A facilitative transport system exists on the blood brain barrier (BBB) that has been tacitly assumed to be a path for glutamate entry to brain. But glutamate is a non-essential amino acid whose brain content is much greater than plasma, and studies in vivo show that glutamate does not enter brain in material quantities except in those small regions with fenestrated capillaries (circumventricular organs). The situation became understandable when luminal (blood facing) and abluminal (brain facing) membranes were isolated and studied separately. Facilitative transport of glutamate and glutamine exist only on the luminal membranes whereas Na+-dependent transport systems for glutamate, glutamine and some other amino acids are present only on the abluminal membrane. The Na+-dependent cotransporters of the abluminal membrane are in a position to actively transport amino acids from the extracellular fluid (ECF) into the endothelial cells of the BBB. These powerful secondary active transporters couple the energy of the Na+-gradient to move glutamate and glutamine into the ECF whereupon glutamate can exit to blood on the luminal facilitative glutamate transporter. Glutamine may also exit brain on a separate facilitative transport system that exists on the luminal membranes or glutamine can be hydrolyzed to glutamate within the BBB thereby releasing ammonia that is freely diffusible. The γ-glutamyl participate cycle participates indirectly by producing oxoproline (pyroglutamate) that stimulates almost all secondary active transporters yet discovered in the abluminal membranes of the BBB.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

In this study, we evaluated the antibacterial effect against Staphylococcus aureus and Salmonella Typhimurium in fried fish paste using floating electrode-dielectric barrier discharge (FE-DBD) plasma (1.1 kV, 43 kHz, N2 1.5 m/s, 1-60 min). In addition, quality evaluation (pH, VBN) of fried fish paste was conducted after FE-DBD plasma treatment. When FE-DBD plasma was treated for 1, 5, 10, 20, 30 and 60 min, S. aureus decreased by 0.16-1.13 log10 CFU/g, and S. Typhimurium decreased 0.25-1.13 log10 CFU/g. Both decreased > log10 CFU/g at 60 min. The D-value was 58.92 and R2 was 0.97 for S. aureus using first-order kinetics, and the D-value was 43.60 and R2 was 0.97 for S. Typhimurium using the Weibull model. There was no significant difference in pH after FE-DBD plasma treatment (p > 0.05). However, volatile basic nitrogen (VBN) significantly decreased as the treatment time increased (p < 0.05), and it was the lowest at 60 min to 3.46. Therefore, FE-DBD plasma treatment could be considered as a technology for preserving the quality of processed foods.

In this study, a commercial sodium butyrate protected by a new buffer salt solution (NSB) was tested to determine whether it can be used as an antibiotic alternative in broiler production. 192 1-day-old broilers were randomly allocated to three dietary treatments: soybean meal diet (CON), antibiotic diet (ANT, basal diet + 100 mg/kg aureomycin), and NSB (basal diet + 800 mg/kg NSB). The growth performance, serum anti-inflammatory cytokines, intestinal morphology, gut barrier function, antioxidative parameters, SCFAs content, and cecal microbiota were analyzed. The result showed that NSB significantly improved ADFI, ADG (p < 0.01), and decreased FCR (p < 0.01). Serum anti-inflammatory cytokine IL-10 was up-regulated (p < 0.01), and pro-inflammatory TNF-α was down-regulated (p < 0.05) by NSB supplementation. H&E results showed that VH and VH: CD ratio significantly increased (p < 0.05) in the jejunum and ileum in the NSB group. Furthermore, ZO-1 (p < 0.01), claudin-1 (p < 0.01), and occludin (p < 0.05) in the jejunum and claudin-1 (p < 0.01) and mucin-2 (p < 0.05) in the ileum significantly up-regulated in the NSB group, respectively. Additionally, SOD (p < 0.05) and T-AOC/MDA ratio (p < 0.01) in the jejunum and SOD in the ileum were significantly increased (p < 0.05) in the NSB group. The MDA level also significantly increased (p < 0.01) in the ANT group in the jejunum. Propionic acid (p < 0.05) and butyric acid (p < 0.01) content significantly increased in the NSB group in the jejunum and ileum segments. The 16S rRNA sequencing results showed no significant difference (p > 0.05) in alpha and beta diversity among the groups. LEFSe analysis also indicated that Peptostreptococcaceae, Colidextribacter, Firmicutes, Oscillospira, and Erysipelatoclostridiaceae, which promote SCFA production (p < 0.05), were identified as dominant taxon-enriched bacterial genera in the NSB group. The Spearman correlation analysis revealed that Colidextribacter with ADFI, ADG, VH, claudin-1 (p < 0.05), and unclassified_f__Peptostreptococcaceae with ADFI, IL-10, and ZO-1 were positively correlated (p < 0.05). Furthermore, ADFI and ADG with IL-10, claudin-1, SOD, T-AOC, and butyric acid (p < 0.05), and similarly, ADG with VH (p < 0.05) showed a positive correlation. In conclusion, NSB enhanced the growth performance by improving jejunum and ileum morphology, serum anti-inflammatory cytokines, regulating intestinal barrier function and antioxidant capacity, SCFAs content, and cecum microbiota, showing its potential use as an alternative to antibiotics in poultry nutrition.

In this study, the problem of overcoming the infinite energy barrier separating the bradyonic and tachyonic realms is investigated. Making use of the Majorana equation for particles with arbitrary spin and the Heisenberg uncertainty principle, it is proved that, under certain conditions of spatial confinement, quantum fluctuations allow particles with very small mass and velocity close to the speed of light to pass in the tachyonic realm, avoiding the problem of the infinite barrier (bradyon–tachyon tunnelling). This theoretical approach allows an avoidance of the difficulties encountered in quantum field theory when it is extended to particles with imaginary rest mass.

Aneuploidy describes the gain or loss of entire chromosomes or chromosome arms. Already more than 100 years ago, aneuploidy was described to be featured in cancer and it is known today to be present in 68-90 % of cancers, depending on tumour entity. Aneuploidy is implicated to affect cancer growth, therapy response and frequently affects prognosis. Chromosomal instability (CIN) is recognized as the main cause of aneuploidy and is characterised as the fluent process of gaining or losing chromosomes. Chromosomally instable cells need to be kept in check, or cleared, to prohibit the sampling of aneuploid karyotypes able to drive tumorigenesis. Of note, even aneuploid cancer cells often show CIN, a feature that promotes therapy related drug-resistance. Here, we review how CIN can be prevented or limited to spread by the induction of cell death and the relevance of different p53 responses triggered in response to mitotic perturbations to prohibit the formation of cancer driving aneuploidies.

In the power plant industry, the turbine inlet temperature (TIT) plays a key role in the efficiency of the gas turbine and, therefore, the overall—in most cases combined—thermal power cycle efficiency. Gas turbine efficiency increases by increasing TIT. However, an increase of TIT would increase the turbine component temperature which can be critical (e.g., hot gas attack). Thermal barrier coatings (TBCs)—porous media coatings—can avoid this case and protect the surface of the turbine blade. This combination of TBC and film cooling produces a better cooling performance than conventional cooling processes. The effective thermal conductivity of this composite is highly important in design and other thermal/structural assessments. In this article, the effective thermal conductivity of a simplified model of TBC is evaluated. This work details a numerical study on the steady-state thermal response of two-phase porous media in two dimensions using personal finite element analysis (FEA) code. Specifically, the system response quantity (SRQ) under investigation is the dimensionless effective thermal conductivity of the domain. A thermally conductive matrix domain is modeled with a thermally conductive circular pore arranged in a uniform packing configuration. Both the pore size and the pore thermal conductivity are varied over a range of values to investigate the relative effects on the SRQ. In this investigation, an emphasis is placed on using code and solution verification techniques to evaluate the obtained results. The method of manufactured solutions (MMS) was used to perform code verification for the study, showing the FEA code to be second-order accurate. Solution verification was performed using the grid convergence index (GCI) approach with the global deviation uncertainty estimator on a series of five systematically refined meshes for each porosity and thermal conductivity model configuration. A comparison of the SRQs across all domain configurations is made, including uncertainty derived through the GCI analysis.

Deficit schizophrenia is characterized by leaky tight and adherens junctions and bacterial translocation. Here we examine whether (deficit) schizophrenia is accompanied by leaky paracellular, transcellular and vascular barriers in the gut and blood brain barriers. We measured IgA responses to occludin, claudin-5, E-cadherin and β-catenin (paracellular pathway, PARA), talin, actin, vinculin and epithelial intermediate filament (transcellular pathway, TRANS) and plasmalemma vesicle-associated protein (PLVAP, vascular pathway) in 78 schizophrenia patients and 40 controls. IgA responses to claudin-5, E-cadherin and β-catenin, the sum of the four PARA proteins and the ratio PARA/TRANS were significantly higher in deficit schizophrenia than in non-deficit schizophrenia and controls. A large part of the variance in PHEMN (psychosis, hostility, excitation, mannerism and negative) symptoms, psychomotor retardation, formal thought disorders, verbal fluency, word list memory, word list recall and executive functions was explained by the PARA/TRANS ratio coupled with plasma IgA responses to Gram-negative bacteria, IgM to malondialdehyde, CCL-11 (eotaxin), IgA levels of the ratio of noxious to more protective tryptophan catabolites (NOX/PRO TRYCATs) and a plasma immune activation index. Moreover, IgA levels to Gram-negative bacteria were significantly associated with IgA to E-cadherin, β-catenin and PLVAP, while IgA levels to claudin-5 were significantly predicted by IgA to E-cadherin, NOX/PRO TRYCAT ratio, Gram-negative bacteria and CCL11. The phenomenology of the deficit syndrome is to a large extent explained by the cumulative effects of lowered natural IgM, breakdown of the paracellular and vascular pathways, increased bacterial translocation, peripheral immune-inflammatory responses and indices of BBB breakdown.

As common industrial by-products, airborne engineered nanomaterials are considered important environmental toxicants to monitor due to their potential health risks to humans and animals. The main uptake routes of airborne nanoparticles are nasal and/or oral inhalation, which are known to enable the transfer of nanomaterials into the blood stream resulting in rapid distribution in the body. Consequently, mucosal barriers present in nose, buccal and lung have been identified and intensively studied as the key tissue barrier to nanoparticle translocation. Despite decades of research, surprisingly little is known about the differences among various mucosa tissue types to tolerate nanoparticle exposures. One limitation in comparing nanotoxicological data sets can be linked to a lack of harmonization and standardization of cell-based assays, where a) different cultivation conditions such as air-liquid interface or submerged cultures, b) varying barrier maturity and c) diverse media substitutes have been used. The current comparative nanotoxicological study therefore aims at analyzing the toxic effects of nanomaterials on four human mucosa barrier models including nasal (RPMI2650), buccal (TR146), alveolar (A549), and bronchial (Calu-3) mucosal cell lines to better understand the modulating effects of tissue maturity, cultivation conditions and tissue type using standard Transwell cultivations at liquid-liquid and air-liquid interfaces. Overall, cell size, confluency, tight junction localization, and cell viability as well as barrier formation using 50% and 100% confluency was monitored using trans-epithelial-electrical resistance (TEER) measurements and Presto Blue assays of immature (e.g. 5 days) and mature (e.g. 22 days) cultures in the presence and absence of corticosteroids such as hydrocortisone. Results of our study show that cellular responses to increasing nanoparticle exposures are highly cell type specific, where bronchial mucosal cell barriers models cultivated under ALI conditions showed less tolerance to acute ZnO nanoparticle exposures. Additionally, stronger toxicities are found using early mucosa barriers compared to later barrier models being maturated under air-liquid cultivation conditions.

The preparation of new materials based on starch for the development of biodegradable packaging is increasing, however, the poor properties of this biopolymer for this application causes an area of opportunities for the improvement of water vapour permeability (WVP), mechanical properties, thermal properties, hydrophilicity, water absorption, among others. Hence, starch has been combined with other polymers such as polyvinyl alcohol, which has shown an improvement in the mechanical properties of starch, also, the use of clays suggests that the properties of response to water can be improved. Therefore, in this work, the preparation and characterization of starch-PVA-nanoclay films prepared by solvent casting is reported. The results obtained suggest that the sonication of nanoclay is necessary to reach a good dispersion, which promotes a strong interaction among starch-PVA-nanoclay. In addition, the properties of WVP and mechanical properties of films improved with incorporation of nanoclay, the concentration of 0.5% w/v of nanoclay showed to be the best concentration due to concentrations of 1.0 and 1.5% w/v were poorer than 0.5% w/v. Accordingly, the successful incorporation of nanoclays into the matrix starch-PVA suggests that this material is a good candidate for use as packaging.

We consider open non-twist Hamiltonian systems represented by an area-preserving two-dimensional map describing incompressible planar flows in the reference frame of a propagating wave, and possessing exits through which map orbits can escape. The corresponding escape basins have a fractal nature that can be revealed by the so-called basin entropy, a novel concept developed to quantify final-state uncertainty in dynamical systems. Since the map considered violates locally the twist condition, there is a shearless barrier that prevents global chaotic transport. In this paper we show that it is possible to determine the shearless barrier breakup by considering the variation of the escape basin entropy with a tunable parameter.

Blood-brain-barrier is a major obstacle in treating brain-related disorders as it does not allow to deliver drugs in the brain. In order to facilitate delivery of drugs in brain, we developed a method for predicting blood-brain-barrier penetrating peptides. These blood-brain barriers penetrating peptides (B3PPs) can act as therapeutic as well as drug delivery agents. We trained, tested, and evaluated our models on blood-brain-barrier peptides obtained from the B3Pdb database. First, we compute a wide range of peptide features then we select relevant peptide features. Finally, we developed numerous machine learning-based models for predicting blood-brain-barrier peptides using selected features. Our model based on random forest performed best on the top 80 selected features and achieved a maximum 85.08% accuracy with 0.93 AUROC. We also developed a web server, B3pred that implements our best models. It has three major modules that allow users to; i) predict B3PPs, ii) scanning B3PPs in a protein sequence, and iii) designing B3PPs using analogs. Our web server and standalone software is freely available at https://webs.iiitd.edu.in/raghava/b3pred/.

The blood-brain barrier (BBB), built by brain endothelial cells (BECs), is impermeable to biologics. Liposomes and other nanoparticles are good candidates for delivery of biologics across the BECs, as they can encapsulate numerous molecules of interest in an omnipotent manner. The liposomes need attachment of a targeting molecule, as BECs unfortunately are virtually incapable of uptake of non-targeted liposomes from the circulation. Experiments of independent research groups have qualified antibodies targeting the transferrin receptor as superior for targeted delivery of nanoparticles to BECs. Functionalization of nanoparticles via conjugation with anti-transferrin receptor antibodies leads to nanoparticle uptake by endothelial cells of both brain capillaries and post-capillary venules. Reducing the density of transferrin receptor-targeted antibodies conjugated to liposomes limits uptake in BECs. Opposing the transport of nanoparticles conjugated to high-affine anti-transferrin receptor antibodies, lowering the affinity of the targeting antibodies or implementing monovalent antibodies increase uptake by BECs and allows for further transport across the BBB. The novel demonstration of transport of targeted liposomes in post-capillary venules from blood to the brain is interesting and clearly warrants further mechanistic pursuit. The recent evidence for passing targeted nanoparticles through the BBB shows great promise for future drug delivery of biologics to the brain.

The neurodegenerative diseases (Alzheimers, Parkinsons, amyotrophic lateral sclerosis, Huntingdons) and the prion disorders, have in common a dysregulation of metalloprotein chemistry involving redox metals (Cu,Fe,Mn). The consequent oxidative stress gives rise to protein plaques and neuronal cell death. An equilibrium exists between the functional requirement of the brain for Cu and Fe and their destructive potential with the production of reactive oxygen species. The importance of the brain barrier is highlighted in regulating the import of these metals. Upregulation of key transporters occurs in foetal and neonatal life when brain metal requirement is high and is down-regulated in adult life when need is minimal. By contrast a neonatal mode of CTR1 upregulation persists in feral N.Ronaldsay sheep. This has led to the premise that metal regulation may return to the default setting in ageing with implications for neurodegenerative disease.

: Polymer single screw extrusion is a major industrial processing technique used to obtain plastics products. To assure high outputs, tight dimensional tolerances, and excellent product performance, extruder screws may show different design characteristics. Barrier screws, which contain a second flight in the compression zone, have become quite popular as they promote and stabilize polymer melting. Therefore, it is important to design efficiently extruder screws and decide whether a conventional screw will do the job efficiently, or a barrier-screw should be considered instead. This work uses multi-objective evolutionary algorithms to design conventional and barrier screws (Maillefer screws will be studied) with optimized geometry. Processing of two polymers, Low Density Polyethylene and Polypropylene, is analyzed. A methodology based on the use of Artificial Intelligence (AI) techniques, namely data mining, decision making and evolutionary algorithms, is presented and utilized to obtain results with practical significance, based on relevant performance measures (objectives) used in the optimization. For the various case studies selected, Maillefer screws were generally advantageous for processing LDPE, while for PP the use of both types of screws would be feasible.

The peripheral lymphatic system plays a crucial role in the recovery mechanisms after many pathological changes, such as infection, trauma, vascular, or metabolic diseases. The lymphatic clearance of different tissues from waste products, viruses, bacteria and toxic proteins significantly contributes to the correspondent recovery processes. However, understanding of the meningeal lymphatics functions is a challenging problem. The exploration of mechanisms of lymphatic communication with brain fluids as well as the role of the lymphatic system in the brain drainage, clearance and recovery are still in its infancy. Here we review novel concepts on the anatomy and physiology of the lymphatics in the brain, which warrant a substantial revision of our knowledge about the role of lymphatics in the rehabilitation of the brain functions after neural pathologies. We discuss a new vision on how to recruit the meningeal lymphatics by the opening of blood-brain barrier as a trigger mechanism of activation of the meningeal lymphatic drainage. This leads to innovative strategies in neurorehabilitation therapy.

P-glycoprotein (Pgp) determines resistance to a broad spectrum of drugs in glioblastoma multiforme (GB) because it is highly expressed in GB stem cells and in brain-blood barrier (BBB), the peculiar endothelium surrounding brain. Inhibiting Pgp activity in BBB and GB is still an open challenge. Here, we tested the efficacy of a small library of tetrahydroisoquinoline derivatives with an EC₅₀ for Pgp < 50 nM, in primary human BBB cells and in patients-derived GB, from which we isolated differentiated/adherent cells (AC, i.e. Pgp-negative/doxorubicin-sensitive cells) and stem cells (neurospheres, NS, i.e. Pgp-positive/doxorubicin-resistant cells). At 1 nM, 3 compounds increased the delivery of doxorubicin, a typical substrate of Pgp, across BBB monolayer, without altering expression and activity of other transporters. The compounds increased the drug accumulation within NS, restoring necrosis, apoptosis and reduction in cell viability induced by doxorubicin. In co-culture systems, the compounds added to the luminal face of BBB increased the delivery of doxorubicin to NS growing under BBB and rescued the drug’s cytotoxicity. Our work identified new ligands of Pgp active at low nanomolar concentrations, that effectively reduce Pgp activity in BBB and GB, and can improve chemotherapy efficacy in this tumor.

(1) Background: Applied health services research (AHSR) relies upon coordination across multiple organizational boundaries. Our aim was to understand how competing organizational and professional goals enhance or impede the conduct of high quality AHSR. (2) Methods: A qualitative study was conducted in two local health care systems in the UK, linked to a feasibility trial of a clinic-based intervention in secondary care. Data collection involved 24 semi-structured interviews with research managers, clinical research staff, health professionals, and patients. (3) Results: This study required a dynamic network of interactions between heterogeneous health and social care stakeholders, each characterized by differing ways of organizing activities which constitute their core functions; cultures of collaboration and interaction and understanding of what research involves and how it contributes to patient care. These interrelated factors compounded the occupational and organizational boundaries that hindered communication and coordination. (4) Conclusions: Despite the strategic development of multiple organizations to foster inter-professional collaboration, the competing goals of research and clinical practice can impede the conduct of high quality AHSR. To remedy this requires the alignment and streamlining of organizational goals, so that all agencies involved in AHSR develop a shared understanding and mutual respect for the progress of evidence-based medicine and the complex and often nuanced environments in which it is created and practiced.

The tumor microenvironment plays a pivotal role in the behavior and development of solid tumors as well as shaping the immune response against them. As the tumor cells proliferate, the space they occupy and their physical interactions with the surrounding tissue increases. The growing tumor tissue becomes a complex dynamic structure, containing connective tissue, vascular structures, and extracellular matrix that facilitates stimulation, oxygenation, and nutrition, necessary for its fast growth. Mechanical cues such as stiffness, solid stress, interstitial fluid pressure, matrix density, and microarchitecture influence cellular functions and ultimately tumor progression and metastasis. In this fight, our body is equipped with T cells as its spearhead against tumors. However, the altered biochemical and mechanical environment of the tumor niche affects T cell efficacy and leads to their exhaustion. Understanding the mechanobiological properties of the tumor microenvironment and their effects on T cells is key for developing novel adoptive tumor immunotherapies.

In this review paper, an overview of the application of n-type 4H-SiC Schottky barrier diodes (SBDs) as radiation detectors is given. We have chosen 4H-SiC SBDs among other semiconductor devices such as PiN diodes or metal-oxide-semiconductor (MOS) structures, as significant progress has been achieved in radiation detection applications of SBDs in the last decade. Here, we present the recent advances at all key stages in the application of 4H-SiC SBDs as radiation detectors, namely: SBDs fabrication, electrical characterization of SBDs, and their radiation response. Main achievements are highlighted, and main challenges are discussed.

Mandibular critical size defect (CSD) due to pathological conditions, trauma, and congenital disease can not heal spontaneously and predominantly filled with fibrous tissue. Therefore, a Guided Bone Regeneration (GBR) combined with bone grafting can be performed. The researchers considered using Demineralized Dentin Material Membrane (DDMM) from bovine dentine as an alternative GBR. This study aimed to determine the amount of fibroblast and collagen density after DDMM and bone graft implantation on CSD. Thirty-six Rattus norvegicus rats were used as samples. Mandibular bone defect 5x5 mm was made, then filled with bone graft and covered with Bovine Pericardium Collagen Membrane (BPCM) in the control group and DDMM in the treatment group. Six samples were sacrificed on 7, 14, and 21 days post-surgical for histology examination. There were no significant differences in the amount of fibroblast and collagen density (p-value > 0,05). The amount of fibroblast is lower and the collagen density is higher in treatment group. DDMM has microporosity to prevent connective tissue ingrowth and dentine tubules to allow growth factors release. DDMM and bone graft implantation can reduce the amount of fibroblasts and increase collagen density of CSD which potentially being used as a CSD alternative treatment for bone regeneration.

The new barrier mode in Apache Spark allows embedding distributed deep learning training as a Spark stage to simplify the distributed training workflow. In Spark, a task in a stage doesn’t depend on any other tasks in the same stage, and hence it can be scheduled independently. However, several algorithms require more sophisticated inter-task communications, similar to the MPI paradigm. By combining distributed message passing (using asynchronous network IO), OpenJDK’s new auto-vectorization and Spark’s barrier execution mode, we can add non-map/reduce based algorithms, such as Cannon’s distributed matrix multiplication to Spark. We document an efficient distributed matrix multiplication using Cannon’s algorithm, which improves significantly on the performance of the existing MLlib implementation. Used within a barrier task, the algorithm described herein results in an up to 24% performance increase on a 10,000x10,000 square matrix with a significantly lower memory footprint. Applications of efficient matrix multiplication include, among others, accelerating the training and implementation of deep convolutional neural network based workloads, and thus such efficient algorithms can play a ground-breaking role in faster, more efficient execution of even the most complicated machine learning tasks

Aberrant neutrophil extracellular trap (NET) formation and the loss of barrier integrity in inflamed intestinal tissues have long been associated with inflammatory bowel disease (IBD). However, whether NETs alter intestinal epithelium permeability during colitis remains elusive. Here, we demonstrated that NETs promote the breakdown in intestinal barrier function for the pathogenesis of intestinal inflammation in mouse models of colitis. NETs were abundant in the colon of mice with colitis experimentally induced by dextran sulfate sodium (DSS) or 2,4,6-trinitrobenzene sulfonic acid (TNBS). Analysis of the intestinal barrier integrity revealed that NETs impaired gut permeability, enabling the initiation of luminal bacterial translocation and inflammation. Furthermore, NETs induced the apoptosis of epithelial cells and disrupted the integrity of tight junctions and adherens junctions. Intravenous administration of DNase I, an enzyme that dissolves the web-like DNA filaments of NETs, during colitis restored the mucosal barrier integrity which reduced the dissemination of luminal bacteria, and attenuated intestinal inflammation in both DSS and TNBS models. We conclude that NETs serve a detrimental factor in the gut epithelial barrier function leading to the pathogenesis of mucosal inflammation during acute colitis.

This study presents a new bionanocomposite coating on poly(ethylene terephthalate) (PET) made of pullulan and synthetic mica. Mica nanolayers have a very high aspect ratio (α) at levels much greater than that of conventional exfoliated clay layers (e.g., montmorillonite). A very small amount of mica (0.02 wt%, which is ϕ ≈ 0.00008) in pullulan coatings dramatically improved the oxygen barrier performance of the nanocomposite films under dry conditions, whereas this performance was partly lost as the environmental relative humidity (RH) increased. This outcome was explained in terms of the perturbation of the spatial ordering of mica sheets within the main pullulan phase because of RH fluctuations, as confirmed by modelling of the experimental OTR data according to Cussler’s model. The presence of the synthetic nanobuilding block (NBB) led to a decrease in both static and kinetic coefficients of friction compared with neat PET (≈12% and 23%, respectively) and PET coated with unloaded pullulan (≈ 26% reduction in both coefficients). In spite of the presence of the filler, all of the coating formulations did not significantly impair the overall optical properties of the final material, which exhibited haze values below 3% and transmittance above 85%, with the only exception represented by the formulation with the highest loading of mica (1.5 wt%, which is ϕ ≈ 0.01). These findings revealed, for the first time, the potential of the NBB mica to produce nanocomposite coatings in combination with biopolymers for the generation of new functional features, such as transparent high oxygen barrier materials.

One of the hallmarks of microgravity-induced effects in several cellular models is represented by the alteration of oxidative balance with the consequent accumulation of Reactive Oxygen Species (ROS). It is well known that male germ cells are sensitive to oxidative stress and to changes of gravitational force even if published data on germ cell models are scarce. To gain more insights into the mechanisms of male germ cell response to altered gravity, a 3D cell culture model has been established from TCam-2 cells, a seminoma-derived cell line considered the only human cell line available to study in vitro mitotically active human male germ cells. TCam-2 cell spheroids were cultured for 24 hours under unitary gravity (Ctr) or simulated microgravity (s-microgravity) conditions, these last ones were obtained using the Random Positioning Machine (RPM). A significant increase in intracellular ROS and mitochondria superoxide anion levels has been observed after RPM exposure. In line with these results a trend of protein and lipid oxidation increase, and increased pCAMKII expression levels were observed after RPM exposure. The ultrastructural analysis by Transmission Electron Microscopy revealed that RPM-exposed mitochondria appeared enlarged and, even if seldom, disrupted. Notably, even the expression of the main enzymes involved in the redox homeostasis appears modulated by RPM exposure in a compensatory way, being GPX1, NCF1, and CYBB downregulated, whereas NOX4 and HMOX1 upregulated. Interestingly, HMOX1 is involved in the heme catabolism of mitochondria cytochromes, and therefore the positive modulation of this marker can be associated to the observed mitochondria alteration. All together, these data demonstrate TCam-2 spheroid sensitivity to acute SM exposure and indicate the capability of these cells to trigger compensatory mechanisms that allow to overcome the exposure to altered gravitational force.

Molluscs are significant species in aquatic ecology. Molluscs are crucial for maintaining ecological balance as secondary consumers and serving as bioindicator species in biomonitoring systems. Molluscs are threatened by pesticides such as commonly used pyrethroid insecticides. Pyrethroids are typical insecticides used to control insects in agriculture and gardening. Pyrethroids are increasingly being utilized in both agricultural and human activities. Pyrethroids enter aquatic bodies through rainfall and drainage systems. The use of pyrethroids is becoming a significant concern for aquatic creatures, particularly molluscs. The discussion will focus on the increasing issue of pyrethroids becoming a nightmare for molluscs. Pyrethroids, due to their lipophilic nature, pose a significant risk to molluscs by affecting their metabolites, producing reactive oxygen species, and influencing neurotransmitter actions. Molluscs are crucial organisms in aquatic ecosystems, and their threats warrant significant discussion and attention. This review will delve into the behaviour of pyrethroids on molluscs.

We report a novel dual-band barrier infrared detector (DBIRD) design using type-II superlattices (T2SLs). The DBIRD structure consists of back-to-back barrier diodes: a "blue channel" (BC) diode which has an nBp architecture, an n-type layer of larger bandgap for absorbing blue band infrared/barrier/p-type layer, and a "red channel" (RC) diode which has an pBn architecture, a p-type layer of smaller bandgap for absorbing red band infrared/barrier/n-type layer. Each has a unipolar barrier using a T2SL lattice matched to a GaSb substrate to impede the flow of majority carriers from the absorbing layer. Each channel in the DBIRD can be independently accessed with a low bias voltage, as is preferable for high-speed thermal imaging. Device modeling of DBIRDs and simulation results of the current-voltage characteristics under dark and illuminated conditions are also presented. They predict that dual-band operation of the DBIRD will produce low dark currents and 27-33% quantum efficiencies for the in-band photons in the BC with λc=5.58 μm, and a nearly-constant 33% in the RC with λc=8.05 μm. The spectral quantum efficiency of the BC for 500 K blackbody radiation is approximately 20% over the range of λ=3 − 4.2 μm, while that of the RC has a peak of 42% at 5.7 μm. The DBIRD may provide improved high-speed dual-band imaging in comparison with NBn dual-band detectors.

Recent studies have confirmed that lung microvascular endothelial injury plays a critical role in the pathophysiology of COVID-19. Our group and others have demonstrated the beneficial effects of H2S in several pathological processes and provided a rationale for considering the therapeutic implications of H2S in COVID-19 therapy. Here, we evaluated the effect of the slow-releasing H2S donor, GYY4137, on the barrier function of a lung endothelial cell monolayer in vitro, after challenging the cells with plasma samples from COVID-19 patients or inactivated SARS-CoV-2 virus. We also assessed how the cytokine/chemokine profile of patients’ plasma, endothelial barrier permeability, and disease severity correlated with each other. Alterations of barrier permeability after treatments with patient plasma, inactivated virus, and GYY4137 were monitored and assessed by electrical impedance measurements in real-time. We present evidence that GYY4137 treatment reduced endothelial barrier permeability after plasma challenge and completely reversed the endothelial barrier disruption caused by inactivated SARS-CoV-2 virus. We also showed that disease severity correlated with the cytokine/chemokine profile of the plasma but not with barrier permeability changes in our assay. Overall, these data demonstrate that treatment with H2S-releasing compounds has the potential to ameliorate SARS-CoV-2–associated lung endothelial barrier disruption.

One of the notable temporal properties of dynamical systems is that a set of initial states leads the solutions to reach desired states avoiding a predetermined unsafe set.This property, that we call safe reachability has been studied in literature for autonomous systems using Barrier functionand Barrier densities [1]. In this paper, we generalize a sufficient condition for safe reachability of autonomous systemto switched systems under arbitrary switching signals. The condition relies upon the existence of a common Barrier density function for each subsystem. We apply the condition using the sum of squares method together with Putinar Positivstellensatz.

Vinyltriethoxysilane (VTES) was covalently bonded onto graphene oxide. Several methods, including X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction, were used to demonstrate the presence of VTES on the surface of graphene oxide and the creation of this covalent link. Following that, different quantities of the resultant vinyltriethoxysilane functionalized graphene oxide (VTESFGO) were mixed with polyvinyl alcohol (PVA) to form VTESFGO/PVA nanocomposite films (NCFs) with a 3-dimensional network structure. The creation of these NCFs and the presence of a three-dimensional network were confirmed by Fourier transform infrared spectroscopy. The three-dimensional network structure provided these NCFs extraordinary characteristics. The mechanical and thermal stability, oxygen transfer rate (OTR), and water resistance pressure (WRP) of the NCFs were investigated. The nanocomposite film (NCF) with the highest weight percentage of VTESFGO (3.0 wt.%) was 47.5% more thermally stable than pure PVA, with an oxygen transmission rate of 0.3 cm3/m2 per day and a water resistance pressure of 780 mm/cm2. However, as the weight percentage of VTESFGO increased, the mechanical strength of the NCFs decreased as a result of silanol self-condensation, resulting in particulate formation, as confirmed by scanning electron microscopy.

During the pandemic, home-cooked meals have received more attention as people get more time for themselves and their families. It cannot deny that people have more time to prepare meals, and it is safer to cook at home since they can avoid direct contact with people who can potentially F0 or F1. For that particular reason, the number of home cooking has increased rapidly. In the article, the author pointed out that in comparison to the previous time, 42.0 percent of respondents said they cooked more frequently during the lockdown, while just 7.0 percent said they cooked less frequently. The increase in cooking frequency had a more significant impact on women than on men (p<0.05). Those who said they cooked more regularly spent more time preparing meals (78\%) and trying new recipes (73.6\%), as well as spending more time baking (67.1 percent ). In particular, the consumption of “comfort” foods (salty snacks, sweets) showed a significant rise, ranging from (23\%) to (60\%) of respondents who declared snacking more studied.Moreover, articles pointed out that in conjunction with the dramatic reduction in energy expenditure due to the impossibility of going out, this situation could have led to energy imbalance and, thus, weight gain. Noticing the massive rise in home cooking, the search for new recipes, and the need for balance meals, the idea for a cooking app called "Cooking Papa" has been proposed. As far as the research goes, the concept of "cooking" seems close but yet not easy to define. The Oxford English Dictionary defines cooking as “to prepare food by the action of heat. However, limited evidence suggests that people interpret the meaning of cooking quite differently. Moreover, the terms ‘homemade’, ‘convenience,’ ‘proper cooking,’ ‘cook,’ ‘basic ingredients,’ and ‘ready prepared’ are not uniformly understood.

The blood brain barrier (BBB) is an essential component in regulating and maintaining the homeostatic microenvironment of the central nervous system (CNS). During the occurrence and development of glioblastoma (GBM), BBB is pathologically disrupted with markedly increased permeability. Due to the obstruction imposed by the BBB, strategies currently employed for GBM therapeutics still obtain a very low success rate and lead to systemic toxicity. Moreover, chemotherapy could promote pathological BBB functional restoration, accompanied with a prominent decrease of intracerebral therapeutics transportion during GBM multiple administration, resulting in chemotherapy failure for GBM treatment. The effective delivery of therapeutics into the brain still faces with severe challenges. Regulation of pathological BBB for enhanced transporting of therapeutics across the barrier may provide new opportunities for effective and safe treatment of GBM. This article reviews the structure and function of BBB in physiological state, the mechanisms underlying BBB pathological fenestration during the development of GBM, and the therapeutic strategies of GBM based on BBB intervention and therapeutic drugs transporting across the BBB.

Pericytes are increasingly recognized as being important in the control of blood-brain barrier permeability and vascular flow. Research on this important cell type has been hindered by widespread confusion regarding the phenotypic identity and nomenclature of pericytes and other perivascular cell types. In addition, pericyte heterogeneity and mouse-human species differences have contributed to confusion. Herein we summarize our present knowledge on the identification of pericytes and pericyte subsets in humans, primarily focusing on recent findings in humans and nonhuman primates. Precise identification and definition of pericytes and pericyte subsets in humans may help us to better understand pericyte biology and develop new therapeutic approaches specifically targeting disease-associated pericyte subsets.

Maintenance of intestinal barrier integrity is crucial for preventing inflammatory bowel diseases (IBDs) onset and exacerbations. In this work we study the effect of a fixed combination of Lactobacillus reuteri and Lactobacillus acidophilus and herbal extracts in an in vitro inflammation experimental model. Caco-2 cell monolayer was exposed to INF-γ+TNF-α or to LPS; Trans Epithelial Electrical Resistance (TEER) and paracellular permeability were investigated. ZO-1 and occludin tight junctions (TJs) were also investigated by mean of immunofluorescence. The pre-treatment with the fixed combination of probiotics and herbal extracts prevented the inflammation-induced TEER decrease, paracellular permeability increase and TJs translocation. In summary the fixed combination of probiotics and herbal extracts investigated in this research was found to be an interesting candidate for targeting the re-establishment of intestinal barrier function in IBDs conditions.

The Great Barrier Reef (GBR) is currently experiencing widespread crown of thorns starfish (CoTS) outbreaks as part of the fourth wave of outbreaks since 1962. It is believed that outbreaks have become more frequent on the GBR and elsewhere in the Indo-Pacific associated with anthropogenic causes. The two widely accepted potential causes are (1) anthropogenic nutrient enrichment leading to increased biomass of phytoplankton, the food of the planktonic stage of larval CoTS; and (2) overfishing of predators on the juvenile to adult stages of CoTS, for example, commercial fished species such as coral trout. In this study, we show the evidence for the nutrient enrichment causation hypothesis is strong based on a large number of recent studies in the GBR. We also hypothesise that secondary outbreaks in the region between Cairns and Townsville can also be enhanced by nutrient enriched conditions associated with the annual nutrient discharge from Wet Tropics rivers.

Device-mediated, non-invasive drug delivery across the blood-brain barrier (BBB) represents a significant advancement in treating neurological diseases. The BBB is a tightly packed layer of endothelial cells that shields the brain from harmful substances in the blood, allowing necessary nutrients to pass through. It is a highly selective barrier, which poses a challenge to delivering therapeutic agents into the brain. Several non-invasive techniques and devices have been proposed or investigated to enhance drug delivery across the BBB. This paper presents the current state of the art and case studies that address the pharmacology, technology, delivery systems, regulatory approval, ethical concerns, and future possibilities.

Background: In order to achieve the best possible hearing and understanding with a cochlear implant (CI), regular hearing speech therapy treatment is necessary after implantation. This treatment should also be accessible to the growing proportion of hearing-impaired people with a migration background. This requires an alternative to therapy in the therapist's native language. The aim of this study was to evaluate six multilingual conversation applications with regard to their usefulness for therapy. Material and Methods: The six most commonly used applications were reviewed in terms of accuracy of content and grammatical translation, as well as pronunciation for English, Spanish, Arabic, Turkish, and Russian by native speakers. The number of available languages, availability, cost, and additional features were also analyzed. The accuracy of the content and grammatical translation as well as the pronunciation were statistically evaluated, and the differences were highlighted. The results of the different applications were compared with the performance of a native speaker. Results: All applications tested differed significantly from the native speaker level, with Google Translator showing the closest approximation to the native speaker level. All apps offer translations for multiple languages and, with exceptions, are available in both app stores. Furthermore, all apps have additional therapist-facilitating features. Conclusion: Multilingual conversation apps can make speech therapy in a foreign language much easier when used with patients. An adaptation of the software to the specific requirements of a hearing speech therapy is necessary to achieve a linguistic level that corresponds to the native language of the therapist and to enable an easy use in the therapy.

With the proportional reduction of MOSFET size, the leakage-to-barrier reduction (DIBL) effect leads to a more significant increase in the tunneling current on the gate, and the appearance of the gate tunneling current also seriously affects the static characteristics of the device. In this paper, a new theoretical model of the relationship between the direct tunneling current and the thickness of the oxide layer under the DIBL effect is proposed for the MOSFET device with ultra-thin oxide layer. On this basis, the characteristics of the MOSFET device are studied in detail by using HSPICE, and their working conditions are quantitatively analyzed. The characteristic variation trend of small-size devices under the influence of gate tunneling current is predicted. The simulation results using BSIM4 model are consistent with the theoretical model. The theory and data in this paper will provide useful reference for large scale integrated circuit design.

The effect of Alzheimer's disease (AD) medications on CD4+ T cells homing has not been thoroughly investigated. Alzheimer's disturbs the life of at least five million persons in the USA. CD4+ T cells could both exacerbate and reduce AD symptoms. Regulating CD4+ T cells homing to the leaky blood-brain barrier (BBB) constitutes a new hope for enhancing AD prognosis. Alzheimer's drugs such as Donepezil (Aricept), Rivastigmine (Exelon), Galantamine (Razadyne) and memantine are known to play an important part in regulating the neurotransmitters mechanisms. However, little is known about the effect of these drugs on CD4+ T cells homing. In this review, we focus on current and new drugs that could modulate CD4+ T cells interactions with the BBB in AD.

We report on the fabrication and electrical characteristics of zinc-oxide (ZnO) based metal-insulator-semiconductor (MIS) type Schottky barrier diodes (SBHs). ZnO thin layer on the p-type silicon substrate was fabricated by atomic layer deposition (ALD). The structure and surface properties of the thin film were characterized by X-ray diffraction (XRD), atomic force microscope (AFM) and secondary ion mass spectrometer (SIMS). The current-voltage (I-V) characteristics of Al/ALD-grown ZnO/p-Si diodes were measured under dark at room temperature. The electrical parameters such as ideality factor (n), series resistance (R_s) and barrier height (ϕ_b) of the diodes were analyzed using standard thermionic emission (TE) theory, Norde and Cheung method. The barrier height value obtained from I-V and Cheung method was found to be 0.73 eV and 0.76 eV, respectively. The interface state density (Dit) of the diodes was determined from the I-V characteristics. The nonideal behavior of measured parameters suggested the presence of interface states. The obtained results showed that the prepared diode can be used for NIR Schottky photodetector applications.

Several coastal barriers experienced significant erosion and change in shape throughout the Mediterranean coasts over the past decades, and the issue has become of increasing concern for scientists and policymakers. With reference to a case study and by meteorological and geomorphological investigations, this note aims to infer recent shoreline dynamics and define coastal phenomena shaping the beach-dune barrier of Cesine Lagoon (South Italy), to finally point out the weather-driven processes. A challenge for this research was to obtain significant results from publicly available sources and simple and inexpensive methods. The retreat of the dune toe, the accretion of washover fans, and the formation of gravel beaches have been related to the analyzed wind-wave conditions. Net longshore transport was found in accordance with the direction of the more intense winds. The role of extreme events in the shaping of coastal landforms is yet to be established even if they greatly increase the vulnerability to flooding of the study area. The results achieved so far are starting points for further data collection and analysis in the perspective of assessing the impact of climate changes on the lagoon barrier.

In the present study, a multilayer high barrier thin blown film based on a polybutylene adipate terephthalate (PBAT) blend with polyhydroxyalkanoate (PHA), and composed of four layers, including a cellulose nanocrystals (CNC) barrier layer and an electrospun poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) hot-tack layer, was characterized in terms of surface roughness, surface tension, migration, mechanical and peel performance, barrier properties and disintegration rate. The results showed a material with a smooth surface. The overall migration test showed that the material was suitable for its use as a food contact layer. The addition of the CNC interlayer had a significant effect on the mechanical properties of the system, drastically reducing the elongation at break and, thus, the flexibility of the material. However, the material retained its elastic modulus and tensile strength. The CNC coating had a negative impact on the peeling strength, weakening the inherently strong interlayer adhesivity of the electrospun PHBV fibers. The multilayer had a good barrier to water vapor, and especially to oxygen, with its permeance reduced by up to a 90 % when the CNC layer was present. Finally, the monolayer blend film disintegrated in a period of less than 55 days in a laboratory-scale composting experiment, while the multilayer system disintegrated in 60 days. Overall, the multilayer system formed a fully compostable structure with great potential for use in food packaging applications.

The effects of the coolant pulsation and the film cooling with the plasma aerodynamic actuation (PAA) could be herein explored via large eddy simulations. The electrohydrodynamic force derived from the PAA was solved through the phenomenological plasma model. The Strouhal number of the sinusoidal coolant pulsation and the averaged pulsation blowing ratio were 0.25 and 1.0, respectively. Comprehensive analyses were carried out on the time-averaged flow fields, and the results revealed that the pulsed cooling jet might cause a deeper penetration into the crossflow, and this phenomenon could be remarkably mitigated by the downward force of the PAA. Furthermore, because of the coolant pulsation, the counter rotating vortex pair (CRVP) expanded to lifted off the wall less well, and the PAA lessened the negative lift-off impact and entrapment from the CRVP. Then, the spatial-temporal development of the coherent structures was figured out by the alterations of the centerline temperature, reflecting formation of the intermittent coherent structures rather than hairpin vortices due to the coolant pulsation, and their size and upcast behaviors were reduced by the PAA. Consequently, there was a basic suppression of the turbulent mixing of the cooling fluid with the crossflow. Finally, the three-dimensional streamlines confirmed that the coherent structure dynamic behaviors were significantly regulated by the PAA for alleviating the adverse influences of the coolant pulsation. In summary, through controlling how the dominating coherent structures evolve throughout time and space, the PAA can effectively increase the pulsed film cooling efficiency.

Barrier coverage is a fundamental application in wireless sensor networks, which is widely used to protect a region through intruder detection for smart city. In this paper, we study a new branch of barrier coverage, named warning barrier coverage (WBC). Different from the classic barrier coverage, WBC has the inverse protect direction, which protects unexpected visitors by warning them away from the region enclosed by sensor barriers. The WBC holds a promising prospect in many danger keep out applications for smart city. For example, a WBC can enclose the debris area in the sea and alarm any approaching ships in order to avoid their damaging propellers. One special feature of WBC is that the target region is usually dangerous and its boundary is previously unknown. Hence, the scattered mobile nodes need to detect the boundary and form the barrier coverage themselves. It is challenging to form these distributed sensor nodes into a barrier because a node can sense only the local information and there is no global information of the unknown region or other nodes. To this end, we propose a novel solution AutoBar for mobile sensor nodes to automatically form a WBC for smart city. To pursue the high coverage quality, we theoretically derive the optimal distribution pattern of sensor nodes using convex theory. Based on the analysis, we design a fully distributed algorithm that enables nodes to collaboratively move towards the optimal distribution pattern. In addition, AutoBar is able to reorganize the barrier even any node is broken. To validate the feasibility of AutoBar, we develop the prototype of the specialized mobile node, which consists of two kinds of sensors: one for boundary detection and another for visitor detection. Based on the prototype, we conduct extensive real trace driven simulations in various smart city scenarios. Performance results demonstrate that AutoBar outperforms the existing barrier coverage strategies in terms of coverage quality, formation duration, and communication overhead.

Methylmercury is a neurotoxin present in fish tissues that permeates the blood-brain barrier after consumption. Previous research has shown that methylmercury is harmful to neurons, causing pH alterations, oxidative stress, excitotoxicity, and parenchymal damage. Methylmercury is a known factor of neurological disorders including Alzheimer's and Parkinson's. The method by which methylmercury passes through the blood-brain barrier is largely unknown. According to preliminary studies, one way methylmercury crosses the blood-brain barrier is by creating a complex with L-Cysteine, which facilitates its passage by the LATs system through mimicking another amino acid existing in the body. The human blood-brain barrier was studied using C. elegans as a model organism. It was hypothesized that if methylmercury passes through the blood-brain barrier of C. elegans faster with L-Cysteine present than without L-Cysteine present, the methylmercury's adverse effects (death and locomotive difficulty) will occur sooner. Each of the four experimental groups contained one C. elegans: the control, the L-Cysteine group, the methylmercury group, and the methylmercury and L-Cysteine combination group. The effects of L-Cysteine and methylmercury on C. elegans were studied using three metrics: viability, locomotive disability, and time for locomotive effects to occur. The group that received both methylmercury and L-Cysteine had reduced viability rates and a decreased time for locomotive difficulty to develop, supporting the hypothesis. These findings suggest that L-Cysteine aids methylmercury permeation through the blood-brain barrier. Because the experiment indicates how methylmercury penetrates the blood-brain barrier, these results aid in finding a therapeutic solution to reverse methylmercury neurotoxicity in the brain. Additionally, this study further opens channels into potential therapeutic and preventative measures for dementia, improving morbidity and mortality in neurodegenerative diseases.

Life-threatening inflammatory conditions such as acute respiratory distress syndrome or sepsis often go hand in hand with severe vascular leakage. During inflammation, endothelial cell integrity and intact barrier function are crucial to limit leukocyte and plasma extravasation. Prostaglandin D₂ (PGD₂) is a potent inflammatory lipid mediator with vasoactive properties. It has been suggested that PGD^­₂ is involved in the regulation of endothelial barrier function; however, it is unclear whether this is also true for primary human pulmonary microvascular endothelial cells. Furthermore, as PGD₂ is a highly promiscuous ligand, we set out to determine which receptors are important in human pulmonary endothelial cells. In the current study, we found that PGD₂ and the DP1 agonist BW245c potently strengthened pulmonary and dermal microvascular endothelial cell barrier function and protected against thrombin-induced barrier disruption. Yet surprisingly, these effects were mediated only to a negligible extent via DP1 receptor activation. In contrast, we observed that the EP4 receptor was most important and mediated the barrier enhancement by PGD₂ and BW245c. These data demonstrate a novel mechanism by which PGD₂ may modulate inflammation and emphasizes the role of EP4 receptors in human endothelial cell function.

This paper investigates the problem of a relativistic Dirac half-integer spin free particle tunneling through a rectangular quantum-mechanical barrier. If the energy difference between the barrier and the particle is positive, and the barrier width is large enough, there is proof that the tunneling may be superluminal. For first spinor components of particle and antiparticle states, the tunneling is always superluminal regardless the barrier width. Conversely, the second spinor components of particle and antiparticle states may be either subluminal or superluminal depending on the barrier width. These results derive from studying the tunneling time in terms of phase time. For the first spinor components of particle and antiparticle states, it is always negative while for the second spinor components of particle and antiparticle states, it is always positive, whatever the height and width of the barrier. In total, the tunneling time always remains positive for particle states while it becomes negative for antiparticle ones. Furthermore, the phase time tends to zero, increasing the potential barrier both for particle and antiparticle states. This agrees with the interpretation of quantum tunneling that the Heisenberg uncertainty principle provides. This study’s results are innovative with respect to those available in the literature. Moreover, they show that the superluminal behaviour of particles occurs in those processes with high-energy confinement.

In this study the formation of thin-film barrier coatings based on a highly-conducting Bi1.60Er0.4O3 (EDB) solid electrolyte on supporting Ce0.8Sm0.2O1.9 (SDC) electrolyte substrates is implemented for the first time using electrophoretic deposition (EPD). Electrokinetic properties of EDB-based suspensions in a non-aqueous dispersion medium of isopropanol modified with small additions of polyethyleneimine (PEI, 0.26 g/L) and acetylacetone (0.15 g/L), as well as in a mixed isopropanol/acetylacetone (70/30 vol.%) medium are studied. The dependences of the thickness of EDB coatings on voltage and deposition time are obtained using deposition on a model Ni-foil electrode. Preliminary synthesis of a conductive polypyrrole (PPy) polymer film is used to create surface conductivity of non-conductive SDC substrates. The efficiency of using a modified dispersion medium based on isopropanol to obtain a continuous EDB coating 12 μm thick, sintered at a temperature of 850 °C for 5 h, is shown. The microstructure and morphology of the surface of the EDB coating are studied. Pt/SDC/EDB/Pt cell is used to characterize the coating conductivity. The EPD method is shown to be promising for the formation of barrier coatings based on doped bismuth oxide. The developed method can be used for creating cathode barrier layers in SOFC technology.

Controlling CD4+ immune cells infiltration of the brain is a leading aim in designing therapeutic strategies for a range of neuropathological disorders such as; multiple sclerosis, Alzheimer and depression. CD4+ T cells are a highly heterogeneous and reprogrammable family, that includes various distinctive cell types such as Th17, Th1, and Tregs. Interestingly Th17 and Tregs share a related transcriptomic profile, where the TGFβ-SMADS pathway plays a fundamental role in regulating the differentiation of both of these cell types. However, Th17 could be highly pathogenic and was shown to promote inflammation in various neuropathological disorders. Conversely, Treg is anti-inflammatory and is known to inhibit Th17. It could be noticed that Th17 frequencies of infiltration of the blood-brain barrier (BBB) in various neurological disorders are significantly upregulated. However, Treg infiltration numbers are significantly low. The reasons behind these contradicting observations are still unknown. In this perspective, we propose that the difference in the TCR repertoire diversity, diapedesis pathways, chemokine expression and mechanical properties of these two cell types could be contributing to answering this intriguing question.

Eruca sativa is a commonly used edible plant in Italian cuisine. E. sativa 70% ethanol extract (ES) was fractionated with five organic solvents. Ethyl acetate fraction(EEA) had the highest antioxidant activity, which was correlated with the total polyphenol and flavonoid content. ES and EEA acted as PPAR-α ligands by PPAR-α competitive binding assay. EEA significantly increased cornified envelope formation as a keratinocyte terminal differentiation marker in HaCaT cells. Further, it significantly reduced nitric oxide and pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 cells. The main flavonol forms detected in high amounts from EEA are mono-, and di-glycoside of each aglycone. Flavonol mono-glycosides were shown to be a potent PPAR-α ligand using molecular docking simulation and showed the inhibition of nitric oxide. These results suggest that E. sativa is suitable for use in improving skin barrier function and inflammation in skin disorders, such as atopic dermatitis.

Diabetes mellitus is one of the most common metabolic diseases worldwide, and its long-term complications include neuropathy, referring both to the peripheral and to the central nervous system. Detrimental effects of dysglycemia, especially hyperglycemia, on the structure and function of blood-brain barrier (BBB) seem to be a significant backgrounds of diabetic neuropathy pertaining to the central nervous system (CNS). Effects of hyperglycemia, including excessive glucose influx to insulin independent cells, may induce oxidative stress and secondary innate immunity dependent inflammatory response which can damage cells within the CNS, thus promoting neurodegeneration and dementia. Advanced glycation end products (AGE) may exert similar, pro-inflammatory effects through activating receptors for advanced glycation end products (RAGE), as well as some pattern-recognition receptors (PRR). Moreover, long-term hyperglycemia can promote brain insulin resistance, which may in turn promote Aβ aggregate accumulation and tau hyperphosphorylation. This review is focused on a detailed analysis of the effects mentioned above towards the CNS, with special regard to mechanisms taking part in the pathogenesis of central long-term complications of diabetes mellitus initiated by the loss of BBB integrity.

This study evaluated the anti-inflammatory effects, protection of gut barrier integrity, and stimulation of phagocytosis in peripheral cells of a nutritional supplement based on a synergistic combination of yeast-based ingredients with a unique 1,3/1,6-glucan complex and a consortium of postbiotic Saccharomyces cerevisiae rich in selenium and zinc. The anti-inflammatory effect in Caco-2 cells in the presence and absence of a pro-inflammatory challenge (tumour necrosis factor alpha [TNF-α]/interferon gamma [IFN-ɣ]) showed statistically significant reductions of IFN-ɣ induced protein-10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) levels vs. controls (p &lt; 0.001). Disruption of the gut integrity in the presence or absence of Escherichia coli (ETEC H10407) showed transepithelial electrical resistance (TEER) values higher in the ABB C1® group after 6 hours of testing. Spontaneous build-up of the gut epithelium monolayer over 22 days was also greater in the ABB C1® condition vs. a negative control. ABB C1® showed a significantly higher capacity to stimulate phagocytosis as compared with controls of algae β-1,3-glucan and yeast β-1,3/1,6 glucan (p &lt; 0.001). This study supports the mechanism of action by which ABB C1® may improve the immune response and be useful to prevent infection and allergy in clinical practice.

The neurovascular niche is crucial for constant blood supply and blood-brain barrier (BBB) function and is altered in a number of different neurological conditions, making this an intensely active field of research. Brain vasculature is unique for its tight association of endothelial cells with astrocytic endfeet processes. Separation of the vascular compartment by centrifugation-based methods confirmed enrichment of astrocytic endfeet processes, making it possible to study the entire vascular niche with such methods. Several centrifugation-based separation protocols are found in the literature; however, with some constraints which limit their applicability and the scope of the studies. Here, we describe and validate a protocol for physically separating the neurovascular niche from the parenchyma, which is optimized for smaller tissue quantities. Using endothelial, neuronal and astrocyte markers, we show that quantitative Western blot-based target detection can be performed of both the vascular and parenchymal fractions using as little as a single mouse brain hemisphere. Validation of our protocol in rodent stroke models by detecting changes in serum albumin signals and astrocyte activation, i.e. increased glial fibrillary acidic protein expression, between the ipsilateral and the lesion-free contralateral hemisphere demonstrates this protocol as a new way of detecting BBB breakdown and astrogliosis, respectively.

One of the hallmarks of Alzheimer’s disease (AD) is the accumulation of beta-amyloid peptide (Aβ) leading to formation of soluble neurotoxic Aβ oligomers and insoluble amyloid plaques in various parts of the brain. Aβ undergoes post-translational modifications that alter its pathogenic properties. Aβ is produced not only in brain, but also in the peripheral tissues. Such Aβ, including its post-translationally modified forms, can enter the brain from circulation by binding to RAGE and contribute to the pathology of AD. However, the transport of modified forms of Aβ across the blood–brain barrier (BBB) has not been investigated. Here, we used a transwell BBB model as a controlled environment for permeability studies. We found that Aβ42 containing isomerized Asp7 residue (iso-Aβ42) and Aβ42 containing phosphorylated Ser8 residue crossed the BBB better than unmodified Aβ42, which correlated with different contribution of endocytosis mechanisms to the transport of these isoforms. Using microscale thermophoresis, we observed that RAGE binds to iso-Aβ42 an order of magnitude weaker than to Aβ42. Thus, post-translational modifications of Aβ increase the rate of its transport across the BBB and modify the mechanisms of the transport, which may be important for AD pathology and treatment.

Background: SARS-CoV-2 continues to impact human health globally, with airborne transmission being a significant mode for transmission. In addition to tools like vaccination and testing, counter-measures that reduce viral spread in indoor settings are critical. This study aims to assess the efficacy of UV-C light, utilizing the Violett sterilization device, as a countermeasure against airborne transmission of SARS-CoV-2 in the highly susceptible Golden Syrian hamster model. Methods: Two cohorts of naïve hamsters were subjected to airborne transmission from experimentally infected hamsters; one cohort was exposed to air treated with UV-C sterilization, while the other cohort was exposed to un-treated air. Results: Treatment of air with UV-C light prevented the airborne transmission of SARS-CoV-2 from experimentally exposed hamster to naïve hamsters. Notably, this protection was sustained over a muti-day exposure period during peak viral shedding from hamsters. Conclusion: These findings demonstrate the efficacy of the UV-C light to mitigate airborne SARS-CoV-2 transmission. As variants continue to emerge, UV-C light holds promise as a tool to reduce infections in diverse indoor settings, ranging from healthcare facilities to households. This study reinforces the urgency of implementing innovative methods to reduce airborne disease transmission and safeguard public health against emerging biological threats.

This paper introduces a novel approach to addressing the challenge of accurately timing short distance runs, a critical aspect in the assessment of athletic performance. Electronic photoelectric barriers, although recognized for their dependability and accuracy, have remained largely inaccessible to non-professional athletes and smaller sport clubs due to their high costs. A comprehensive review of existing timing systems reveals that claimed accuracies beyond 30 milliseconds lack experimental validation across most available systems.To bridge this gap, a mobile, camera-based timing system is proposed, capitalizing on consumer-grade electronics and smartphones to provide an affordable and easily accessible alternative. By leveraging readily available hardware components, the construction of the proposed system is detailed, ensuring its cost-effectiveness and simplicity. Experiments involving track and field athletes demonstrate the proficiency of the proposed system in accurately timing short distance sprints. Comparative assessments against a professional photoelectric cells timing system reveal a remarkable accuracy of 62 milliseconds, firmly establishing the reliability and effectiveness of the proposed system. This finding places the camera-based approach on par with existing commercial systems, thereby offering non-professional athletes and smaller sport clubs an affordable means to achieve accurate timing.In an effort to foster further research and development, open access to the device's schematics and software is provided. This accessibility encourages collaboration and innovation in the pursuit of enhanced performance assessment tools for athletes.

Over past decades, a frequent co-morbidity of cerebrovascular pathology and Alzheimer's disease pathology has been observed. Numerous published studies indicate that preservation of healthy cerebrovascular endothelium can be an important therapeutic target. By incorporating appropriate drug(s) into biomimetic (lipid cubic-phase) nanocarriers, one obtains a multitasking combination therapeutic which targets certain cell-surface scavenger receptors, mainly class B type 1 (i.e., SR-BI), and crosses the blood-brain barrier. This targeting allows for various Alzheimer’s-related cell types to be simultaneously searched out for localized drug treatment in vivo.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a complex gastrointestinal disorder with a multifactorial etiology, including environmental triggers, autoimmune mechanisms, and genetic predisposition. Despite advancements in therapeutic strategies for IBD, its associated mortality rate continues to rise, which is often attributed to unforeseen side effects of conventional treatments. In this context, we explored the potential of Ecklonia cava extract (ECE) derived from an edible marine alga known for its anti-inflammatory and antioxidant properties in mitigating IBD. This study investigated the effectiveness of ECE as a preventive agent in a murine model of dextran sulfate sodium (DSS)-induced colitis. Our findings revealed that pretreatment with ECE significantly ameliorated colitis severity as evidenced by increased colon length, reduced spleen weight, and histological improvements demonstrated by immunohistochemical analysis. Furthermore, ECE significantly attenuated the upregulation of inflammatory cytokines and mediators and the infiltration of immune cells known to be prominent features of colitis in mice. Notably, ECE restored dysbiosis of intestinal microflora and aided in the recovery of damaged intestinal mucosa. Mechanistically, ECE exhibited protective effects against pathogenic colitis by inhibiting the NLRP3/NF-κB pathway known to be pivotal regulators in the inflammatory signaling cascade. These compelling results suggest that ECE holds promise as a potential candidate for IBD prevention. It might be developed into a functional food for promoting gastrointestinal health. This research sheds light on the preventive potential of natural compounds like ECE in the management of IBD, offering a safer and more effective approach to combating this challenging disease.

Obstructive sleep apnea (OSA) is a chronic condition characterized by intermittent hypoxia (IH) and sleep fragmentation (SF). In murine models, chronic SF can impair endothelial function and induce cognitive declines. These deficits are likely mediated, at least in part, by alterations in Blood-Brain Barrier (BBB) integrity. Male C57Bl/6J mice were randomly assigned to SF or sleep control (SC) conditions for 4 or 9 weeks, and in a subset 2 or 6 weeks of normal sleep recovery. Presence of inflammation and microglia activation were evaluated. Explicit memory function was assessed with the novel object recognition (NOR) test, while BBB permeability was determined by systemic dextran-4kDA-FITC injection and Claudin 5 expression. SF exposures resulted in decreased NOR performance and in increased inflammatory markers and microglial activation as well as enhanced BBB permeability. Explicit memory and BBB permeability were significantly associated. BBB permeability remained elevated after 2 weeks of sleep recovery (p<0.01) and returned to baseline values only after 6 weeks. Chronic SF exposures mimicking the fragmentation of sleep that characterizes patient with OSA elicits evidence of inflammation in brain regions and explicit memory impairments in mice. Similarly, SF is also associated with increased BBB permeability, the magnitude of which is closely associated with cognitive functional losses. Despite normalization of sleep patterns, BBB functional recovery is a protracted process that merits further investigation.

The synergistic efficacy of combined treatment mild heat (MH) and dielectric barrier discharge (DBD) plasma in Bacillus cereus-contaminated red pepper powder was tested. A cocktail of three strains of B. cereus (NCCP 10623, NCCP 14579, ATCC 11778) was inoculated onto red pepper powder and then treated with MH (60 ℃ for 5-20 min) and DBD plasma (5-20 min). Treatment with MH and DBD plasma alone for 5~20 min resulted in reductions of 0.23~1.43 and 0.12~0.96 log CFU/g, respectively. Combined treatment with MH and DBD plasma was the most effective at reducing B. cereus counts on red pepper powder and resulted in log-reductions of ≥ 6.0 log CFU/g. The largest synergistic values (4.24-4.42 log) against B. cereus in red pepper powder were obtained by the combination of 20 min MH and 5~15 min DBD plasma. Hunter color ‘‘L’’, ‘‘a’’, and ‘‘b’’ values of the combination-treated samples were not significantly different from those of non-treated samples. Also, no significant (p > 0.05) differences in pH values between samples were observed. Therefore, these results suggest that the combination of MH treatment and DBD plasma can be potentially utilized in the food industry to effectively inactivate B. cereus without incurring quality deterioration of red pepper powder.

Little is known about how individual virus lineages replicating during acute Human Immunodeficiency Virus or Simian Immunodeficiency Virus (HIV/SIV) infection persist into chronic infection. In this study, we use molecularly barcoded SIV (SIVmac239M) to track distinct viral lineages for 12 weeks after intravenous and intrarectal challenge in macaques. Two Mafa-A1*063+ cynomolgus macaques (Macaca fascicularis) were challenged intravenously (IV), and two Mamu-A1*001+ rhesus macaques (Macaca mulatta) were challenged intrarectally (IR) with 200,000 Infectious Units (IU) of SIVmac239M. We deep sequenced the molecular barcode from all animals over 12 weeks to characterize the diversity and persistence of virus lineages, as well as the sequences of T cell epitopes during acute SIV infection. During the first three weeks post-infection, we found ~175-950 times more unique virus lineages circulating in the animals challenged intravenously than those challenged intrarectally, suggesting that challenge route is the primary driver restricting the transmission of individual viral lineages. Additionally, the emergence of escape variants can occur on multiple virus templates simultaneously, but elimination of some templates is likely a consequence of additional host factors. These data imply that virus lineages present during acute infection can be eliminated from the virus population even after initial T cell selection.

Patterns of age and growth of a sedentary damsel fish Acanthochromis polyacanthus were tested over a latitudinal range of approximately 10 degrees (1,200 km) on the Great Barrier Reef, Australia. Within latitudes these patterns were also compared on reefs across a continental shelf that ranged in width from 52 to 128 km. Although variation in length-max, growth, age-max and the von-Bertalanffy metrics of L, and K were found within and among latitudes, greatest variation in some demographic characteristics were found across the shelf regardless of latitude. Fish were always smaller at inner shelf reefs and grew more slowly when compared to mid and outer shelf reefs. The oldest fish collected was 11 years old and, there were no consistent variation in age-max among distances from shore. On outer reefs, there was a linear relationship with age-max and latitude. This ‘tropical gradient’ of age only explained 34% of the variation, further this was not found when the oldest 10% of fish were considered. Fish only reached an age-max of 6 years on the southern-most reefs. There was a trend for a smaller L with latitude but, it was not significant and L did not vary predictably with water temperature. The sampling of MPAs did not confound the resultant patterns. Instantaneous mortality rates were 0.245-0.685, highest at inner reefs and showed no consistent MPA-related patterns. Our study suggested that the mid and outer shelf waters of the GBR appeared best suited for growth of A. polyacanthus. In conclusion, position on continental shelves and related local environmental conditions needs to be considered in spatial models of growth.

Hydrogen fuel is gaining particular attention in internal combustion engines. In addition to zero-carbon emissions, major advantages relate to its combustion characteristics, which allow significant increase in thermal efficiency under ultra-lean operation and with very low NOx levels. The ignition system is one of the main technology enablers, as it determines the capability to control ultra-lean operations, avoid backfire phenomena, or reduce the risks of abnormal combustions. The latter results from the hydrogen low ignition energy and it is associated with factors like high-temperature residuals, hot spots, and irregular spark plug discharge. ACIS gen 2-Barrier Discharge Igniter excels in accelerating the initial flame growth speed by the generation of non-equilibrium low-temperature plasma, strong ignition promoter for the combined action of kinetic and thermal effects. Moreover, its volumetric discharge facilitates combustion initiation on a wide region, in contrast to the localized ignition of traditional spark systems. In this work we present for the first time, to the best of our knowledge, experimental results showing the performance of a hydrogen engine with a low-temperature plasma discharge. Tests were conducted on a single-cylinder research engine, achieving ultra-lean conditions with cycle-to-cycle variability results below 2.5%. The analysis indicates that the H2 - BDI combined solution is capable of accelerating the evolution of the flame front compared to traditional spark plugs, leading to a significant reduction in the cycle-to-cycle variability. A meticulous adjustment of the BDI control parameters further enhances igniter performance and contributes to a deeper understanding of the innovative approach proposed in this study.

Development of new neurotherapeutics is strongly depending on appropriate animal model chosen in preclinical studies. A cuprizone model is an effective tool for studying demyelination and re-myelination processes in the brain, but BBB integrity in cuprizone model is still a topic for debate. Several publications claim that BBB remains intact during cuprizone-induced demyelination; others demonstrate results that could be explained by the increased BBB permeability. In our work we aim to analyze permeability of BBB for different macromolecules, particularly, antibody-conjugates in cuprizone-intoxicated mice. We compared the traditional approach using Evans blue injection with following dye extraction and detection of antibody-conjugates using magnetic resonance imaging (MRI) and confocal microscopy to analyze BBB permeability in cuprizone model. First, we validated our model of demyelination by detecting changes in gene expression of myelin basic protein and proteolipid protein, and by performing MRI and histological analysis. Our results suggest that the methods with better sensitivity were able to detect the accumulation of macromolecules (such as fluorescent-labeled or gadolinium-labeled antibody conjugates) in the brain, suggesting a local BBB disruption in the demyelinating area. These findings support previous investigations that ques-tioned BBB integrity in cuprizone model and demonstrate possibility for delivery of anti-body-conjugates to demyelinated corpus callosum

Abstract. The purpose of this review is to investigate the nature of privacy concerns in the context of Smart Local Energy Systems (SLES) to understand how SLES providers can minimize both users’ concern, and cause for concern, around privacy. We conducted a rapid realist review and thematic framework analysis against Bronfrenbrenner’s socio-ecological model to understand privacy concerns in different contexts. A common privacy concern was that sharing detailed energy use data had the potential to reveal information about home life, and to intrude upon people’s sense of autonomy, choice and control. Evidence suggests that people are willing to accept newdata sharing technologies if the benefits of doing so are clear, anticipated, and mutually beneficial. Building trust, through increasing knowledge and understanding was a mechanism for overcoming privacy concerns, but this was mediated by the organization providing the information. Non-profit organizations were more trusted to ensure appropriate safeguards to privacy were in place. One key barrier to participation with good supporting evidence was that people can resist perceived intrusions on their privacy. This could be actively resisted by refusing to install data collection technologies or passively by non-participation in adapting energy use behaviors: both of which are necessary for SLES to achieve their goals of managing energy demand and building resilience in smart grids.

The study experimentally investigated a novel approach for producing hydrogen from methane cracking in dielectric barrier discharge catalytic plasma reactor using a nanocatalyst. Plasma-catalytic methane (CH4) cracking was undertaken in a dielectric barrier discharge (DBD) catalytic plasma reactor using Ni/MgAl2O4. The Ni/MgAl2O4 was synthesised through co-precipitation followed customised hydrothermal method. The physicochemical properties of the catalyst were examined using X-ray diffraction (XRD), scanning electron microscopy - energy dispersive X-ray spectrometry (SEM-EDX) and thermogravimetric analysis (TGA). The Ni/MgAl2O4 shows a porous structure spinel MgAl2O4 and thermal stability. In the catalytic-plasma methane cracking, the Ni/MgAl2O4 shows 80% of the maximum conversion of CH4 with H2 selectivity 75%. Furthermore, the stability of the catalyst was encouraging 16 hours with CH4 conversion above 75%, and the selectivity of H2 was above 70%. This is attributed to the synergistic effect of the catalyst and plasma. The plasma-catalytic CH4 cracking is a promising technology for the simultaneous H2 and carbon nanotubes (CNTs) production for energy storage applications.

Trueperella pyogenes is a common opportunistic pathogen which is one of the main causes of postpartum endometritis in dairy cows. As a substitute for antibiotics, the probiotic Lactobacillus rhamnosus GR-1 has been used in a wide range of clinical treatments. Our experiments were designed to establish a model of anti-damage which LGR-1 was used to protect bovine endometrial epithelial cells (BEECs) from inflammatory damage and cell destruction caused by T. pyogenes. Increased expression of NLRP3 inflammasomes and cytokines was observed following T. pyogenes challenge, but this increase was relieved by LGR-1 pretreatment. Immunofluorescence and Western blot analyses revealed that T. pyogenes infection also results in the damage of tight junction proteins in BEECs. The expression levels of Claudin-1, Occludin, and ZO-1 were decreased in cells only infected with T. pyogenes but not in cells pretreated with LGR-1. Moreover, the detection of the anti-apoptotic protein Bcl-2 and apoptotic proteins BAX, cytochrome c, as well as the activating effector caspase-3 revealed that T. pyogenes induced apoptosis of BEECs, which was also confirmed by DAPI staining to observe the morphological changes of the nuclei of cell apoptosis and by TUNEL staining to locate the cells undergoing apoptosis. Our data indicate that LGR-1 ameliorates the T. pyogenes–induced barrier dysfunction of BEECs and pre-application of LGR-1 could be an effective strategy for controlling T. pyogenes infection.

The small intestinal villus is covered with a thick layer of mucus that is secreted by goblet cells and functions primarily to first barrier from damage by toxic substance. Recent studies showed that goblet cells and mucins involved in complex immune function. Lipopolysaccharide (LPS) is widespread in the housing of livestock, which can induce bacterial infection symptoms and immunological stress within a short of time. Therefore, we aimed to study the effects of long-term exposure to different doses of LPS on intestinal mucus layer and immune barrier. The result showed that mucus layer thickness and goblet cell functions were significantly increased after low doses of LPS. The intestinal mucosal barrier can block the bacteria of the lumen, but LPS can penetrate this barrier into the blood, putting the body in a state of chronic low-grade inflammation and reducing the body’s immune function. However, after long-term exposure to high doses of LPS, a large number of lysosomes in goblet cells caused loss of function, and mucus layer thickness was significantly decreased. A large amount of LPS stuck to the mucus, leading to normal LPS and inflammatory cytokines level of plasma. The intestinal tissue morphology was damaged, and a number of immune cells were necrosis in the intestine. Collectively, long-term exposure to low doses of LPS lead to chronic low-grade inflammation in the body. Long-term exposure to high doses of LPS can be directly linked to the severity of the immunosuppression in the body.

Microfluidic systems offer precise control over physiological, biochemical, and mechanical stimuli in cell culture, allowing in vitro emulation of tissue or tumor microenvironments. This study aims to advance our understanding of tumor biology and contribute to personalized therapy development. Overcoming challenges in cell culture, including cell density and microfluidic device properties, is essential for this purpose. We designed a microfluidic system to facilitate the interaction of diverse cell lineages, incorporating human brain microvascular endothelial cells (HBEC5i), glioblastoma multiforme cells (U87MG), and astrocytes (ScienceCells 1800). Post-fabrication, we assessed the system's functionality and systematically evaluated cell inoculation conditions. Photographic acquisitions comprehensively captured cell culture and their interactions. The device successfully enabled assessment of cellular proliferation, invasion, and migration, supporting the growth of monolayers and tumor organoids. Importantly, each channel demonstrated independence in study processes while allowing cellular intercommunication, both physically and biochemically. In conclusion, the functional microfluidic device facilitated the study of cell migration, tumor invasion, and organoid growth, faithfully replicating biological features observed in a tumor microenvironment. This research contributes to advancing our understanding of tumor biology for the development of personalized therapies.

Background: Mounting evidence supports the role of the endocannabinoid system in neurophysiology, includ-ing blood-brain barrier (BBB) function. Recent work has demonstrated that activation of endocannabinoid re-ceptors can mitigate insults to the BBB during neurological disorders, like traumatic brain injury, cortical spreading depression and stroke. As alterations to the BBB are associated with worsening clinical outcomes in these conditions, studies herein sought to examine the impact of endocannabinoid depletion on BBB integrity. Methods: Barrier integrity was investigated in vitro via bEnd.3 cell monolayers to assess endocannabinoid syn-thesis, barrier function, calcium influx, junctional protein expression, and proteome-wide changes. Results: In-hibition of 2-AG synthesis using DAGLα inhibition and siRNA inhibition of DAGLα led to loss of barrier in-tegrity via altered expression of VE-cadherin, which could be partially rescued by exogenous application of 2-AG. Moreover, the deleterious effects of DAGLα inhibition on BBB integrity showed both calcium and PKC (protein kinase C)-dependency. Conclusions: These data indicate that disruption of 2-AG homeostasis in brain endothelial cells, in the absence of insult, is sufficient to disrupt BBB integrity thus supporting the role of the endocannabinoid system in neurovascular disorders.

Objective: To evaluate the effect of care bundles on treatment compliance and intestinal barrier function in patients with refractory septic shock in the intensive care units (ICUs). Methods: In this retrospective study, the clinical data of 94 patients with refractory septic shock admitted to our hospital between June 2020 and April 2022 were collected. Patients with routine nursing were included in the routine group, and those with care bundles were assigned to the care bundles group, with 47 cases in each group. Outcome measures included nursing efficiency, treatment compliance, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE II) score, intestinal barrier function, inflammation factor level, treatment outcome and complications. Results: Care bundles resulted in significantly higher nursing efficiency and treatment compliance versus routine care (P<0.05). Patients receiving care bundles showed significantly higher SOFA scores and APACHE II scores than those receiving routine care (P<0.05). Intestinal fatty-acid binding protein (I-FABP), diamine oxidase (DAO), lactate, endotoxin, and intestinal dysfunction scores in the care bundles group were significantly lower than those in the conventional group after treatment (P<0.05). Care bundles were associated with significantly lower levels of procalcitonin (PCT) and hypersensitive C-reactive protein (hsCRP), shorter time to symptom relief, ICU treatment time, and duration of mechanical ventilation, and lower 28-d morbidity and mortality versus routine care (P<0.05). Patients in the care bundles group had a significantly lower incidence of complications than those in the routine group (P<0.05). Conclusion: Care bundles effectively enhance treatment compliance, improve intestinal barrier function and treatment outcomes, reduce the inflammatory response, and decrease the risk of SOFA score, APACHE II score, and complications in patients with refractory septic shock.

Objective: To evaluate the effect of care bundles on treatment compliance and intestinal barrier function in patients with refractory septic shock in the intensive care units (ICUs). Methods: In this retrospective study, the clinical data of 94 patients with refractory septic shock admitted to our hospital between June 2020 and April 2022 were collected. Patients with routine nursing were included in the routine group, and those with care bundles were assigned to the care bundles group, with 47 cases in each group. Outcome measures included nursing efficiency, treatment compliance, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation (APACHE II) score, intestinal barrier function, inflammation factor level, treatment outcome and complications. Results: Care bundles resulted in significantly higher nursing efficiency and treatment compliance versus routine care (P<0.05). Patients receiving care bundles showed significantly higher SOFA scores and APACHE II scores than those receiving routine care (P<0.05). Intestinal fatty-acid binding protein (I-FABP), diamine oxidase (DAO), lactate, endotoxin, and intestinal dysfunction scores in the care bundles group were significantly lower than those in the conventional group after treatment (P<0.05). Care bundles were associated with significantly lower levels of procalcitonin (PCT) and hypersensitive C-reactive protein (hsCRP), shorter time to symptom relief, ICU treatment time, and duration of mechanical ventilation, and lower 28-d morbidity and mortality versus routine care (P<0.05). Patients in the care bundles group had a significantly lower incidence of complications than those in the routine group (P<0.05). Conclusion: Care bundles effectively enhance treatment compliance, improve intestinal barrier function and treatment outcomes, reduce the inflammatory response, and decrease the risk of SOFA score, APACHE II score, and complications in patients with refractory septic shock.

In order to improve the adaptability of broilers to low-temperature environments and their ability to resist acute cold stress (ACS), 240 one-day-old broilers were selected and randomly divided into three groups. The control treatment (CC) was raised at the conventional feeding temperature from 1-43 days (d), the cold stimulation treatments (CS) were kept at 3 °C below the temperature of CC at 1-d intervals for 3 and 6 hours from 15 to 35 d, namely CS3 and CS6, respectively. Then all broilers were kept at 20 °C from 36 to 43 d. ACS was then carried out at 44 d, and the ambient temperature was dropped to 10 °C for 6 hours. The study investigated the production perfor-mance, as well as levels of intestinal barrier genes (including Claudin-1, E-cadherin, Occludin, ZO-1, ZO-2 and Mucin2), secretory IgA in duodenum and jejunum, and immunoglobulins (IgA and IgG) in serum. The results showed that IMCS could increase the daily weight gain and decrease the feed conversion ratio. During the IMCS, the expression levels of intestinal barrier genes were up-regulated and the content of secretory IgA was increased. When IMCS ceased for one week, the level of immunoglobulins in serum stabilized, and the expression levels of Occludin, ZO-2 and Mucin2 still maintained high levels. After ACS, broilers that received IMCS training maintained the high levels of intestinal barrier genes and secretory IgA.

The blood-brain barrier (BBB) is a selectively permeable boundary that separates the circulating blood from the extracellular fluid of the brain and is an essential component for brain homeostasis. In glioblastoma (GBM), the BBB of peritumoral vessels is often disrupted. Pericytes, being important to maintain the BBB integrity, can be functionally modified by GBM cells by inducing proliferation and cell motility via the TGF-β-mediated induction of central epithelial to mesenchymal transition (EMT) factors., We demonstrate that pericytes strengthen the integrity of the BBB in primary endothelial cell/pericyte co-cultures as in vitro BBB model, using TEER measurement of the barrier integrity. In contrast, this effect was abrogated by TGF-β or conditioned medium from TGF-β secreting GBM cells, finally leading to the disruption of a so far intact and tight BBB. TGF-β dramatically changed the metabolic behavior of pericytes, such as shutting down the TCA cycle, driving energy generation from oxidative phosphorylation towards glycolysis, and by shifting the cells towards the activation of pathways that are necessary to produce molecules used for proliferation and cell division. Furthermore, combined metabolomics and RNASeq analyses indicated that the observed functional changes of TGF-β-treated pericytes are closely connected with their behavior.

We presents results obtained from the numerical simulation of the gas-phase chemical kinetics in atmospheric pressure air non-equilibrium plasmas. In particular we have addressed the effect of pulsed operation mode of a planar dielectric barrier discharge. As it was conjectured, the large difference in the time scales involved in the fast dissociation of molecules in plasmas and their subsequent reactions to produce stable chemical species, makes the presence of a continuously repeated plasma production stage unnecessary and a waste of electrical power and efficiency. Results on NOx remediation, ozone production, water vapor and ammonia dissociation are discussed. A few comparisons with experimental findings in a dielectric barrier discharge reactor already used for applications is briefly addressed too. Our results clearly indicate a pattern for the optimization of the discharge using a carefully designed repetition rate and duty-cycle.

The blood-brain barrier (BBB) acts as a specialized structure separating the brain from peripheral blood circulation and plays an important role in brain function. Following an ischaemic stroke or cerebral ischaemia, the BBB is damaged leading to degraded proteins being released into blood circulation. However, little is known about cerebral ischaemia and reperfusion (I/R) induced BBB damage and changes in circulatory biomarkers. This study aims to use both immunohistochemistry and western blotting (WB) to examine neuronal death, glial cell alterations and changes in BBB tight junction (TJ) proteins such as zonula occludens-1 (ZO-1), Occludin and Claudin-5 in the hippocampus in a murine model of cerebral I/R. The changes in these proteins in the blood serum of this model were assessed by enzyme-linked immunosorbent assay. The results showed neuronal death and a significant increase in glial fibrillary acidic protein (GFAP), a protein primarily expressed in astrocytes and a significant decrease in TJ proteins, ZO-1, Occludin and Claudin-5 in the hippocampus of occluded mice as compared to sham-operated mice. These changes are associated with an increased level of these proteins in blood serum in ischaemic mice, suggesting that these proteins can be used as potential biomarkers for determining ischaemic stroke.

A vehicle boom barrier gate system is one of the recently developed technologies operating at the entrances to the restricted areas. This paper aims to design and control of vehicle’s boom barrier gate system using robust augmentation technique. H 2 optimal and H infinity synthesis controllers are used to improve the performance of the system. The open loop response analysis of the vehicle boom barrier gate system shows that the input of the system need to be improved. Comparison of the vehicle boom barrier gate system with H2 optimal and H infinity synthesis controllers have been done to track a set point desired angular position using a step and operational open and close input signals and a promising results have been observed.

Pronounced differences exist in the biodiversity and structure of coral reef assemblages with increasing distance from shore, which may be expected given marked cross-shelf gradients in environmental conditions. Cross-shelf variation in the abundance of coral reef organisms is likely to be caused, at least in part, by differences in demography (e.g., growth and survival), though this has rarely been tested. This study quantified growth of three distinct coral taxa (Acropora nasuta, Pocillopora spp., and Stylophora pistillata) at 6 sites on Australia’s Great Barrier Reef (GBR), encompassing inshore, mid-shelf and outer-shelf reefs. Replicate colonies (up to 15 colonies per species, per reef) were stained using Alizarin red in December 2015 and retrieved 1-year later to quantify linear extension on replicate branches for each colony. Annual linear extension varied within and among coral taxa, with pronounced differences among reefs. For A. nausta. and S. pistillata, growth rates were highest at Orpheus Island, which is an inner shelf reef. However, inter-reef differences in coral growth were not explained by shelf position. Based on differences in skeletal density, which did vary according to shelf position, branching corals at the inshore sites may actually have higher rates of calcification compared to conspecifics on mid- and outer-shelf reefs. This study shows that growth of branching corals is not lower at inshore sites (and perhaps even higher) compared to sites at mid-shelf and outer reefs, despite generally higher levels of sedimentation and turbidity.

Herein, we introduce a boron nitride nanosheet (BNNS)-reinforced cellulose nanofiber (CNF) film as a sustainable oxygen barrier film that can potentially be applied in food packaging. Most of commodity plastics are oxygen-permeable. CNF exhibits an ideal oxygen transmittance rate (OTR) of <1 cc/m²/day in highly controlled conditions. A CNF film typically fabricated by the air drying of a CNF aqueous solution reveals an OTR of 19.08 cc/m²/day. The addition of 0-5 wt% BNNS to the CNF dispersion before drying results in a composite film with highly improved OTR, 4.7 cc/m²/day, which is sufficient for meat and cheese packaging. BNNS as a 2D nanomaterial increases the pathway of oxygen gas and reduces the chances of pin-hole formation during film fabrication involving water drying. In addition, BNNS improves the mechanical properties of the CNF films (Young’s modulus and tensile strength) without significant elongation reductions, probably due to the good miscibility of CNF and BNNS in the aqueous solution. BNNS addition also produces negligible color change, which is important for film aesthetics. An in vitro cell experiment was performed to reveal the low cytotoxicity of the CNF/BNNS composite. This composite film has great potential as a sustainable high-performance food packaging material.

Gut microbiota dysfunction is a key factor affecting chronic kidney disease (CKD) susceptibility. Puerariae Lobatae Radix (PLR), a traditional Chinese medicine and food homologous herb, is known to promote gut microbiota homeostasis, however, its role in renoprotection remains unknown. This study aimed to investigate the efficacy and potential mechanism of PLR to alleviate CKD. An 8-week 2% NaCl-feeding murine model was applied to induce CKD and evaluate the therapeutic effect of PLR supplementary. After gavage for 8 weeks, PLR significantly alleviated CKD-associated creatinine, urine protein increasement and nephritic histopathological injury. Moreover, PLR protected kidney from fibrosis by reducing inflammatory response and down-regulating the canonical Wnt / β-catenin pathway. Further, PLR rescued gut microbiota dysbiosis and protected high salt-induced gut barrier dysfunction. We found enrichment of Akkermansia and Bifidobacterium after PLR intervention, the relative abundance of which were in positive correlation with normal maintenance of renal histology and function. Next, fecal microbiota transplantation experiment verified that the positive effect of PLR on CKD was at least partially exerted through gut microbiota reestablishment and down-regulation of the Wnt / β-catenin pathway. Our study provides evidence for new function of PLR on kidney protection and put forward a potential therapeutic strategy target for CKD.

This study presents an innovative approach named Optimal Adaptive Continuous Barrier Function Terminal Sliding Mode Control (OACBF-TSMC) approach with a novel switching manifold, to control mathematical model of nonlinear systems under model uncertainties and external disturbances. The proposed OACBF-TSMC approach combines the advantages of adaptive control, continuous barrier functions, and terminal sliding mode control to achieve robust stability of the mathematical model of nonlinear systems, and by using a genetic algorithm that tries to optimize the controller parameters as much as possible so that the proposed controller is the most to have efficiency and performance. The proposed method is designed to address the challenges of systems and provide superior performance in terms of stabilization accuracy, disturbance rejection, and robustness against uncertainties. However, the critical challenge facing the proposed controller is the complete elimination of the chattering phenomenon, which is the most important problem of ordinary sliding mode controllers. The simulation results show that the system trajectories in the proposed approach have converged to the origin with minimal overshoot and under-shoot in a finite time; In addition, the chattering problem in the control inputs has been well eliminated, which makes the proposed method suitable for various systems, including chaotic systems, energy sources, and distributed production systems. Furthermore, the OACBF-TSMC approach has the potential to enhance the stability and reliability of control systems, contributing to the integration of the system states.

In this study, a new approach to pesticide permeation through the apple peel into the pulp is discussed. The tested compounds can be classified, based on mode of action, as systemic (boscalid, cyprodinil, pirimicarb, propiconazole and tebuconazole) or contact (captan, cypermethrin and fludioxonil) pesticides. The barrier effect was assessed using a Franz flow-type vertical diffusion cell system. Residue analysis was performed using a modified quick, easy, cheap, efficient, rugged and safe (QuEChERS) extraction method coupled to gas chromatography with tandem mass spectrometry (GC-MS/MS). The limits of detection (LODs) ranged between 2.6 µg kg-1 (pirimicarb) and 17 µg kg-1 (captan), with the coefficient of variability (CV) lower than 6%, while recoveries ranged from 85% (boscalid) to 112% (captan) at 0.1 and 1 mg kg-1 spiked levels. The highest peel penetration was observed for pirimicarb, captan and cyprodinil, with cumulative permeation of 90, 19 and 17 µg cm-2, respectively. The total absorption was in the range from 0.32% (tebuconazole) to 32% (pirimicarb). Only cypermethrin was not quantitatively detected in the pulp and its use can be recommended in crop protection techniques. The obtained results indicate that molecular weight, octanol-water partition coefficient and water solubility are important parameters determining the process of pesticide absorption.

There is a huge interest in developing novel hollow fiber (HF) membranes able to modulate neural differentiation to produce in vitro blood-brain barrier (BBB) models for biomedical and pharmaceutical research, due to the low cell-inductive properties of the polymer HFs used in current BBB models. In this work, poly(ε-caprolactone) (PCL) and composite PCL/graphene (PCL/G) HF membranes were prepared by phase inversion and were characterized in terms of mechanical, electrical, morphological, chemical, and mass transport properties. The presence of graphene in PCL/G membranes enlarged the pore size and the water flux and presented significantly higher electrical conductivity than PCL HFs. Biocompatibility assay showed that PCL/G HFs significantly increased C6 cells adhesion and differentiation towards astrocytes, may be attributed to their higher electrical conductivity in comparison to PCL HFs. On the other hand, PCL/G membranes produced a cytotoxic effect on the endothelial cell line HUVEC presumably related with a higher production of intracellular reactive oxygen species induced by the nanomaterial in this particular cell line. These results prove the potential of PCL HF membranes to grow endothelial cells and PCL/G HF membranes to differentiate astrocytes, the two characteristic cell types that could develop in vitro BBB models in future 3D co-culture systems.

Intrauterine adhesions (IUA) has become one of the main causes of female infertility, how to effectively prevent postoperative re-adhesion has been a clinical challenge. In this study, a mussel-inspired dual-network hydrogel was proposed for postoperative anti-adhesion of IUA. First, calcium alginate/polyacrylamide (CA-PAM) hydrogel was prepared by covalent and Ca2+ cross-linking. Benefiting from abundant phenolic hydroxyl groups, polydopamine (PDA) was introduced to further enhance the adhesion ability and biocompatibility. This CA-PAM hydrogel immersed in 10 mg/mL dopamine solution possessed remarkable mechanical strength (elastic modulus > 5 kPa) and super stretchability (with a breaking elongation of 720%). At the same time, it shown excellent adhesion more than 6 kPa. Surprisingly, the coagulation index of the hydrogel was 27.27 ± 4.91, demonstrating attractive coagulation performance in vitro and the potential for rapid hemostasis after surgery.

Reactive oxygen species (ROS) are a major risk factor for the development of oxidation and inflammation. Ryegrass (pasture), a natural dietary fiber source, acts as an antioxidant with well-known anti-inflammatory properties. The current study aimed to examine the alkaline phosphatase (ALP)-dependent Kelch-like-ECH-associated protein 1- Nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) signaling pathway that facilitates the anti-oxidative and anti-inflammatory properties of pasture and its protective effects on ileal permeability, systemic inflammation, nutrient absorption, liver dysfunction, growth performance, intestinal organ development, and metabolic syndrome in commercial diet-challenged geese. The lipopolysaccharides (LPS), ALP, ROS, and tight junction proteins were determined from the ileum tissues, and the antioxidant enzymes, immunoglobulins, and metabolic syndrome were determined from liver tissues via Enzyme-linked immunosorbent assay (ELISA) kits. While the Nrf2 and LPS/ROS/Keap1-induced inflammatory cytokines were determined by the quantitative reverse transcription polymerase chain reaction (RT-qPCR) method. The intestinal morphology was examined by Hematoxylin and Eosin (H&E) staining to determine nutrient absorption in ileal tissues. Pasture-dependent ALP activity significantly ameliorated commercial diet-induced LPS and ROS-facilitated ileal barrier dysfunction and systemic inflammation. The pasture supplementation induced nutrient absorption by influencing intestinal organ development. Our biochemical assays showed that the activation of Nrf2 significantly increased antioxidant enzymes and immunoglobulins, and decreased Keap1 and malondialdehyde (MDA) concentrations in the liver tissues after pasture supplementation. The correlation analysis of ALP, LPS, ROS, and Keap1-Nrf2 pathway-dependent antioxidant enzymes with other host markers showed that pasture supplementation induced intestinal barrier function via reducing LPS/ROS-induced intestinal permeability and systemic inflammation in the ileum and liver tissues. Pasture intake might attenuate LPS/ROS-induced gut permeability, systemic inflammation, and metabolic syndrome and augment gut barrier functions, nutrient absorption, immunity, and growth performance, possibly by its Keap1-Nrf2 pathway-dependent antioxidant properties.

Antimicrobial peptides (AMPs) are generally membrane-active compounds that physically disrupt bacterial membranes. Despite extensive research, the precise mode of action of AMPs is still a topic of great debate. This work demonstrates that the initial interaction between the Gram-negative E. coli and AMPs is driven by lipopolysaccharides (LPS) that act as kinetic barriers for the binding of AMPs to the bacterial membrane. A combination of SPR and NMR experiments provide evidence suggesting that cationic AMPs first bind to the negatively charged LPS before reaching a binding place in the lipid bilayer. In the event that the initial LPS-binding is too strong (corresponding to a low dissociation rate), the cationic AMPs cannot effectively get from the LPS to the membrane and their antimicrobial potency will thus be diminished. On the other hand, the AMPs must also be able to effectively interact with the membrane to exert its activity. The ability of the studied cyclic hexapeptides to bind LPS and to translocate into a lipid membrane is related to the nature of the cationic charge (arginine vs lysine) and to the distribution of hydrophobicity along the molecule (alternating vs clumped tryptophan).

Therapeutic antibodies targeting immune checkpoints have shown limited efficacy in clinical trials in glioblastoma (GBM) patients. Ultrasound-mediated blood-brain barrier opening (UMBO) using low-intensity pulsed ultrasound improved drug delivery to the brain. We explored the safety and the efficacy of UMBO plus immune checkpoint inhibitors in preclinical models of GBM. A Blood-brain barrier (BBB) opening was performed using a 1 MHz preclinical ultrasound system in combination with 10µl/g microbubbles. Brain penetration of immune checkpoint inhibitors was determined, and immune cell populations were evaluated using flow cytometry. The impact of repeated treatments on survival was determined. In syngeneic GL261-bearing immunocompetent mice, we showed that UMBO safely and repeatedly open the BBB. BBB opening was confirmed visually and microscopically using Evans’s blue dye and magnetic resonance imaging. UMBO plus anti-PDL-1 was associated with a significant improvement of the overall survival compared to anti-PD-L1 alone. Using mass spectroscopy, we showed that the penetration of therapeutic antibodies can be increased when delivered intravenously compared to non-sonicated brains. Furthermore, we observed an enhancement of activated microglia percentage when combined with anti-PD-L1. Here, we report that the combination of UMBO and anti-PD-L1 dramatically increases GL261-bearing mice's survival compared to their counterparts treated with anti-PD-L1 alone. Our study highlights the BBB as a limitation to overcome to increase the efficacy of anti-PD-L1 in GBM and supports clinical trials combining UMBO and in GBM patients.

Compact solar-powered plasma water generator: enhanced on-site aged seed germination with the corona dielectric barrier discharger

Angiostrongylus cantonensis, a zoonotic parasite, can invade the human central nervous system (CNS) and cause acute eosinophilic meningitis or eosinophilic meningoencephalitis. Mice infected with A. cantonensis show elevated levels of pro-inflammatory cytokines, plasminogen activators, and matrix metalloproteinase-9, resulting in disruption of the blood-brain barrier (BBB) and immune cell infiltration into the CNS. Caveolin-1 (Cav-1) regulates the permeability of the BBB, which affects immune cells and cerebrospinal fluid. This intricate interaction ultimately fuels the progression of brain damage and edema. This study aims to investigate the regulatory role of Cav-1 in the pathogenesis of meningoencephalitis induced by A. cantonensis infection. We investigate pathological alterations by triphenyl-tetrazolium chloride, brain water content, BBB permeability, Western blot analysis, and gelatin zymography in BALB/c mice after A. cantonensis. The study evaluates the critical role of Cav-1 regulation through the TLR4 / MyD88 signaling pathway, modulates tight junction proteins, influences BBB permeability, and contributes to brain damage in A. cantonensis-induced meningoencephalitis.

Emollients are valued ingredients of many cosmetic products and medical devices used to support the treatment and prevention of many skin diseases. Despite the fact that they are one of the oldest cosmetic ingredients, raw materials as well as new recipe solutions are constantly being sought, the main goal of which is to obtain products with the most favorable physicochemical properties while improving the hydration of the stratum corneum and softening and smoothing the skin. This article presents the results of physicochemical tests of selected emollients: natural [Macadamia Integrifolia Seed Oil, Ricinus Communis Seed Oil, Prunus Amygdalus Dulcis, Vitis Vinifera (Grape) Seed Oil], semi-synthetic Caprylic/Capric Triglyceride and synthetic (Octyldodecanol, Dicaprylyl Carbonate, Dibutyl Adipate). Then, recipes for cosmetic oils were developed, differing in the type and concentration of emollients used. The obtained formulations were subjected to physicochemical tests (dynamic viscosity, surface tension, wetting angle, color assessment) and selected parameters of the epidermal barrier function (skin hydration and lubrication) were assessed. By appropriately selecting the type and concentration of emollients in the cosmetic oil recipe, it is possible to obtain products with the appropriate ability to spread on the skin, form a uniform protective layer on the skin and remain on the skin for a sufficiently long time. The observed improvement in skin hydration and the level of lubrication after using formulations containing mixtures of natural and semi-synthetic/synthetic emollients confirms that both groups of these raw materials can be components of cosmetic body oil recipes with an emollient effect, and the products themselves constitute an important element of the care of skin affected by the disease process.

Inflammatory bowel disease (IBD) comprises systemic inflammatory conditions primarily affecting the gastrointestinal tract, including Crohn's disease and ulcerative colitis. This research aims to analyze the clinical symptoms and pathogenesis of Dextran sodium sulfate (DSS)-induced canine IBD model, and evaluate the restorative effect of ginsenoside from a pathogenesis perspective. We established the DSS-induced canine IBD model and studied the pathological mechanisms. Additionally, we examined the therapeutic effect of ginsenosides by assessing the Canine Inflammatory Bowel Disease Activity Index (CIBDAI), C-reactive protein (CRP) levels, colonic tissue morphology, protein expression, and mucosal bacterial community analysis. Our findings revealed a total ginsenoside content of 22.7% in the ginsenoside extract. Animal experiments demonstrated that dogs with IBD exhibited decreased mental state, significantly increased CIBDAI and CRP levels, disrupted colonic epithelial tissue structure, decreased expression of mucin, tight junctions, and adherens junctions, as well as reduced diversity of the colonic mucosal bacterial community. Furthermore, correlation analysis highlighted a total of 38 bacterial strains correlated with physiological indices. Significantly, ginsenoside treatment could improve these symptoms and reverse the relative abundance of some bacterial communities. In conclusion, Alterations in the properties of the colonic mucus layer or the reduction of MUC2, its core component, in dogs with IBD can lead to bacterial penetration of the mucus layer and subsequent contact with intestinal epithelial cells, resulting in inflammation. Remarkably, ginsenoside intervention showcased the capacity to positively influence the relative abundance of bacteria and impact the colonic mucus layer properties, thereby offering promising prospects for IBD management and recovery.

Neurodegenerative diseases encompass a broad spectrum of profoundly disabling disorders that impact millions of individuals globally. While their underlying causes and pathophysiol-ogy display considerable diversity and remain incompletely understood, a mounting body of evidence indicates that the disruption of blood-brain barrier (BBB) permeability, resulting in brain damage and neuroinflammation, constitutes a shared characteristic among them. Con-sequently, targeting the BBB has emerged as an innovative therapeutic strategy for address-ing neurological diseases. Within this review, we not only explore the neuroprotective, neu-rotrophic, and immunomodulatory benefits of mesenchymal stem cells (MSCs) in combating neurodegeneration but also delve into their recent role in modulating the BBB. We will delve into the cellular and molecular mechanisms through which MSC treatment impacts primary age-related neurological disorders like Alzheimer’s disease, Parkinson’s disease, and stroke as well as immune-mediated conditions such as multiple sclerosis. Our focus will center on how MSCs participate in the modulation of cell transporters, matrix remodeling, stabilization of cell-junction components, and restoration of BBB network integrity in these pathological con-texts.

This work aimed to characterize a DBD plasma equipment through optical and electrical measurements, seeking to obtain a greater knowledge of the plasma production process and how it behaves through the adopted parameters, such as frequency and voltage applied between electrodes, at a fixed distance of 1.7 mm. In order to measure them, three different characterization techniques were applied. The first method was the Lissajous figures, a technique quite effective for a complete electrical characterization of DBD equipment. The second technique used was the Optical Emission Spectroscopy, a tool used for the diagnosis of plasma, being it possible to identify the excited species produced in filamentary and diffuse discharge in the plasma. And finally, the triple Langmuir probe technique was used to obtain the electron temperature and electron density. Based on this study, it was possible to identify the equipment efficiency in different regimes. The electron temperature measurement for both systems analyzed were 27.96 eV and 20.69 eV to the filamentary and diffuse regimes, respectively. The density of electrons number to these regimes were 1.09 × 10²¹ m⁻³ and 1.56 × 10²¹ m⁻³.

The main neurovascular unit of the Blood Brain Barrier (BBB) consists of a cellular component, which includes endothelial cells, astrocytes, pericytes, microglia, neurons and oligodendrocytes, as well as a non-cellular component resulting from the extracellular matrix. The endothelial cells are the major vital component of the BBB able to preserve the brain homeostasis; these cells are situated along the demarcation line between the bloodstream and the brain. Therefore, an alteration or the progressive disruption of the endothelial layer may clearly impair the brain homeostasis. The proper functioning of the brain endothelial cells is generally ensured by two elements: 1) the presence of junction proteins; 2) the preservation of a specific polarity involving an apical-luminal and a basolateral-abluminal membrane. In view of the above, this review intends to identify the molecular mechanisms underlying BBB function and their changes occurring in early stages of neurodegenerative processes in order to develop novel therapeutic strategies aimed to counteract neurodegenerative disorders.

Cryphonectria is a fungal genus associated with economically significant disease of trees. Herein we characterized a novel double-stranded RNA virus from the fungal species Cryphonectria naterciae, a species unexplored as a virus host. De novo assembly of RNA-seq data and Sanger sequencing of RACE (rapid amplification of cDNA ends) clones gave the complete, non-segmented genome (10,164 bp) of the virus termed Cryphonectria naterciae fusagravirus (CnFGV1) that was phylogenetically placed within the previously proposed viral family Fusagraviridae. Of 31 field-collected strains of C. naterciae, 40% tested CnFGV1-positive. Co-cultivation resulted in within-species transmission of CnFGV1 to virus-free strains of C. naterciae. Comparison of the mycelium phenotype and the growth rate of CnFGV1-infected and virus-free isogenic strains revealed frequent sectoring and growth reduction in C. naterciae. Co-culturing also led to cross-species transmission of CnFGV1 to Cryphonectria carpinicola and Cryphonectria radicalis, but not to Cryphonectria parasitica. The virus-infected C. naterciae and the experimentally infected Cryphonectria spp. readily transmitted CnFGV1 through asexual spores to the next generation. CnFGV1 strongly reduced conidiation and in some cases vegetative growth of C. carpinicola, which is involved in the European hornbeam disease. This study is the first report of a fusagravirus in the family Cryphonectriaceae and lays the groundwork for assessing a hypovirulence effect of CnFGV1 against the hornbeam decline in Europe.

The effects of orally administered lactic acid bacteria metabolites on the skin were studied using an atopic dermatitis-like murine model created by feeding mice with HR-AD. The lactic acid bacteria metabolites were obtained by inoculating 35 strains of 16 species of lactic acid bacteria into soy milk and culturing them. The atopic dermatitis-like murine model was created by feeding HR-1 mice HR-AD for 40 days. The skin condition of mice that were fed HR-AD worsened compared with normal mice, i.e., reduced water content in the stratum corneum, increased transepidermal water loss (TEWL), reduced ceramide AP content in the stratum corneum, and increased epidermis thickness. When mice that had been fed the HR-AD diet was administered a raw liquid of lactic acid bacteria metabolites orally, the measured values related to water content in the stratum corneum, TEWL, ceramide AP content in the stratum corneum, and epidermis thickness improved. To find out the active components for these effects, filtrate and residue from the raw liquid of lactic acid bacteria metabolites and lipid components extracted from the raw liquid were examined at the same time. Results showed that the water-soluble components or residue after filtration did not demonstrate effects but the raw liquid and the lipid fraction did. These findings suggest that lactic acid bacteria metabolites improve skin injury in an atopic dermatitis-like murine model.

The Victorian Government Inquiry into wildfires that killed 173 people in 2009 has driven an Australian policy shift from self-evacuation or staying and defending a well-prepared property (‘go or stay’) to self-evacuation under catastrophic fire weather (‘leave early’). The Inquiry also led to the establishment of national ‘performance standards’ for Private Fire Shelters (PFS, that also known as bunkers). Nonetheless, incorporation of PFS into national bushfire policy remains embryonic with only Victoria having streamlined accreditation and planning approval processes. Arguments against PFS include potentially engendering complacency about preparing dwellings to survive fire and encourage risky behavior in response to a fire threat. Counteracting these arguments is research that shows that residents without PFS have low engagement with bushfire preparation and typically delay evacuation. In any case, because wildfire is unpredictable it is accepted that self-evacuation plans must have fallback positions that include sheltering ‘in place’ from the bushfire, making properly used and well maintained PFS an important element of bushfire safety. A less discussed barrier to PFS uptake outside Victoria appears to hinge on a lack of clarity about obligations for their design, certification, and consistency with planning approvals. The escalating Australian fire crisis demands much greater research and development in legal frameworks, policy and planning processes for PFS, as well as design and construction standards.

We investigated the influence of the fuel change, from pure hydrogen to hydrogen-ammonia mixture at different percentage, on the electrochemical behaviour of 50 mm in diameter Solid Oxide Fuel Cells (SOFC) with sputtered thin buffer layers of Gd doped Ceria, varying the working temperatures from 800°C to 650°C. The results show that the performances of the cells are not affected by the fuel change for the high working temperatures (800°C and 750°C). As an example, a power density value of 802 mW∙cm-2 at 1 A∙cm-2 is found when directly feeding the cell with 8 Nml∙min-1cm-2 of ammonia and with an equivalent flowrate of 12 Nml∙min-1cm-2 of H2. These power density output values are comparable to those obtained in industrial State of Art (SoA) SOFC cells with screen printed buffer layers fed with higher hydrogen flowrates, thanks to the improved electrochemical performances obtained in the case of cells with sputtered thin buffer layers of Gd doped Ceria. At lower working temperatures (700°C and 650°C), slight changes in the electrochemical behaviour of the cells are observed. Nevertheless, also in this temperature range, we obtain an output current density value of 0.54 A∙cm-2 in pure ammonia flowrate of 12 Nml min-1cm-2, at 800 mV and 700°C, equal to the value observed in SoA button cells with industrial screen printed GDC barrier layer fuelled with 16 Nml∙min-1cm-2 of H2. These results pave the way towards the use of innovative SOFC structures with sputtered thin buffer layers fuelled by ammonia.

Dynamic contrast-enhanced MRI (DCE-MRI) is increasingly used to quantify and map the spatial distribution of blood-brain barrier (BBB) leakage in neurodegenerative disease, including cerebral small vessel disease and dementia. However, the subtle nature of leakage and resulting small signal changes make quantification challenging. While simplified one-dimensional simulations have probed the impact of noise, scanner drift, and model assumptions, the impact of spatio-temporal effects such as gross motion, k-space sampling and motion artefacts on parametric leakage maps has been overlooked. Moreover, evidence on which to base the design of imaging protocols is lacking due to practical difficulties and the lack of a reference method. To address these problems, we present an open-source computational model of the DCE-MRI acquisition process for generating four-dimensional Digital Reference Objects (DROs), using a high-resolution brain atlas and incorporating realistic patient motion, extra-cerebral signals, noise and k-space sampling. Simulations using the DROs demonstrated a dominant influence of spatio-temporal effects on both the visual appearance of parameter maps and on measured tissue leakage rates. The computational model permits a greater understanding of the sensitivity and limitations of subtle BBB leakage measurement and provides a non-invasive means of testing and optimising imaging protocols for future studies.