This paper introduces a novel chattering-free terminal sliding mode control(SMC)strategy to address chaotic behavior in permanent magnet synchronous generators(PMSG)for offshore wind turbine systems.By integrating an ...This paper introduces a novel chattering-free terminal sliding mode control(SMC)strategy to address chaotic behavior in permanent magnet synchronous generators(PMSG)for offshore wind turbine systems.By integrating an adaptive exponential reaching law with a continuous barrier function,the proposed approach eliminates chattering and ensures robust performance under model uncertainties.The methodology combines adaptive SMC with dynamic switching to estimate and compensates for unknown uncertainties,providing smooth and stable control.Finally,the performance and effectiveness of the proposed approach are compared with those of a previous study.展开更多
Emerging evidence of the beneficial effects of defatted rice bran(DFRB)on gut health has advanced the development of fermented defatted rice bran as a potential functional food.However,less is known about its effects ...Emerging evidence of the beneficial effects of defatted rice bran(DFRB)on gut health has advanced the development of fermented defatted rice bran as a potential functional food.However,less is known about its effects and underlying mechanisms on gut health.In this study,a mouse model together with fecal microbiota transplantation(FMT)was utilized to study the effects and mechanisms of fermented DFRB(FR)on gut barrier function.We found that FR improved the intestinal morphology,gut tight junction proteins,mucin,antimicrobial peptides,and interleukin 22(IL-22)and promoted the gut Clostridium butyricum and butyrate.Notably,correlation analysis indicated gut C.butyricum and butyrate were two FR-induced effectors that improved gut health.FMT results suggested that C.butyricum,butyrate,and fecal microbiota from the FR group all reduced prolyl hydroxylase 2(PHD2)expression by activating peroxisome proliferator-activated receptor gamma(PPARγ)in the mouse colon.This decrease in gut PHD2 subsequently upregulated the hypoxia-inducible factor-1 alpha(HIF-1α)expression,which in turn increased the expression of its targeted downstream tight junction proteins,mucin and antimicrobial peptides,and colonic IL-22 secretion.Overall,FR-derived C.butyricum and butyrate might improve gut barrier function through the HIF-1 signaling pathway,which provides a reference for the application of fermented DFRB as a potential functional food for improving of gut barrier function.展开更多
The objective of this paper is to present a robust safety-critical control system based on the active disturbance rejection control approach, designed to guarantee safety even in the presence of model inaccuracies, un...The objective of this paper is to present a robust safety-critical control system based on the active disturbance rejection control approach, designed to guarantee safety even in the presence of model inaccuracies, unknown dynamics, and external disturbances. The proposed method combines control barrier functions and control Lyapunov functions with a nonlinear extended state observer to produce a robust and safe control strategy for dynamic systems subject to uncertainties and disturbances. This control strategy employs an optimization-based control, supported by the disturbance estimation from a nonlinear extended state observer. Using a quadratic programming algorithm, the controller computes an optimal, stable, and safe control action at each sampling instant. The effectiveness of the proposed approach is demonstrated through numerical simulations of a safety-critical interconnected adaptive cruise control system.展开更多
This study systematically reviews the pharmacological mechanisms of Huanglian Wendan Decoction in improving intestinal barrier function in ulcerative colitis(UC),including the regulation of intestinal chemical barrier...This study systematically reviews the pharmacological mechanisms of Huanglian Wendan Decoction in improving intestinal barrier function in ulcerative colitis(UC),including the regulation of intestinal chemical barrier,the regulation of intestinal immune barrier,and the improvement of intestinal biological barrier,in order to provide theoretical basis and new ideas for the clinical treatment of UC.展开更多
Background The aim of this study was to determine whether and how Zn proteinate with moderate chelation strength(Zn-Prot M)can alleviate heat stress(HS)-induced intestinal barrier function damage of broilers.A complet...Background The aim of this study was to determine whether and how Zn proteinate with moderate chelation strength(Zn-Prot M)can alleviate heat stress(HS)-induced intestinal barrier function damage of broilers.A completely randomized design was used for comparatively testing the effects of Zn proteinate on HS and non-HS broilers.Under high temperature(HT),a 1(Control,HT-CON)+2(Zn source)×2(added Zn level)factorial arrangement of treatments was used.The 2 added Zn sources were Zn-Prot M and Zn sulfate(ZnS),and the 2 added Zn levels were 30 and 60 mg/kg.Under normal temperature(NT),a CON group(NT-CON)and pair-fed group(NT-PF)were included.Results The results showed that HS significantly reduced mRNA and protein expression levels of claudin-1,occludin,junctional adhesion molecule-A(JAMA),zonula occludens-1(ZO-1)and zinc finger protein A20(A20)in the jejunum,and HS also remarkably increased serum fluorescein isothiocyanate dextran(FITC-D),endotoxin and interleukin(IL)-1βcontents,serum diamine oxidase(DAO)and matrix metalloproteinase(MMP)-2 activities,nuclear factor kappa-B(NF-κB)p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum.However,dietary supplementation with Zn,especially organic Zn as Zn-Prot M at 60 mg/kg,significantly decreased serum FITC-D,endotoxin and IL-1βcontents,serum DAO and MMP-2 activities,NF-κB p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum of HS broilers,and notably promoted mRNA and protein expression levels of claudin-1,ZO-1 and A20.Conclusions Our results suggest that dietary Zn,especially 60 mg Zn/kg as Zn-Prot M,can alleviate HS-induced intestinal barrier function damage by promoting the expression of TJ proteins possibly via induction of A20-mediated suppression of the NF-κB p65/MMP-2 pathway in the jejunum of HS broilers.展开更多
BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis.Peroxisome prolifer...BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis.Peroxisome proliferator activated receptor(PPAR)α and δ play a key role in lipid metabolism and intestinal barrier homeostasis,which are major contributors to the pathological progression of ALD.Meanwhile,elafibranor(EFN),which is a dual PPARαand PPARδagonist,has reached a phase III clinical trial for the treatment of metabolic dysfunctionassociated steatotic liver disease and primary biliary cholangitis.However,the benefits of EFN for ALD treatment is unknown.AIM To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model.METHODS ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol(EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly(1 mL/kg)for 8 weeks.EFN(3 and 10 mg/kg/day)was orally administered during the experimental period.Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis,fibrosis,and intestinal barrier integrity.The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays.RESULTS The hepatic steatosis,apoptosis,and fibrosis in the ALD mice model were significantly attenuated by EFN treatment.EFN promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells,primarily through PPARαactivation.Moreover,EFN inhibited the Kupffer cell-mediated inflammatory response,with blunted hepatic exposure to lipopolysaccharide(LPS)and toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling.EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses.The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cells was predominantly mediated by PPARδ activation.CONCLUSION EFN reduced ALD-related fibrosis by inhibiting lipid accumulation and apoptosis,enhancing hepatocyte autophagic and antioxidant capacities,and suppressing LPS/TLR4/NF-κB-mediated inflammatory responses by restoring intestinal barrier function.展开更多
Deoxynivalenol(DON)is a mycotoxin that is produced by various species of Fusarium and is ubiquitous in food and feed.At low concentrations,it can cause metabolic disorders in animals and humans and,at high concentrati...Deoxynivalenol(DON)is a mycotoxin that is produced by various species of Fusarium and is ubiquitous in food and feed.At low concentrations,it can cause metabolic disorders in animals and humans and,at high concentrations,it can lead to pathological changes in the body.The impact of DON on human/animal health and animal productivity has thus attracted a great deal of attention around the world.DON causes severe damage to the intestine,including compromised intestinal barrier,mucosal damage,weakened immune function,and alterations in gut microbiota composition.These effects exacerbate intestinal infections and inflammation in livestock and poultry,posing adverse effects on overall health.Furthermore,research into biological methods for DON detoxification is a crucial avenue for future studies.This includes the utilization of adsorption,enzymatic degradation,and other biological approaches to mitigate DON's impact,offering new strategies for prevention and treatment of DON-induced diseases.Future research will focus on identifying highly efficient detoxifying microorganisms or enzymes to reduce DON levels in food and feed,thereby mitigating its risks to both animals and human health.展开更多
Background Deoxynivalenol(DON)is a mycotoxin that has received recognition worldwide because of its ability to cause growth delay,nutrient malabsorption,weight loss,emesis,and a reduction of feed intake in livestock.S...Background Deoxynivalenol(DON)is a mycotoxin that has received recognition worldwide because of its ability to cause growth delay,nutrient malabsorption,weight loss,emesis,and a reduction of feed intake in livestock.Since DON-contaminated feedstuff is absorbed in the gastrointestinal tract,we used chicken organoids to assess the DON-induced dysfunction of the small intestine.Results We established a culture system using chicken organoids and characterized the organoids at passages 1 and 10.We confirmed the mRNA expression levels of various cell markers in the organoids,such as KI67,leucine-rich repeat containing G protein-coupled receptor 5(Lgr5),mucin 2(MUC2),chromogranin A(CHGA),cytokeratin 19(CK19),lysozyme(LYZ),and microtubule-associated doublecortin-like kinase 1(DCLK1),and compared the results to those of the small intestine.Our results showed that the organoids displayed functional similarities in permeability compared to the small intestine.DON damaged the tight junctions of the organoids,which resulted in increased permeability.Conclusions Our organoid culture displayed topological,genetic,and functional similarities with the small intes-tine cells.Based on these similarities,we confirmed that DON causes small intestine dysfunction.Chicken organoids offer a practical model for the research of harmful substances.展开更多
We discuss the article by Koizumi et al published in the World Journal of Gastroenterology.Our focus is on the therapeutic targets for fibrosis associated with alcohol-related liver disease(ALD)and the mechanism of ac...We discuss the article by Koizumi et al published in the World Journal of Gastroenterology.Our focus is on the therapeutic targets for fibrosis associated with alcohol-related liver disease(ALD)and the mechanism of action of elafibranor(EFN),a dual agonist of peroxisome proliferator-activated receptorα(PPARα)and peroxisome PPARδ(PPARδ).EFN is currently in phase III clinical trials for the treatment of metabolic dysfunction-associated fatty liver disease and primary biliary cholangitis.ALD progresses from alcoholic fatty liver to alcoholic steatohepatitis(ASH),with chronic ASH eventually leading to fibrosis,cirrhosis,and,in some cases,hepatocellular carcinoma.The pathogenesis of ALD is driven by hepatic steatosis,oxidative stress,and acetaldehyde toxicity.Alcohol consumption disrupts lipid metabolism by inactivating PPARα,exacerbating the progression of ALD.EFN primarily activates PPARα,promoting lipolysis andβ-oxidation in ethanol-stimulated HepG2 cells,which significantly reduces hepatic steatosis,apoptosis,and fibrosis in an ALD mouse model.Additionally,alcohol disrupts the gut-liver axis at several interconnected levels,contributing to a proinflammatory environment in the liver.EFN helps alleviate intestinal hyperpermeability by restoring tight junction protein expression and autophagy,inhibiting apoptosis and inflammatory responses,and enhancing intestinal barrier function through PPARδactivation.展开更多
The trajectory tracking control performance of nonholonomic wheeled mobile robots(NWMRs)is subject to nonholonomic constraints,system uncertainties,and external disturbances.This paper proposes a barrier function-base...The trajectory tracking control performance of nonholonomic wheeled mobile robots(NWMRs)is subject to nonholonomic constraints,system uncertainties,and external disturbances.This paper proposes a barrier function-based adaptive sliding mode control(BFASMC)method to provide high-precision,fast-response performance and robustness for NWMRs.Compared with the conventional adaptive sliding mode control,the proposed control strategy can guarantee that the sliding mode variables converge to a predefined neighborhood of origin with a predefined reaching time independent of the prior knowledge of the uncertainties and disturbances bounds.Another advantage of the proposed algorithm is that the control gains can be adaptively adjusted to follow the disturbances amplitudes thanks to the barrier function.The benefit is that the overestimation of control gain can be eliminated,resulting in chattering reduction.Moreover,a modified barrier function-like control gain is employed to prevent the input saturation problem due to the physical limit of the actuator.The stability analysis and comparative experiments demonstrate that the proposed BFASMC can ensure the prespecified convergence performance of the NWMR system output variables and strong robustness against uncertainties/disturbances.展开更多
Background The intestinal barrier is the first line of defense against intestinal invasion by pathogens and foreign antigens and is closely associated with the gut microbiota.Astragalus polysaccharides(APS)have a long...Background The intestinal barrier is the first line of defense against intestinal invasion by pathogens and foreign antigens and is closely associated with the gut microbiota.Astragalus polysaccharides(APS)have a long history of use in traditional Chinese medicine owing to its protective properties against intestinal barrier function.The mechanism of APS-induced gut microbiota enhancing intestinal barrier function is urgently needed.Results Dietary polysaccharide deprivation induced intestinal barrier dysfunction,decreased growth performance,altered microbial composition(Faecalibacterium,Dorea,and Coprobacillus),and reduced isobutyrate concentration.The results showed that APS fa cilitates intestinal barrier function in broiler chickens,including a thicker mucus layer,reduced crypt depth,and the growth of tight junction proteins.We studied the landscape of APS-induced gut microbiota and found that APS selectively promoted the growth of Parabacteroides,a commensal bacterium that plays a predominant role in enhancing intestinal barrier function.An in vitro g rowth assan further verified that APS selectively increased the abundance of Parabacteroides distasonis and Bacteroides uniformis.Dietary APS supplementation increased the concentrations of isobutyrate and bile acid(mainly chenodeoxycholic acid and deoxycholate acid)and activated signaling pathways related to intestinal barrier function(such as protein processing in the endoplasmic reticulum,tight junctions,and adherens junction signaling pathways).Conclusions APS intervention restored the dietary polysaccharide-induced dysfunction of the intestinal barrier by selectively promoting the abundance of Parabacteroides distasonis,and increasing the concentrations of isobutyrate and bile acids(mainly CDCA and DCA).These findings suggest that APS-induced gut microbiota and metabolic niches are promising strategies for enhancing intestinal barrier function.展开更多
Background Global warming leading to heat stress(HS)is becoming a major challenge for broiler production.This study aimed to explore the protective effects of seaweed(Enteromorpha prolifera)polysaccharides(EPS)on the ...Background Global warming leading to heat stress(HS)is becoming a major challenge for broiler production.This study aimed to explore the protective effects of seaweed(Enteromorpha prolifera)polysaccharides(EPS)on the intestinal barrier function,microbial ecology,and performance of broilers under HS.A total of 144 yellow-feathered broilers(male,56 days old)with 682.59±7.38 g were randomly assigned to 3 groups:1)TN(thermal neutral zone,23.6±1.8℃),2)HS(heat stress,33.2±1.5℃ for 10 h/d),and 3)HSE(HS+0.1%EPS).Each group contained 6 replicates with 8 broilers per replicate.The study was conducted for 4 weeks;feed intake and body weights were measured at the end of weeks 2 and 4.At the end of the feeding trial,small intestine samples were collected for histomorphology,antioxidant,secretory immunoglobulin A(s Ig A)content,apoptosis,gene and protein expression analysis;cecal contents were also collected for microbiota analysis based on 16S r DNA sequencing.Results Dietary EPS promoted the average daily gain(ADG)of broilers during 3–4 weeks of HS(P<0.05).At the end of HS on broilers,the activity of total superoxide dismutase(T-SOD),glutathione S-transferase(GST),and the content of s Ig A in jejunum were improved by EPS supplementation(P<0.05).Besides,dietary EPS reduced the epithelial cell apoptosis of jejunum and ileum in heat-stressed broilers(P<0.05).Addition of EPS in HS group broilers'diet upregulated the relative m RNA expression of Occludin,ZO-1,γ-GCLc and IL-10 of the jejunum(P<0.05),whereas downregulated the relative m RNA expression of NF-κB p65,TNF-αand IL-1βof the jejunum(P<0.05).Dietary EPS increased the protein expression of Occludin and ZO-1,whereas it reduced the protein expression of NF-κB p65 and MLCK(P<0.01)and tended to decrease the protein expression of TNF-α(P=0.094)in heat-stressed broilers.Furthermore,the proportions of Bacteroides and Oscillospira among the three groups were positively associated with jejunal apoptosis and pro-inflammatory cytokine expression(P<0.05)and negatively correlated with jejunal Occludin level(P<0.05).However,the proportions of Lactobacillus,Barnesiella,Subdoligranulum,Megasphaera,Collinsella,and Blautia among the three groups were positively related to ADG(P<0.05).Conclusions EPS can be used as a feed additive in yellow-feathered broilers.It effectively improves growth performance and alleviates HS-induced intestinal injury by relieving inflammatory damage and improving the tight junction proteins expression.These beneficial effects may be related to inhibiting NF-κB/MLCK signaling pathway activation and regulation of cecal microbiota.展开更多
Objective Atopic dermatitis(AD)is a chronic inflammatory skin disease that may be linked to changes in the gut microbiome.Acupuncture has been proven to be effective in reducing AD symptoms without serious adverse eve...Objective Atopic dermatitis(AD)is a chronic inflammatory skin disease that may be linked to changes in the gut microbiome.Acupuncture has been proven to be effective in reducing AD symptoms without serious adverse events,but its underlying mechanism is not completely understood.The purpose of this study was to investigate whether the potential effect of acupuncture on AD is gut microbiota-dependent.Methods AD-like skin lesions were induced by applying MC903 topically to the cheek of the mouse.Acupuncture was done at the Gok-Ji(LI11)acupoints.AD-like symptoms were assessed by lesion scores,scratching behavior,and histopathological changes;intestinal barrier function was measured by fecal output,serum lipopolysaccharide levels,histopathological changes,and mRNA expression of markers involved in intestinal permeability and inflammation.Gut microbiota was profiled using 16S rRNA gene sequencing from fecal samples.Results Acupuncture effectively improved chronic itch as well as the AD-like skin lesions with epidermal thickening,and also significantly altered gut microbiota structure as revealed byβ-diversity indices and analysis of similarities.These beneficial effects were eliminated by antibiotic depletion of gut microbiota,but were reproduced in gut microbiota-depleted mice that received a fecal microbiota transplant from acupuncture-treated mice.Interestingly,AD mice had intestinal barrier dysfunction as indicated by increased intestinal permeability,atrophy of the mucosal structure(reduced villus height and crypt depth),decreased expression of tight junctions and mucus synthesis genes,and increased expression of inflammatory mediators in the ileum.Acupuncture attenuated these abnormalities,which was gut microbiota-dependent.Conclusion Acupuncture ameliorates AD-like phenotypes in a gut microbiota-dependent manner and some of these positive benefits are explained by modulation of the intestinal barrier,providing new perspective for non-pharmacological strategies for modulating gut microbiota to prevent and treat AD.展开更多
●AIM:To evaluate the role of semaphorin 7A(Sema7A)and its associated regulatory mechanisms in modulating the barrier function of cultured human corneal epithelial cells(HCEs).●METHODS:Barrier models of HCEs were tre...●AIM:To evaluate the role of semaphorin 7A(Sema7A)and its associated regulatory mechanisms in modulating the barrier function of cultured human corneal epithelial cells(HCEs).●METHODS:Barrier models of HCEs were treated with recombinant human Sema7A at concentrations of 0,125,250,or 500 ng/mL for 24,48,or 72h in vitro.Transepithelial electrical resistance(TEER)as well as Dextran-fluorescein isothiocyanate(FITC)permeability assays were conducted to assess barrier function.To quantify tight junctions(TJs)such as occludin and zonula occludens-1(ZO-1)at the mRNA level,reverse transcriptionpolymerase chain reaction(RT-PCR)analysis was performed.Immunoblotting was used to examine the activity of the nuclear factor-kappa B(NF-κB)signaling pathway and the production of TJs proteins.Immunofluorescence analyses were employed to localize the TJs.Enzyme-linked immunosorbent assay(ELISA)and RT-PCR were utilized to observe changes in interleukin(IL)-1βlevels.To investigate the role of NF-κB signaling activation and IL^(-1)βin Sema7A’s anti-barrier mechanism,we employed 0.1μmol/L IκB kinase 2(IKK2)inhibitor IV or 500 ng/mL IL^(-1)receptor(IL-1R)antagonist.●RESULTS:Treatment with Sema7A resulted in decreased TEER and increased permeability of Dextran-FITC in HCEs through down-regulating mRNA and protein levels of TJs in a time-and dose-dependent manner,as well as altering the localization of TJs.Furthermore,Sema7A stimulated the activation of inhibitor of kappa B alpha(IκBα)and expression of IL-1β.The anti-barrier function of Sema7A was significantly suppressed by treatment with IKK2 inhibitor IV or IL-1R antagonists.●CONCLUSION:Sema7A disrupts barrier function through its influence on NF-κB-mediated expression of TJ proteins,as well as the expression of IL-1β.These findings suggest that Sema7A could be a potential therapeutic target for the diseases in corneal epithelium.展开更多
Although constraint satisfaction approaches have achieved fruitful results,system states may lose their smoothness and there may be undesired chattering of control inputs due to switching characteristics.Furthermore,i...Although constraint satisfaction approaches have achieved fruitful results,system states may lose their smoothness and there may be undesired chattering of control inputs due to switching characteristics.Furthermore,it remains a challenge when there are additional constraints on control torques of robotic systems.In this article,we propose a novel high-order control barrier function(HoCBF)-based safety control method for robotic systems subject to input-output constraints,which can maintain the desired smoothness of system states and reduce undesired chattering vibration in the control torque.In our design,augmented dynamics are introduced into the HoCBF by constructing its output as the control input of the robotic system,so that the constraint satisfaction is facilitated by HoCBFs and the smoothness of system states is maintained by the augmented dynamics.This proposed scheme leads to the quadratic program(QP),which is more user-friendly in implementation since the constraint satisfaction control design is implemented as an add-on to an existing tracking control law.The proposed closed-loop control system not only achieves the requirements of real-time capability,stability,safety and compliance,but also reduces undesired chattering of control inputs.Finally,the effectiveness of the proposed control scheme is verified by simulations and experiments on robotic manipulators.展开更多
Objective:Jianpi huoxue decoction(JHD),a Chinese herbal formula,is commonly used for treating alcohol-associated liver disease(ALD).This study aimed to investigate the mechanism by which JHD affects intestinal barrier...Objective:Jianpi huoxue decoction(JHD),a Chinese herbal formula,is commonly used for treating alcohol-associated liver disease(ALD).This study aimed to investigate the mechanism by which JHD affects intestinal barrier function in ALD rats.Methods:The Sprague-Dawley rats were randomly divided into three groups:control group,model group and JHD group.They were pair-fed a modified Lieber-DeCarli liquid diet containing alcohol(model group,n=10;JHD group,n=10)or isocaloric maltose dextrin(control group,n=10)for 6 weeks.After 3 weeks of feeding,the mice in the JHD group were given JHD(10 mL/kg/day)by gavage for 3 weeks,and those in the control and model groups received equal amounts of double-distilled water for the same period of time.Afterwards,all the rats were given lipopolysaccharide(LPS)by gavage and sacrificed 3.5 h later.LPS levels were measured in the portal blood to evaluate gut leakage.Transmission electron microscopy(TEM)was used to observe ultrastructural changes in the intestinal tract.Adherens junction(AJ)and tight junction(TJ)proteins were detected by Western blotting,immunofluorescence or immunohistochemistry.Results:JHD ameliorated Lieber-DeCarli liquid diet-induced hepatic steatosis,inflammation and LPS expression.It improved pathological changes in the liver and alleviated intestinal ultrastructure injury.Moreover,it significantly enhanced the integrity of tight junctions by increasing the expression of zonula occludens‐1(ZO-1)and occludin.It suppressed the activation of myosin light chain(MLC)phosphorylation.Conclusion:JHD improves intestinal barrier function and reduces gut leakiness in ALD rats.展开更多
BACKGROUND We previously showed,using the Traditional Chinese Medicine System Pharmacology Database,that Gegen Qinlian decoction(GQD)had a direct antitumor effect,and was combined with programmed cell death protein(PD...BACKGROUND We previously showed,using the Traditional Chinese Medicine System Pharmacology Database,that Gegen Qinlian decoction(GQD)had a direct antitumor effect,and was combined with programmed cell death protein(PD)-1 inhibitors to treat microsatellite stable(MSS)tumor-bearing mice.However,the effect of GQD on patients with colorectal cancer(CRC)is not clear.AIM To determine the therapeutic mechanism of GQD in improving immune function,reducing inflammation and protecting intestinal barrier function.METHODS Seventy patients with CRC were included in this study:37 in the control group and 33 in the treatment group.The proportions of CD4+T,CD8+T,natural killer(NK),NKT and T regulatory cells were measured by flow cytometry.Levels of the cytokines tumor necrosis factor(TNF)-α,interferon(IFN)-γ,interleukin(IL)-2,IL-6,IL-10 and serotonin(5-hydroxytryptamine;5-HT)in serum were assessed by enzyme-linked immunosorbent assay(ELISA).The expression of zonula occludens(ZO)-1,occludin,nuclear factor(NF)-κB and TNF-αin tumor and normal tissues was measured by immunohistochemistry.The composition of gut microbiota from patients in the treatment group was assessed using 16S rDNA analysis.RESULTS There were no adverse events in the treatment group.The proportion of CD4+T cells and NKT cells in the post-treatment group was significantly higher than that in the pre-treatment and control groups(P<0.05).The level of TNF-αin the posttreatment group was significantly lower than that in the pre-treatment and control groups(P<0.05).The concentration of 5-HT in the post-treatment group was significantly lower than that in the pre-treatment group(P<0.05).The expression of ZO-1 and occludin in tumor tissues in the treatment group was significantly higher than that in the control group(P<0.05).The expression of ZO-1 in normal tissues of the treatment group was significantly higher than that in the control group(P=0.010).Compared with the control group,expression of NF-κB and TNF-αin tumor tissues of the treatment group was significantly decreased(P<0.05).Compared with the pre-treatment group,GQD decreased the relative abundance of Megamonas and Veillonella.In addition,GQD increased the relative abundance of Bacteroides,Akkermansia and Prevotella.CONCLUSION GQD enhances immunity and protects intestinal barrier function in patients with CRC by regulating the composition of gut microbiota.展开更多
Objective: To evaluate the effect of early intrajejunalnutrition in attenuating bacterial and/or endotoxintranslocation and improving gut barrier function ofsevere acute pancreatitis (SAP) in dogs.Methods: 15 dogs wer...Objective: To evaluate the effect of early intrajejunalnutrition in attenuating bacterial and/or endotoxintranslocation and improving gut barrier function ofsevere acute pancreatitis (SAP) in dogs.Methods: 15 dogs were divided into parenteral nutrition(PN) group(7 dogs)and early intrajejunal nutrition(EIN) group(8). EIN was delivered nutrients via a nee-dle jejunostomy catheter feeding at 48h after operation.SAP model was induced by injecting 1 ml/kg of com-bined solution of 5% sodium taurocholate and 8000-10000 BAEE units trypsin/ml into the pancreas via thepancreatic duct. Systemic blood samples were ob-tained before and 1, 3, 5, 7 d following SAP, and culturedby aerobic as well as anaerobic bacterial growth. Systemicplasma and portal vein endotoxin levels were quantifiedby the chromogenic limulus amebocyte lysate (LAL)technique. Portal vein blood and specimens of tissuefrom the mesenteriolum and mesocolon lymph nodes,lung, pulmonary portal lymph nodes, pancreatitis tissueand periopancreas tissue were adopted before the experi-ment was finished. Aliquots of the homogenata were cul-tured as blood mentioned above to determine the magnitudeof the bacteria DNA, protein and the villi, the thickness ofmucosa, and the whole bowel wall of the ileum and trans-verse colon were measured.Results: The study showed that the levels of systemicplasma endotoxin and the magnitude of bacterialtranslocation to the portal and systemic blood and dis-tant organ were reduced significantly in the EINgroup as compared with the TPN group. The contentsof protein and DNA, the height of villi, the thicknessof mucosa and whole bowel wall of the ileum andtransverse colon in the EIN group were higher thanthose in the PN group.Conclusion: Our results suggested that EIN is safe andeffective to be adopted by intrajejunal delivery of nu-trients in SAP, decreases the occurrence of gut bacterialtranslocation, and improves the gut barrier function.展开更多
BACKGROUND: Most patients waiting for liver transplantation have end-stage liver diseases with malnutrition, which is prone to induce intestinal barrier dysfunction after liver transplantation. We aimed to study the e...BACKGROUND: Most patients waiting for liver transplantation have end-stage liver diseases with malnutrition, which is prone to induce intestinal barrier dysfunction after liver transplantation. We aimed to study the effect of probiotics on intestinal barrier function in malnourished rats following liver transplantation with long-term antibiotics. METHODS: Twelve Lewis rats were selected as donors. Twelve BN rats, which served as recipients, were subjected to malnutrition by semi-starvation for 4-5 weeks. They were randomly divided into two groups: a control group which received phosphate-buffered saline and a probiotics group which received Bifidobacterium and Lactobacillus. All recipients were injected with intramuscular imipenem and subcutaneous cyclosporine A. Furthermore, six normal BN rats without any drugs or operations served as a normal group. Eight days after operation, all rats were sacrificed for examination of the following parameters: serum levels of endotoxin and TNF-α, bacterial translocation, intestinal microflora, ileocecal sIgA, lymphocyte numbers, and phenotypes (CD4, CD8, αβTCR, γδTCR)ofPeyer’spatches. RESULTS: In recipients subjected to malnutrition, weight decreased by 20% and they survived until 8 days after operation. Compared with the normal group, all recipients on postoperative day 8 showed increased levels of serum endotoxin and TNF-α as well as increased counts oftranslocated bacteria. Meanwhile, there were decreases in counts of Bifidobacterium and Lactobacillus in the ileocecum, sIgA concentration, and lymphocytes of Peyer’s patches. Moreover, partial alteration in lymphocyte phenotypes was evidenced by elevated ratios of CD8 + and γδTCR + lymphocytes. In contrast, compared to the control group, supplementation with probiotics reduced the levels of serum endotoxin, TNF-α and bacterial translocation, increased the counts of Bifidobacterium and Lactobacillus, the concentration of sIgA and lymphocytes of Peyer’s patches, and also slightly restored the alteration of lymphocyte phenotypes. CONCLUSION: Supplementation with probiotics including Bifidobac-terium and Lactobacillus promoted partial restoration of intestinal microflora and improved intestinal barrier function in malnourished rats after liver transplantation with long-term use of antibiotics.展开更多
AIM： To investigate the influences of enteral, parenteral nutrition and probiotics delivered by gut on intestinal microecology, epithelial tight junctions, immune and barrier function of rats with abdominal infection...AIM： To investigate the influences of enteral, parenteral nutrition and probiotics delivered by gut on intestinal microecology, epithelial tight junctions, immune and barrier function of rats with abdominal infection. METHODS： Rat abdominal infection models established with cecal ligation and perforation method, were divided into three groups： parenteral nutrition （PN group, n = 7）, PN＋enteral nutrition （EN group, n = 7） and PN ＋ EN ＋ probiotics （probiotics group, n = 7） via the needle jejunostomy and neck vein for five days. The total nutritional supplement of the three groups was isonitrogenic and isocaloric. Probiotics was delivered by jejunostomy 10 mL/d （1 x 10^8 cfu/mL）. The rats were killed on the sixth day. The feces in the cecum were cultured for anaerobic bacterial growth and analyzed with bacterial group DNA fingerprint profile with random amplified polymorphic DNA. The transmembrane binding proteins （occludin） and IgA level in plasma cells of intestine epithelium in colon and terminal ileum were measured by an immunohistochemistry method. The ultrastructure of intestinal epithelial tight junctions in colon and small intestine was observed by electronmicroscopy. Vena cava blood and the homogenated tissue of liver, lung and mesenteric lymph nodes were cultured to determine the bacterial translocations, and endotoxin in the blood from portal vein was detected. RESULTS： （1） The amount of bacteria of gut species in EN group and probiotic group was higher than that in PN group. The DNA-proflles in EN group and probiotic group were similar to that of normal rats. The number of DNAprofiles in probiotics group was much more than that in PN group and EN group. Moreover, there were strange stripes in PN group. （2） The expression of occludin and IgA in the small and large intestine in EN group （2.309 ± 0.336, 15.440 ± 2.383） and probiotic group （2.938 ± 0.515, 16.230 ± 3.183） was improved as compared with PN group （1.207 ± 0.587, P 〈 0.05, 11.189 ± 2.108, P 〈 0.01）. The expression of occludin in probiotic group （intestine： 2.93 ± 0.515; cecum： 3.40 ± 0.617） was higher than that in EN group （intestine： 2.309 ± 0.336; cecum： 2.076 ± 0.670; P 〈 0.05）. The expression of IgA, especially in EN group （intestine： 15.440 ± 2.383） and probiotic EN group （large intestine： 12.516 ± 1.542） significantly increased as compared with PN group （intestine： 11.189 ± 2.108; cecum： 10.160 ± 1.643; P 〈 0.01）. The intestinal epithelial tight junctions and microvilli of the probiotic group were more intact than those in the PN group. （3） The bacterial translocations in blood, liver, lung and mesenteric lymph nodes, and the levels of endotoxin were significantly reduced in probiotic （0.082 ± 0.029） and EN （0.125 ± 0.040） groups as compared with PN group （0.403 ± 0.181, P 〈 0.05）. CONCLUSION： Application of EN combined with probiotics could improve the expression of transmembrane binding proteins （occludin） and IgA, correct the intestinal flora disturbance, maintain gut barrier functions and tight junctions, and reduce the occurrence of gut bacterial translocation.展开更多
文摘This paper introduces a novel chattering-free terminal sliding mode control(SMC)strategy to address chaotic behavior in permanent magnet synchronous generators(PMSG)for offshore wind turbine systems.By integrating an adaptive exponential reaching law with a continuous barrier function,the proposed approach eliminates chattering and ensures robust performance under model uncertainties.The methodology combines adaptive SMC with dynamic switching to estimate and compensates for unknown uncertainties,providing smooth and stable control.Finally,the performance and effectiveness of the proposed approach are compared with those of a previous study.
基金supported by grants from the National Key R&D Program(2023YFD1301303)National Natural Science Foundation of China(32472950,U21A20249)+1 种基金China Agriculture Research System of MOF and MARA(CARS-35)National Center of Technology Innovation for Pigs,Zhejiang Agricultural Talents,Taishan Industrial Leading Talents Project.
文摘Emerging evidence of the beneficial effects of defatted rice bran(DFRB)on gut health has advanced the development of fermented defatted rice bran as a potential functional food.However,less is known about its effects and underlying mechanisms on gut health.In this study,a mouse model together with fecal microbiota transplantation(FMT)was utilized to study the effects and mechanisms of fermented DFRB(FR)on gut barrier function.We found that FR improved the intestinal morphology,gut tight junction proteins,mucin,antimicrobial peptides,and interleukin 22(IL-22)and promoted the gut Clostridium butyricum and butyrate.Notably,correlation analysis indicated gut C.butyricum and butyrate were two FR-induced effectors that improved gut health.FMT results suggested that C.butyricum,butyrate,and fecal microbiota from the FR group all reduced prolyl hydroxylase 2(PHD2)expression by activating peroxisome proliferator-activated receptor gamma(PPARγ)in the mouse colon.This decrease in gut PHD2 subsequently upregulated the hypoxia-inducible factor-1 alpha(HIF-1α)expression,which in turn increased the expression of its targeted downstream tight junction proteins,mucin and antimicrobial peptides,and colonic IL-22 secretion.Overall,FR-derived C.butyricum and butyrate might improve gut barrier function through the HIF-1 signaling pathway,which provides a reference for the application of fermented DFRB as a potential functional food for improving of gut barrier function.
基金supported by the Fondo para el Primer Proyecto of the Comitépara el Desarrollo de la Investigación(CODI)at the Universidad de Antioquia(Grant Number PRV2024-78509)。
文摘The objective of this paper is to present a robust safety-critical control system based on the active disturbance rejection control approach, designed to guarantee safety even in the presence of model inaccuracies, unknown dynamics, and external disturbances. The proposed method combines control barrier functions and control Lyapunov functions with a nonlinear extended state observer to produce a robust and safe control strategy for dynamic systems subject to uncertainties and disturbances. This control strategy employs an optimization-based control, supported by the disturbance estimation from a nonlinear extended state observer. Using a quadratic programming algorithm, the controller computes an optimal, stable, and safe control action at each sampling instant. The effectiveness of the proposed approach is demonstrated through numerical simulations of a safety-critical interconnected adaptive cruise control system.
基金Supported by Major Project of Zhongshan Science and Technology Bureau(2021B3009).
文摘This study systematically reviews the pharmacological mechanisms of Huanglian Wendan Decoction in improving intestinal barrier function in ulcerative colitis(UC),including the regulation of intestinal chemical barrier,the regulation of intestinal immune barrier,and the improvement of intestinal biological barrier,in order to provide theoretical basis and new ideas for the clinical treatment of UC.
基金Key International Cooperation Program of the National Natural Science Foundation of China(32120103011)Jiangsu Shuang Chuang Tuan Dui program(JSSCTD202147)+1 种基金Jiangsu Shuang Chuang Ren Cai program(JSSCRC2021541)Initiation Funds of Yangzhou University for Distinguished Scientists.
文摘Background The aim of this study was to determine whether and how Zn proteinate with moderate chelation strength(Zn-Prot M)can alleviate heat stress(HS)-induced intestinal barrier function damage of broilers.A completely randomized design was used for comparatively testing the effects of Zn proteinate on HS and non-HS broilers.Under high temperature(HT),a 1(Control,HT-CON)+2(Zn source)×2(added Zn level)factorial arrangement of treatments was used.The 2 added Zn sources were Zn-Prot M and Zn sulfate(ZnS),and the 2 added Zn levels were 30 and 60 mg/kg.Under normal temperature(NT),a CON group(NT-CON)and pair-fed group(NT-PF)were included.Results The results showed that HS significantly reduced mRNA and protein expression levels of claudin-1,occludin,junctional adhesion molecule-A(JAMA),zonula occludens-1(ZO-1)and zinc finger protein A20(A20)in the jejunum,and HS also remarkably increased serum fluorescein isothiocyanate dextran(FITC-D),endotoxin and interleukin(IL)-1βcontents,serum diamine oxidase(DAO)and matrix metalloproteinase(MMP)-2 activities,nuclear factor kappa-B(NF-κB)p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum.However,dietary supplementation with Zn,especially organic Zn as Zn-Prot M at 60 mg/kg,significantly decreased serum FITC-D,endotoxin and IL-1βcontents,serum DAO and MMP-2 activities,NF-κB p65 mRNA expression level,and protein expression levels of NF-κB p65 and MMP-2 in the jejunum of HS broilers,and notably promoted mRNA and protein expression levels of claudin-1,ZO-1 and A20.Conclusions Our results suggest that dietary Zn,especially 60 mg Zn/kg as Zn-Prot M,can alleviate HS-induced intestinal barrier function damage by promoting the expression of TJ proteins possibly via induction of A20-mediated suppression of the NF-κB p65/MMP-2 pathway in the jejunum of HS broilers.
文摘BACKGROUND Alcohol-associated liver disease(ALD)is a leading cause of liver-related morbidity and mortality,but there are no therapeutic targets and modalities to prevent ALD-related liver fibrosis.Peroxisome proliferator activated receptor(PPAR)α and δ play a key role in lipid metabolism and intestinal barrier homeostasis,which are major contributors to the pathological progression of ALD.Meanwhile,elafibranor(EFN),which is a dual PPARαand PPARδagonist,has reached a phase III clinical trial for the treatment of metabolic dysfunctionassociated steatotic liver disease and primary biliary cholangitis.However,the benefits of EFN for ALD treatment is unknown.AIM To evaluate the inhibitory effects of EFN on liver fibrosis and gut-intestinal barrier dysfunction in an ALD mouse model.METHODS ALD-related liver fibrosis was induced in female C57BL/6J mice by feeding a 2.5% ethanol(EtOH)-containing Lieber-DeCarli liquid diet and intraperitoneally injecting carbon tetrachloride thrice weekly(1 mL/kg)for 8 weeks.EFN(3 and 10 mg/kg/day)was orally administered during the experimental period.Histological and molecular analyses were performed to assess the effect of EFN on steatohepatitis,fibrosis,and intestinal barrier integrity.The EFN effects on HepG2 lipotoxicity and Caco-2 barrier function were evaluated by cell-based assays.RESULTS The hepatic steatosis,apoptosis,and fibrosis in the ALD mice model were significantly attenuated by EFN treatment.EFN promoted lipolysis and β-oxidation and enhanced autophagic and antioxidant capacities in EtOH-stimulated HepG2 cells,primarily through PPARαactivation.Moreover,EFN inhibited the Kupffer cell-mediated inflammatory response,with blunted hepatic exposure to lipopolysaccharide(LPS)and toll like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)signaling.EFN improved intestinal hyperpermeability by restoring tight junction proteins and autophagy and by inhibiting apoptosis and proinflammatory responses.The protective effect on intestinal barrier function in the EtOH-stimulated Caco-2 cells was predominantly mediated by PPARδ activation.CONCLUSION EFN reduced ALD-related fibrosis by inhibiting lipid accumulation and apoptosis,enhancing hepatocyte autophagic and antioxidant capacities,and suppressing LPS/TLR4/NF-κB-mediated inflammatory responses by restoring intestinal barrier function.
基金funded by the National Natural Science Foundation of China(32273074,31972746,31872538 and 31772809)the Basic Scientific Research Project of Liaoning Provincial Department of Education,China(LJKZ0632)。
文摘Deoxynivalenol(DON)is a mycotoxin that is produced by various species of Fusarium and is ubiquitous in food and feed.At low concentrations,it can cause metabolic disorders in animals and humans and,at high concentrations,it can lead to pathological changes in the body.The impact of DON on human/animal health and animal productivity has thus attracted a great deal of attention around the world.DON causes severe damage to the intestine,including compromised intestinal barrier,mucosal damage,weakened immune function,and alterations in gut microbiota composition.These effects exacerbate intestinal infections and inflammation in livestock and poultry,posing adverse effects on overall health.Furthermore,research into biological methods for DON detoxification is a crucial avenue for future studies.This includes the utilization of adsorption,enzymatic degradation,and other biological approaches to mitigate DON's impact,offering new strategies for prevention and treatment of DON-induced diseases.Future research will focus on identifying highly efficient detoxifying microorganisms or enzymes to reduce DON levels in food and feed,thereby mitigating its risks to both animals and human health.
基金This research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(2022R1I1A3070740).
文摘Background Deoxynivalenol(DON)is a mycotoxin that has received recognition worldwide because of its ability to cause growth delay,nutrient malabsorption,weight loss,emesis,and a reduction of feed intake in livestock.Since DON-contaminated feedstuff is absorbed in the gastrointestinal tract,we used chicken organoids to assess the DON-induced dysfunction of the small intestine.Results We established a culture system using chicken organoids and characterized the organoids at passages 1 and 10.We confirmed the mRNA expression levels of various cell markers in the organoids,such as KI67,leucine-rich repeat containing G protein-coupled receptor 5(Lgr5),mucin 2(MUC2),chromogranin A(CHGA),cytokeratin 19(CK19),lysozyme(LYZ),and microtubule-associated doublecortin-like kinase 1(DCLK1),and compared the results to those of the small intestine.Our results showed that the organoids displayed functional similarities in permeability compared to the small intestine.DON damaged the tight junctions of the organoids,which resulted in increased permeability.Conclusions Our organoid culture displayed topological,genetic,and functional similarities with the small intes-tine cells.Based on these similarities,we confirmed that DON causes small intestine dysfunction.Chicken organoids offer a practical model for the research of harmful substances.
基金Supported by the National Natural Science Foundation of China,No.82474164,No.82305046,and No.82000572Natural Science Foundation of Jiangsu Province,No.BK20220467+1 种基金Major Project of the Natural Science Research of Jiangsu Higher Education Institutions,No.22KJB310013Science and Technology Project of Jiangsu Province,No.BK20200840.
文摘We discuss the article by Koizumi et al published in the World Journal of Gastroenterology.Our focus is on the therapeutic targets for fibrosis associated with alcohol-related liver disease(ALD)and the mechanism of action of elafibranor(EFN),a dual agonist of peroxisome proliferator-activated receptorα(PPARα)and peroxisome PPARδ(PPARδ).EFN is currently in phase III clinical trials for the treatment of metabolic dysfunction-associated fatty liver disease and primary biliary cholangitis.ALD progresses from alcoholic fatty liver to alcoholic steatohepatitis(ASH),with chronic ASH eventually leading to fibrosis,cirrhosis,and,in some cases,hepatocellular carcinoma.The pathogenesis of ALD is driven by hepatic steatosis,oxidative stress,and acetaldehyde toxicity.Alcohol consumption disrupts lipid metabolism by inactivating PPARα,exacerbating the progression of ALD.EFN primarily activates PPARα,promoting lipolysis andβ-oxidation in ethanol-stimulated HepG2 cells,which significantly reduces hepatic steatosis,apoptosis,and fibrosis in an ALD mouse model.Additionally,alcohol disrupts the gut-liver axis at several interconnected levels,contributing to a proinflammatory environment in the liver.EFN helps alleviate intestinal hyperpermeability by restoring tight junction protein expression and autophagy,inhibiting apoptosis and inflammatory responses,and enhancing intestinal barrier function through PPARδactivation.
基金the China Scholarship Council(202106690037)the Natural Science Foundation of Anhui Province(19080885QE194)。
文摘The trajectory tracking control performance of nonholonomic wheeled mobile robots(NWMRs)is subject to nonholonomic constraints,system uncertainties,and external disturbances.This paper proposes a barrier function-based adaptive sliding mode control(BFASMC)method to provide high-precision,fast-response performance and robustness for NWMRs.Compared with the conventional adaptive sliding mode control,the proposed control strategy can guarantee that the sliding mode variables converge to a predefined neighborhood of origin with a predefined reaching time independent of the prior knowledge of the uncertainties and disturbances bounds.Another advantage of the proposed algorithm is that the control gains can be adaptively adjusted to follow the disturbances amplitudes thanks to the barrier function.The benefit is that the overestimation of control gain can be eliminated,resulting in chattering reduction.Moreover,a modified barrier function-like control gain is employed to prevent the input saturation problem due to the physical limit of the actuator.The stability analysis and comparative experiments demonstrate that the proposed BFASMC can ensure the prespecified convergence performance of the NWMR system output variables and strong robustness against uncertainties/disturbances.
基金supported by the National Natural Science Foundation of China(32272916)National key Research&Development Program of China(2023YFD1301400)+1 种基金the Program for Shaanxi Science&Technology from Shaanxi Provincial Science and Technology Department(2022GDTSLD-46-0302,2023KXJ-243,2023GXJS-02-01,K3031223075,L2022-QCYZXNY-004,2021TD-30,019HBGC-16,2019ZDXM3-02)the Yongjiang Innovative Research Team。
文摘Background The intestinal barrier is the first line of defense against intestinal invasion by pathogens and foreign antigens and is closely associated with the gut microbiota.Astragalus polysaccharides(APS)have a long history of use in traditional Chinese medicine owing to its protective properties against intestinal barrier function.The mechanism of APS-induced gut microbiota enhancing intestinal barrier function is urgently needed.Results Dietary polysaccharide deprivation induced intestinal barrier dysfunction,decreased growth performance,altered microbial composition(Faecalibacterium,Dorea,and Coprobacillus),and reduced isobutyrate concentration.The results showed that APS fa cilitates intestinal barrier function in broiler chickens,including a thicker mucus layer,reduced crypt depth,and the growth of tight junction proteins.We studied the landscape of APS-induced gut microbiota and found that APS selectively promoted the growth of Parabacteroides,a commensal bacterium that plays a predominant role in enhancing intestinal barrier function.An in vitro g rowth assan further verified that APS selectively increased the abundance of Parabacteroides distasonis and Bacteroides uniformis.Dietary APS supplementation increased the concentrations of isobutyrate and bile acid(mainly chenodeoxycholic acid and deoxycholate acid)and activated signaling pathways related to intestinal barrier function(such as protein processing in the endoplasmic reticulum,tight junctions,and adherens junction signaling pathways).Conclusions APS intervention restored the dietary polysaccharide-induced dysfunction of the intestinal barrier by selectively promoting the abundance of Parabacteroides distasonis,and increasing the concentrations of isobutyrate and bile acids(mainly CDCA and DCA).These findings suggest that APS-induced gut microbiota and metabolic niches are promising strategies for enhancing intestinal barrier function.
基金funded by the National Nature Science Foundation of China(32002196)。
文摘Background Global warming leading to heat stress(HS)is becoming a major challenge for broiler production.This study aimed to explore the protective effects of seaweed(Enteromorpha prolifera)polysaccharides(EPS)on the intestinal barrier function,microbial ecology,and performance of broilers under HS.A total of 144 yellow-feathered broilers(male,56 days old)with 682.59±7.38 g were randomly assigned to 3 groups:1)TN(thermal neutral zone,23.6±1.8℃),2)HS(heat stress,33.2±1.5℃ for 10 h/d),and 3)HSE(HS+0.1%EPS).Each group contained 6 replicates with 8 broilers per replicate.The study was conducted for 4 weeks;feed intake and body weights were measured at the end of weeks 2 and 4.At the end of the feeding trial,small intestine samples were collected for histomorphology,antioxidant,secretory immunoglobulin A(s Ig A)content,apoptosis,gene and protein expression analysis;cecal contents were also collected for microbiota analysis based on 16S r DNA sequencing.Results Dietary EPS promoted the average daily gain(ADG)of broilers during 3–4 weeks of HS(P<0.05).At the end of HS on broilers,the activity of total superoxide dismutase(T-SOD),glutathione S-transferase(GST),and the content of s Ig A in jejunum were improved by EPS supplementation(P<0.05).Besides,dietary EPS reduced the epithelial cell apoptosis of jejunum and ileum in heat-stressed broilers(P<0.05).Addition of EPS in HS group broilers'diet upregulated the relative m RNA expression of Occludin,ZO-1,γ-GCLc and IL-10 of the jejunum(P<0.05),whereas downregulated the relative m RNA expression of NF-κB p65,TNF-αand IL-1βof the jejunum(P<0.05).Dietary EPS increased the protein expression of Occludin and ZO-1,whereas it reduced the protein expression of NF-κB p65 and MLCK(P<0.01)and tended to decrease the protein expression of TNF-α(P=0.094)in heat-stressed broilers.Furthermore,the proportions of Bacteroides and Oscillospira among the three groups were positively associated with jejunal apoptosis and pro-inflammatory cytokine expression(P<0.05)and negatively correlated with jejunal Occludin level(P<0.05).However,the proportions of Lactobacillus,Barnesiella,Subdoligranulum,Megasphaera,Collinsella,and Blautia among the three groups were positively related to ADG(P<0.05).Conclusions EPS can be used as a feed additive in yellow-feathered broilers.It effectively improves growth performance and alleviates HS-induced intestinal injury by relieving inflammatory damage and improving the tight junction proteins expression.These beneficial effects may be related to inhibiting NF-κB/MLCK signaling pathway activation and regulation of cecal microbiota.
基金supported by grants from the National Research Foundation of Korea funded by the Korean government(No.2020R1A4A1018598,NRF-2021R1A2C2006818,2022M3A9B6017813 and NRF-2023R1A2C1006836).
文摘Objective Atopic dermatitis(AD)is a chronic inflammatory skin disease that may be linked to changes in the gut microbiome.Acupuncture has been proven to be effective in reducing AD symptoms without serious adverse events,but its underlying mechanism is not completely understood.The purpose of this study was to investigate whether the potential effect of acupuncture on AD is gut microbiota-dependent.Methods AD-like skin lesions were induced by applying MC903 topically to the cheek of the mouse.Acupuncture was done at the Gok-Ji(LI11)acupoints.AD-like symptoms were assessed by lesion scores,scratching behavior,and histopathological changes;intestinal barrier function was measured by fecal output,serum lipopolysaccharide levels,histopathological changes,and mRNA expression of markers involved in intestinal permeability and inflammation.Gut microbiota was profiled using 16S rRNA gene sequencing from fecal samples.Results Acupuncture effectively improved chronic itch as well as the AD-like skin lesions with epidermal thickening,and also significantly altered gut microbiota structure as revealed byβ-diversity indices and analysis of similarities.These beneficial effects were eliminated by antibiotic depletion of gut microbiota,but were reproduced in gut microbiota-depleted mice that received a fecal microbiota transplant from acupuncture-treated mice.Interestingly,AD mice had intestinal barrier dysfunction as indicated by increased intestinal permeability,atrophy of the mucosal structure(reduced villus height and crypt depth),decreased expression of tight junctions and mucus synthesis genes,and increased expression of inflammatory mediators in the ileum.Acupuncture attenuated these abnormalities,which was gut microbiota-dependent.Conclusion Acupuncture ameliorates AD-like phenotypes in a gut microbiota-dependent manner and some of these positive benefits are explained by modulation of the intestinal barrier,providing new perspective for non-pharmacological strategies for modulating gut microbiota to prevent and treat AD.
基金Supported by the National Natural Science Foundation of China(No.81770889)Zhuhai Science and Technology Program(No.ZH22036201210134PWC).
文摘●AIM:To evaluate the role of semaphorin 7A(Sema7A)and its associated regulatory mechanisms in modulating the barrier function of cultured human corneal epithelial cells(HCEs).●METHODS:Barrier models of HCEs were treated with recombinant human Sema7A at concentrations of 0,125,250,or 500 ng/mL for 24,48,or 72h in vitro.Transepithelial electrical resistance(TEER)as well as Dextran-fluorescein isothiocyanate(FITC)permeability assays were conducted to assess barrier function.To quantify tight junctions(TJs)such as occludin and zonula occludens-1(ZO-1)at the mRNA level,reverse transcriptionpolymerase chain reaction(RT-PCR)analysis was performed.Immunoblotting was used to examine the activity of the nuclear factor-kappa B(NF-κB)signaling pathway and the production of TJs proteins.Immunofluorescence analyses were employed to localize the TJs.Enzyme-linked immunosorbent assay(ELISA)and RT-PCR were utilized to observe changes in interleukin(IL)-1βlevels.To investigate the role of NF-κB signaling activation and IL^(-1)βin Sema7A’s anti-barrier mechanism,we employed 0.1μmol/L IκB kinase 2(IKK2)inhibitor IV or 500 ng/mL IL^(-1)receptor(IL-1R)antagonist.●RESULTS:Treatment with Sema7A resulted in decreased TEER and increased permeability of Dextran-FITC in HCEs through down-regulating mRNA and protein levels of TJs in a time-and dose-dependent manner,as well as altering the localization of TJs.Furthermore,Sema7A stimulated the activation of inhibitor of kappa B alpha(IκBα)and expression of IL-1β.The anti-barrier function of Sema7A was significantly suppressed by treatment with IKK2 inhibitor IV or IL-1R antagonists.●CONCLUSION:Sema7A disrupts barrier function through its influence on NF-κB-mediated expression of TJ proteins,as well as the expression of IL-1β.These findings suggest that Sema7A could be a potential therapeutic target for the diseases in corneal epithelium.
基金supported in part by the National Natural Science Foundation of China(62273311,61773351)Henan Provincial Science Foundation for Distinguished Young Scholars(242300421051)。
文摘Although constraint satisfaction approaches have achieved fruitful results,system states may lose their smoothness and there may be undesired chattering of control inputs due to switching characteristics.Furthermore,it remains a challenge when there are additional constraints on control torques of robotic systems.In this article,we propose a novel high-order control barrier function(HoCBF)-based safety control method for robotic systems subject to input-output constraints,which can maintain the desired smoothness of system states and reduce undesired chattering vibration in the control torque.In our design,augmented dynamics are introduced into the HoCBF by constructing its output as the control input of the robotic system,so that the constraint satisfaction is facilitated by HoCBFs and the smoothness of system states is maintained by the augmented dynamics.This proposed scheme leads to the quadratic program(QP),which is more user-friendly in implementation since the constraint satisfaction control design is implemented as an add-on to an existing tracking control law.The proposed closed-loop control system not only achieves the requirements of real-time capability,stability,safety and compliance,but also reduces undesired chattering of control inputs.Finally,the effectiveness of the proposed control scheme is verified by simulations and experiments on robotic manipulators.
基金supported by the National Natural Science Foundation of China(No.30801536).
文摘Objective:Jianpi huoxue decoction(JHD),a Chinese herbal formula,is commonly used for treating alcohol-associated liver disease(ALD).This study aimed to investigate the mechanism by which JHD affects intestinal barrier function in ALD rats.Methods:The Sprague-Dawley rats were randomly divided into three groups:control group,model group and JHD group.They were pair-fed a modified Lieber-DeCarli liquid diet containing alcohol(model group,n=10;JHD group,n=10)or isocaloric maltose dextrin(control group,n=10)for 6 weeks.After 3 weeks of feeding,the mice in the JHD group were given JHD(10 mL/kg/day)by gavage for 3 weeks,and those in the control and model groups received equal amounts of double-distilled water for the same period of time.Afterwards,all the rats were given lipopolysaccharide(LPS)by gavage and sacrificed 3.5 h later.LPS levels were measured in the portal blood to evaluate gut leakage.Transmission electron microscopy(TEM)was used to observe ultrastructural changes in the intestinal tract.Adherens junction(AJ)and tight junction(TJ)proteins were detected by Western blotting,immunofluorescence or immunohistochemistry.Results:JHD ameliorated Lieber-DeCarli liquid diet-induced hepatic steatosis,inflammation and LPS expression.It improved pathological changes in the liver and alleviated intestinal ultrastructure injury.Moreover,it significantly enhanced the integrity of tight junctions by increasing the expression of zonula occludens‐1(ZO-1)and occludin.It suppressed the activation of myosin light chain(MLC)phosphorylation.Conclusion:JHD improves intestinal barrier function and reduces gut leakiness in ALD rats.
基金The study was reviewed and approved by the Fourth Hospital of Hebei Medical University Institutional Review Board(Approval No.2019082).
文摘BACKGROUND We previously showed,using the Traditional Chinese Medicine System Pharmacology Database,that Gegen Qinlian decoction(GQD)had a direct antitumor effect,and was combined with programmed cell death protein(PD)-1 inhibitors to treat microsatellite stable(MSS)tumor-bearing mice.However,the effect of GQD on patients with colorectal cancer(CRC)is not clear.AIM To determine the therapeutic mechanism of GQD in improving immune function,reducing inflammation and protecting intestinal barrier function.METHODS Seventy patients with CRC were included in this study:37 in the control group and 33 in the treatment group.The proportions of CD4+T,CD8+T,natural killer(NK),NKT and T regulatory cells were measured by flow cytometry.Levels of the cytokines tumor necrosis factor(TNF)-α,interferon(IFN)-γ,interleukin(IL)-2,IL-6,IL-10 and serotonin(5-hydroxytryptamine;5-HT)in serum were assessed by enzyme-linked immunosorbent assay(ELISA).The expression of zonula occludens(ZO)-1,occludin,nuclear factor(NF)-κB and TNF-αin tumor and normal tissues was measured by immunohistochemistry.The composition of gut microbiota from patients in the treatment group was assessed using 16S rDNA analysis.RESULTS There were no adverse events in the treatment group.The proportion of CD4+T cells and NKT cells in the post-treatment group was significantly higher than that in the pre-treatment and control groups(P<0.05).The level of TNF-αin the posttreatment group was significantly lower than that in the pre-treatment and control groups(P<0.05).The concentration of 5-HT in the post-treatment group was significantly lower than that in the pre-treatment group(P<0.05).The expression of ZO-1 and occludin in tumor tissues in the treatment group was significantly higher than that in the control group(P<0.05).The expression of ZO-1 in normal tissues of the treatment group was significantly higher than that in the control group(P=0.010).Compared with the control group,expression of NF-κB and TNF-αin tumor tissues of the treatment group was significantly decreased(P<0.05).Compared with the pre-treatment group,GQD decreased the relative abundance of Megamonas and Veillonella.In addition,GQD increased the relative abundance of Bacteroides,Akkermansia and Prevotella.CONCLUSION GQD enhances immunity and protects intestinal barrier function in patients with CRC by regulating the composition of gut microbiota.
文摘Objective: To evaluate the effect of early intrajejunalnutrition in attenuating bacterial and/or endotoxintranslocation and improving gut barrier function ofsevere acute pancreatitis (SAP) in dogs.Methods: 15 dogs were divided into parenteral nutrition(PN) group(7 dogs)and early intrajejunal nutrition(EIN) group(8). EIN was delivered nutrients via a nee-dle jejunostomy catheter feeding at 48h after operation.SAP model was induced by injecting 1 ml/kg of com-bined solution of 5% sodium taurocholate and 8000-10000 BAEE units trypsin/ml into the pancreas via thepancreatic duct. Systemic blood samples were ob-tained before and 1, 3, 5, 7 d following SAP, and culturedby aerobic as well as anaerobic bacterial growth. Systemicplasma and portal vein endotoxin levels were quantifiedby the chromogenic limulus amebocyte lysate (LAL)technique. Portal vein blood and specimens of tissuefrom the mesenteriolum and mesocolon lymph nodes,lung, pulmonary portal lymph nodes, pancreatitis tissueand periopancreas tissue were adopted before the experi-ment was finished. Aliquots of the homogenata were cul-tured as blood mentioned above to determine the magnitudeof the bacteria DNA, protein and the villi, the thickness ofmucosa, and the whole bowel wall of the ileum and trans-verse colon were measured.Results: The study showed that the levels of systemicplasma endotoxin and the magnitude of bacterialtranslocation to the portal and systemic blood and dis-tant organ were reduced significantly in the EINgroup as compared with the TPN group. The contentsof protein and DNA, the height of villi, the thicknessof mucosa and whole bowel wall of the ileum andtransverse colon in the EIN group were higher thanthose in the PN group.Conclusion: Our results suggested that EIN is safe andeffective to be adopted by intrajejunal delivery of nu-trients in SAP, decreases the occurrence of gut bacterialtranslocation, and improves the gut barrier function.
基金supported by grants from the National Basic Research Program (973) of China (2007CB513005, 2009CB522406)a Research Grant awarded by the Health Bureau Fund ofZhejiang Province (2007QN006, 2008A050)
文摘BACKGROUND: Most patients waiting for liver transplantation have end-stage liver diseases with malnutrition, which is prone to induce intestinal barrier dysfunction after liver transplantation. We aimed to study the effect of probiotics on intestinal barrier function in malnourished rats following liver transplantation with long-term antibiotics. METHODS: Twelve Lewis rats were selected as donors. Twelve BN rats, which served as recipients, were subjected to malnutrition by semi-starvation for 4-5 weeks. They were randomly divided into two groups: a control group which received phosphate-buffered saline and a probiotics group which received Bifidobacterium and Lactobacillus. All recipients were injected with intramuscular imipenem and subcutaneous cyclosporine A. Furthermore, six normal BN rats without any drugs or operations served as a normal group. Eight days after operation, all rats were sacrificed for examination of the following parameters: serum levels of endotoxin and TNF-α, bacterial translocation, intestinal microflora, ileocecal sIgA, lymphocyte numbers, and phenotypes (CD4, CD8, αβTCR, γδTCR)ofPeyer’spatches. RESULTS: In recipients subjected to malnutrition, weight decreased by 20% and they survived until 8 days after operation. Compared with the normal group, all recipients on postoperative day 8 showed increased levels of serum endotoxin and TNF-α as well as increased counts oftranslocated bacteria. Meanwhile, there were decreases in counts of Bifidobacterium and Lactobacillus in the ileocecum, sIgA concentration, and lymphocytes of Peyer’s patches. Moreover, partial alteration in lymphocyte phenotypes was evidenced by elevated ratios of CD8 + and γδTCR + lymphocytes. In contrast, compared to the control group, supplementation with probiotics reduced the levels of serum endotoxin, TNF-α and bacterial translocation, increased the counts of Bifidobacterium and Lactobacillus, the concentration of sIgA and lymphocytes of Peyer’s patches, and also slightly restored the alteration of lymphocyte phenotypes. CONCLUSION: Supplementation with probiotics including Bifidobac-terium and Lactobacillus promoted partial restoration of intestinal microflora and improved intestinal barrier function in malnourished rats after liver transplantation with long-term use of antibiotics.
基金Supported by the National Natural Science Foundation of China, No.30471687
文摘AIM： To investigate the influences of enteral, parenteral nutrition and probiotics delivered by gut on intestinal microecology, epithelial tight junctions, immune and barrier function of rats with abdominal infection. METHODS： Rat abdominal infection models established with cecal ligation and perforation method, were divided into three groups： parenteral nutrition （PN group, n = 7）, PN＋enteral nutrition （EN group, n = 7） and PN ＋ EN ＋ probiotics （probiotics group, n = 7） via the needle jejunostomy and neck vein for five days. The total nutritional supplement of the three groups was isonitrogenic and isocaloric. Probiotics was delivered by jejunostomy 10 mL/d （1 x 10^8 cfu/mL）. The rats were killed on the sixth day. The feces in the cecum were cultured for anaerobic bacterial growth and analyzed with bacterial group DNA fingerprint profile with random amplified polymorphic DNA. The transmembrane binding proteins （occludin） and IgA level in plasma cells of intestine epithelium in colon and terminal ileum were measured by an immunohistochemistry method. The ultrastructure of intestinal epithelial tight junctions in colon and small intestine was observed by electronmicroscopy. Vena cava blood and the homogenated tissue of liver, lung and mesenteric lymph nodes were cultured to determine the bacterial translocations, and endotoxin in the blood from portal vein was detected. RESULTS： （1） The amount of bacteria of gut species in EN group and probiotic group was higher than that in PN group. The DNA-proflles in EN group and probiotic group were similar to that of normal rats. The number of DNAprofiles in probiotics group was much more than that in PN group and EN group. Moreover, there were strange stripes in PN group. （2） The expression of occludin and IgA in the small and large intestine in EN group （2.309 ± 0.336, 15.440 ± 2.383） and probiotic group （2.938 ± 0.515, 16.230 ± 3.183） was improved as compared with PN group （1.207 ± 0.587, P 〈 0.05, 11.189 ± 2.108, P 〈 0.01）. The expression of occludin in probiotic group （intestine： 2.93 ± 0.515; cecum： 3.40 ± 0.617） was higher than that in EN group （intestine： 2.309 ± 0.336; cecum： 2.076 ± 0.670; P 〈 0.05）. The expression of IgA, especially in EN group （intestine： 15.440 ± 2.383） and probiotic EN group （large intestine： 12.516 ± 1.542） significantly increased as compared with PN group （intestine： 11.189 ± 2.108; cecum： 10.160 ± 1.643; P 〈 0.01）. The intestinal epithelial tight junctions and microvilli of the probiotic group were more intact than those in the PN group. （3） The bacterial translocations in blood, liver, lung and mesenteric lymph nodes, and the levels of endotoxin were significantly reduced in probiotic （0.082 ± 0.029） and EN （0.125 ± 0.040） groups as compared with PN group （0.403 ± 0.181, P 〈 0.05）. CONCLUSION： Application of EN combined with probiotics could improve the expression of transmembrane binding proteins （occludin） and IgA, correct the intestinal flora disturbance, maintain gut barrier functions and tight junctions, and reduce the occurrence of gut bacterial translocation.
