDD02008)。
文摘With the rise of probiotics fermentation in food industry,fermented foods have attracted worldwide attention.In this study,protective effects of Rosa roxburghii&edible fungus fermentation broth(REFB)on immune function and gut health in Cyclophosphamide induced immunosuppressed mice were investigated.Results showed that REFB could improve the immune organ index,and promote the proliferation and differentiation of splenic T lymphocytes.In addition,it attenuated intestinal mucosal damage and improved intestinal cellular immunity.REFB administration also up-regulated the expression of IL-4,INF-γ,TNF-α,T-bet and GATA-3 mRNA in small intestine.Furthermore,administration of REFB modulated gut microbiota composition and increased the relative abundance of beneficial genus,such as Bacteroides.It also increased the production of fecal short-chain fatty acids.These indicate that REFB has the potential to improve immunity,alleviate intestinal injury and regulate gut microbiota in immunosuppressed mice.
基金Shanghai Chongming District Sustainable Development Science and Technology Innovation Action Plan,No.CKY2020-11.
文摘BACKGROUND Gastric cancer remains a leading cause of cancer-related mortality globally.Traditional open surgery for gastric cancer is often associated with significant morbidity and prolonged recovery.AIM To evaluate the effectiveness of laparoscopic minimally invasive surgery as an alternative to traditional open surgery for gastric cancer,focusing on its potential to reduce trauma,accelerate recovery,and achieve comparable oncological out-comes.METHODS This study retrospectively analyzed 203 patients with gastric cancer who underwent surgery at the Shanghai Health Medical College Affiliated Chongming Hospital from January 2020 to December 2023.The patients were divided into two groups:Minimally invasive surgery group(n=102),who underwent laparoscopic gastrectomy,and open surgery group(n=101),who underwent traditional open gastrectomy.We compared surgical indicators(surgical incision size,intraop-erative blood loss,surgical duration,and number of lymph nodes dissected),recovery parameters(time to first flatus,time to start eating,time to ambulation,and length of hospital stay),immune function(levels of IgA,IgG,and IgM),intestinal barrier function(levels of D-lactic acid and diamine oxidase),and stress response(levels of C-reactive protein,interleukin-6,and procalcitonin).RESULTS The minimally invasive surgery group demonstrated significantly better outcomes in terms of surgical indicators,including smaller incisions,less blood loss,shorter surgery time,and more lymph nodes dissected(P<0.05 for all).Recovery was also faster in the minimally invasive surgery group,with earlier return of bowel function,earlier initiation of diet,quicker mobilization,and shorter hospital stays(P<0.05 for all).Furthermore,patients in the minimally invasive surgery group had better preserved immune function,superior intestinal barrier function,and a less pronounced stress response postoperatively(P<0.05 for all).CONCLUSION Laparoscopic minimally invasive surgery for gastric cancer not only provides superior surgical indicators and faster recovery but also offers advantages in preserving immune function,protecting intestinal barrier function,and mitigating the stress response compared to traditional open surgery.These findings support the broader adoption of laparoscopic techniques in the management of gastric cancer.
基金Supported by the Zhejiang Provincial Natural Science Foundation of China(No.LY23D060002)the Key Scientific and Technological Grant of Zhejiang for Breeding New Agricultural Varieties(No.2021C02069-5)+1 种基金the Pingyang County Science and Technology Strengthening Agriculture Industry Upgrading Project(No.2023PY003)the National Natural Science Foundation of China(No.41906107)。
文摘Our previous study found that feeding with Lactobacillus plantarum Ep-M17 could effectively affect the growth performance,immune response,and gut microbiota of Penaeus vannamei.However,high temperature and pressure during feed pelletizing is the main problem that can lead to a decrease in the activity of probiotics or cause their inactivation.Further investigation needs to investigate whether inactivated Ep-M17 can exert similar effects as live Ep-M17.Therefore,we evaluated the effects of inactivated L.plantarum Ep-M17 on growth performance,immune response,disease resistance,and gut microbiota in P.vannamei.Results show that adding inactivated Ep-M17 to the feed also promoted body weight gain and increased relative immune protection in shrimp.Also,histological examination revealed that the administration of inactivated Ep-M17 led to improvements in the density and distribution of microvilli in the intestines and enhancements in the abundance of B and R cells in the hepatopancreas.Additionally,the inactivated Ep-M17 supplementation resulted in increased activity levels of nutrient immune-related enzymes in both the shrimp hepatopancreas and intestines.Moreover,it stimulated the expression of Lvlec,PEN-3a,Crustin,LGBP,Lysozyme,and proPo genes in both the hepatopancreas and intestines.Furthermore,the inactivated Ep-M17 also increased bacterial diversity in the gut of shrimp and promoted the abundance of specific flora,facilitating the host organism’s metabolism and immunity to improve the disease resistance of shrimp.Therefore,supplementation of inactivated L.plantarum Ep-M17 in shrimp diets can exert similar effects as live L.plantarum Ep-M17 effectively improving growth performance,gut microbiota,immune response,and disease resistance in P.vannamei.
基金the financial support from the National Natural Science Foundation of China (No. 82372019, 82022034, 82173327)Jiangsu Province Natural Science Foundation of China (BK20200032)Double First Class Foundation of China Pharmaceutical University(CPUQNJC22_03)
文摘Photothermal and photodynamic therapies(PTT/PDT)hold promise for localized tumor treatment,yet their full potential is hampered by limitations such as the hypoxic tumor microenvironment and inadequate systemic immune activation.Addressing these challenges,we present a novel near-infrared(NIR)-triggered RNS nanoreactor(PBNO-Ce6)to amplify the photodynamic and photothermal therapy efficacy against triple-negative breast cancer(TNBC).The designed PBNOCe6 combines sodium nitroprusside-doped Prussian Blue nanoparticles with Chlorin e6 to enable on-site RNS production through NIR-induced concurrent NO release and ROS generation.This not only enhances tumor cell eradication but also potentiates local and systemic antitumor immune responses,protecting mice from tumor rechallenge.Our in vivo evaluations revealed that treatment with PBNO-Ce6 leads to a remarkable 2.7-fold increase in cytotoxic T lymphocytes and a 62%decrease in regulatory T cells in comparison to the control PB-Ce6(Prussian Blue nanoparticles loaded with Chlorin e6),marking a substantial improvement over traditional PTT/PDT.As such,the PBNO-Ce6 nanoreactor represents a transformative approach for improving outcomes in TNBC and potentially other malignancies affected by similar barriers.
基金supported by the National Key Research and Development Program,China(Grant Nos.:2021YFC2101500 and 2021YFC2103900)the National Natural Science Foundation of China(Grant Nos.:22278335 and 21978236)the Natural Science Basic Research Program of Shaanxi,China(Grant No.:2023-JC-JQ-17).
文摘The gut microbiota plays a pivotal role in the immunomodulatory and protumorigenic microenvironment of colorectal cancer(CRC).However,the effect of ginsenoside Rk3(Rk3)on CRC and gut microbiota remains unclear.Therefore,the purpose of this study is to explore the potential effect of Rk3 on CRC from the perspective of gut microbiota and immune regulation.Our results reveal that treatment with Rk3 significantly suppresses the formation of colon tumors,repairs intestinal barrier damage,and regulates the gut microbiota imbalance caused by CRC,including enrichment of probiotics such as Akkermansia muciniphila and Barnesiella intestinihominis,and clearance of pathogenic Desulfovibrio.Subsequent metabolomics data demonstrate that Rk3 can modulate the metabolism of amino acids and bile acids,particularly by upregulating glutamine,which has the potential to regulate the immune response.Furthermore,we elucidate the regulatory effects of Rk3 on chemokines and inflammatory factors associated with group 3 innate lymphoid cells(ILC3s)and T helper 17(Th17)signaling pathways,which inhibits the hyperactivation of the Janus kinase-signal transducer and activator of transcription 3(JAK-STAT3)signaling pathway.These results indicate that Rk3 modulates gut microbiota,regulates ILC3s immune response,and inhibits the JAK-STAT3 signaling pathway to suppress the development of colon tumors.More importantly,the results of fecal microbiota transplantation suggest that the inhibitory effect of Rk3 on colon tumors and its regulation of ILC3 immune responses are mediated by the gut microbiota.In summary,these findings emphasize that Rk3 can be utilized as a regulator of the gut microbiota for the prevention and treatment of CRC.
基金supported by grants from the Brazilian Agencies:Coordenação de Aperfeiçoamento de Pessoal de Nível Superior(CAPES-Financial code 001)Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)Fundação Cearense de Apoio ao Desenvolvimento Científico e Tecnológico(FUNCAP).
文摘Objective:To evaluate the immunological response elicited by an inactivated bacterial vector carrying the K39 antigen of Leishmania infantum,and a purified antigen.Methods:Mice were subjected to the following treatments:(1)Purified recombinant K39(rK39)protein at a 20μg dose with complete Freund’s adjuvant;(2)Inactivated Escherichia coli(BL21 DE3)carrying the K39 protein at an equivalent total protein content of 200μg;(3)Inactivated bacteria lacking the K39 protein;(4)Non-immunized control animals.Serological monitoring was performed.All groups were challenged by intraperitoneal injection of 10^(7) Leishmania infantum promastigotes.After euthanasia,the liver and spleen were collected to analyze the levels of TNF,IFN-γ,IL-12,IL-4,and IL-10.Results:Mice immunized with purified rK39 or the inactivated bacterial vector carrying the K39 antigen of Leishmania infantum showed a long-lasting immune response with high levels of polyclonal antibodies specifically recognizing the recombinant proteins.The IgG1 subclass was the predominant immunoglobulin;however,the induction of IgG2a and the profile of cytokines produced were indicative of the induction of a mixed-type response.Conclusions:The inactivated bacterial vector carrying the K39 antigen,as well as the purified antigen can induce a long-lasting immune response in immunized mice,predominantly favouring a Th2 profile response.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82260940)the Yunnan Provincial(Traditional Chinese Medicine)Clinical Dermatology Center,12th Five-year Key Construction Discipline of State Administration of Traditional Chinese Medicine“Dai Pharmacy”+1 种基金Open Project of Yunnan Key Laboratory of Dai and Yi Medicines(No.30971101100)Key Laboratory of Chemistry in Ethnic Medicinal Resources,State Ethnic Affairs Commission&Ministry of Education,Yunnan Minzu University.
文摘Background:This study aimed to assess how acupoint catgut-embedding therapy influences Th2-type immune response and the infiltration of CD4^(+)and CD8^(+)cells in DNCB-induced atopic dermatitis in BALB/c mice.It also conducted an initial examination of the underlying molecular mechanisms.Methods:Seventy-two mice were randomly divided into four groups:normal control,DNCB-induced atopic dermatitis model(AD),AD with acupoint catgut-embedding treatment(ADA),and AD with sham-acupoint catgut-embedding treatment.After DNCB challenge to induce AD,the ADA group received acupoint catgut-embedding therapy treatment at Zusanli(ST 36)and Quchi(LI 11)acupoints every other week from day 8.Mice in the AD with sham-acupoint catgut-embedding treatment group underwent the same procedure as the ADA group but without catgut implantation.Severity was assessed using SCORAD on treatment days 1,10,and 20.On day 18,nine mice per group were euthanized,and the remaining on day 28.Histopathological changes were observed using hematoxylin-eosin and immunohistochemistry staining.TNF-α,IL-4,IL-6,and IL-13 levels were analyzed by ELISA,and GATA3 and STAT6 protein levels by western blot.Results:After 20 days of acupoint catgut-embedding therapy treatment,mice showed reduced dermatitis scores compared to DNCB-induced AD-like mice.Significant decreases occurred in serum IL-4,IL-6,IL-13,and TNF-αlevels.Skin analysis revealed marked reductions in CD4^(+)and CD8^(+)cell infiltration,as well as GATA3 and STAT6 protein levels.Conclusion:Acupoint catgut-embedding therapy may effectively alleviate atopic dermatitis by suppressing Th2 immune responses via the STAT6-GATA3 pathway and reducing CD4^(+)and CD8^(+)T cell infiltration in skin lesions.
基金supported by grants from the Major Program of National Key Research and Development Project,Nos.2020YFA0112600(to ZH)the National Natural Science Foundation of China,No.82171270(to ZL)+5 种基金Public Service Platform for Artificial Intelligence Screening and Auxiliary Diagnosis for the Medical and Health Industry,Ministry of Industry and Information Technology of the People’s Republic of China,No.2020-0103-3-1(to ZL)the Natural Science Foundation of Beijing,No.Z200016(to ZL)Beijing Talents Project,No.2018000021223ZK03(to ZL)Beijing Municipal Committee of Science and Technology,No.Z201100005620010(to ZL)CAMS Innovation Fund for Medical Sciences,No.2019-I2M-5-029(to YW)Shanghai Engineering Research Center of Stem Cells Translational Medicine,No.20DZ2255100(to ZH).
文摘Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger age.China,in particular,bears a high burden of stroke cases.In recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its treatment.This review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and astrocytes.Additionally,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell therapy.Overall,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient outcomes.Stem cell therapy may potentially become an important component of ischemic stroke treatment.
基金Basic Research Spe-cial Project of Suzhou Science and Technology Bureau(SSD2024050).
文摘Objective Venous thromboembolism is a highly prevalent condition after polytrauma,and recognized as an important factor contributing to poor prognosis.The aim of this study was to investigate the risk factors for lower extremity deep venous thrombosis(LEDVT)in a severely traumatized population and to evaluate their predictive value for LEDVT.Methods This was a retrospective,single-center observational study.All subjects were severely traumatized patients who were admitted to the Traumatic Intensive Care Unit from January 2021 to May 2024.Based on Doppler ultrasound findings of both lower extremities from the time of injury to 30 days post-injury,patients who developed LEDVT were enrolled in the LEDVT group,and those who did not develop LEDVT were enrolled in the NLEDVT group.Demographic,clinical,and laboratory data were collected upon admission.Multivariable logistic regression analysis was performed to identify risk factors for LEDVT.Receiver operating characteristic(ROC)curve was used to evaluate the overall fit of the final model.Results There were 56 patients enrolled in the LEDVT group and 81 patients in the NLEDVT group.Age,Aggregate Index of Systemic Inflammation(AISI),Systemic Inflammation Response Index(SIRI),ICU length of stay,and albumin were identified as independent risk factors for LEDVT(all P<0.05).The area under their ROC curves were 0.604,0.657,0.694,0.668,and 0.405,respectively.Combined model for early clinical prediction of LEDVT in severely traumatized patients by age,SIRI,AISI,and albumin resulted in an area under the ROC curve of 0.805(95%CI:0.73-0.88,SE=0.037).Conclusion The combination of age,SIRI,AISI,and albumin has a predictive value for LEDVT in severely traumatized patients.
基金supported by the National Natural Science Foundation of China, No.82274616the Key Laboratory Project for General Universities in Guangdong Province, No.2019KSYS005Guangdong Province Science and Technology Plan International Cooperation Project, No.2020A0505100052 (all to QW)。
文摘Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.
基金supported by the National Natural Science Foundation of China (Grant Nos. 81972761 and 82202837)the National Key R&D Program of China (Grant Nos. 2016YFC1303200 and 2022YFC2505100)。
文摘Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.
基金supported by the National Key Research and Development Program of China(2018YFE0112500)the Natural Science Basic Research Program of Shannxi Province(2024JCYBMS-183).We thank Professor Hui-shan Guo from the Institute of Microbiology,Chinese Academy of Sciences for providing the pNat-Tef-TrpC and pGKO-HPT vector,and Dr.Siwei Zhang from Northwest A&F University for providing the pER8-NeYFP,pER8-CeYFP,and pGEX-4T-1 vectors.
文摘Verticillium dahliae is an important soil-borne fungal pathogen that causes great yield losses in many cash crops.Effectors of this fungus are known to regulate plant immunity but the mechanism much remains unclear.A glycine-rich nuclear effector,VdCE51,was able to suppress immune responses in tobacco against Botrytis cinerea and Sclerotinia sclerotiorum.This effector was a required factor for full virulence of V.dahliae,and its nuclear localization was a requisite for suppressing plant immunity.The thioredoxin GhTRXH2,identified as a positive regulator of plant immunity,was a host target of VdCE51.Our findings show a virulence regulating mechanism whereby the secreted nuclear effector VdCE51 interferes with the transcription of PR genes,and the SA signaling pathway by inhibiting the accumulation of GhTRXH2,thus suppressing plant immunity.
基金The research that yielded these results,was funded by the Belgian Federal Public Service of Health,Food Chain Safety and Environment through the contract RF 17/6314 LactoPigHealthMatthias Dierick is supported by the Flemish fund for scientific research(FWO3S036319).
文摘Background Post-weaned piglets suffer from F18+Escherichia coli(E.coli)infections resulting in post-weaning diar-rhoea or oedema disease.Frequently used management strategies,including colistin and zinc oxide,have contrib-uted to the emergence and spread of antimicrobial resistance.Novel antimicrobials capable of directly interacting with pathogens and modulating the host immune responses are being investigated.Lactoferrin has shown promising results against porcine enterotoxigenic E.coli strains,both in vitro and in vivo.Results We investigated the influence of bovine lactoferrin(bLF)on the microbiome of healthy and infected weaned piglets.Additionally,we assessed whether bLF influenced the immune responses upon Shiga toxin-producing E.coli(STEC)infection.Therefore,2 in vivo trials were conducted:a microbiome trial and a challenge infection trial,using an F18+STEC strain.BLF did not affect theα-andβ-diversity.However,bLF groups showed a higher relative abundance(RA)for the Actinobacteria phylum and the Bifidobacterium genus in the ileal mucosa.When analysing the immune response upon infection,the STEC group exhibited a significant increase in F18-specific IgG serum levels,whereas this response was absent in the bLF group.Conclusion Taken together,the oral administration of bLF did not have a notable impact on theα-andβ-diversity of the gut microbiome in weaned piglets.Nevertheless,it did increase the RA of the Actinobacteria phylum and Bifi-dobacterium genus,which have previously been shown to play an important role in maintaining gut homeostasis.Furthermore,bLF administration during STEC infection resulted in the absence of F18-specific serum IgG responses.
基金financed by the National Key Research and Development Program of China(2017YFD0200900)。
文摘Fusarium graminearum,the primary pathogenic fungus responsible for Fusarium head blight(FHB)in wheat,secretes abundant chemical compounds that interact with host plants.In this study,a secreted protein FgHrip1,isolated from the culture filtrate of F.graminearum,was found to induce typical cell death in tobacco.The FgHrip1 gene was then cloned and expressed in Escherichia coli.Further bioassay analysis showed that the recombinant FgHrip1 induced early defense induction events,such as reactive oxygen species(ROS)production,callose deposition,and up-regulation of defense-related genes in tobacco.Furthermore,FgHrip1 significantly enhanced immunity in tobacco seedlings against Pseudomonas syringae pv.tabaci 6605(Pst.6605)and tobacco mosaic virus(TMV).FgHrip1-treated wheat spikes also exhibited defense-related transcript accumulation and developed immunity against FHB infection.Whereas the expression of FgHrip1 was induced during the infection process,the deletion of the gene impaired the virulence of F.graminearum.Our results suggest that FgHrip1triggers immunity and induces disease resistance in tobacco and wheat,thereby providing new insight into strategy for biocontrol of FHB.
基金funded by the National Natural Science Foundation of China(32060637 and 32260708)the Highlevel Talent Innovation and Entrepreneurship Funding Project in Guizhou Province,China((2021)01)+3 种基金the Guizhou Provincial Science and Technology Innovation Talent Team Project,China(Qian Ke He Pingtai RencaiCXTD(2021)004)the Systematic and Applied Acarology Society International Joint Project,England(2022(01))the Growth Project of Youth Talent in Ordinary Universities in Guizhou Province,China((2021)079)the Natural Science Special Project in Guizhou University,China((2020)02)。
文摘Parasitoids are key regulators in ecological communities and widely used as agents in biocontrol programmes.The fall armyworm,Spodoptera frugiperda,recently invaded multiple continents and caused substantial economic losses in agriculture.Pyemotes zhonghuajia,a newly identified mite parasitoid,has shown potential for controlling various agricultural insect pests.Therefore,this study tested the performance of P.zhonghuajia in parasitising S.frugiperda.We also investigated the sublethal effects of parasitism by P.zhonghuajia on host fitness traits,transgenerational impacts,and cellular and humoral immunity.Our result showed that the fifth-instar larvae of S.frugiperda parasitised by 40 P.zhonghuajia were all dead(i.e.,a lethal effect),while parasitism by 5 or 10 P.zhonghuajia was considered sublethal since many S.frugiperda survived to adulthood and produced offspring after mating.The sublethal influences from parasitism by P.zhonghuajia resulted in reduced pupal weight,adult emergence rate and fecundity,but increased developmental time and longevity.Parasitism at both lethal(40 mites)and sublethal(10 mites)levels impaired the cellular and humoral immunity of S.frugiperda.This study presents the first empirical evidence that mite parasitoids can negatively influence host immunity.Moreover,it provides insights into the biocontrol potential of mite parasitoids and their interactions with hosts.
基金supported by grants from the Natural Science Foundation of Hunan Province(2022JJ80044)the Youth Science Foundation of Xiangya Hospital(2019Q13).
文摘Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is limited research on the relationship between CRABP2 and immunotherapy response.This study found that negative correlations of CRABP2 and immune checkpoint markers(PD-1,PD-L1,and CTLA-4)were observed in breast invasive carcinoma(BRCA),skin cutaneous melanoma(SKCM),stomach adenocarcinoma(STAD)and testicular germ cell tumors(TGCT).In particular,in SKCM patients who were treated with PD-1 inhibitors,high levels of CRABP2 predicted poor prognosis.Additionally,CRABP2 expression was elevated in cancer-associated fibroblasts(CAFs)at the single-cell level.The expression of CRABP2 was positively correlated with markers of CAFs,such as MFAP5,PDPN,ITGA11,PDGFRα/βand THY1 in SKCM.To validate the tumor-promoting effect of CRABP2 in vivo,SKCM xenograft mice models with CRABP2 overexpression have been constructed.These models showed an increase in tumor weight and volume.Enrichment analysis indicated that CRABP2 may be involved in immunerelated pathways of SKCM,such as extracellular matrix(ECM)receptor interaction and epithelial-mesenchymal transition(EMT).The study suggests that CRABP2 may regulate immunotherapy in SKCM patients by influencing infiltration of CAFs.In conclusion,this study provides new insights into the role of CRABP2 in immunotherapy response.The findings suggest that CRABP2 may be a promising biomarker for PD-1 inhibitors in SKCM patients.Further research is needed to confirm these findings and to explore the clinical implications of CRABP2 in immunotherapy.
