Glial derived neurotrophic factor: a sufficient essential molecular regulator of mammalian blood-nerve barrier tight junction formation

Peripheral nerves coordinate signal transduction from the periphery to the central nervous system for processing and transmission back as required for normal mammalian function.Peripheral nerves and nerve roots are structurally divided into three compartments:the outermost epineurium,inner perineurium that surrounds nerve fascicles and the innermost endoneurium(Mizisin and Weerasuriya,2011).

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.

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.

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.

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.

Practice of Barrier Measures against COVID-19 Among Diabetic People Followed at Departmental University Hospital Center Ouémé-Plateau, Benin, in 2021

Introduction: COVID-19 is a pandemic disease caused by the coronavirus SARS-COV2 appeared in China in 2019. The aim of the study was to evaluate the practice of barrier measures against COVID-19 and to identify associated factors among diabetics followed at Departmental University Hospital Center Ouémé-Plateau, Benin, in 2021. Methods: This was a cross-sectional study conducted from June to August 2021, including diabetics aged 18 and over, hospitalized or received for medical visits in the department of medicine at the target hospital. Data were collected during an interview with each participant thanks to a questionnaire. “Good practice” was defined as regular practice of at least two of three barrier measures: hand washing, physical distancing and mask-wearing. Results: A total of 110 diabetics were included with a female predominance (55.5%) and a mean age of 57 ± 11.3 years. Among them, 89.1% washed their hands, 41.8% respected physical distancing and 12.7% wore a mask. The proportion of good practice was 47.3%. Only 5 practiced the three barrier measures. Only age group was associated with good practice. Conclusion: The study showed a low proportion of good practice of barrier measures against COVID-19 among diabetic people surveyed. It is important to continue the action for COVID-19 prevention among diabetic people in the targeted hospital and in other hospitals in Benin.

Effect of dielectric material on the uniformity of nanosecond pulsed dielectric barrier discharge

Dielectric barrier discharge(DBD)is considered as a promising technique to produce large volume uniform plasma at atmospheric pressure,and the dielectric barrier layer between the electrodes plays a key role in the DBD processes and enhancing discharge uniformity.In this work,the uniformity and discharge characteristics of the nanosecond(ns)pulsed DBD with dielectric barrier layers made of alumina,quartz glass,polycarbonate(PC),and polypropylene(PP)are investigated via discharge image observation,voltage-current waveform measurement and optical emission spectral diagnosis.Through analyzing discharge image by gray value standard deviation method,the discharge uniformity is quantitatively calculated.The effects of the space electric field intensity,the electron density(Ne),and the space reactive species on the uniformity are studied with quantifying the gap voltage Ug and the discharge current Ig,analyzing the recorded optical emission spectra,and simulating the temporal distribution of Ne with a one-dimensional fluid model.It is found that as the relative permittivity of the dielectric materials increases,the space electric field intensity is enhanced,which results in a higher Ne and electron temperature(Te).Therefore,an appropriate value of space electric field intensity can promote electron avalanches,resulting in uniform and stable plasma by the merging of electron avalanches.However,an excessive value of space electric field intensity leads to the aggregation of space charges and the distortion of the space electric field,which reduce the discharge uniformity.The surface roughness and the surface charge decay are measured to explain the influences of the surface properties and the second electron emission on the discharge uniformity.The results in this work give a comprehensive understanding of the effect of the dielectric materials on the DBD uniformity,and contribute to the selection of dielectric materials for DBD reactor and the realization of atmospheric pressure uniform,stable,and reactive plasma sources.

Barriers and Motivators of Young Dutch Elite Athletes for Optimizing Their Nutritional Intake

Many young elite athletes do not meet their daily energy and nutrient requirements. However, little research has been done on why these athletes do not meet their daily needs. The aim was to research the barriers and motivators of young Dutch elite athletes to optimize their nutritional intake. Quantitative and qualitative research was conducted among 8 handball and 4 volleyball players at the Dutch National Sports Center (17.2 ± 0.8 years). First, the nutritional intake was tracked through food diaries and analyzed in Nutritics. Thereupon, five semi-structured interviews based on the COM-B model were carried out. The interviews were transcribed and coded. The athletes had a reduced intake of energy, carbohydrates, vitamins A, C, E, D, calcium, potassium, zinc, and iron compared to their requirements. Seven themes for optimizing their nutritional intake emerged in the interviews: needs assessment, practical translation, portion size, lack of time, involvement, individuality, and food distribution. Barriers that the athletes experienced were that they did not know what their total daily nutritional needs were and how this translates into practice. In addition, the portion size at dinner was too small. They also had little time to eat a full meal due to time pressure from training and school. On the other hand, motivators were receiving meal options to translate their needs into practice with a distribution of moments when they need to eat. Covering these topics in nutritional workshops where athletes actively participate with more individual focus, could contribute to the optimization of their nutritional intake.

Effects of Enteromorpha prolifera polysaccharides on growth performance,intestinal barrier function and cecal microbiota in yellow-feathered broilers under heat stress

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.

Targeting brain tumors with innovative nanocarriers:bridging the gap through the blood-brain barrier

Background:Glioblastoma multiforme(GBM)is recognized as the most lethal and most highly invasive tumor.The high likelihood of treatment failure arises fromthe presence of the blood-brain barrier(BBB)and stemcells around GBM,which avert the entry of chemotherapeutic drugs into the tumormass.Objective:Recently,several researchers have designed novel nanocarrier systems like liposomes,dendrimers,metallic nanoparticles,nanodiamonds,and nanorobot approaches,allowing drugs to infiltrate the BBB more efficiently,opening up innovative avenues to prevail over therapy problems and radiation therapy.Methods:Relevant literature for this manuscript has been collected from a comprehensive and systematic search of databases,for example,PubMed,Science Direct,Google Scholar,and others,using specific keyword combinations,including“glioblastoma,”“brain tumor,”“nanocarriers,”and several others.Conclusion:This review also provides deep insights into recent advancements in nanocarrier-based formulations and technologies for GBM management.Elucidation of various scientific advances in conjunction with encouraging findings concerning the future perspectives and challenges of nanocarriers for effective brain tumor management has also been discussed.

Assessing Barriers to Mental Healthcare Interventions for Deaf People in Ghana

While mental health issues are increasingly gaining attention in Ghana, little is known about the situation among deaf people. This study assessed the mental health care needs of deaf people in Ghana. A descriptive design, consisting of interviews and focus group discussions, was used to collect data from 97 participants. Findings indicated that participants had limited knowledge on mental health issues. Mental health stigma, inaccessible mental health information and exclusion from mental health programmes were the major barriers hindering access to mental health care services. This study bridges the knowledge gap and provides evidence for the implementation of deaf-friendly services.