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ABSTRACT Background Aims Methods Results Conclusions Skin barrier health is crucial for preventive and corrective skincare across all skin types. Witch hazel (Hamamelis virginiana) extracts show potential in addressing skin issues, but their efficacy in treating chronic inflammation, improving skin barrier function, and combating UV‐induced oxidation requires further investigation.To evaluate the efficacy of a novel formula containing witch hazel extracts in treating chronic inflammation, improving skin barrier function, and combating UV‐induced oxidation.We employed a novel ex vivo chronic inflammation model to assess anti‐inflammatory effects, measuring key pro‐inflammatory cytokines. Barrier function markers, such as loricrin and transglutaminase‐1, were analyzed. An ex vivo model with UV‐induced Reactive Oxygen Species (ROS) elevation was used to evaluate antioxidant properties, measuring specific ROS markers like 4‐Hydroxynonenal and carbonylated protein.The novel witch hazel formula significantly reduced pro‐inflammatory cytokines in both 2D and ex vivo models, including IL‐6 and IL‐8, demonstrating potent anti‐inflammatory effects. Barrier function markers showed notable improvements compared to the inflamed condition. In the UV‐induced ROS model, the formula remarkably decreased ROS levels, specifically 4‐Hydroxynonenal and carbonylated protein, indicating strong antioxidant properties.Our findings demonstrate that the novel witch hazel formula exhibits potent anti‐inflammatory and antioxidant properties while enhancing skin barrier function. This natural, well‐tolerated ingredient offers a promising treatment option for improving overall skin health, presenting new opportunities in skincare formulation and treatment strategies. [ABSTRACT FROM AUTHOR]

Introduction: Conventional 2D intestinal epithelial cell lines have been widely used in investigating intestinal functions, yet with limitations in recapitulating the in vivo gut physiology of chickens. A recently established chicken enteroid model with apical-out nature and the presence of leukocyte components represents intestinal mucosal functions. The objectives of this study were to 1) evaluate basic gut nutrient transport and barrier functions in this model and 2) identify the model's effectiveness in studying inflammation and oxidative stress responses. Methods: Enteroids were generated from individual villus units isolated from the small intestine of Cobb500 broiler embryos. Enteroid viability, morphology, and epithelial cell markers were monitored; barrier function was evaluated based on the permeability to fluorescein isothiocyanate–dextran (FD4) with or without EDTA and lipopolysaccharide (LPS) challenges; nutrient transport was evaluated by fluorescence-labeled glucose (2NBD-G) with or without transporter blockade; the oxidative status was indicated by reactive oxygen species (ROS). Inflammatory and oxidative challenges were induced by LPS and menadione treatment, respectively. Selected marker gene expressions, including tight junction proteins (CLDN-1, CLDN-2, ZO-1, and OCCL), epithelial cell markers (Lgr-5, LYZ, and MUC-2), cytokines (IL-1β, IL-6, IL-8, IL-10, TNF-α, and INF-γ), and antioxidant enzymes (Nrf-2, catalase, and SOD), were determined by using RT-qPCR. Data were analyzed by one-way ANOVA among treatment groups. Results: Enteroid cell activity was stable from day (d) 2 to d 6 and declined at d 7. Epithelial cell marker and cytokine expressions were stable from d 4 to d 6. FD4 permeability was increased after the EDTA treatment (P ≤ 0.05). Transporter-mediated 2NBD-G absorption was observed, which was reduced with glucose transporter blockade (P ≤ 0.05). Enteroids showed classic responses to LPS challenges, including upregulated gene expressions of IL-1β and IL-6, downregulated gene expressions of ZO-1 and OCCL, and increased FD4 permeability (P ≤ 0.05). Enteroids showed increased ROS generation (P ≤ 0.05) in response to oxidative stress. Discussion: In conclusion, this apical-out enteroid model is a stable alternative in vitro model that exhibits intestinal barrier, nutrient transport, oxidation, and inflammation functions. With this enteroid model, we developed two challenge protocols for evaluating intestinal functions under oxidative stress and inflammation conditions. [ABSTRACT FROM AUTHOR]

In this paper, a novel controller designed for robust tracking control of a flexible‐link manipulator operating in the presence of parameter uncertainties and external disturbances within the joint space is introduced. The proposed controller employs an adaptive sliding mode control approach, incorporating an improved barrier function, to ensure that trajectory errors remain within predefined performance bounds. This design enhances the tracking performance without overestimating control‐switching gains. Additionally, a fixed‐time adaptive sliding mode control, featuring a rapid nonsingular terminal sliding mode variable, is introduced to expedite the convergence rate of the system state during the initial stages. The efficacy of the proposed control scheme is established through the Lyapunov method, demonstrating finite‐time convergence of the trajectory error to a specified neighborhood of zero. Experimental validation on a flexible‐link system supports the effectiveness and advantages of the proposed control strategy, as evidenced via comparisons with two existing adaptive control schemes. [ABSTRACT FROM AUTHOR]

Apical cell-cell junctions, including adherens junctions and tight junctions, adhere epithelial cells to one another and regulate selective permeability at both bicellular junctions and tricellular junctions (TCJs). Although several specialized proteins are known to localize at TCJs, it remains unclear how actomyosin-mediated tension transmission at TCJs contributes to the maintenance of junction integrity and barrier function at these sites. Here, utilizing the embryonic epithelium of gastrula-stage Xenopus laevis embryos, we define a mechanism by which the mechanosensitive protein Vinculin helps anchor the actomyosin network at TCJs, thus maintaining TCJ integrity and barrier function. Using an optogenetic approach to acutely increase junctional tension, we find that Vinculin is mechanosensitively recruited to apical junctions immediately surrounding TCJs. In Vinculin knockdown (KD) embryos, junctional actomyosin intensity is decreased and becomes disorganized at TCJs. Using fluorescence recovery after photobleaching (FRAP), we show that Vinculin KD reduces actin stability at TCJs and destabilizes Angulin-1, a key tricellular tight junction protein involved in regulating barrier function at TCJs. When Vinculin KD embryos are subjected to increased tension, TCJ integrity is not maintained, filamentous actin (F-actin) morphology at TCJs is disrupted, and breaks in the signal of the tight junction protein ZO-1 signal are detected. Finally, using a live imaging barrier assay, we detect increased barrier leaks at TCJs in Vinculin KD embryos. Together, our findings show that Vinculin-mediated actomyosin organization is required to maintain junction integrity and barrier function at TCJs and reveal new information about the interplay between adhesion and barrier function at TCJs. [Display omitted] • Vinculin is mechanosensitively recruited to tricellular junctions • Vinculin's actin-binding function is needed for tricellular actomyosin organization • Vinculin reinforces tricellular junction integrity in response to increased tension • Vinculin is required to maintain barrier function at tricellular junctions Epithelial tricellular junctions are vulnerable to disruption. Here, van den Goor et al. reveal that Vinculin is mechanosensitively recruited to vertebrate tricellular junctions, where it regulates actomyosin organization and barrier function. Vinculin reinforces tricellular junction integrity when epithelia experience increased mechanical force. [ABSTRACT FROM AUTHOR]

Simple Summary: The intestines of layers during the late laying phase usually exhibit lipid metabolism disorders, concurrent with impaired energy production and antioxidant capacity. Therefore, it is necessary to explore feed additives that can enhance production performance through preserving gut barrier integrity and balancing the microbiota. Chlorogenic acid (CGA) exhibits potent pharmacological effects, including antioxidant, anti-inflammatory, antibacterial, antiviral, and lipid metabolism-regulating properties. However, the impact of CGA on late-peak laying hens remains to be further studied. In this study, we investigated the effects of CGA on gut antioxidant status, morphology, barrier function, immunity, and cecal microbiota of late-peak laying hens. Our study provides evidence that CGA treatment can enhance intestinal antioxidant status, improve intestinal morphology, strengthen intestinal barrier and immune function, and promote beneficial gut microbiota growth in laying hens during the late-peak laying period. This study examined the influence of chlorogenic acid (CGA) on gut antioxidant status, morphology, barrier function, immunity, and cecal microbiota in late-peak laying hens. A total of 240 Hy-Line Brown hens, aged 43 weeks, were randomly assigned to four groups, the basal diet +0, 400, 600, and 800 mg/kg CGA, for 12 weeks. The results revealed that CGA significantly reduced ileal H2O2 and malondialdehyde levels; increased duodenal height, ileal villus height, and villus height-to-crypt depth ratio; while decreasing jejunal crypt depth. The 600 and 800 mg/kg CGA significantly upregulated the duodenal, jejunal, and ileal ZO-1 and occludin gene expression; increased IgG levels in serum and ileum; and upregulated ileal IgA gene expression. The 600 mg/kg CGA significantly upregulated CD3D and CD4 gene expression, while downregulating IL-1β gene expression in duodenum, jejunum, and ileum. Moreover, CGA changed the gut microbiota structure. The SCFA-producing bacteria unclassified_f__Peptostreptococcaceae, unclassified_f_Oscillospiraceae, Pseudoflavonifractor, Lachnospiraceae_FCS020_group, Oscillospira, Elusimicrobium, Eubacterium_ventriosum_group, Intestinimonas, and norank_f_Coriobacteriales_Incertae_Sedis were significantly enriched in the 400, 600, and/or 800 mg/kg CGA groups. The bacteria Lactobacillus, Bacillus, and Akkermansia were significantly enriched in the 600 mg/kg CGA group. Conclusively, dietary CGA (600–800 mg/kg) improved intestinal antioxidant status, morphology, barrier and immune function, and beneficial microbiota growth in late-peak laying hens. [ABSTRACT FROM AUTHOR]

ABSTRACT Safety analysis of power systems is concerned with the system's ability to maintain critical variables within specified limits following a disturbance. Frequency control adequacy has become increasingly important as the system inertia decreases due to the increase in renewable energy penetration. Various controllers for inverters have been proposed to improve the system frequency response and few are capable to ensure the safety of the response. In this article, a diesel‐wind energy system is considered and modeled as a switching system between normal, faulted, and post‐fault modes. A safety feedback controller is designed as a supplementary signal for a wind turbine generator such that the speed of the diesel generator stays within a permissible range in the presence of a finite energy disturbance. Numerical results on the modified 33‐bus microgrid system obtained of the proposed novel approach indicate that the suggested control configuration can guarantee adequate frequency response without excessive conservativeness. [ABSTRACT FROM AUTHOR]

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects premature infants and leads to long-term pulmonary complications. The pathogenesis of BPD has not been fully elucidated yet. In recent years, the microbiome and its metabolites, especially short-chain fatty acids (SCFAs), in the gut and lungs have been demonstrated to be involved in the development and progression of the disease. This review aims to summarize the current knowledge on the potential involvement of the microbiome and SCFAs, especially the latter, in the development and progression of BPD. First, we introduce the gut-lung axis, the production and functions of SCFAs, and the role of SCFAs in lung health and diseases. We then discuss the evidence supporting the involvement of the microbiome and SCFAs in BPD. Finally, we elaborate on the potential mechanisms of the microbiome and SCFAs in BPD, including immune modulation, epigenetic regulation, enhancement of barrier function, and modulation of surfactant production and the gut microbiome. This review could advance our understanding of the microbiome and SCFAs in the pathogenesis of BPD, which also helps identify new therapeutic targets and facilitate new drug development. [ABSTRACT FROM AUTHOR]

Changes in the expression of cornified envelope (CE) components are a hallmark of numerous pathological skin conditions and aging, underlying the importance of this stratum corneum structure in the homeostasis of the epidermal barrier. We performed a detailed characterisation of LCE6A, a member of the Late Cornified Envelope protein family. Immunohistochemical and immunoblot experiments confirmed that LCE6A is expressed late during epidermal differentiation. Crosslinking assays of recombinant LCE6A performed either in situ on human skin sections or in vitro demonstrated that LCE6A is indeed a substrate of transglutaminases and crosslinked to CEs. LCE6A‐derived peptides containing a glutamine‐lysine sequence retained these properties of the full‐length protein and reinforced the mechanical resistance of CE submitted to sonication. We designed P26, a LCE6A‐derived biomimetic peptide that similarly reinforced CE in vitro, and evaluated its protective properties ex vivo, on human skin explants, and in two double blind and vehicle‐controlled clinical trials. P26 was able to protect the skin from barrier disruption, to limit the damage resulting from a defective barrier, and could improve the signs of aging such as loss of skin firmness and increased skin roughness. Hence, our detailed characterisation of LCE6A as a component of the CE enabled us to develop a LCE6A‐derived peptide, biologically active with a new and original mode of action that could be of great interest as a cosmetic ingredient and a pharmacologic agent. [ABSTRACT FROM AUTHOR]

Coagulation factor XI (FXI) has increasingly been shown to play an integral role in several physiologic and pathological processes. FXI is among several zymogens within the blood coagulation cascade that are activated by proteolytic cleavage, with FXI converting to the active serine protease form (FXIa). The evolutionary origins of FXI trace back to duplication of the gene that transcribes plasma prekallikrein, a key factor in the plasma kallikrein–kinin system, before further genetic divergence led to FXI playing a unique role in blood coagulation. While FXIa is canonically known for activating the intrinsic pathway of coagulation by catalyzing the conversion of FIX into FIXa, it is promiscuous in nature and has been shown to contribute to thrombin generation independent of FIX. In addition to its role in the intrinsic pathway of coagulation, FXI also interacts with platelets, endothelial cells, and mediates the inflammatory response through activation of FXII and cleavage of high-molecular-weight kininogen to generate bradykinin. In this manuscript, we critically review the current body of knowledge surrounding how FXI navigates the interplay of hemostasis, inflammatory processes, and the immune response and highlight future avenues for research. As FXI continues to be clinically explored as a druggable therapeutic target, understanding how this coagulation factor fits into physiological and disease mechanisms becomes increasingly important. [ABSTRACT FROM AUTHOR]

This study investigated the effects of solid-state fermentation with Clostridium butyricum on the microstructure of wheat bran, the release of dietary fiber and phenolic compounds, and antioxidant capacity. Compared with unfermented wheat bran, insoluble dietary fiber and phytic acid content decreased, whereas soluble dietary fiber and water-extractable arabinoxylan content increased in C. butyricum culture. Because of the increased release of phenolic compounds, such as ferulic acid and apigenin, and organic acids, such as isobutyric acid, the antioxidant capacity of the culture was considerably improved. Furthermore, the culture of C. butyricum treated with dextran sulfate sodium-induced ulcerative colitis in mice enhanced the expression of intestinal mucus and tight-junction proteins, modulating the gut microbiota structure, increasing the levels of short-chain fatty acids in the intestine, and restoring the essential functions of the gut microbiota. These anti-inflammatory effects stemmed from the combined action of various effective components. [ABSTRACT FROM AUTHOR]

BACKGROUND: The relationship between insulin resistance and intestinal mucosal permeability may be related to excess fat, inflammation and oxidative stress. At present, the influence of different kinds of exercise on this relationship has not been fully studied, and the relevant mechanism needs to be further studied. OBJECTIVE: To study the effects of continuous exercise and cumulative exercise on intestinal mucosal permeability of insulin-resistant mice induced by high fat diet, and to compare the effects of different intensities of exercise, thereby evaluating the health-promoting effects of cumulative exercise. METHODS: Four-week-old male C57BL/6J mice were fed high-fat diet to induce insulin resistance, and mice with successful modeling were randomly divided into five groups: high-fat insulin resistance group, general dietary insulin resistance group, moderate-intensity continuous exercise group, moderate-intensity cumulative exercise group, and high-intensity cumulative exercise group. Mice in the high-fat insulin resistance group received high-fat diet and mice in the other groups were fed normally. All the exercise groups received 8 weeks of different forms of treadmill training. Mice in the moderate-intensity sustained exercise group exercised for 50 minutes at a speed of 11 m/min. Mice in the moderate-intensity cumulative exercise group were subjected to 12.5 minutes of exercise, four times a day (3 hours between sessions), at a speed of 11 m/min. Mice in the high-intensity cumulative exercise group exercised for 7.5 minutes once, four times a day (3 hours between sessions), at a speed of 19 m/min. At 48 hours after the final session, the levels of lipopolysaccharide and D-lactic acid in serum of mice were detected, the pathological changes of ileal tissue were observed by hematoxylin-eosin staining, and the expression of intestinal compact linking protein was detected by western blot. The expression of interleukin-10, tumor necrosis factor αin blood and ileum and intestinal secreted immunoglobulin A were detected by ELISA. RESULTS AND CONCLUSION: High-fat diet-induced insulin resistance was associated with body mass gain. The serum levels of endotoxin and D-lactic acid significantly increased, and the levels of tumor necrosis factor-α in serum and small intestine were significantly increased. Long-term regular cumulative exercise and continuous exercise could reduce the body mass of insulin-resistant mice, significantly improve glucose metabolism, and correct or improve insulin resistance symptoms. Both long-term regular cumulative exercise and continuous exercise could increase the expression of zonula occludens protein 1 and increase the secretion of secreted immunoglobulin A in intestinal mucosal tissue, thereby improving intestinal mucosal permeability, enhancing intestinal immune function, reducing the content of lipopolysaccharide in serum, and reducing the expression of pro-inflammatory factors in circulating blood and intestinal tissue. Finally, it could protect the intestinal mucosal barrier of insulin-resistant mice. Compared with medium-intensity cumulative exercise and continuous exercise, high-intensity cumulative exercise had more obvious effects on reducing body mass, improving insulin resistance symptoms and protecting intestinal mucosal barrier in insulin-resistant mice. [ABSTRACT FROM AUTHOR]

Simple Summary: Current evidence suggests that protein synthesis dysfunction within the endoplasmic reticulum (ER) of the small intestine in animals with intrauterine growth retardation (IUGR) may be a potential factor contributing to the adverse postnatal outcomes associated with intestinal growth and development. However, little is known about whether the impaired protein-folding capacity of ER triggers the adaptive cellular response known as the unfolded protein response (UPR), as well as the subsequent signaling pathways leading to cellular apoptosis in the intestines of IUGR pigs. Therefore, this study aimed to evaluate the structural integrity of the ER and elucidate the potential signaling cascade of the UPR, which may mitigate the effects of ER stress (ERS) within the intestinal mucosa of IUGR neonates. The results showed that the mitochondrial swelling and ER dilation in the intestinal mucosa, resulting from restricted intrauterine development, occur on the neonatal day. The activation of the IRE1α and PERK pathways within the UPR, in response to ERS, was observed in the intestines of IUGR newborn piglets, leading to apoptosis in intestinal cells mediated by the transcription factor CHOP. Understanding this apoptotic mechanism underlying the structural and functional impairment in the guts of animals with IUGR is crucial for identifying potential preventive strategies. Intrauterine growth retardation (IUGR) in piglets is associated with a high rate of morbidity and mortality after birth due to gut dysfunction, and the underlying mechanisms remain poorly understood. This study selected six pairs of IUGR newborn male piglets and normal birth weight newborn piglets (Large White × Landrace) to investigate differences in intestinal structure and digestive functions, intestinal ERS and apoptosis, intestinal barrier function, and inflammatory response. The results showed that IUGR significantly reduced the jejunal villi height (p < 0.05) and the ratio of villus-height-to-crypt-depth (p = 0.05) in neonatal piglets. Additionally, the microvilli in the jejunum of IUGR neonatal piglets were shorter than those in normal-weight piglets, and swelling of the mitochondria and expansion of the endoplasmic reticulum were observed. IUGR also significantly reduced serum glucose and lactase levels (p < 0.05) while significantly increasing mRNA levels of jejunal IRE1α, EIF2α, CHOP, Bax, Caspase9, Mucin2, Claudin-1, Occludin, ZO-1, Bcl-2, IL-6, and IFN-γ (p < 0.05), as well as GRP78 protein levels in neonatal piglets (p < 0.05). These findings suggest that IUGR impairs intestinal structure and barrier function in newborn piglets by enhancing intestinal inflammatory responses, activating intestinal ERS and the signaling pathways related to the unfolded protein response, thereby inducing ERS-related apoptosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Dietary energy level impacts rumen function and the microflora in ruminants, which are closely related to their growth and well-being. This study explored how dietary energy levels affect sheep's growth performance, nutrient digestibility, rumen fermentation, barrier function, and microflora. Our findings indicated that the average daily weight gain and nutrient digestibility improve with the increase of dietary energy. Meanwhile, the concentration of total volatile fatty acids and propionate in rumen increased, which indicated the enhancement of rumen fermentation. The content and expression of tight junction proteins, which represents rumen barrier function, increased with the increase of dietary energy. In addition, the bacterial diversity in rumen decreased, and the relative abundance of some bacteria like Prevotellaceae, Muribaculaceae, Saccharofermentans, Prevotella and Succiniclasticum changed at the family and genus levels. Ultimately, the growth performance, fermentation characteristics and barrier function were the best when the daily dietary metabolizable energy was 9.8–10.4 MJ/kg. This study revealed the complex interaction between diet, microbiota, and rumen health, ultimately guiding the development of more effective and scientifically informed animal feeding strategies. Dietary energy is crucial for ruminants' performance and health. To determine optimal dietary energy levels for growing sheep, we evaluated their growth performance, nutrient digestibility, rumen fermentation, barrier function, and microbiota under varying metabolic energy (ME) diets. Forty-five growing Yunnan semi-fine wool sheep, aged 10 months and weighing 30.8 ± 1.9 kg, were randomly allocated to five treatments, each receiving diets with ME levels of 8.0, 8.6, 9.2, 9.8 or 10.4 MJ/kg. The results showed that with increasing dietary energy, the average daily gain (ADG) as well as the digestibility of dry matter (DM) and organic matter (OM) increased (p < 0.05), while the feed conversion ratio (FCR) decreased linearly (p = 0.01). The concentration of total VFA (p = 0.03) and propionate (p = 0.01) in the rumen increased linearly, while rumen pH (p < 0.01) and the acetate–propionate ratio (p = 0.01) decreased linearly. Meanwhile, the protein contents of Claudin-4, Claudin-7, Occludin and ZO-1 as well as the relative mRNA expression of Claudin-4 and Occludin also increased (p < 0.05). In addition, rumen bacterial diversity decreased with the increase of dietary energy, and the relative abundance of some bacteria (like Saccharofermentans, Prevotella and Succiniclasticum) changed. In conclusion, increasing dietary energy levels enhanced growth performance, nutrient digestibility, rumen fermentation, and barrier function, and altered the rumen bacterial community distribution. The optimal dietary ME for these parameters in sheep at this growth stage was between 9.8 and 10.4 MJ/kg. [ABSTRACT FROM AUTHOR]

This study focuses on addressing the challenge of adaptive fuzzy tracking control for stochastic nonlinear systems while considering full-state constraints. To tackle this issue, we introduce a fuzzy logic system to approximate the unknown nonlinear terms in the system. Additionally, a barrier Lyapunov function is utilized to confine the system state within a specific range. In order to design a novel tracking controller, the backstepping design method and the fuzzy control approach are combined. To optimize system performance, a hysteresis quantizer is integrated. To evaluate the effectiveness of the proposed control strategy, two simulation examples are presented. The simulation results demonstrate that the proposed control strategy effectively limits all state variables to a predefined range. Additionally, the tracking error of the system steadily converges to a negligible range near zero. [ABSTRACT FROM AUTHOR]

The present study aims to evaluate the effects of the antibacterial peptide Microcin J25 (ABP MccJ25) on growth performance, intestinal barrier function, antioxidant capacity and ileal microbiota in pigeon squabs. The 80 pairs of American Silver King pigeon parents and 240 healthy day 1 squabs were randomly divided into four groups, including 4 parent pairs and 12 pigeon squabs per group with 5 replicates. Parent pigeons were fed a basal diet (CON) or the addition of 100, 200, 300 mg/kg of ABP MccJ25 (ABP100, ABP200, and ABP300, respectively) for 4 weeks. Results showed that the group ABP200 remarkably reduced the feed conversion ratio and increased average daily gain in pigeon squabs from 7 to 21 d (p

Keita Okoshi,1 Shotaro Ito,1 Megumi Matsuoka,1 Yoshinori Kinugasa,1 Eri Shimizu,2 Kosei Tanaka,2 Joji Okada,3 Takahiro Nishizaka,1 Azumi Nagasawa,1 Tsuyoshi Seki,1 Makoto Iijima,1 Masatoshi Abe,4 Osamu Nemoto4 1Human Health Care Products Research, Kao Corporation, Tokyo, Japan; 2Analytical Science Research, Kao Corporation, Tochigi, Japan; 3Skin Care Products Research, Kao Corporation, Tokyo, Japan; 4Sapporo Skin Clinic, Sapporo, JapanCorrespondence: Azumi Nagasawa, Human Health Care Products Research, Kao Corporation, 2-1-3, Bunka, Sumida-ku, Tokyo, 131-8501, Japan, Tel +81-3-5630-7690, Fax +81-3-5630-9342, Email nagasawa.azumi@kao.comPurpose: Atopic dermatitis is characterized by chronic inflammation and dryness accompanied by severe itching. The combined use of moisturizers and topical anti-inflammatory drugs is essential for alleviating atopic dermatitis. We have developed a topical anti-inflammatory drug with a steroid and a moisturizer with heparinoid, both in lamellar structure-based formulations containing synthetic pseudo-ceramides. Here, assessed the efficacy of this combination in the treatment of atopic dermatitis.Methods: We included 22 patients with mild to moderate atopic dermatitis and subjected them to a seven-week treatment with the test formulations, followed by a four-week post-treatment period.Results: Clinical findings and the quality of life of participants remarkably improved after one week of treatment. Furthermore, skin hydration and transepidermal water loss considerably improved at weeks one and three, respectively. The Cer [NP]/[NS] ratio, an indicator of epidermal turnover, substantially increased during the treatment period and remained elevated even thereafter. The improvement in stratum corneum function was distinctive in participants with lower barrier function.Conclusion: These findings indicated that the combined use of the anti-inflammatory drug and moisturizer, both in lamellar structure-based formulations, is effective in treating atopic dermatitis in patients with fragile barrier function.Keywords: base formulations, lamellar structure, steroid, heparinoid, barrier function, TEWL

The term natural oil refers to a fixed (non‐volatile) oil of animal or plant origin. These types of oils – in contrast to essential (volatile) oils, which are obtained by steam distillation methods of plant matter – are typically obtained from plant seeds and nuts by a mechanical pressing technique or solvent extraction. The natural movement in cosmetics of the 21st century has led to renewed interest in formulating skin care products with botanical ingredients. In this article, we discuss the benefits and caveats of natural oil treatments as moisturizing agents (as occlusives and emollients) as well as their utility in wound healing and treatment of skin diseases. We also address the paradoxical behaviour of natural oils in relation to barrier function and highlight the current state of our knowledge with respect to the use of natural oils in neonatal skin care. Finally, we provide a comparison of natural oils to conventional petroleum‐based oils. [ABSTRACT FROM AUTHOR]

Objective: While there are a wide range of approaches for the assessment of skin hydration, it is not always clear how data from them relate to one another or to the skin itself. With the development of in vivo Confocal Raman Spectroscopy (ICRS), it has become possible to measure water concentration as a function of protein/depth within the stratum corneum (SC). This article reports a comparison between electrical skin hydration measures/visual/optical grading and water concentration profiles measured using ICRS, to better understand the relationship between these approaches. Methods: SC hydration of lower‐leg skin with varying degrees of dryness was assessed using visual grading (live and from digital images), Corneometer®, Visioscan and ICRS. In addition, a custom fingerprint sensor was used to image surface capacitance (as a surrogate of SC hydration), and SC barrier function was assessed using evaporimetry (to measure trans‐epidermal water loss; TEWL). Results: Significant correlations were observed between a number of different skin grading/measurement approaches and ICRS data. ICRS hydration profiles also revealed a region near the SC surface with a relatively flat water profile in dry skin subjects. Conclusions: The advent of quantitative in vivo analytical techniques such as ICRS, which can be used in a clinical setting, has enabled greater insight into more conventional approaches for assessing skin dryness. While traditional skin grading and biophysical methods for measuring skin hydration have varying degrees of correlation with one another, they also provide comparatively unique information about different regions within the SC. This should enable a more informed approach to product development in the future. [ABSTRACT FROM AUTHOR]

Through improved insights into the increasing incidence and detrimental effects of acute kidney injury (AKI), its clinical relevance has become more and more apparent. Although treatment strategies for AKI have also somewhat improved, an adequate remedy still does not exist. Finding one is complicated by a multifactorial pathophysiology and by heterogeneity in the patient population. Alkaline phosphatase (ALP) has been suggested as a therapy for sepsis-associated AKI because of its protective effects against lipopolysaccharide (LPS)-induced inflammation and kidney injury in animals. However, its effectiveness as an AKI treatment has not been demonstrated definitively. Because the anti-inflammatory properties of ALP are likely not reliant on a direct effect on LPS itself, we postulate that other pathways are much more important in explaining the renoprotective properties ascribed to ALP. The re-evaluation of which properties of the ALP enzyme are responsible for the benefit seen in the lab is an important step in determining where the true potential of ALP as a treatment strategy for AKI in the clinic lies. In this review we will discuss how ALP can prevent activation of harmful pro-inflammatory receptors, redirect cell–cell signalling and protect barrier tissues, which together form the basis for current knowledge of the role of ALP in the kidney. With this knowledge in mind and by analysing currently available clinical evidence, we propose directions for new research that can determine whether ALP as a treatment strategy for AKI has a future in the clinical field. [ABSTRACT FROM AUTHOR]

Hypoxia plays an important role in the pathological process of bladder outlet obstruction. Previous research has mostly focused on the dysfunction of bladder smooth muscle cells, which are directly related to bladder contraction. This study delves into the barrier function changes of the urothelial cells under exposure to hypoxia. Results indicated that after a 5‐day culture, SV‐HUC‐1 formed a monolayer and/or bilayer of cell sheets, with tight junction formation, but no asymmetrical unit membrane was observed. qPCR and western blotting revealed the expression of TJ‐associated proteins (occludin, claudin1 and ZO‐1) was significantly decreased in the hypoxia group in a time‐dependent manner. No expression changes were observed in uroplakins. When compared to normoxic groups, immunofluorescent staining revealed a reduction in the expression of TJ‐associated proteins in the hypoxia group. Transepithelial electrical resistance (TEER) revealed a statistically significant decrease in resistance in the hypoxia group. Fluorescein isothiocyanate‐conjugated dextran assay was inversely proportional to the results of TEER. Taken together, hypoxia down‐regulates the expression of TJ‐associated proteins and breaks tight junctions, thus impairing the barrier function in human urothelial cells. [ABSTRACT FROM AUTHOR]

Lympho-epithelial Kazal-type-related inhibitor (LEKTI) is a serine protease inhibitor consisting of multiple domains. A loss of function mutation is described in Netherton patients that show severe symptoms of atopic lesions and itch. LEKTI domain 6 (LD6) has shown strong serine protease-inhibitory action in in vitro assays and thus it was tested in vitro and in vivo for potential anti-inflammatory action in models of atopic skin disease. Human skin equivalents were treated with LD6 and an inflammatory reaction was challenged by kallikrein-related endopeptidase 5 (KLK5). Furthermore, LD6 was tested on dorsal root ganglia cells stimulated with KLK5, SLIGRL and histamine by calcium imaging. The effect of topically administered LD6 (0.4–0.8%) in lipoderm was compared to a topical formulation of betamethasone-diproprionate (0.1%) in a therapeutic setting on atopic dermatitis-like lesions in NC/Nga mice sensitized to house dust mite antigen. Endpoints were clinical scoring of the mice as well as determination of scratching behaviour. KLK5 induced an upregulation of CXCL-8, CCL20 and IL-6 in skin equivalents. This upregulation was reduced by pre-incubation with LD6. KLK5 as well as histamine induced calcium influx in a population of neurons. LD6 significantly reduced the calcium response to both stimuli. When administered onto lesional skin of NC/Nga mice, both LD6 and betamethasone-dipropionate significantly reduced the inflammatory reaction. The effect on itch behaviour was less pronounced. Topical administration of LD6 might be a new therapeutic option for treatment of lesional atopic skin. • LEKTI domain 6 reduces activation of sensory neurons provoked by proteases. • LEKTI domain 6 reduces activation of sensory neurons provoked by histamine. • LEKTI domain 6 reduces the inflammatory response in skin constructs. • LEKTI domain 6 reduces the inflammatory response in a murine atopic dermatitis model. [ABSTRACT FROM AUTHOR]

Cholangiocarcinoma (CCA), or bile duct cancer, is the second most common liver malignancy, with an increasing incidence in Western countries. The lack of effective treatments associated with the absence of early symptoms highlights the need to search for new therapeutic targets for CCA. Sulfatides (STs), a type of sulfoglycosphingolipids, have been found in the biliary tract, with increased levels in CCA and other types of cancer. STs are involved in protein trafficking and cell adhesion as part of the lipid rafts of the plasma membrane. We aimed to study the role of STs in CCA by the genetic targeting of GAL3ST1, an enzyme involved in ST synthesis. We used the CRISPR-Cas9 system to generate GAL3ST1-deficient TFK1 cells. GAL3ST1 KO cells showed lower proliferation and clonogenic activity and reduced glycolytic activity compared to TFK1 cells. Polarized TFK1 GAL3ST1 KO cells displayed increased transepithelial resistance and reduced permeability compared to TFK1 wt cells. The loss of GAL3ST1 showed a negative effect on growth in 30 out of 34 biliary tract cancer cell lines from the DepMap database. GAL3ST1 deficiency partially restored epithelial identity and barrier function and reduced proliferative activity in CCA cells. Sulfatide synthesis may provide a novel therapeutic target for CCA. [ABSTRACT FROM AUTHOR]

In this article, a novel positive semi-definite barrier function based adaptive recursive terminal sliding mode control for a class of uncertain nonlinear systems with actuator saturation is proposed. The method explicitly considers the actuator saturation and uncertainty, and achieves high-speed and high-precision control of the system with a lower amplitude adaptive gain, while without require the knowledge of the upper bound of the disturbance. First, in order to avoid the singularity problem and effectively improve the tracking accuracy, an error-based adaptive recursive terminal sliding surface is constructed; Then, a positive semi-definite barrier function, which realizes the adaptive adjustment of the controller gain in a lower amplitude mode is considered. It ensures that the sliding variable converges to a predefined region even when it is in the presence of actuator saturation and external disturbance. In addition, in order to prevent the problem of excessive positive semi-definite barrier function gain caused by sudden large disturbances, a modified barrier function gain form which can vary with the disturbance amplitude is also proposed, therefore the overestimation of the gain which may be difficult to achieve in reality is effectively avoided; Finally, the stability analysis of the above two control strategies is carried out in detail, and it is proved that both the systematic error and its derivative can converge to a predefined region in finite time. Numerical simulations show that in the presence of actuator saturation and external disturbances, the proposed control method not only improve the convergence performance and the control accuracy of the system, but also better prevent actuator saturation. The proposed method is also applied to a multi-cylinder hydraulic press servo system, and the results show its effectiveness. [ABSTRACT FROM AUTHOR]

IntroductionConventional 2D intestinal epithelial cell lines have been widely used in investigating intestinal functions, yet with limitations in recapitulating the in vivo gut physiology of chickens. A recently established chicken enteroid model with apical-out nature and the presence of leukocyte components represents intestinal mucosal functions. The objectives of this study were to 1) evaluate basic gut nutrient transport and barrier functions in this model and 2) identify the model’s effectiveness in studying inflammation and oxidative stress responses.MethodsEnteroids were generated from individual villus units isolated from the small intestine of Cobb500 broiler embryos. Enteroid viability, morphology, and epithelial cell markers were monitored; barrier function was evaluated based on the permeability to fluorescein isothiocyanate–dextran (FD4) with or without EDTA and lipopolysaccharide (LPS) challenges; nutrient transport was evaluated by fluorescence-labeled glucose (2NBD-G) with or without transporter blockade; the oxidative status was indicated by reactive oxygen species (ROS). Inflammatory and oxidative challenges were induced by LPS and menadione treatment, respectively. Selected marker gene expressions, including tight junction proteins (CLDN-1, CLDN-2, ZO-1, and OCCL), epithelial cell markers (Lgr-5, LYZ, and MUC-2), cytokines (IL-1β, IL-6, IL-8, IL-10, TNF-α, and INF-γ), and antioxidant enzymes (Nrf-2, catalase, and SOD), were determined by using RT-qPCR. Data were analyzed by one-way ANOVA among treatment groups.ResultsEnteroid cell activity was stable from day (d) 2 to d 6 and declined at d 7. Epithelial cell marker and cytokine expressions were stable from d 4 to d 6. FD4 permeability was increased after the EDTA treatment (P ≤ 0.05). Transporter-mediated 2NBD-G absorption was observed, which was reduced with glucose transporter blockade (P ≤ 0.05). Enteroids showed classic responses to LPS challenges, including upregulated gene expressions of IL-1β and IL-6, downregulated gene expressions of ZO-1 and OCCL, and increased FD4 permeability (P ≤ 0.05). Enteroids showed increased ROS generation (P ≤ 0.05) in response to oxidative stress.DiscussionIn conclusion, this apical-out enteroid model is a stable alternative in vitro model that exhibits intestinal barrier, nutrient transport, oxidation, and inflammation functions. With this enteroid model, we developed two challenge protocols for evaluating intestinal functions under oxidative stress and inflammation conditions.

Continued daily exposure to fine particulate matter (PM2.5) is linked to increasing risks of ocular surface diseases. However, further study is needed to understand how real-ambient PM2.5 disrupts the barrier function of the corneal epithelial layers and its underlying mechanism. In our study, we utilized a real-ambient PM2.5 exposure system to investigate its effects on the corneal epithelial barrier in C57BL/6Jmice over 4 and 8 weeks. The mean concentration of PM2.5 in the exposure chambers over 8 weeks was 140.18 μg/m3. Following 4 and 8 weeks of continuous PM2.5 exposure, we observed disorganized cellular arrangements in the corneal epithelium of mice. Moreover, PM2.5 exposure led to a significant loss of microvilli on the surface of corneal epithelial cells and noticeable disconnections among epithelial cell layers. Subsequent in vitro analysis revealed that 100 μg/mL PM2.5 activated the Wnt/β-catenin signaling pathway in corneal epithelium, resulting in decreased expression 1.81 fold and 2.25 fold of E-cadherin and ZO-1, respectively, ultimately impairing the corneal epithelial barrier function. Our findings provide the knowledge base for promoting eye health in the context of atmospheric pollution.

Early weaning-induced stress precipitates diarrhoea, significantly curtailing the growth performance of piglets. A pivotal contributor to this postweaning affliction is the emergence of gut bacterial dysbiosis. Enterococcus hirae, a promising probiotic, has indicated unclear effects and mechanisms on intestinal health. In this study, we investigated the effects and underlying mechanisms of oral supplementation with Ningxiang pig-derived Enterococcus hirae HNAU0516 orally supplementation on the gut bacterial community, immune response and gut barrier function in piglets. 21 d age Duroc × (Landrace × Yorkshire) piglets with a similar BW were randomly allocated to two groups. The Enterococcus hirae HNAU0516 administration group was inoculated orally with Ningxiang pig-derived Enterococcus hirae HNAU0516 throughout the trial period. Conversely, the control group received the same volume of physiological saline. Our findings revealed that Enterococcus hirae HNAU0516 supplementation effectively reduced diarrhoea rates of piglets (P = 0.010). Notably, this probiotic promoted intestinal development and enhanced intestinal barrier function. It also showed potential anti-inflammatory properties. Furthermore, Enterococcus hirae HNAU0516 supplementation significantly remodelled the colonic microbiota and increased the production of acetate (P = 0.007). In conclusion, our study highlights that Ningxiang pig-derived Enterococcus hirae HNAU0516 improves postweaning diarrhoea by promoting intestinal development, enhancing intestinal barrier function, decreasing intestinal permeability, modulating intestinal microbiota, and increasing short-chain fatty acids production.

Fengxia Zhan,1 Wei Song,2 Yong Fan,3 Fangjian Wang,1 Qian Wang4,5 1Department of Clinical Laboratory, Hospital of Shandong University, Jinan, 250100, People’s Republic of China; 2Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao, 266061, People’s Republic of China; 3Qingdao Mental Health Center, Qingdao University, Qingdao, People’s Republic of China; 4Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan, 250012, People’s Republic of China; 5Department of Clinical Laboratory, Qilu Hospital (Qingdao), Shandong University, Qingdao, 266035, People’s Republic of ChinaCorrespondence: Qian Wang, Email wq028038@qlyyqd.comPurpose: Cucurbitacins, which are found in a variety of medicinal plants, vegetables and fruits, were known for their diverse pharmacological and biological activities, including anticancer, anti-oxidative and anti-inflammatory effects. Cucurbitacin E, one of the major cucurbitacins, was recently proved to inhibit inflammatory response.Methods: To explore the therapeutic effects of cucurbitacin E on colitis and the underlying mechanisms, male mice drunk water containing 2.5% dextran sulfate sodium (DSS) to establish colitis model and administrated with cucurbitacin E during and after DSS treatment. The disease activity index was scored and colonic histological damage was observed. Intestinal tight junction and inflammatory response were determined. 16S rRNA and transcriptome sequencing were performed to analyze gut microbiota composition and gene expression, respectively.Results: We found that cucurbitacin E alleviated DSS-induced body weight loss and impaired colonic morphology. Cucurbitacin E decreased the expression of inflammatory cytokines and cell apoptosis, and maintained barrier function. Additionally, cucurbitacin E retrieved DSS-induced alterations in the bacterial community composition. Furthermore, a variety of differentially expressed genes (DEGs) caused by cucurbitacin E were enriched in several pathways including the NFκB and TNF signaling pathways as well as in Th17 cell differentiation. There was a close relationship between DEGs and bacteria such as Escherichia-Shigella and Muribaculaceae.Conclusion: Our results revealed that cucurbitacin E may exert protective effects on colitis via modulating inflammatory response, microbiota composition and host gene expression. Our study supports the therapeutic potential of cucurbitacin E in colitis and indicates that gut microbes are potentially therapeutic targets.Keywords: barrier function, colitis, cucurbitacins, inflammation, microbiota

AIM: To evaluate the role of semaphorin 7A (Sema7A) and its associated regulatory mechanisms in modulating the barrier function of cultured human corneal epithelial cells (HCEs). METHODS: Barrier models of HCEs were treated with recombinant human Sema7A at concentrations of 0, 125, 250, or 500 ng/mL for 24, 48, or 72h in vitro. Transepithelial electrical resistance (TEER) as well as Dextran-fluorescein isothiocyanate (FITC) permeability assays were conducted to assess barrier function. To quantify tight junctions (TJs) such as occludin and zonula occludens-1 (ZO-1) at the mRNA level, reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed. Immunoblotting was used to examine the activity of the nuclear factor-kappa B (NF-κB) signaling pathway and the production of TJs proteins. Immunofluorescence analyses were employed to localize the TJs. Enzyme-linked immunosorbent assay (ELISA) and RT-PCR were utilized to observe changes in interleukin (IL)-1β levels. To investigate the role of NF-κB signaling activation and IL-1β in Sema7A's anti-barrier mechanism, we employed 0.1 µmol/L IκB kinase 2 (IKK2) inhibitor IV or 500 ng/mL IL-1 receptor (IL-1R) antagonist. RESULTS: Treatment with Sema7A resulted in decreased TEER and increased permeability of Dextran-FITC in HCEs through down-regulating mRNA and protein levels of TJs in a time- and dose-dependent manner, as well as altering the localization of TJs. Furthermore, Sema7A stimulated the activation of inhibitor of kappa B alpha (IκBα) and expression of IL-1β. The anti-barrier function of Sema7A was significantly suppressed by treatment with IKK2 inhibitor IV or IL-1R antagonists. CONCLUSION: Sema7A disrupts barrier function through its influence on NF-κB-mediated expression of TJ proteins, as well as the expression of IL-1β. These findings suggest that Sema7A could be a potential therapeutic target for the diseases in corneal epithelium.

Ellagic acid (EA) contributes to the immunity and anti-oxidant function of body, whereas there are few reports about its effect on the intestinal health and growth performance of broiler chickens. Hence, the present study was arranged to investigate the effect of dietary supplementary with EA on the intestinal barrier function and flora structure of broiler chickens challenged with Escherichia coli K88 (E. coli K88). A total of 216 healthy 1-day-old, Ross 308 broilers with uniform weight were randomly assigned into three treatment groups, six replicates in each group and twelve birds in each replicate. Broilers in the control (CTR) group and E. coli K88 infected group (ETEC) were fed with the basic diet, and 200 mg/kg EA was supplemented into the diet of the E. coli K88 infected group treated with EA (EAETEC). The animal trial had lasted for 42 days, and the outcomes showed that the ADG and ADFI during the animal trial, the jejunal villi height (VH) and the ratio of VH to crypt depth (CD) tended to be decreased with E. coli K88 treated (P< 0.05). Additionally, the level of serum diamine oxidase (DAO) and intestinal malondialdehyde (MDA) were elevated, the activity of intestinal total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px), the mRNA levels in jejunal claudin-1 and occludin were down-regulated with E. coli K88 treated as well as the transcription levels of ileal Mucin-2, aquaporin-3 (AQP-3) and Na+/H+ exchanger proteins-3 (NHE-3) (P< 0.05). In addition, E. coli K88 down-regulated the α-diversity index of cecal flora, the ratio of Bacteroidota to Firmicutes and the relative abundance of Barnesiella were up-regulated and it of Alistipes was descended with E. coli K88 treated (P< 0.05). Beyond that, the content of propionic acid in the cecal chyme was decreased and the amino acid metabolic pathways were inhibited with E. coli K88 challenged (P< 0.05). Additionally, there was a significant positive correlation between the relative abundance of Alistipes and the levels of butyric acid in the caecal chyme and the activity of GSH-Px in the intestine (P< 0.05). Interestingly, dietary supplementary with EA could reshape the intestinal flora structure and alleviate the above negative effects of E. coli K88 on broiler chickens. In conclusion, dietary supplementary with ellagic acid improved the intestinal barrier function and flora structure of broiler chickens challenged with E. coli K88.

Autonomous driving has the potential to revolutionize transportation, but developing safe and reliable systems remains a significant challenge. Reinforcement learning (RL) has emerged as a promising approach for learning optimal control policies in complex driving environments. However, existing RL-based methods often suffer from low sample efficiency and lack explicit safety constraints, leading to unsafe behaviors. In this paper, we propose a novel framework for safe reinforcement learning in autonomous driving that addresses these limitations. Our approach incorporates a latent dynamic model that learns the underlying dynamics of the environment from bird's-eye view images, enabling efficient learning and reducing the risk of safety violations by generating synthetic data. Furthermore, we introduce state-wise safety constraints through a barrier function, ensuring safety at each state by encoding constraints directly into the learning process. Experimental results in the CARLA simulator demonstrate that our framework significantly outperforms baseline methods in terms of both driving performance and safety. Our work advances the development of safe and efficient autonomous driving systems by leveraging the power of reinforcement learning with explicit safety considerations. [ABSTRACT FROM AUTHOR]

In practice, disturbances, including model uncertainties and unknown external disturbances, are always widely present and have a significant impact on the cooperative control performance of a networked multi-agent system. In this work, the distributed consensus tracking control problem for a class of multi-agent systems subject to matched and mismatched uncertainties is addressed. In particular, the dynamics of the leader agent are modeled with uncertain terms, i.e., the leader's higher-order information, such as velocity and acceleration, is unknown to all followers. To solve this problem, a robust consensus tracking control scheme that combines a neural network-based distributed observer, a barrier function-based disturbance observer, and a tracking controller based on the back-stepping method was developed in this study. Firstly, a neural network-based distributed observer is designed, which is able to achieve effective estimation of leader information by all followers. Secondly, a tracking controller was designed utilizing the back-stepping technique, and the boundedness of the closed-loop error system was proved using the Lyapunov-like theorem, which enables the followers to effectively track the leader's trajectory. Meanwhile, a barrier function-based disturbance observer is proposed, which achieves the effective estimation of matched and mismatched uncertainties of followers. Finally, the effectiveness of the robust consensus tracking control method designed in this study was verified through numerical simulations. [ABSTRACT FROM AUTHOR]

One of the primary complications in generating physiologically representative skin tissue is the inability to integrate vasculature into the system, which has been shown to promote the proliferation of basal keratinocytes and consequent keratinocyte differentiation, and is necessary for mimicking representative barrier function in the skin and physiological transport properties. We created a 3D vascularized human skin equivalent (VHSE) with a dermal and epidermal layer, and compared keratinocyte differentiation (immunomarker staining), epidermal thickness (H&E staining), and barrier function (transepithelial electrical resistance (TEER) and dextran permeability) to a static, organotypic avascular HSE (AHSE). The VHSE had a significantly thicker epidermal layer and increased resistance, both an indication of increased barrier function, compared to the AHSE. The inclusion of keratin in our collagen hydrogel extracellular matrix (ECM) increased keratinocyte differentiation and barrier function, indicated by greater resistance and decreased permeability. Surprisingly, however, endothelial cells grown in a collagen/keratin extracellular environment showed increased cell growth and decreased vascular permeability, indicating a more confluent and tighter vessel compared to those grown in a pure collagen environment. The development of a novel VHSE, which incorporated physiological vasculature and a unique collagen/keratin ECM, improved barrier function, vessel development, and skin structure compared to a static AHSE model. [ABSTRACT FROM AUTHOR]

In this paper, a nonoverestimated adaptive prescribed performance sliding mode control algorithm based on time‐varying barrier function is proposed, for high‐order integrator systems subject to bounded but unknown disturbances. The developed algorithm has some remarkable features. Firstly, it is able to ensure that the system states are confined in a performance function from the initial instant. Secondly, it is easy‐implementable and some exponential stability and practical fixed‐time stability algorithms can be easily obtained. Finally, with the system states to be known, the size of the performance function is independent of the upper bound of the external disturbance. To show the efficiency of the developed algorithm, some numerical simulations are provided. [ABSTRACT FROM AUTHOR]

The development of novel strategies to counteract diseases related to barrier dysfunction is a priority, since sepsis and acute respiratory distress syndrome are still associated with high mortality rates. In the present study, we focus on the effects of the unfolded protein response suppressor (UPR) 4-Phenylbutyrate (4-PBA) in Lipopolysaccharides (LPS)-induced endothelial injury, to investigate the effects of that compound in the corresponding damage. 4-PBA suppressed binding immunoglobulin protein (BiP) - a UPR activation marker - and potentiated LPS - induced signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated protein kinase (ERK) 1/2 activation. In addition to those effects, 4-PBA enhanced paracellular hyperperme-ability in inflamed bovine pulmonary endothelial cells, and did not affect cell viability in moderate concentrations. Our observations suggest that UPR suppression due to 4-PBA augments LPS-induced endothelial injury, as well as the corresponding barrier disruption. [ABSTRACT FROM AUTHOR]

Broiler chickens in livestock production face numerous challenges that can impact their health and welfare, including mycotoxin contamination and heat stress. In this study, we aimed to investigate the combined effects of two mycotoxins, deoxynivalenol (DON) and fumonisins (FBs), along with short-term heat stress conditions, on broiler gut health and endotoxin translocation. An experiment was conducted to assess the impacts of mycotoxin exposure on broilers, focusing on intestinal endotoxin activity, gene expression related to gut barrier function and inflammation, and the plasma concentration of the endotoxin marker 3-OH C14:0 either at thermoneutral conditions or short-term heat stress conditions. Independently of heat stress, broilers fed DON-contaminated diets exhibited reduced body weight gain during the starter phase (Day 1–12) compared to the control group, while broilers fed FB-contaminated diets experienced decreased body weight gain throughout the entire trial period (Day 1–24). Furthermore, under thermoneutral conditions, broilers fed DON-contaminated diets showed an increase in 3-OH C14:0 concentration in the plasma. Moreover, under heat stress conditions, the expression of genes related to gut barrier function (Claudin 5, Zonulin 1 and 2) and inflammation (Toll-like receptor 4, Interleukin-1 beta, Interleukin-6) was significantly affected by diets contaminated with mycotoxins, depending on the gut segment. This effect was particularly prominent in broilers fed diets contaminated with FBs. Notably, the plasma concentration of 3-OH C14:0 increased in broilers exposed to both DON- and FB-contaminated diets under heat stress conditions. These findings shed light on the intricate interactions between mycotoxins, heat stress, gut health, and endotoxin translocation in broiler chickens, highlighting the importance of understanding these interactions for the development of effective management strategies in livestock production to enhance broiler health and welfare. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is symptomatically worse in the evening, but the mechanism driving nocturnal eczema remains elusive. Our objective was to determine the circadian rhythm of skin barrier function measured by transepidermal water loss (TEWL) in AD patients and explore the molecular underpinnings. A pilot study was performed on a diverse group of AD (n = 4) and control (n = 2) young patients. We used an inpatient tightly controlled, modified, constant routine protocol. TEWL was measured at least every 90 min in the antecubital fossa (lesional) and forearm, while whole blood samples were collected every 4 h. Results show a significant difference in the antecubital fossa TEWL in the AD group versus controls. TEWL in control skin decreases starting a few hours prior to bedtime, both in the antecubital fossa and in the forearm, while in the AD forearm skin, pre-bedtime TEWL increases. We identified 1576 differentially expressed genes using a time-dependent model. The top 20 upregulated gene ontology pathways included neuronal pathways, while the downregulated functional terms included innate immune signaling and viral response. Similar pathways positively correlated with forearm TEWL in controls and inversely with the AD group. Upregulation in sensory perception pathways correlated with increases in lesional (antecubital fossa) TEWL in the evening. Results show skin barrier function worsens in the evening in the AD group, at a time when barrier is normally rejuvenating in healthy skin. This timing and the detection of transcriptomic signatures of sensory perception and diminished viral response might correspond to the nocturnal itch. Larger studies are needed to evaluate these associations in the skin. [ABSTRACT FROM AUTHOR]

Background: Reconstructed epidermis models, obtained from 3D keratinocytes culture, have gained significant prominence as prototypes for safety and efficacy testing in skin research. To effectively evaluate these models, it is essential to perform molecular and functional characterization. The skin's barrier function is one of the essential aspects of the epidermis that needs to be assessed. A noninvasive method is thus required for the evaluation of the skin barrier in these models. With this perspective, the aim of this feasibility study is to apply the speckle technique for the assessment of the skin barrier in the Reconstructed Human Epidermis (RHE). Materials and methods: Speckle analysis as well as Raman microspectroscopy were performed on RHE samples at two maturation days, D17 and D20. Results: Between D17 and D20, our study showed an increase in various Raman parameters, including stratum corneum percentage, lateral lipid packing, lipid‐to‐protein ratio, and protein secondary structure. Furthermore, the degree of light polarization and the speckle grain size also increased over this period. Conclusion: The speckle technique proved to be effective for evaluating the skin barrier in Reconstructed Human Epidermis (RHE) models. Comparison with Raman validates this approach and provides comprehensive molecular and functional characterization of reconstructive skin models. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with pruritus, an impaired cutaneous barrier function and a disrupted water holding capacity. Levels of ceramides, which are major components of intercellular lipids and are crucial for their functions, are decreased in the stratum corneum of patients with AD. Treatments to increase ceramide levels are effective for AD care. Synthetic pseudo-ceramide (cetyl PG hydroxyethyl palmitamide (SLE66)), which has a structure developed via molecular designs, and a eucalyptus leaf extract (ELE) enhance ceramide synthesis in the epidermis. The topical application of a skin moisturizer containing SLE66 and ELE improves the barrier functions and water holding capacity of AD skin accompanied by an improvement in skin symptoms. This is a multifaceted review that summarizes the efficacy of the topical application of a skin moisturizer containing SLE66 and ELE on atopic dermatitis. [ABSTRACT FROM AUTHOR]

The gut mucosal epithelium is one of the largest organs in the body and plays a critical role in regulating the crosstalk between the resident microbiome and the host. To this effect, the tight control of what is permitted through this barrier is of high importance. There should be restricted passage of harmful microorganisms and antigens while at the same time allowing the absorption of nutrients and water. An increased gut permeability, or "leaky gut", has been associated with a variety of diseases ranging from infections, metabolic diseases, and inflammatory and autoimmune diseases to neurological conditions. Several factors can affect gut permeability, including cytokines, dietary components, and the gut microbiome. Here, we discuss how the gut microbiome impacts the permeability of the gut epithelial barrier and how this can be harnessed for therapeutic purposes. [ABSTRACT FROM AUTHOR]

Barrier-function-based adaptive fast-terminal sliding-mode control approaches have been devised to enhance the precision of speed regulation of permanent magnet synchronous motors (PMSMs). Firstly, the speed loop utilizes fast-terminal sliding-mode control, which contributes to a faster convergence rate and enhances the robustness of the system. By adopting this control technique, the system can quickly reach the desired speed setpoint and effectively handle disturbances. Secondly, an adaptive law based on the barrier function is employed to adjust the control gain adaptively. The proposed adaptive law considers the magnitude of the disturbance and effectively mitigates chattering resulting from excessive switching gain. Unlike conventional control methods, the design of the adaptive fast-terminal sliding-mode control does not require attaining the upper limit of the lumped disturbances. Experimental results are presented to validate the proposed approach. These results demonstrate that the proposed method outperforms the conventional terminal sliding mode control technique in terms of handling both external and internal disturbances. [ABSTRACT FROM AUTHOR]

Vitamin D3 regulates a variety of biological processes irrespective of its wellknown importance for calcium metabolism. Epidemiological and animal studies indicate a role in immune regulation, intestinal barrier function and microbiome diversity. Here, we analyzed the impact of different vitamin D3- containing diets on C57BL/6 and BALB/c mice, with a particular focus on gut homeostasis and also investigated effects on immune cells in vitro. Weak regulatory effects were detected on murine T cells. By trend, the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 suppressed IFN, GM-CSF and IL-10 cytokine secretion in T cells of C57BL/6 but not BALB/c mice, respectively. Using different vitamin D3-fortified diets, we found a tissue-specific enrichment of mainly CD11b+ myeloid cells but not T cells in both mouse strains e.g. in spleen and Peyer's Patches. Mucin Reg3γ and Batf expression, as well as important proteins for gut homeostasis, were significantly suppressed in the small intestine of C57BL76 but not BALB/c mice fed with a high-vitamin D3 containing diet. Differences between both mouse stains were not completely explained by differences in vitamin D3 receptor expression which was strongly expressed in epithelial cells of both strains. Finally, we analyzed gut microbiome and again an impact of vitamin D3 was detected in C57BL76 but not BALB/c. Our data suggest strain-specific differences in vitamin D3 responsiveness under steady state conditions which may have important implications when choosing a murine disease model to study vitamin D3 effects. [ABSTRACT FROM AUTHOR]

The skin is a multifunctional organ, forming a barrier between the external and internal environment, thereby functioning as a safeguard against extrinsic factors. Autophagy has been implicated in epidermal differentiation and in preserving skin homeostasis. LC3-associated phagocytosis (LAP) uses some but not all components of autophagy. The Atg16l1 (Δ WD) mouse model lacks the WD40 domain required for LAP and has been widely used to study the effects of LAP deficiency and autophagy on tissue homeostasis and response to infection.In this study, the Δ WD model was used to study the relationship between LAP and skin homeostasis by determining whether LAP-deficient mice display a cutaneous phenotype. Skin histology of wild-type and Δ WD mice aged 1 year revealed minor morphological differences in the tail skin dermal layer. RT-qPCR and western blot analysis showed no differences in key keratin expression between genotypes. Skin barrier formation, assessed by dye permeation assays, demonstrated full and proper formation of the skin barrier at embryonic day 18.5 in both genotypes. Biomechanical analysis of the skin showed decreased skin elasticity in aged Δ WD but not wild-type mice. In summary, the LAP-deficient Δ WD mice displayed subtle alterations in dermal histology and age-related biomechanical changes.

ABSTRACT: Zinc (Zn) could alleviate the adverse effect of high temperature (HT) on intestinal integrity and barrier function of broilers, but the underlying mechanisms remain unclear. We aimed to investigate the possible protective mechanisms of Zn on primary cultured broiler jejunal epithelial cells exposed to thermal stress (TS). In Exp.1, jejunal epithelial cells were exposed to 40℃ (normal temperature, NT) and 44℃ (HT) for 1, 2, 4, 6, or 8 h. Cells incubated for 8 h had the lowest transepithelial resistance (TEER) and the highest phenol red permeability under HT. In Exp.2, the cells were preincubated with different Zn sources (Zn sulfate as iZn and Zn proteinate with the moderate chelation strength as oZn) and Zn supplemental levels (50 and 100 µmol/L) under NT for 24 h, and then continuously incubated under HT for another 8 h. TS increased phenol red permeability, lactate dehydrogenase (LDH) activity and p-PKC/PKC level, and decreased TEER, cell proliferation, mRNA levels of claudin-1, occludin, zona occludens-1 (ZO-1), PI3K, AKT and mTOR, protein levels of claudin-1, ZO-1 and junctional adhesion molecule-A (JAM-A), and the levels of p-ERK/ERK, p-PI3K/PI3K and p-AKT/AKT. Under HT, oZn was more effective than iZn in increasing TEER, occludin, ZO-1, PI3K, and AKT mRNA levels, ZO-1 protein level, and p-AKT/AKT level; supplementation with 50 μmol Zn/L was more effective than 100 μmol Zn/L in increasing cell proliferation, JAM-A, PI3K, AKT, and PKC mRNA levels, JAM-A protein level, and the levels of p-ERK/ERK and p-PI3K/PI3K; furthermore, supplementation with 50 μmol Zn/L as oZn had the lowest LDH activity, and the highest ERK, JNK-1, and mTOR mRNA levels. Therefore, supplemental Zn, especially 50 μmol Zn/L as oZn, could alleviate the TS-induced integrity and barrier function damage of broiler jejunal epithelial cells possibly by promoting cell proliferation and tight junction protein expression via the MAPK and PI3K/AKT/mTOR signaling pathways.

Epithelial tissues cover the surfaces and lumens of the internal organs of multicellular animals and crucially contribute to internal environment homeostasis by delineating distinct compartments within the body. This vital role is known as epithelial barrier function. Epithelial cells are arranged like cobblestones and intricately bind together to form an epithelial sheet that upholds this barrier function. Central to the restriction of solute and fluid diffusion through intercellular spaces are occluding junctions, tight junctions in vertebrates and septate junctions in invertebrates. As part of epithelial tissues, cells undergo constant renewal, with older cells being replaced by new ones. Simultaneously, the epithelial tissue undergoes relative rearrangement, elongating, and shifting directionally as a whole. The movement or shape changes within the epithelial sheet necessitate significant deformation and reconnection of occluding junctions. Recent advancements have shed light on the intricate mechanisms through which epithelial cells sustain their barrier function in dynamic environments. This review aims to introduce these noteworthy findings and discuss some of the questions that remain unanswered.

Demodex mites are commensal parasites of hair follicles (HFs). Normally asymptomatic, inflammatory outgrowth of mites can accompany malnutrition, immune dysfunction, and aging, but mechanisms restricting Demodex outgrowth are not defined. Here, we show that control of mite HF colonization in mice required group 2 innate lymphoid cells (ILC2s), interleukin-13 (IL-13), and its receptor, IL-4Ra-IL-13Ra1. HF-associated ILC2s elaborated IL-13 that attenuated HFs and epithelial proliferation at anagen onset; in their absence, Demodex colonization led to increased epithelial proliferation and replacement of gene programs for repair by aberrant inflammation, leading to the loss of barrier function and HF exhaustion. Humans with rhinophymatous acne rosacea, an inflammatory condition associated with Demodex, had increased HF inflammation with decreased type 2 cytokines, consistent with the inverse relationship seen in mice. Our studies uncover a key role for skin ILC2s and IL-13, which comprise an immune checkpoint that sustains cutaneous integrity and restricts pathologic infestation by colonizing HF mites.

Abstract Background Deoxynivalenol (DON) is a mycotoxin that has received recognition worldwide because of its ability to cause growth delay, nutrient malabsorption, weight loss, emesis, and a reduction of feed intake in livestock. Since DON-contaminated feedstuff is absorbed in the gastrointestinal tract, we used chicken organoids to assess the DON-induced dysfunction of the small intestine. Results We established a culture system using chicken organoids and characterized the organoids at passages 1 and 10. We confirmed the mRNA expression levels of various cell markers in the organoids, such as KI67, leucine-rich repeat containing G protein-coupled receptor 5 (Lgr5), mucin 2 (MUC2), chromogranin A (CHGA), cytokeratin 19 (CK19), lysozyme (LYZ), and microtubule-associated doublecortin-like kinase 1 (DCLK1), and compared the results to those of the small intestine. Our results showed that the organoids displayed functional similarities in permeability compared to the small intestine. DON damaged the tight junctions of the organoids, which resulted in increased permeability. Conclusions Our organoid culture displayed topological, genetic, and functional similarities with the small intestine cells. Based on these similarities, we confirmed that DON causes small intestine dysfunction. Chicken organoids offer a practical model for the research of harmful substances.