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
●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
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 Rosemary extract(RE)has been reported to exert antioxidant property.However,the application of RE in late-phase laying hens on egg quality,intestinal barrier and microbiota,and oviductal function has not be...Background Rosemary extract(RE)has been reported to exert antioxidant property.However,the application of RE in late-phase laying hens on egg quality,intestinal barrier and microbiota,and oviductal function has not been systematically studied.This study was investigated to detect the potential effects of RE on performance,egg quality,serum parameters,intestinal heath,cecal microbiota and metabolism,and oviductal gene expressions in late-phase laying hens.A total of 21065-week-old“Jing Tint 6”laying hens were randomly allocated into five treatments with six replicates and seven birds per replicate and fed basal diet(CON)or basal diet supplemented with chlortetracycline at 50 mg/kg(CTC)or RE at 50 mg/kg(RE50),100 mg/kg(RE100),and 200 mg/kg(RE200).Results Our results showed that RE200 improved(P<0.05)Haugh unit and n-6/n-3 of egg yolk,serum superoxide dismutase(SOD)compared with CON.No significant differences were observed for Haugh unit and n-6/n-3 of egg yolk among CTC,RE50,RE100 and RE200 groups.Compared with CTC and RE50 groups,RE200 increased serum SOD activity on d 28 and 56.Compared with CON,RE supplementation decreased(P<0.05)total cholesterol(TC)level.CTC,RE100 and RE200 decreased(P<0.05)serum interleukin-6(IL-6)content compared with CON.CTC and RE200 increased jejunal m RNA expression of ZO-1 and Occludin compared with CON.The biomarkers of cecal microbiota and metabolite induced by RE 200,including Firmicutes,Eisenbergiella,Paraprevotella,Papillibacter,and butyrate,were closely associated with Haugh unit,n-6/n-3,SOD,IL-6,and TC.PICRUSt2 analysis indicated that RE altered carbohydrate and amino acid metabolism of cecal microbiota and increased butyrate synthesizing enzymes,including 3-oxoacid Co A-transferase and butyrate-acetoacetate Co A-transferase.Moreover,transcriptomic analysis revealed that RE200 improved gene expressions and functional pathways related to immunity and albumen formation in the oviductal magnum.Conclusions Dietary supplementation with 200 mg/kg RE could increase egg quality of late-phase laying hens via modulating intestinal barrier,cecal microbiota and metabolism,and oviductal function.Overall,RE could be used as a promising feed additive to improve egg quality of laying hens at late stage of production.展开更多
The skin’s primary function is to protect the body against a spectrum of environmental stressors, including mechanical insults, microorganisms, chemicals, and allergens. Located in the outermost layers, the primary s...The skin’s primary function is to protect the body against a spectrum of environmental stressors, including mechanical insults, microorganisms, chemicals, and allergens. Located in the outermost layers, the primary structures and components responsible for the skin’s barrier function are susceptible to environmental variables, dermatological conditions, and the aging process. The ensuing alterations to structure, composition, and organizational attributes of the epidermal barrier can impact its integrity and functionality. The aim of this study was to assess the effect of a novel complex composed of a ceramide, energizing peptide, and Camu Camu extract (SUPCERAT<sup>TM</sup> complex) on specific markers of epidermal barrier integrity, as well as epidermal and dermal function. All the experiments were conducted on fresh human abdominal skin explants. Intradermal production of hyaluronic acid, epidermal claudin-1, and ceramide synthase 3 expressions, as well as epidermal lipids content were assessed using specific fluorescent stainings on ex vivo skin after the application of the complex or placebo. Additionally, dermal elastase and collagenase activities were assessed using in tubo enzymatic assays. Lastly, the effect of a cosmetic cream containing SUPCERAT<sup>TM</sup> complex was assessed using subjective Global Aesthetic Improvement Scale (GAIS) in a small cohort of patients after 60 days of use. The application of the SUPCERAT<sup>TM</sup> complex on ex vivo skin led to significant increase in dermal hyaluronic acid content and epidermal activity of claudin-1, ceramide synthase 3 and epidermal ceramide content. Furthermore, in tubo enzymatic assays demonstrated inhibition of both dermal elastase and collagenase activities. In addition, the patient-reported results indicated significant improvements in skin quality and appearance. .展开更多
This paper presents an adaptive gain,finite-and fixedtime convergence super-twisting-like algorithm based on a revised barrier function,which is robust to perturbations with unknown bounds.It is shown that this algori...This paper presents an adaptive gain,finite-and fixedtime convergence super-twisting-like algorithm based on a revised barrier function,which is robust to perturbations with unknown bounds.It is shown that this algorithm can ensure a finite-and fixed-time convergence of the sliding variable to the equilibrium,no matter what the initial conditions of the system states are,and maintain it there in a predefined vicinity of the origin without violation.Also,the proposed method avoids the problem of overestimation of the control gain that exists in the current fixed-time adaptive control.Moreover,it shows that the revised barrier function can effectively reduce the computation load by obviating the need of increasing the magnitude of sampling step compared with the conventional barrier function.This feature will be beneficial when the algorithm is implemented in practice.After that,the estimation of the fixed convergence time of the proposed method is derived and the impractical requirement of the preceding fixed-time adaptive control that the adaptive gains must be large enough to engender the sliding mode at time t=0 is discarded.Finally,the outperformance of the proposed method over the existing counterpart method is demonstrated with a numerical simulation.展开更多
Emerging evidence shows that dietary oligosaccharides are important prebiotics that can improve intestinal flora,while dietary polyphenols can act directly on intestinal cells.However,information about their synergist...Emerging evidence shows that dietary oligosaccharides are important prebiotics that can improve intestinal flora,while dietary polyphenols can act directly on intestinal cells.However,information about their synergistic effects on gut health is still limited.In this study,alginate oligosaccharide(AOS)and cyanidin-3-O-glucoside(C3G)were selected as a common marine plant oligosaccharide and terrestrial plant polyphenol,respectively,to study their effects on intestinal health.The results show that,in comparison to their individual applications,the combination of AOS and C3G(mass ratio,3:1)displayed a stronger ability to up-regulate the expression of tight junction proteins,while enhanced intestinal epithelial barrier was also observed and levels of mucin-2 andβ-defensins were simultaneously increased in the intestinal mucus.Interestingly,the secretion of immunoglobulin A and immune-related cytokines were approximately doubled by the AOS+C3G mixture.In addition,the AOS+C3G mixture was found to be more conducive to the positive transformation of intestinal flora,which stimulated the growth of beneficial bacteria Akkermansia,Lachnospiraceae and Feacalibaculum while inhibiting the growth of harmful bacteria Helicobacter and Turicibacter.The data generated herein thus suggests that dietary oligosaccharides and dietary polyphenols may be more beneficial to intestinal health when applied in combination than their individual effects alone.展开更多
This paper studies the moving path following(MPF)problem for fixed-wing unmanned aerial vehicle(UAV)under output constraints and wind disturbances.The vehicle is required to converge to a reference path moving with re...This paper studies the moving path following(MPF)problem for fixed-wing unmanned aerial vehicle(UAV)under output constraints and wind disturbances.The vehicle is required to converge to a reference path moving with respect to the inertial frame,while the path following error is not expected to violate the predefined boundaries.Differently from existing moving path following guidance laws,the proposed method removes complex geometric transformation by formulating the moving path following problem into a second-order time-varying control problem.A nominal moving path following guidance law is designed with disturbances and their derivatives estimated by high-order disturbance observers.To guarantee that the path following error will not exceed the prescribed bounds,a robust control barrier function is developed and incorporated into controller design with quadratic program based framework.The proposed method does not require the initial position of the UAV to be within predefined boundaries.And the safety margin concept makes error-constraint be respected even if in a noisy environment.The proposed guidance law is validated through numerical simulations of shipboard landing and hardware-in-theloop(HIL)experiments.展开更多
This survey provides a brief overview on the control Lyapunov function(CLF)and control barrier function(CBF)for general nonlinear-affine control systems.The problem of control is formulated as an optimization problem ...This survey provides a brief overview on the control Lyapunov function(CLF)and control barrier function(CBF)for general nonlinear-affine control systems.The problem of control is formulated as an optimization problem where the optimal control policy is derived by solving a constrained quadratic programming(QP)problem.The CLF and CBF respectively characterize the stability objective and the safety objective for the nonlinear control systems.These objectives imply important properties including controllability,convergence,and robustness of control problems.Under this framework,optimal control corresponds to the minimal solution to a constrained QP problem.When uncertainties are explicitly considered,the setting of the CLF and CBF is proposed to study the input-to-state stability and input-to-state safety and to analyze the effect of disturbances.The recent theoretic progress and novel applications of CLF and CBF are systematically reviewed and discussed in this paper.Finally,we provide research directions that are significant for the advance of knowledge in this area.展开更多
For autonomous vehicles and driver assist systems,path planning and collision avoidance algorithms benefit from accurate predictions of future location of other vehicles and intent of their drivers.In the literature,t...For autonomous vehicles and driver assist systems,path planning and collision avoidance algorithms benefit from accurate predictions of future location of other vehicles and intent of their drivers.In the literature,the algorithms that provide driver intent belong to two categories:those that use physics based models with some type of filtering,and machine learning based approaches.In this paper we employ barrier functions(BF)to decide driver intent.BFs are typically used to prove safety by establishing forward invariance of an admissible set.Here,we decide if the“target”vehicle is violating one or more possibly fictitious(i.e.,non-physical)barrier constraints determined based on the context provided by the road geometry.The algorithm has a very small computational footprint and better false positive and negative rates than some of the alternatives.The predicted intent is then used by a control barrier function(CBF)based collision avoidance system to prevent unnecessary interventions,for either an autonomous or human-driven vehicle.展开更多
This paper is concerned with bipartite consensus tracking for multi-agent systems with unknown disturbances.A barrier function-based adaptive sliding-mode control(SMC)approach is proposed such that the bipartite stead...This paper is concerned with bipartite consensus tracking for multi-agent systems with unknown disturbances.A barrier function-based adaptive sliding-mode control(SMC)approach is proposed such that the bipartite steady-state error is converged to a predefined region of zero in finite time.Specifically,based on an error auxiliary taking neighboring antagonistic interactions into account,an SMC law is designed with an adaptive gain.The gain can switch to a positive semi-definite barrier function to ensure that the error auxiliary is constrained to a predefined neighborhood of zero,which in turn guarantees practical bipartite consensus tracking.A distinguished feature of the proposed controller is its independence on the bound of disturbances,while the input chattering phenomenon is alleviated.Finally,a numerical example is provided to verify the effectiveness of the proposed controller.展开更多
The skin is a formidable physical and biological barrier which communicates continuously with the outside of the body. And the stratum corneum, the outermost layer of human epidermis, plays a central role in the inter...The skin is a formidable physical and biological barrier which communicates continuously with the outside of the body. And the stratum corneum, the outermost layer of human epidermis, plays a central role in the interaction between the cutaneous tissue and the external environment. The horny layer, and more generally the whole skin layers, avoid the penetration of harmful exogenous agents, produce molecules named anti-microbial peptides which impact the composition of the cutaneous microbiota, regulate the internal corporal temperature, avoid the water loss from the inside of the body and constitute an incredible efficient anti-oxidant network. Nevertheless, nowadays, the skin is more and more solicited by the different elements of the cutaneous exposome, including atmospheric pollution and solar radiations, which can cause a dramatic acceleration of the skin ageing process. As a consequence, due to the multifunctional protective role of the skin, during the recent decade the cosmetic industry invested massively in the development of new raw materials and end-products (dermo-cosmetics) able to preserve an optimal state of the skin regarding the external environment. Based on their physical-chemical properties thermal spring waters, which are extremely rich in inorganics ions, are interesting and powerful candidates to be part, as integral component, of new efficient dermo-cosmetic formulations dedicated to protect the skin from the external stimuli. The aim of the present work was to investigate and characterize the activity of Jonzac thermal spring water on the skin. Using different models, we proved for the first time that Jonzac thermal spring water reinforces the barrier function of the skin by modulating the expression of key markers including filaggrin and human beta defensin 2 on ex vivo human skin. The ex vivo and in vivo hydration activity, by Raman spectroscopy and corneometry respectively, has been also demonstrated. We have also shown that Jonzac thermal spring water ameliorates significantly the cutaneous microrelief in vivo. To conclude, we characterize the soothing effect of Jonzac thermal spring water by the analysis of histamine release in Substance P treated skin explants and by measuring the redness of the skin following UV exposure of the skin in vivo. We observed that both parameters decreased following a preventive treatment of the skin with Jonzac thermal spring water. Taken together our results indicate that Jonzac thermal spring water is a promising and powerful dermo-cosmetic which can be used to preserve an optimal state of the cutaneous tissue.展开更多
The placenta plays an important role in nutrient transport to maintain the growth and development of the embryo.Gestational diabetes mellitus(GDM),the most common complication during pregnancy,highly affects placental...The placenta plays an important role in nutrient transport to maintain the growth and development of the embryo.Gestational diabetes mellitus(GDM),the most common complication during pregnancy,highly affects placental function in late gestation.Advanced glycation end-products(AGEs),a complex and heterogeneous group of compounds engaged by the receptor for AGEs(RAGE),are closely associated with diabetes-related complications.In this study,AGEs induced a decrease in the expression of tight junction(TJ)proteins in BeWo cells and increased the paracellular permeability of trophoblast cells by regulating RAGE/NF-κB.Sprague-Dawley(SD)rats injected with 100 mg/kg AGEs-rat serum albumin(RSA)via the tail vein from embryo day 2 were set as the placental barrier dysfunction model group(n=10).The effect of AGEs on placental permeability was determined using the Evans-Blue dye extravasation method.The ultrastructure of the placenta samples was observed by transmission electron microscopy.The effects of AGEs on the placenta were confirmed by treating rats with RAGE antagonist FPS-ZM1 and soluble forms of RAGE(sRAGE).AGEs treatment increased placental permeability and disrupted the tight junctions in pregnant rat placenta,but has no effect on blood glucose.The expression of TJ-related proteins,including ZO-1,Occludin,and Claudin 5,were downregulated after AGEs treatment.Further,AGEs treatment increased the expression of RAGE and nuclear factor-κB in the placenta of rats and upregulated the levels of vascular endothelial growth factor.The effects of AGEs on the placenta were blocked by RAGE antagonist FPS-ZM1 and sRAGE.This study demonstrates the mechanism underlying AGEs-induced disturbance in placental function in pregnant rats and highlights the potential of AGEs in the treatment of GDM.展开更多
Defects in the endothelial cell barrier accompany diverse malfunctions of the central nervous system such as neurodegenerative diseases,stroke,traumatic brain injury,and systemic diseases such as sepsis,viral and bact...Defects in the endothelial cell barrier accompany diverse malfunctions of the central nervous system such as neurodegenerative diseases,stroke,traumatic brain injury,and systemic diseases such as sepsis,viral and bacterial infections,and cancer.Compromised endothelial sealing leads to leaking blood vessels,followed by vasogenic edema.Brain edema as the most common complication caused by stroke and traumatic brain injury is the leading cause of death.Brain microvascular endothelial cells,together with astrocytes,pericytes,microglia,and neurons form a selective barrier,the so-called blood-brain barrier,which regulates the movement of molecules inside and outside of the brain.Mechanisms that regulate blood-brain barrier permeability in health and disease are complex and not fully understood.Several newly discovered molecules that are involved in the regulation of cellular processes in brain microvascular endothelial cells have been described in the literature in recent years.One of these molecules that are highly expressed in brain microvascular endothelial cells is protocadherin gamma C3.In this review,we discuss recent evidence that protocadherin gamma C3 is a newly identified key player involved in the regulation of vascular barrier function.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
Background:The effects of dietary garcinol on diarrhea and intestinal barrier function associated with its modulation of gut microbiota in weaned piglets were investigated.Method:One hundred forty four weaned piglets(...Background:The effects of dietary garcinol on diarrhea and intestinal barrier function associated with its modulation of gut microbiota in weaned piglets were investigated.Method:One hundred forty four weaned piglets(Duroc×Yorkshire×Landrace)from 16 pens(9 piglets per pen)were randomly divided into four treatment groups:controls(CON)or those supplemented with 200 mg/kg(LOW),400 mg/kg(MID),or 600 mg/kg(HIGH)diet garcinol.After 14-day trial,three piglets per pen were chosen to collect plasma,intestinal tissue and colonic digesta samples.Results:We demonstrated for the first time that garcinol promoted growth performance,as increased average daily feed intake(ADFI)and decreased feed/gain ratio(F/G);and reduced diarrhea incidence(P<0.05);and strengthened antioxidant capacity,as an increased antioxidative index(P<0.05).Additionally,garcinol ameliorated intestinal barrier dysfunction,as an increased villus height to crypt depth ratio,increased zonula occludens protein 1(ZO-1),occludin and claudin-1 expression in the jejunum and ileum(P<0.05),and decreased intestinal permeability(P<0.05);and reduced inflammation,as decreased cytokine interleukin(IL)-6,IL-10,IL-1βand tumor necrosis factor-α(TNF-α)levels in the mucosa of the jejunum and ileum,and NF-κB p65 translocation(P<0.05).Moreover,garcinol inhibited the growth of most harmful bacteria in the gut,especially Escherichia coli,and increased the growth of the beneficial bacteria Lactobacillus.Conclusion:This work provides a fundamental basis for the future development of garcinol-functional food use for improving diarrhea and intestinal barrier function in weaned piglets and for understanding the biological effects of garcinol and its potential as a functional feed additive.展开更多
AIM To investigate toll-like receptor 2(TLR2) and TLR4 expression, following bifidobacteria and low-dose EPEC endotoxin treatment, and intestinal barrier function in rat intestinal epithelial cell-18(IEC-18).METHODS S...AIM To investigate toll-like receptor 2(TLR2) and TLR4 expression, following bifidobacteria and low-dose EPEC endotoxin treatment, and intestinal barrier function in rat intestinal epithelial cell-18(IEC-18).METHODS Six experimental groups were established-normal control, EPEC, Bifidobacteria infantis(B. infantis), B. longum, B. bifidum, and B. youth groups. Optimal EPEC endotoxin concentration, bifidobacteria fold dilution, and treatment duration were determined. Quantitative real-time polymerase chain reaction and western blot, respectively, were conducted to detect TLR2 and TLR4 m RNA and protein expression in IEC-18 cells. Transepithelial electrical resistance(TEER) was measured by the EVOM chopstick voltohmmeter in each group. All experiments were conducted in triplicate and data were analyzed on SPSS 16.RESULTS TLR2 and TLR4 m RNA and protein expression in the EPEC group were significantly higher than in the control group(P < 0.05). TLR2 m RNA and protein expression in the B. infantis, B. longum and B. youth groups were significantly lower than in the normal control group(P < 0.05). TLR4 m RNA and protein expression in the B. bifidum and B. youth groups were significantly lower than in normal controls(P < 0.05). In addition, the TEER in B. infantis, B. longum, B. bifidum, and B. youth groups were decreased by 19%, 18%, 23% and 23%, respectively, after 120 min of intervention, as compared to the control group. However, the TEER in the EPEC group was significantly decreased by 67% in comparison to the normal control group(P < 0.05).CONCLUSION Bifidobacteria protect IEC-18 cells against injury by down-regulating TLR2 and TLR4 expression and enhance intestinal barrier function to protect the intestinal epithelial cells from pathogenic invasion.展开更多
Background:Enterotoxigenic Escherichia coli(ETEC)F4 commonly colonizes the small intestine and releases enterotoxins that impair the intestinal barrier function and trigger inflammatory responses.Although Bacillus lic...Background:Enterotoxigenic Escherichia coli(ETEC)F4 commonly colonizes the small intestine and releases enterotoxins that impair the intestinal barrier function and trigger inflammatory responses.Although Bacillus licheniformis(B.licheniformis)has been reported to enhance intestinal health,it remains to be seen whether there is a functional role of B.licheniformis in intestinal inflammatory response in intestinal porcine epithelial cell line(IPEC-J2)when stimulated with ETEC F4.Methods:In the present study,the effects of B.licheniformis PF9 on the release of pro-inflammation cytokines,cell integrity and nuclear factor-κB(NF-κB)activation were evaluated in ETEC F4-induced IPEC-J2 cells.Results:B.licheniformis PF9 treatment was capable of remarkably attenuating the expression levels of inflammation cytokines tumor necrosis factor-α(TNF-α),interleukin(IL)-8,and IL-6 during ETEC F4 infection.Furthermore,the gene expression of Toll-like receptor 4(TLR4)-mediated upstream related genes of NF-κB signaling pathway has been significantly inhibited.These changes were accompanied by significantly decreased phosphorylation of p65 NF-κB during ETEC F4 infection with B.licheniformis PF9 treatment.The immunofluorescence and western blotting analysis revealed that B.licheniformis PF9 increased the expression levels of zona occludens 1(ZO-1)and occludin(OCLN)in ETEC F4-infected IPEC-J2 cells.Meanwhile,the B.licheniformis PF9 could alleviate the injury of epithelial barrier function assessed by the trans-epithelial electrical resistance(TEER)and cell permeability assay.Interestingly,B.licheniformis PF9 protect IPEC-J2 cells against ETEC F4 infection by decreasing the gene expressions of virulence-related factors(including luxS,estA,estB,and elt)in ETEC F4.Conclusions:Collectively,our results suggest that B.licheniformis PF9 might reduce inflammation-related cytokines through blocking the NF-κB signaling pathways.Besides,B.licheniformis PF9 displayed a significant role in the enhancement of IPEC-J2 cell integrity.展开更多
Background:Galacto-oligosaccharides(GOS)have been shown to modulate the intestinal microbiota of suckling piglets to exert beneficial effects on intestinal function.However,the modulation of intestinal microbiota and ...Background:Galacto-oligosaccharides(GOS)have been shown to modulate the intestinal microbiota of suckling piglets to exert beneficial effects on intestinal function.However,the modulation of intestinal microbiota and intestinal function by GOS in intestinal inflammation injury models has rarely been reported.In this study,we investigated the effects of GOS on the colonic mucosal microbiota composition,barrier function and inflammatory response of lipopolysaccharides(LPS)-challenged suckling piglets.Methods:A total of 18 newborn suckling piglets were divided into three groups,the CON group,the LPS-CON group and the LPS-GOS group.Piglets in the LPS-GOS group were orally fed with 1 g/kg body weight of GOS solution every day.On the d 14,piglets in the LPS-CON and LPS-GOS group were challenged intraperitoneally with LPS solution.All piglets were slaughtered 2 h after intraperitoneal injection and sampled.Results:We found that the colonic mucosa of LPS-challenged piglets was significantly injured and shedding,while the colonic mucosa of the LPS-GOS group piglets maintained its structure.Moreover,GOS significantly reduced the concentration of malondialdehyde(MDA)and the activity of reactive oxygen species(ROS)in the LPS-challenged suckling piglets,and significantly increased the activity of total antioxidant capacity(T-AOC).GOS significantly increased the relative abundance of norank_f_Muribaculaceae and Romboutsia,and significantly decreased the relative abundance of Alloprevotella,Campylobacter and Helicobacter in the colonic mucosa of LPS-challenged suckling piglets.In addition,GOS increased the concentrations of acetate,butyrate and total short chain fatty acids(SCFAs)in the colonic digesta of LPS-challenged suckling piglets.GOS significantly reduced the concentrations of interleukin 1β(IL-1β),interleukin 6(IL-6),tumor necrosis factor-α(TNF-α)and cluster of differentiation 14(CD14),and the relative mRNA expression of Toll-like receptor 4(TLR4)and myeloid differentiation primary response 88(MyD88)in the LPS-challenged suckling piglets.In addition,GOS significantly reduced the relative mRNA expression of mucin2(MUC2),and significantly increased the protein expression of Claudin-1 and zonula occluden-1(ZO-1)in LPS-challenged suckling piglets.Conclusions:These results suggested that GOS can modulate the colonic mucosa-associated microbiota composition and improve the intestinal function of LPS-challenged suckling piglets.展开更多
Background:The independent and interactive effects of dietary fiber(DF)and threonine(Thr)were investigated in growing pigs challenged with either systemic E.coli lipopolysaccharide(LPS)or enteric Salmonella Typhimuriu...Background:The independent and interactive effects of dietary fiber(DF)and threonine(Thr)were investigated in growing pigs challenged with either systemic E.coli lipopolysaccharide(LPS)or enteric Salmonella Typhimurium(ST)to characterise their effect on intestinal barrier function.Results:In experiment 1,intestinal barrier function was assessed via oral lactulose and mannitol(L:M)gavage and fecal mucin analysis in pigs challenged with E.coli LPS and fed low fiber(LF)or high fiber(HF)diets with graded dietary Thr.Urinary lactulose recovery and L:M ratio increased(P<0.05)during the LPS inoculation period in LF fed pigs but not in HF fed pigs.Fecal mucin output was increased(P<0.05)in pigs fed HF compared to LF fed pigs.In experiment 2,RT-qPCR,ileal morphology,digesta volatile fatty acid(VFA)content,and fecal mucin output were measured in Salmonella Typhimurium challenged pigs,fed LF or HF diets with standard or supplemented dietary Thr.Salmonella inoculation increased(P<0.05)fecal mucin output compared to the unchallenged period.Supplemental Thr increased fecal mucin output in the HF-fed pigs(Fib×Thr;P<0.05).Feeding HF increased(P<0.05)VFA concentration in cecum and colon.No effect of either Thr or fiber on expression of gene markers was observed except a tendency(P=0.06)for increased MUC2 expression with the HF diet.Feeding HF increased goblet cell numbers(P<0.05).Conclusion:Dietary fiber appears to improve barrier function through increased mucin production capacity(i.e.,goblet cell numbers,MUC2 gene expression)and secretion(i.e.,fecal mucin output).The lack of effect of dietary Thr in Salmonella-challenged pigs provides further evidence that mucin secretion in the gut is conserved and,therefore,Thr may be limiting for growth under conditions of increased mucin production.展开更多
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 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 China Postdoctoral Science Foundation(2022M723370)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA23080603)。
文摘Background Rosemary extract(RE)has been reported to exert antioxidant property.However,the application of RE in late-phase laying hens on egg quality,intestinal barrier and microbiota,and oviductal function has not been systematically studied.This study was investigated to detect the potential effects of RE on performance,egg quality,serum parameters,intestinal heath,cecal microbiota and metabolism,and oviductal gene expressions in late-phase laying hens.A total of 21065-week-old“Jing Tint 6”laying hens were randomly allocated into five treatments with six replicates and seven birds per replicate and fed basal diet(CON)or basal diet supplemented with chlortetracycline at 50 mg/kg(CTC)or RE at 50 mg/kg(RE50),100 mg/kg(RE100),and 200 mg/kg(RE200).Results Our results showed that RE200 improved(P<0.05)Haugh unit and n-6/n-3 of egg yolk,serum superoxide dismutase(SOD)compared with CON.No significant differences were observed for Haugh unit and n-6/n-3 of egg yolk among CTC,RE50,RE100 and RE200 groups.Compared with CTC and RE50 groups,RE200 increased serum SOD activity on d 28 and 56.Compared with CON,RE supplementation decreased(P<0.05)total cholesterol(TC)level.CTC,RE100 and RE200 decreased(P<0.05)serum interleukin-6(IL-6)content compared with CON.CTC and RE200 increased jejunal m RNA expression of ZO-1 and Occludin compared with CON.The biomarkers of cecal microbiota and metabolite induced by RE 200,including Firmicutes,Eisenbergiella,Paraprevotella,Papillibacter,and butyrate,were closely associated with Haugh unit,n-6/n-3,SOD,IL-6,and TC.PICRUSt2 analysis indicated that RE altered carbohydrate and amino acid metabolism of cecal microbiota and increased butyrate synthesizing enzymes,including 3-oxoacid Co A-transferase and butyrate-acetoacetate Co A-transferase.Moreover,transcriptomic analysis revealed that RE200 improved gene expressions and functional pathways related to immunity and albumen formation in the oviductal magnum.Conclusions Dietary supplementation with 200 mg/kg RE could increase egg quality of late-phase laying hens via modulating intestinal barrier,cecal microbiota and metabolism,and oviductal function.Overall,RE could be used as a promising feed additive to improve egg quality of laying hens at late stage of production.
文摘The skin’s primary function is to protect the body against a spectrum of environmental stressors, including mechanical insults, microorganisms, chemicals, and allergens. Located in the outermost layers, the primary structures and components responsible for the skin’s barrier function are susceptible to environmental variables, dermatological conditions, and the aging process. The ensuing alterations to structure, composition, and organizational attributes of the epidermal barrier can impact its integrity and functionality. The aim of this study was to assess the effect of a novel complex composed of a ceramide, energizing peptide, and Camu Camu extract (SUPCERAT<sup>TM</sup> complex) on specific markers of epidermal barrier integrity, as well as epidermal and dermal function. All the experiments were conducted on fresh human abdominal skin explants. Intradermal production of hyaluronic acid, epidermal claudin-1, and ceramide synthase 3 expressions, as well as epidermal lipids content were assessed using specific fluorescent stainings on ex vivo skin after the application of the complex or placebo. Additionally, dermal elastase and collagenase activities were assessed using in tubo enzymatic assays. Lastly, the effect of a cosmetic cream containing SUPCERAT<sup>TM</sup> complex was assessed using subjective Global Aesthetic Improvement Scale (GAIS) in a small cohort of patients after 60 days of use. The application of the SUPCERAT<sup>TM</sup> complex on ex vivo skin led to significant increase in dermal hyaluronic acid content and epidermal activity of claudin-1, ceramide synthase 3 and epidermal ceramide content. Furthermore, in tubo enzymatic assays demonstrated inhibition of both dermal elastase and collagenase activities. In addition, the patient-reported results indicated significant improvements in skin quality and appearance. .
文摘This paper presents an adaptive gain,finite-and fixedtime convergence super-twisting-like algorithm based on a revised barrier function,which is robust to perturbations with unknown bounds.It is shown that this algorithm can ensure a finite-and fixed-time convergence of the sliding variable to the equilibrium,no matter what the initial conditions of the system states are,and maintain it there in a predefined vicinity of the origin without violation.Also,the proposed method avoids the problem of overestimation of the control gain that exists in the current fixed-time adaptive control.Moreover,it shows that the revised barrier function can effectively reduce the computation load by obviating the need of increasing the magnitude of sampling step compared with the conventional barrier function.This feature will be beneficial when the algorithm is implemented in practice.After that,the estimation of the fixed convergence time of the proposed method is derived and the impractical requirement of the preceding fixed-time adaptive control that the adaptive gains must be large enough to engender the sliding mode at time t=0 is discarded.Finally,the outperformance of the proposed method over the existing counterpart method is demonstrated with a numerical simulation.
基金supported by National Key Research and Development Program of China(2019YFC1605003-3)Fujian Science Foundation for Distinguished Young Scholars(2020J06024).
文摘Emerging evidence shows that dietary oligosaccharides are important prebiotics that can improve intestinal flora,while dietary polyphenols can act directly on intestinal cells.However,information about their synergistic effects on gut health is still limited.In this study,alginate oligosaccharide(AOS)and cyanidin-3-O-glucoside(C3G)were selected as a common marine plant oligosaccharide and terrestrial plant polyphenol,respectively,to study their effects on intestinal health.The results show that,in comparison to their individual applications,the combination of AOS and C3G(mass ratio,3:1)displayed a stronger ability to up-regulate the expression of tight junction proteins,while enhanced intestinal epithelial barrier was also observed and levels of mucin-2 andβ-defensins were simultaneously increased in the intestinal mucus.Interestingly,the secretion of immunoglobulin A and immune-related cytokines were approximately doubled by the AOS+C3G mixture.In addition,the AOS+C3G mixture was found to be more conducive to the positive transformation of intestinal flora,which stimulated the growth of beneficial bacteria Akkermansia,Lachnospiraceae and Feacalibaculum while inhibiting the growth of harmful bacteria Helicobacter and Turicibacter.The data generated herein thus suggests that dietary oligosaccharides and dietary polyphenols may be more beneficial to intestinal health when applied in combination than their individual effects alone.
基金supported in part by the National Natural Science Foundations of China(62173016,62073019)the Fundamental Research Funds for the Central Universities(YWF-23-JC-04,YWF-23-JC-02)。
文摘This paper studies the moving path following(MPF)problem for fixed-wing unmanned aerial vehicle(UAV)under output constraints and wind disturbances.The vehicle is required to converge to a reference path moving with respect to the inertial frame,while the path following error is not expected to violate the predefined boundaries.Differently from existing moving path following guidance laws,the proposed method removes complex geometric transformation by formulating the moving path following problem into a second-order time-varying control problem.A nominal moving path following guidance law is designed with disturbances and their derivatives estimated by high-order disturbance observers.To guarantee that the path following error will not exceed the prescribed bounds,a robust control barrier function is developed and incorporated into controller design with quadratic program based framework.The proposed method does not require the initial position of the UAV to be within predefined boundaries.And the safety margin concept makes error-constraint be respected even if in a noisy environment.The proposed guidance law is validated through numerical simulations of shipboard landing and hardware-in-theloop(HIL)experiments.
基金supported in part by the National Natural Science Foundation of China(U22B2046,62073079,62088101)in part by the General Joint Fund of the Equipment Advance Research Program of Ministry of Education(8091B022114)in part by NPRP(NPRP 9-466-1-103)from Qatar National Research Fund。
文摘This survey provides a brief overview on the control Lyapunov function(CLF)and control barrier function(CBF)for general nonlinear-affine control systems.The problem of control is formulated as an optimization problem where the optimal control policy is derived by solving a constrained quadratic programming(QP)problem.The CLF and CBF respectively characterize the stability objective and the safety objective for the nonlinear control systems.These objectives imply important properties including controllability,convergence,and robustness of control problems.Under this framework,optimal control corresponds to the minimal solution to a constrained QP problem.When uncertainties are explicitly considered,the setting of the CLF and CBF is proposed to study the input-to-state stability and input-to-state safety and to analyze the effect of disturbances.The recent theoretic progress and novel applications of CLF and CBF are systematically reviewed and discussed in this paper.Finally,we provide research directions that are significant for the advance of knowledge in this area.
文摘For autonomous vehicles and driver assist systems,path planning and collision avoidance algorithms benefit from accurate predictions of future location of other vehicles and intent of their drivers.In the literature,the algorithms that provide driver intent belong to two categories:those that use physics based models with some type of filtering,and machine learning based approaches.In this paper we employ barrier functions(BF)to decide driver intent.BFs are typically used to prove safety by establishing forward invariance of an admissible set.Here,we decide if the“target”vehicle is violating one or more possibly fictitious(i.e.,non-physical)barrier constraints determined based on the context provided by the road geometry.The algorithm has a very small computational footprint and better false positive and negative rates than some of the alternatives.The predicted intent is then used by a control barrier function(CBF)based collision avoidance system to prevent unnecessary interventions,for either an autonomous or human-driven vehicle.
文摘This paper is concerned with bipartite consensus tracking for multi-agent systems with unknown disturbances.A barrier function-based adaptive sliding-mode control(SMC)approach is proposed such that the bipartite steady-state error is converged to a predefined region of zero in finite time.Specifically,based on an error auxiliary taking neighboring antagonistic interactions into account,an SMC law is designed with an adaptive gain.The gain can switch to a positive semi-definite barrier function to ensure that the error auxiliary is constrained to a predefined neighborhood of zero,which in turn guarantees practical bipartite consensus tracking.A distinguished feature of the proposed controller is its independence on the bound of disturbances,while the input chattering phenomenon is alleviated.Finally,a numerical example is provided to verify the effectiveness of the proposed controller.
文摘The skin is a formidable physical and biological barrier which communicates continuously with the outside of the body. And the stratum corneum, the outermost layer of human epidermis, plays a central role in the interaction between the cutaneous tissue and the external environment. The horny layer, and more generally the whole skin layers, avoid the penetration of harmful exogenous agents, produce molecules named anti-microbial peptides which impact the composition of the cutaneous microbiota, regulate the internal corporal temperature, avoid the water loss from the inside of the body and constitute an incredible efficient anti-oxidant network. Nevertheless, nowadays, the skin is more and more solicited by the different elements of the cutaneous exposome, including atmospheric pollution and solar radiations, which can cause a dramatic acceleration of the skin ageing process. As a consequence, due to the multifunctional protective role of the skin, during the recent decade the cosmetic industry invested massively in the development of new raw materials and end-products (dermo-cosmetics) able to preserve an optimal state of the skin regarding the external environment. Based on their physical-chemical properties thermal spring waters, which are extremely rich in inorganics ions, are interesting and powerful candidates to be part, as integral component, of new efficient dermo-cosmetic formulations dedicated to protect the skin from the external stimuli. The aim of the present work was to investigate and characterize the activity of Jonzac thermal spring water on the skin. Using different models, we proved for the first time that Jonzac thermal spring water reinforces the barrier function of the skin by modulating the expression of key markers including filaggrin and human beta defensin 2 on ex vivo human skin. The ex vivo and in vivo hydration activity, by Raman spectroscopy and corneometry respectively, has been also demonstrated. We have also shown that Jonzac thermal spring water ameliorates significantly the cutaneous microrelief in vivo. To conclude, we characterize the soothing effect of Jonzac thermal spring water by the analysis of histamine release in Substance P treated skin explants and by measuring the redness of the skin following UV exposure of the skin in vivo. We observed that both parameters decreased following a preventive treatment of the skin with Jonzac thermal spring water. Taken together our results indicate that Jonzac thermal spring water is a promising and powerful dermo-cosmetic which can be used to preserve an optimal state of the cutaneous tissue.
基金This work was financially supported by The Jiangsu Provincial Maternal and Child Health Key Talents Project(F202042).
文摘The placenta plays an important role in nutrient transport to maintain the growth and development of the embryo.Gestational diabetes mellitus(GDM),the most common complication during pregnancy,highly affects placental function in late gestation.Advanced glycation end-products(AGEs),a complex and heterogeneous group of compounds engaged by the receptor for AGEs(RAGE),are closely associated with diabetes-related complications.In this study,AGEs induced a decrease in the expression of tight junction(TJ)proteins in BeWo cells and increased the paracellular permeability of trophoblast cells by regulating RAGE/NF-κB.Sprague-Dawley(SD)rats injected with 100 mg/kg AGEs-rat serum albumin(RSA)via the tail vein from embryo day 2 were set as the placental barrier dysfunction model group(n=10).The effect of AGEs on placental permeability was determined using the Evans-Blue dye extravasation method.The ultrastructure of the placenta samples was observed by transmission electron microscopy.The effects of AGEs on the placenta were confirmed by treating rats with RAGE antagonist FPS-ZM1 and soluble forms of RAGE(sRAGE).AGEs treatment increased placental permeability and disrupted the tight junctions in pregnant rat placenta,but has no effect on blood glucose.The expression of TJ-related proteins,including ZO-1,Occludin,and Claudin 5,were downregulated after AGEs treatment.Further,AGEs treatment increased the expression of RAGE and nuclear factor-κB in the placenta of rats and upregulated the levels of vascular endothelial growth factor.The effects of AGEs on the placenta were blocked by RAGE antagonist FPS-ZM1 and sRAGE.This study demonstrates the mechanism underlying AGEs-induced disturbance in placental function in pregnant rats and highlights the potential of AGEs in the treatment of GDM.
文摘Defects in the endothelial cell barrier accompany diverse malfunctions of the central nervous system such as neurodegenerative diseases,stroke,traumatic brain injury,and systemic diseases such as sepsis,viral and bacterial infections,and cancer.Compromised endothelial sealing leads to leaking blood vessels,followed by vasogenic edema.Brain edema as the most common complication caused by stroke and traumatic brain injury is the leading cause of death.Brain microvascular endothelial cells,together with astrocytes,pericytes,microglia,and neurons form a selective barrier,the so-called blood-brain barrier,which regulates the movement of molecules inside and outside of the brain.Mechanisms that regulate blood-brain barrier permeability in health and disease are complex and not fully understood.Several newly discovered molecules that are involved in the regulation of cellular processes in brain microvascular endothelial cells have been described in the literature in recent years.One of these molecules that are highly expressed in brain microvascular endothelial cells is protocadherin gamma C3.In this review,we discuss recent evidence that protocadherin gamma C3 is a newly identified key player involved in the regulation of vascular barrier function.
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.
基金This study was partly supported by National Key Research and Development Program(grant no.2018YFD0500600)National Natural Science Foundation of China(grant no.31572409)Hubei Provincial Natural Science Foundation of China(grant no.2018CFA071).
文摘Background:The effects of dietary garcinol on diarrhea and intestinal barrier function associated with its modulation of gut microbiota in weaned piglets were investigated.Method:One hundred forty four weaned piglets(Duroc×Yorkshire×Landrace)from 16 pens(9 piglets per pen)were randomly divided into four treatment groups:controls(CON)or those supplemented with 200 mg/kg(LOW),400 mg/kg(MID),or 600 mg/kg(HIGH)diet garcinol.After 14-day trial,three piglets per pen were chosen to collect plasma,intestinal tissue and colonic digesta samples.Results:We demonstrated for the first time that garcinol promoted growth performance,as increased average daily feed intake(ADFI)and decreased feed/gain ratio(F/G);and reduced diarrhea incidence(P<0.05);and strengthened antioxidant capacity,as an increased antioxidative index(P<0.05).Additionally,garcinol ameliorated intestinal barrier dysfunction,as an increased villus height to crypt depth ratio,increased zonula occludens protein 1(ZO-1),occludin and claudin-1 expression in the jejunum and ileum(P<0.05),and decreased intestinal permeability(P<0.05);and reduced inflammation,as decreased cytokine interleukin(IL)-6,IL-10,IL-1βand tumor necrosis factor-α(TNF-α)levels in the mucosa of the jejunum and ileum,and NF-κB p65 translocation(P<0.05).Moreover,garcinol inhibited the growth of most harmful bacteria in the gut,especially Escherichia coli,and increased the growth of the beneficial bacteria Lactobacillus.Conclusion:This work provides a fundamental basis for the future development of garcinol-functional food use for improving diarrhea and intestinal barrier function in weaned piglets and for understanding the biological effects of garcinol and its potential as a functional feed additive.
基金Supported by Medjaden Academy and Research Foundation for Young Scientists,No.MJA20170410
文摘AIM To investigate toll-like receptor 2(TLR2) and TLR4 expression, following bifidobacteria and low-dose EPEC endotoxin treatment, and intestinal barrier function in rat intestinal epithelial cell-18(IEC-18).METHODS Six experimental groups were established-normal control, EPEC, Bifidobacteria infantis(B. infantis), B. longum, B. bifidum, and B. youth groups. Optimal EPEC endotoxin concentration, bifidobacteria fold dilution, and treatment duration were determined. Quantitative real-time polymerase chain reaction and western blot, respectively, were conducted to detect TLR2 and TLR4 m RNA and protein expression in IEC-18 cells. Transepithelial electrical resistance(TEER) was measured by the EVOM chopstick voltohmmeter in each group. All experiments were conducted in triplicate and data were analyzed on SPSS 16.RESULTS TLR2 and TLR4 m RNA and protein expression in the EPEC group were significantly higher than in the control group(P < 0.05). TLR2 m RNA and protein expression in the B. infantis, B. longum and B. youth groups were significantly lower than in the normal control group(P < 0.05). TLR4 m RNA and protein expression in the B. bifidum and B. youth groups were significantly lower than in normal controls(P < 0.05). In addition, the TEER in B. infantis, B. longum, B. bifidum, and B. youth groups were decreased by 19%, 18%, 23% and 23%, respectively, after 120 min of intervention, as compared to the control group. However, the TEER in the EPEC group was significantly decreased by 67% in comparison to the normal control group(P < 0.05).CONCLUSION Bifidobacteria protect IEC-18 cells against injury by down-regulating TLR2 and TLR4 expression and enhance intestinal barrier function to protect the intestinal epithelial cells from pathogenic invasion.
基金supported by the Agriculture and Agri-Food Canada,AAFC’s IOP project,Manitoba Pork and Swine Innovation PorcCanada Foundation for Innovation(CFI)supported by the Chinese Scholarship Council(CSC).
文摘Background:Enterotoxigenic Escherichia coli(ETEC)F4 commonly colonizes the small intestine and releases enterotoxins that impair the intestinal barrier function and trigger inflammatory responses.Although Bacillus licheniformis(B.licheniformis)has been reported to enhance intestinal health,it remains to be seen whether there is a functional role of B.licheniformis in intestinal inflammatory response in intestinal porcine epithelial cell line(IPEC-J2)when stimulated with ETEC F4.Methods:In the present study,the effects of B.licheniformis PF9 on the release of pro-inflammation cytokines,cell integrity and nuclear factor-κB(NF-κB)activation were evaluated in ETEC F4-induced IPEC-J2 cells.Results:B.licheniformis PF9 treatment was capable of remarkably attenuating the expression levels of inflammation cytokines tumor necrosis factor-α(TNF-α),interleukin(IL)-8,and IL-6 during ETEC F4 infection.Furthermore,the gene expression of Toll-like receptor 4(TLR4)-mediated upstream related genes of NF-κB signaling pathway has been significantly inhibited.These changes were accompanied by significantly decreased phosphorylation of p65 NF-κB during ETEC F4 infection with B.licheniformis PF9 treatment.The immunofluorescence and western blotting analysis revealed that B.licheniformis PF9 increased the expression levels of zona occludens 1(ZO-1)and occludin(OCLN)in ETEC F4-infected IPEC-J2 cells.Meanwhile,the B.licheniformis PF9 could alleviate the injury of epithelial barrier function assessed by the trans-epithelial electrical resistance(TEER)and cell permeability assay.Interestingly,B.licheniformis PF9 protect IPEC-J2 cells against ETEC F4 infection by decreasing the gene expressions of virulence-related factors(including luxS,estA,estB,and elt)in ETEC F4.Conclusions:Collectively,our results suggest that B.licheniformis PF9 might reduce inflammation-related cytokines through blocking the NF-κB signaling pathways.Besides,B.licheniformis PF9 displayed a significant role in the enhancement of IPEC-J2 cell integrity.
基金supported by the National Key R&D Program of China 2017YFD0500505.
文摘Background:Galacto-oligosaccharides(GOS)have been shown to modulate the intestinal microbiota of suckling piglets to exert beneficial effects on intestinal function.However,the modulation of intestinal microbiota and intestinal function by GOS in intestinal inflammation injury models has rarely been reported.In this study,we investigated the effects of GOS on the colonic mucosal microbiota composition,barrier function and inflammatory response of lipopolysaccharides(LPS)-challenged suckling piglets.Methods:A total of 18 newborn suckling piglets were divided into three groups,the CON group,the LPS-CON group and the LPS-GOS group.Piglets in the LPS-GOS group were orally fed with 1 g/kg body weight of GOS solution every day.On the d 14,piglets in the LPS-CON and LPS-GOS group were challenged intraperitoneally with LPS solution.All piglets were slaughtered 2 h after intraperitoneal injection and sampled.Results:We found that the colonic mucosa of LPS-challenged piglets was significantly injured and shedding,while the colonic mucosa of the LPS-GOS group piglets maintained its structure.Moreover,GOS significantly reduced the concentration of malondialdehyde(MDA)and the activity of reactive oxygen species(ROS)in the LPS-challenged suckling piglets,and significantly increased the activity of total antioxidant capacity(T-AOC).GOS significantly increased the relative abundance of norank_f_Muribaculaceae and Romboutsia,and significantly decreased the relative abundance of Alloprevotella,Campylobacter and Helicobacter in the colonic mucosa of LPS-challenged suckling piglets.In addition,GOS increased the concentrations of acetate,butyrate and total short chain fatty acids(SCFAs)in the colonic digesta of LPS-challenged suckling piglets.GOS significantly reduced the concentrations of interleukin 1β(IL-1β),interleukin 6(IL-6),tumor necrosis factor-α(TNF-α)and cluster of differentiation 14(CD14),and the relative mRNA expression of Toll-like receptor 4(TLR4)and myeloid differentiation primary response 88(MyD88)in the LPS-challenged suckling piglets.In addition,GOS significantly reduced the relative mRNA expression of mucin2(MUC2),and significantly increased the protein expression of Claudin-1 and zonula occluden-1(ZO-1)in LPS-challenged suckling piglets.Conclusions:These results suggested that GOS can modulate the colonic mucosa-associated microbiota composition and improve the intestinal function of LPS-challenged suckling piglets.
基金Funding for this project was provided by Alberta Agriculture and Forestry Strategic Research and Development Section,Evonik Nutrition&Care GmbH,and Mitacs Accelerate.
文摘Background:The independent and interactive effects of dietary fiber(DF)and threonine(Thr)were investigated in growing pigs challenged with either systemic E.coli lipopolysaccharide(LPS)or enteric Salmonella Typhimurium(ST)to characterise their effect on intestinal barrier function.Results:In experiment 1,intestinal barrier function was assessed via oral lactulose and mannitol(L:M)gavage and fecal mucin analysis in pigs challenged with E.coli LPS and fed low fiber(LF)or high fiber(HF)diets with graded dietary Thr.Urinary lactulose recovery and L:M ratio increased(P<0.05)during the LPS inoculation period in LF fed pigs but not in HF fed pigs.Fecal mucin output was increased(P<0.05)in pigs fed HF compared to LF fed pigs.In experiment 2,RT-qPCR,ileal morphology,digesta volatile fatty acid(VFA)content,and fecal mucin output were measured in Salmonella Typhimurium challenged pigs,fed LF or HF diets with standard or supplemented dietary Thr.Salmonella inoculation increased(P<0.05)fecal mucin output compared to the unchallenged period.Supplemental Thr increased fecal mucin output in the HF-fed pigs(Fib×Thr;P<0.05).Feeding HF increased(P<0.05)VFA concentration in cecum and colon.No effect of either Thr or fiber on expression of gene markers was observed except a tendency(P=0.06)for increased MUC2 expression with the HF diet.Feeding HF increased goblet cell numbers(P<0.05).Conclusion:Dietary fiber appears to improve barrier function through increased mucin production capacity(i.e.,goblet cell numbers,MUC2 gene expression)and secretion(i.e.,fecal mucin output).The lack of effect of dietary Thr in Salmonella-challenged pigs provides further evidence that mucin secretion in the gut is conserved and,therefore,Thr may be limiting for growth under conditions of increased mucin production.
