Effects of elafibranor on liver fibrosis and gut barrier function in a mouse model of alcohol-associated liver disease

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.

Astrocytes dynamically regulate the blood-brain barrier in the healthy brain

The blood-brain barrier(BBB)(discovered and defined by Max Lewandowsky and Lina Stern,and not,as it is universally,and yet erroneously believed,by Paul Ehrlich(Verkhratsky and Pivoriunas,2023))that separates the nervous system from the circulation is evolutionarily conserved from arthropods to man.The primeval BBB of the invertebrates and some early vertebrates was made solely by glial cells and secured(in invertebrates)by septate junctions.

Rebuilding insight into the pathophysiology of Alzheimer’s disease through new blood-brain barrier models

The blood-brain barrier is a unique function of the microvasculature in the brain parenchyma that maintains homeostasis in the central nervous system.Blood-brain barrier breakdown is a common pathology in various neurological diseases,such as Alzheimer’s disease,stroke,multiple sclerosis,and Parkinson’s disease.Traditionally,it has been considered a consequence of neuroinflammation or neurodegeneration,but recent advanced imaging techniques and detailed studies in animal models show that blood-brain barrier breakdown occurs early in the disease process and may precede neuronal loss.Thus,the blood-brain barrier is attractive as a potential therapeutic target for neurological diseases that lack effective therapeutics.To elucidate the molecular mechanism underlying blood-brain barrier breakdown and translate them into therapeutic strategies for neurological diseases,there is a growing demand for experimental models of human origin that allow for functional assessments.Recently,several human induced pluripotent stem cell-derived blood-brain barrier models have been established and various in vitro blood-brain barrier models using microdevices have been proposed.Especially in the Alzheimer’s disease field,the human evidence for blood-brain barrier dysfunction has been demonstrated and human induced pluripotent stem cell-derived blood-brain barrier models have suggested the putative molecular mechanisms of pathological blood-brain barrier.In this review,we summarize recent evidence of blood-brain barrier dysfunction in Alzheimer’s disease from pathological analyses,imaging studies,animal models,and stem cell sources.Additionally,we discuss the potential future directions for blood-brain barrier research.

Activation of the wnt/β-catenin/CYP1B1 pathway alleviates oxidative stress and protects the blood-brain barrier under cerebral ischemia/reperfusion conditions

Accumulating evidence suggests that oxidative stress and the Wnt/β-catenin pathway participate in stroke-induced disruption of the blood-brain barrier.However,the potential links between them following ischemic stroke remain largely unknown.The present study found that cerebral ischemia leads to oxidative stress and repression of the Wnt/β-catenin pathway.Meanwhile,Wnt/β-catenin pathway activation by the pharmacological inhibito r,TWS119,relieved oxidative stress,increased the levels of cytochrome P4501B1(CYP1B1)and tight junction-associated proteins(zonula occludens-1[ZO-1],occludin and claudin-5),as well as brain microvascular density in cerebral ischemia rats.Moreove r,rat brain microvascular endothelial cells that underwent oxygen glucose deprivation/reoxygenation displayed intense oxidative stress,suppression of the Wnt/β-catenin pathway,aggravated cell apoptosis,downregulated CYP1B1and tight junction protein levels,and inhibited cell prolife ration and migration.Overexpression ofβ-catenin or knockdown ofβ-catenin and CYP1B1 genes in rat brain mic rovascular endothelial cells at least partly ameliorated or exacerbated these effects,respectively.In addition,small interfering RNA-mediatedβ-catenin silencing decreased CYP1B1 expression,whereas CYP1B1 knoc kdown did not change the levels of glycogen synthase kinase 3β,Wnt-3a,andβ-catenin proteins in rat brain microvascular endothelial cells after oxygen glucose deprivatio n/reoxygenation.Thus,the data suggest that CYP1B1 can be regulated by Wnt/β-catenin signaling,and activation of the Wnt/β-catenin/CYP1B1 pathway contributes to alleviation of oxidative stress,increased tight junction levels,and protection of the blood-brain barrier against ischemia/hypoxia-induced injury.

Post-acute ischemic stroke hyperglycemia aggravates destruction of the blood-brain barrier

Post-acute ischemic stroke hyperglycemia increases the risk of hemorrhagic transformation,which is associated with blood-brain barrier disruption.Brain microvascular endothelial cells are a major component of the blood-brain barrier.Intercellular mitochondrial transfer has emerged as a novel paradigm for repairing cells with mitochondrial dysfunction.In this study,we first investigated whether mitochondrial transfer exists between brain microvascular endothelial cells,and then investigated the effects of post-acute ischemic stroke hyperglycemia on mitochondrial transfer between brain microvascular endothelial cells.We found that healthy brain microvascular endothelial cells can transfer intact mitochondria to oxygen glucose deprivation-injured brain microvascular endothelial cells.However,post-oxygen glucose deprivation hyperglycemia hindered mitochondrial transfer and exacerbated mitochondrial dysfunction.We established an in vitro brain microvascular endothelial cell model of the blood-brain barrier.We found that post-acute ischemic stroke hyperglycemia reduced the overall energy metabolism levels of brain microvascular endothelial cells and increased permeability of the blood-brain barrier.In a clinical study,we retrospectively analyzed the relationship between post-acute ischemic stroke hyperglycemia and the severity of hemorrhagic transformation.We found that post-acute ischemic stroke hyperglycemia serves as an independent predictor of severe hemorrhagic transformation.These findings suggest that post-acute ischemic stroke hyperglycemia can aggravate disruption of the blood-brain barrier by inhibiting mitochondrial transfer.

Blood-brain barrier pathology in cerebral small vessel disease

Cerebral small vessel disease is a neurological disease that affects the brain microvasculature and which is commonly observed among the elderly.Although at first it was considered innocuous,small vessel disease is nowadays regarded as one of the major vascular causes of dementia.Radiological signs of small vessel disease include small subcortical infarcts,white matter magnetic resonance imaging hyperintensities,lacunes,enlarged perivascular spaces,cerebral microbleeds,and brain atrophy;however,great heterogeneity in clinical symptoms is observed in small vessel disease patients.The pathophysiology of these lesions has been linked to multiple processes,such as hypoperfusion,defective cerebrovascular reactivity,and blood-brain barrier dysfunction.Notably,studies on small vessel disease suggest that blood-brain barrier dysfunction is among the earliest mechanisms in small vessel disease and might contribute to the development of the hallmarks of small vessel disease.Therefore,the purpose of this review is to provide a new foundation in the study of small vessel disease pathology.First,we discuss the main structural domains and functions of the blood-brain barrier.Secondly,we review the most recent evidence on blood-brain barrier dysfunction linked to small vessel disease.Finally,we conclude with a discussion on future perspectives and propose potential treatment targets and interventions.

Adaptive Trajectory Tracking Control for Nonholonomic Wheeled Mobile Robots:A Barrier Function Sliding Mode Approach

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.

Breaking the brain barrier:cell competition in neural development and disease

General information on cell competition:Social behaviors are the basis of biological life.Like species and populations,cell communities experience Darwinian ecological interactions,and in case space and nutrient availability are not uniform throughout the tissue,they begin to compete for ground occupancy.

Damage on intestinal barrier function and microbial detoxification of deoxynivalenol:A review

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.

Use of graphs to assess well safety in drilling projects and during operations by identification of available barrier elements and consolidation of barrier envelopes

Two independent barrier envelopes are the usual requirement used in most well operations to avoid catastrophic accidents.These are classified as primary-concerning preventing the occurrence of a kick,and secondary-concerning controlling the kick to avoid a blowout.Barrier envelopes consist of barrier elements,thus verifying the quality of these elements is fundamental.Barrier elements may be either redundant or mandatory,and these relationships are what constitute the barrier envelopes.In this work,we present a methodology to evaluate well safety by identifying existing barrier elements and barrier envelopes and mapping their relationships through the usage of graphs technique.This technique explicitly states the relationship between barriers and between them and envelopes.It enables a simpler visualization for well designers and allows the development of computer programs to control the safety and integrity of wells,both in the design phase and during drilling.12 graphs are provided for a 4-phase well(conductor,surface,production,and drill-in),considering both the primary and secondary enve-lopes.Reasoning for constructing each graph is thoroughly provided.If these graphs are used,reliability values can then be assigned to each barrier element,which results in the reliability of entire barrier envelopes.This can be further extended to analyze the safety of each operation by applying the system to operational sequences and even comparing well designs.

Psychosocial and Socioeconomic Barriers to Treatment Adherence in Pediatric Atopic Dermatitis

Research Background: Atopic dermatitis (AD) is a chronic inflammatory skin condition in children that significantly impacts physical health and quality of life. Adherence to treatment regimens is crucial for effective disease management but is often hindered by various psychosocial and socioeconomic barriers. Parental mental health issues, family dynamics, financial constraints, and limited access to specialized care contribute to inconsistent treatment adherence, exacerbating the condition. Purpose/Aim: The aim of this study is to explore the multifaceted barriers to treatment adherence in children with AD and evaluate the effectiveness of current interventions targeting these challenges. The study seeks to identify strategies that can improve adherence and health outcomes by addressing psychosocial and socioeconomic factors. Method: The method involves a comprehensive review of existing literature on the impact of psychosocial and socioeconomic factors on treatment adherence in children with AD. The study also examines various interventions designed to address these barriers, including community support programs, family-centered interventions, financial aid, integrated care models, and telehealth solutions. Results: Results indicate that psychosocial barriers, such as parental anxiety and depression, significantly hinder effective disease management. Family dynamics, including poor communication and single-parent households, complicate adherence efforts. Socioeconomic factors, such as financial constraints and limited healthcare access, further impede adherence. Interventions that address these barriers show promise in improving treatment adherence and health outcomes. Community support programs and family-centered interventions enhance parental mental health and family communication. Financial aid programs and integrated care models help mitigate economic and logistical challenges. Telehealth solutions improve access to specialized care, particularly in underserved areas. Conclusion: The study concludes that a holistic approach integrating medical treatment with psychosocial and socioeconomic support is essential for managing pediatric AD effectively. Policy recommendations include increased funding for community support programs, expanded telehealth services, and the integration of social services with medical care. Addressing these barriers comprehensively can enhance treatment adherence and improve the quality of life for children with AD. Further research should focus on long-term outcomes and diverse populations to refine these interventions and ensure they meet the needs of all affected children.

Establishment of a chicken intestinal organoid culture system to assess deoxynivalenol‑induced damage of the intestinal barrier function

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.

Dissolvable temporary barrier:a novel paradigm for flexible hydrogel patterning in organ-on-a-chip models

A combination of hydrogels and microfluidics allows the construction of biomimetic three-dimensional(3D)tissue models in vitro,which are also known as organ-on-a-chipmodels.The hydrogel patterningwith awell-controlled spatial distribution is typically achieved by embedding sophisticated microstructures to act as a boundary.However,these physical barriers inevitably expose cells/tissues to a less physiologically relevant microenvironment than in vivo conditions.Herein,we present a novel dissolvable temporary barrier(DTB)strategy that allows robust and flexible hydrogel patterning with great freedom of design and desirable flow stimuli for cellular hydrogels.The key aspect of this approach is the patterning of a water-soluble rigid barrier as a guiding path for the hydrogel using stencil printing technology,followed by a barrier-free medium perfusion after the dissolution of the DTB.Single and multiple tissue compartments with different geometries can be established using either straight or curved DTB structures.The effectiveness of this strategy is further validated by generating a 3D vascular network through vasculogenesis and angiogenesis using a vascularized microtumor model.As a new proof-of-concept in vasculature-on-a-chip,DTB enables seamless contact between the hydrogel and the culture medium in closed microdevices,which is an improved protocol for the fabrication ofmultiorgan chips.Therefore,we expect it to serve as a promising paradigm for organ-on-a-chip devices for the development of tumor vascularization and drug evaluation in the future preclinical studies.

High-temperature corrosion of sintered RE_(2)Si_(2)O_(7)(RE=Yb and Ho)environmental barrier coating materials by volcanic ash

Rare-earth silicates are promising environmental barrier coatings(EBCs)that can protect SiC_(f)/Si C_(m)substrates in next-genera tion gas turbine blades.Notably,RE_(2)Si_(2)O_(7)(RE=Yb and Ho)shows potential as an EBC due to its coefficient of thermal expansion(CTE)compatible with substrates and high resistance to water vapor corrosion.The target operating temperature for next-generation tur bine blades is 1400°C.Corrosion is inevitable during adhesion to molten volcanic ash,and thus,understanding the corrosion behavior o the material is crucial to its reliability.This study investigates the high-temperature corrosion behavior of sintered RE_(2)Si_(2)O_(7)(RE=Yb and Ho).Samples were prepared using a solid-state reaction and hot-press method.They were then exposed to volcanic ash at 1400°C for 224,and 48 h.After 48 h of exposure,volcanic ash did not react with Yb_(2)Si_(2)O_(7)but penetrated its interior,causing damage.Meanwhile Ho_(2)Si_(2)O_(7)was partially dissolved in the molten volcanic ash,forming a reaction zone that prevented volcanic ash melts from penetrating the interior.With increasing heat treatment time,the reaction zone expanded,and the thickness of the acicular apatite grains increased The Ca:Si ratios in the residual volcanic ash were mostly unchanged for Yb_(2)Si_(2)O_(7)but decreased considerably over time for Ho_(2)Si_(2)O_(7).Th Ca in volcanic ash was consumed and formed apatite,indicating that RE^(3+)ions with large ionic radii(Ho>Yb)easily precipitated apatit from the volcanic ash.

Assessment of public perspectives and barriers towards dengue preventive practices using the Health Belief Model in Puducherry,India:A cross-sectional study

Objective:To assess the perspectives and barriers towards dengue preventive practices among the residents of Puducherry,India.Methods:A cross-sectional survey was conducted in 300 households in Puducherry,using a population-proportionate(7:3)distribution from urban and rural areas by grid sampling.One adult interview per household was conducted and the participants were selected using a KISH grid.A semi-structured questionnaire based on the Health Belief Model(HBM)with additional questions on knowledge assessment was used.Knowledge was assessed based on the correctness of answers and the HBM scores were calculated on a 5-point Likert scale.Participants were categorized based on the median score under each domain.Logistic regression was used for adjusted analysis and models were built to predict the performances in each domain.Results:Four percent of the participants lacked basic knowledge regarding dengue transmission.While 208(69.3%)participants did not consider themselves at risk of contracting dengue within the next year,majority perceived dengue as a disease with low severity.Around 49.3%(148)were skeptical about the benefit of time and money spent on dengue prevention.Inadequate government efforts were stated as the major barrier(47.0%)and frequent reminders(142,47.3%)as the major cue to action.Age above 50 years(aOR 1.78,95%CI 1.04-3.06,P=0.037)and rural locality(aOR 2.68,95%CI 1.52-4.71,P=0.001)were found to be significantly associated with poor knowledge scores.Urban participants had a significantly higher chance to perceive low susceptibility as compared to the rural counterparts(aOR 1.74,95%CI 1.05-2.9,P=0.03).Participants with less than a high school education had low perceived benefits(aOR 2.46,95%CI 1.52-3.96,P<0.001)and low self-efficacy scores(aOR 2.66,95%CI 1.61-4.39,P<0.001).Conclusions:This study identifies key gaps in dengue prevention,including low perceived susceptibility,mild disease perception,limited knowledge of breeding sites,and overreliance on government efforts.Tailoring interventions to community needs,stratified to factors influencing the community perspectives can significantly improve dengue prevention efforts.

Limited Sea Surface Temperature Cooling Due to the Barrier Layer Promoting Super Typhoon Mangkhut(2018)

This study investigates the impact of the salinity barrier layer(BL)on the upper ocean response to Super Typhoon Mangkhut(2018)in the western North Pacific.After the passage of Mangkhut,a noticeable increase(~0.6 psu)in sea surface salinity and a weak decrease(<1℃)in sea surface temperature(SST)were observed on the right side of the typhoon track.Mangkhut-induced SST change can be divided into the three stages,corresponding to the variations in BL thickness and SST before,during,and after the passage of Mangkhut.During the pre-typhoon stage,SST slightly warmed due to the entrainment of BL warm water,which suppressed the cooling induced by surface heat fluxes and horizontal advection.During the forced stage,SST cooling was controlled by entrainment,and the preexisting BL reduced the total cooling by 0.89℃ d-1,thus significantly weakening the overall SST cooling induced by Mangkhut.During the relaxation stage,the SST cooling was primarily caused by the entrainment.Our results indicate that a preexisting BL can limit typhoon-induced SST cooling by suppressing the entrainment of cold thermocline water,which contributed to Mangkhut becoming the strongest typhoon in 2018.

Does the Hartman effect exist in triangular barriers

We study the phase,Larmor and dwell times of a particle scattered off triangular barriers(TBs).It is interesting that the dependences of dwell,reflective phase and Larmor times on the wave number,barrier width and height for a pair of mirror-symmetric(MS)exact triangular barriers(ETBs)are quite different,as the two ETBs have quite distinct scattering surfaces.In comparison,the dependence of the transmitted phase or Larmor times is exactly the same,since the transmitted amplitudes are the same for a pair of MS TBs.We further study the Hartman effect by defining the phase and Larmor velocities associated with the phase and Larmor times.We find no barrier width saturation effect for the transmitted and reflected times.This is indicated by the fact that all the velocities approach finite constants that are much smaller than the speed of light in vacuum for TBs with positive-slope impact faces.As for ETBs with vertical left edges,the naive velocities seem to also indicate the absence of the Hartman effect.These are quite distinct from rectangular barriers and may shed new light on the clarification of the tunneling time issues.

A Qualitative Look at Decreasing Barriers to Receiving Uninterrupted Care for People Living with HIV in Rural Southern Georgia

Early linkage to antiretroviral therapy (ART) after HIV diagnosis extends life. Low socioeconomic populations with HIV face regional concerns that inhibit early treatment. Barriers include religious-based stigma, lack of local treatment facilities, fear of discovery and purposeful secrecy fostering increased HIV transmission and decreased ART adherence. This ethnographic qualitative study employed semi-structured interviews with 10 health care providers (HCP) and 10 people living with HIV (PLWH) to discover methods to streamline care and increase medication adherence. Clients perceive enhanced care when they are active participants in treatment. HCPs reported positive health outcomes when there was active multidisciplinary communication. Obstacles included a lack of consistent medication assistance programs, homelessness, and limited access to specialized services. There is a need for further investigation on how to provide individualized, holistic treatment to a population of patients with extremely limited federal funding in a geographic region where religious stigma surrounding HIV is widespread.

Effect of annealing on the electrical performance of N-polarity GaN Schottky barrier diodes

A nitrogen-polarity(N-polarity)GaN-based high electron mobility transistor(HEMT)shows great potential for high-fre-quency solid-state power amplifier applications because its two-dimensional electron gas(2DEG)density and mobility are mini-mally affected by device scaling.However,the Schottky barrier height(SBH)of N-polarity GaN is low.This leads to a large gate leakage in N-polarity GaN-based HEMTs.In this work,we investigate the effect of annealing on the electrical characteristics of N-polarity GaN-based Schottky barrier diodes(SBDs)with Ni/Au electrodes.Our results show that the annealing time and tem-perature have a large influence on the electrical properties of N-polarity GaN SBDs.Compared to the N-polarity SBD without annealing,the SBH and rectification ratio at±5 V of the SBD are increased from 0.51 eV and 30 to 0.77 eV and 7700,respec-tively,and the ideal factor of the SBD is decreased from 1.66 to 1.54 after an optimized annealing process.Our analysis results suggest that the improvement of the electrical properties of SBDs after annealing is mainly due to the reduction of the inter-face state density between Schottky contact metals and N-polarity GaN and the increase of barrier height for the electron emis-sion from the trap state at low reverse bias.

Probiotic Pediococcus pentosaceus restored gossypol-induced intestinal barrier injury by increasing propionate content in Nile tilapia

Background Intestinal barrier is a dynamic interface between the body and the ingested food components, however, dietary components or xenobiotics could compromise intestinal integrity, causing health risks to the host. Gossypol, a toxic component in cottonseed meal(CSM), caused intestinal injury in fish or other monogastric animals. It has been demonstrated that probiotics administration benefits the intestinal barrier integrity, but the efficacy of probiotics in maintaining intestinal health when the host is exposed to gossypol remains unclear. Here, a strain(YC) affiliated to Pediococcus pentosaceus was isolated from the gut of Nile tilapia(Oreochromis niloticus) and its potential to repair gossypol-induced intestinal damage was evaluated.Results A total of 270 Nile tilapia(2.20 ± 0.02 g) were allotted in 3 groups with 3 tanks each and fed with 3 diets including CON(control diet), GOS(control diet containing 300 mg/kg gossypol) and GP(control diet containing 300 mg/kg gossypol and 10^(8) colony-forming unit(CFU)/g P. pentosaceus YC), respectively. After 10 weeks, addition of P. pentosaceus YC restored growth retardation and intestinal injury induced by gossypol in Nile tilapia. Transcriptome analysis and si RNA interference experiments demonstrated that NOD-like receptors(NLR) family caspase recruitment domain(CARD) domain containing 3(Nlrc3) inhibition might promote intestinal stem cell(ISC) proliferation, as well as maintaining gut barrier integrity. 16S r RNA sequencing and gas chromatography-mass spectrometry(GC-MS) revealed that addition of P. pentosaceus YC altered the composition of gut microbiota and increased the content of propionate in fish gut. In vitro studies on propionate's function demonstrated that it suppressed nlrc3 expression and promoted wound healing in Caco-2 cell model.Conclusions The present study reveals that P. pentosaceus YC has the capacity to ameliorate intestinal barrier injury by modulating gut microbiota composition and elevating propionate level. This finding offers a promising strategy for the feed industry to incorporate cottonseed meal into fish feed formulations.