Barrier Function Research Articles

Matrine regulates autophagy in ileal epithelial cells in a porcine circovirus type 2-infected murine model

IntroductionPorcine circovirus type 2 (PCV2) is an important pathogen that causes diarrhea in nursery and fattening pigs, resulting in huge economic losses for commercial pig farms. Protective efficacy of vaccines is compromised by mutations in pathogens. There is an urgent need to articulate the mechanism by which PCV2 destroys the host’s intestinal mucosal barrier and to find effective therapeutic drugs. Increasing attention has been paid to the natural antiviral compounds extracted from traditional Chinese medicines. In the present study, we investigated the role of Matrine in mitigating PCV2-induced intestinal damage and enhancing autophagy as a potential therapeutic strategy in mice.MethodsA total of 40 female, specific-pathogen-free-grade Kunming mice were randomly divided into four groups with 10 mice in each group: control, PCV2 infection, Matrine treatment (40 mg/kg Matrine), and Ribavirin treatment (40 mg/kg Ribavirin). Except for the control group, all mice were injected intraperitoneally with 0.5 mL 105.4 50% tissue culture infectious dose (TCID50)/mL PCV2.ResultsWhile attenuating PCV2-induced downregulation of ZO-1 and occludin and restoring intestinal barrier function in a PCV2 Kunming mouse model, treatment with Matrine (40 mg/kg) attenuated ultrastructural damage and improved intestinal morphology. Mechanistically, Matrine reversed PCV2-induced autophagosome accumulation by inhibiting signal transducer and activator of transcription 3 (STAT3) phosphorylation and upregulating Beclin1 protein expression, thus resisting viral hijacking of enterocyte autophagy.DiscussionOur findings demonstrate that Matrine may be a novel, potential antiviral agent against PCV2 by activating intestine cellular autophagy, which provides a new strategy for host-directed drug discovery.

Bioadhesive First‐Aid Patch with Rapid Hemostasis and High Toughness Designed for Sutureless Sealing of Acute Bleeding Wounds

AbstractThe global military and civilian sectors express widespread concern over the significant hemorrhage associated with various acute wounds. Such bleedings lead to numerous casualties in military confrontations, traffic accidents, and surgical injuries. Consequently, the rapid control of the bleedings, particularly for extensive and pressurized wounds, is crucial in first‐aid situations. In this work, a double‐layered bioadhesive patch that combines a superabsorbent adhesive hydrogel with a highly tough antibacterial polyurethane film, which is called as Bio‐Patch, is proposed. The Bio‐Patch demonstrates superior mechanical strength and forms robust bioadhesion to acute bleeding wounds. Furthermore, the Bio‐Patch enables protecting against external Gram‐negative and Gram‐positive bacteria. Thanks to the double‐layered structures having synergistic functions of stable barrier and robust adhesion, the Bio‐Patch provides optimal wound sealing (burst strength exceeding 310 mmHg) both in vitro and in vivo. It also demonstrates superior hemostatic effects (less than 30 s) in vivo. This offers promising opportunities for rapid control of extensive and pressurized hemorrhage in first‐aid clinical scenarios.

Hair follicle stem cells and the collapse of self-tolerance in alopecia: the interplay of barrier function, the microbiome, and immunity

Hair follicle stem cells and the collapse of self-tolerance in alopecia: the interplay of barrier function, the microbiome, and immunity

JAK-STAT1 as therapeutic target for EGFR deficiency-associated inflammation and scarring alopecia

AbstractThe hair follicle stem cell niche is an immune-privileged microenvironment, characterized by reduced antigen presentation, thus shielding against permanent immune-mediated tissue damage. In this study, we demonstrated the protective role of hair follicle-specific epidermal growth factor receptor (EGFR) against scarring hair follicle destruction. Mechanistically, disruption of EGFR signaling generated a cell-intrinsic hypersensitivity within the JAK-STAT1 pathway, which, synergistically with interferon gamma expressing CD8 T-cell and NK-cell-mediated inflammation, compromised the stem cell niche. Hair follicle-specific genetic depletion of either JAK1/2 or STAT1 or therapeutic inhibition of JAK1/2 ameliorated the inflammation, restored skin barrier function and activated the residual stem cells to resume hair growth in mouse models of epidermal and hair follicle-specific EGFR deletion. Skin biopsies from EGFR inhibitor-treated and cicatricial alopecia patients revealed an active JAK-STAT1 signaling signature along with upregulation of antigen presentation and downregulation of key components of the EGFR pathway. Our findings offer molecular insights and highlight a mechanism-based therapeutic strategy for addressing chronic folliculitis associated with EGFR-inhibitor anti-cancer therapy and cicatricial alopecia.

A photocurable and thermocurable composite hydrogel and the application in a contraction resistant full-thickness skin model.

Three-dimensional (3D) organotypic skin in vitro has attracted increasing attention for drug development, cosmetics evaluation, and even clinical applications. However, the severe contraction of these models restricts their application, especially in the analyses based on barrier functions such as percutaneous penetration. For the full-thickness skin equivalents, the mechanical properties of the dermis scaffold plays an important role in the contraction resistance. In this investigation, we optimized a hydrogel composed of gelatine methacrylamide (GelMA), hyaluronic acid methacrylate (HAMA), and type I collagen (Col I), adjusted the elastic moduli to 2.27±0.08 kPa to fit the skin cells growth and resist contraction as well. This optimized hydrogel exhibited a swelling ratio of 23.25 ± 0.94% and demonstrated satisfactory cell viability in fibroblasts cultures. Then, we mixed this hydrogel with fibroblasts of liquid-liquid culture to construct the dermis, on which seeded keratinocytes were seeded for another 14 days of air-liquid culture to form cornified epidermis, and a commercialized hydrogel Ava-FT-Skin was used as control. This optimized skin model could maintained its integrity for a prolonged period of 28 days. Differentiated epidermis presented basal, spinous, granular, and cornified layers, meanwhile, epidermis markers like keratin-10, keratin-14, involucrin, loricrin, filaggrin, and dermis markers vimentin were expressed distinctly in the right distribution. Furthermore, penetration of a 607 Da Cascade blue-labelled dextran was calculated and compared to the Avatarget skin model, both of which could prevent more than 99% of the fluorescent molecule. We consider that this full-thickness skin model could be widely used in pharmaceutical and cosmetic industries, especially in penetration detection, contributing to the excellent contraction resistance.

The gut microbial metabolite indole-3-aldehyde alleviates impaired intestinal development by promoting intestinal stem cell expansion in weaned piglets

BackgroundWeaning stress-induced diarrhea is widely recognized as being associated with gut microbiota dysbiosis. However, it has been challenging to clarify which specific intestinal microbiota and their metabolites play a crucial role in the antidiarrhea process of weaned piglets.ResultsIn this study, we first observed that piglets with diarrhea exhibited a lower average daily gain and higher diarrhea score, and elevated levels of lipopolysaccharide (LPS) and D-lactate (D-LA) compared to healthy piglets. Subsequently, we analyzed the differences in intestinal microbial composition and metabolite levels between healthy and diarrheal weaned piglets. Diarrheal piglets demonstrated intestinal microbiota dysbiosis, characterized primarily by a higher Firmicutes to Bacteroidota ratio, a deficiency of Lactobacillus amylovorus and Lactobacillus reuteri, and an increased abundance of Bacteroides sp.HF-5287 and Bacteroides thetaiotaomicron. Functional profiling of the gut microbiota based on Kyoto Encyclopedia of Genes and Genomes (KEGG) data was performed, and the results showed that tryptophan metabolism was the most significantly inhibited pathway in piglets with diarrhea. Most tryptophan metabolites were detected at lower concentrations in diarrheal piglets than in healthy piglets. Furthermore, we explored the effects of dietary indole-3-aldehyde (IAld), a key tryptophan metabolite, on intestinal development and gut barrier function in weaned piglets. Supplementation with 100 mg/kg IAld in the diet increased the small intestine index and improved intestinal barrier function by promoting intestinal stem cell (ISC) expansion in piglets. The promotion of ISC expansion by IAld was also confirmed in porcine intestinal organoids.ConclusionsThese findings revealed that intestinal microbial tryptophan metabolite IAld alleviates impaired intestinal development by promoting ISC expansion in weaned piglets.

Modulation of the Respiratory Epithelium Physiology by Flavonoids—Insights from 16HBEσcell Model

Extensive evidence indicates that the compromise of airway epithelial barrier function is closely linked to the development of various diseases, posing a significant concern for global mortality and morbidity. Flavonoids, natural bioactive compounds, renowned for their antioxidant and anti-inflammatory properties, have been used for centuries to prevent and treat numerous ailments. Lately, a growing body of evidence suggests that flavonoids can enhance the integrity of the airway epithelial barrier. The objective of this study was to investigate the impact of selected flavonoids representing different subclasses, such as kaempferol (flavonol), luteolin (flavone), and naringenin (flavanone), on transepithelial electrical resistance (TEER), ionic currents, cells migration, and proliferation of a human bronchial epithelial cell line (16HBE14σ). To investigate the effect of selected flavonoids, MTT assay, trypan blue staining, and wound healing were assessed. Additionally, transepithelial resistance and Ussing chamber measurements were applied to investigate the impact of the flavonoids on the electrical properties of the epithelial barrier. This study showed that kaempferol, luteolin, and naringenin at micromolar concentrations were not cytotoxic to 16HBE14σ cells. Indeed, in MTT tests, a statistically significant change in cell metabolic activity for luteolin and naringenin was observed. However, our experiments showed that naringenin did not affect the proliferation of 16HBE14σ cells, while the effect of kaempferol and luteolin was inhibitory. Moreover, transepithelial electrical resistance measurements have shown that all of the flavonoids used in this study improved the epithelial integrity with the slightest effect of kaempferol and the significant impact of naringenin and luteolin. Finally, our observations suggest that luteolin increases the Cl- transport through cystic fibrosis transmembrane conductance regulator (CFTR) channel. Our findings reveal that flavonoids representing different subclasses exert distinct effects in the employed cellular model despite their similar chemical structures. In summary, our study sheds new light on the diverse effects of selected flavonoids on airway epithelial barrier function, underscoring the importance of further exploration into their potential therapeutic applications in respiratory health.

Molecular pathology of skin fragility

The skin's barrier function is primarily maintained by the cohesion of its layers and the specialized stratum corneum. Genetic and autoimmune disorders that result in skin fragility have significantly contributed to understanding the role of various molecular components in the skin. These conditions, characterized by blisters, erosions, wounds, and impaired wound healing, are rare but must be considered in clinical differential diagnoses. Key cutaneous adhesion structures include the epidermal basement membrane, anchoring fibrils, cell-matrix adhesions (e.g., hemidesmosomes and focal adhesions), and cell-cell adhesions (e.g., desmosomes and corneodesmosomes). These multiprotein suprastructures not only provide structural support but also participate in signaling processes and physiological or pathological conditions such as skin aging and wound healing. Additionally, dermal connective tissue plays astructural role and serves as areservoir for proteases, growth factors, and cytokines. Modern techniques like single-cell and spatial transcriptomics, combined with artificial intelligence algorithms, are advancing the molecular mapping of human skin. Moreover, this review highlights the molecular composition of adhesion structures and the specific diseases associated with deficiencies in these components.

A probiotic multi-strain mixture combined with hydroxyectoine improves intestinal barrier function by alleviating inflammation in lipopolysaccharide stimulated differentiated Caco-2 cells.

Many studies have highlighted the role of probiotics in re-establishing the gut microbiota balance and preventing intestinal barrier dysfunction. In fact, they can also contribute to the upregulation of anti-inflammatory genes and the downregulation of pro-inflammatory genes, which are known to contribute to the development of the inflammatory bowel disease (IBD) syndrome. The present study aims to investigate the effect of the compatible solute hydroxyectoine (HOE), to be used as a cryopreservant but also for its intrinsic biological properties, to obtain a new formula containing three probiotic strains (Limosilactobacillus fermentum (L. fermentum), Levilactobacillus brevis SP-48 (L. brevis), and Bifidobacterium lactis HN019 (B. lactis)), and evaluate the latter for its ability to prevent lipopolysaccharide (LPS)-induced inflammation in an in vitro bi-dimensional model of the intestinal barrier using a Caco-2 cell monolayer. The mRNA expression levels of the inflammatory cytokines (IL-6, IL-1β, and TNF-α) were analyzed by real-time PCR. Changes in the modulation of (TLR-4 and NF-κB) proteins were assessed by western blotting, and the effect of the HOE/PRO formula on the intestinal epithelial barrier function was also assessed using an immunofluorescence microscope for the tight junction protein zonula occludens-1 (ZO-1). This study found that this novel probiotic formulation containing HOE is capable of decreasing LPS-induced cytokines, as confirmed by the results of RT-PCR and ELISA and preserving the integrity of tight junctions as demonstrated by the relevant expression of ZO-1. HOE/PRO was shown to be effective in reducing the expression of TLR-4 and NF-κB. The latter plays a key role as an inflammation modulator as shown through experiments run with the THP-1/NF-κB reporter gene. Collectively, our data indicate that the HOE/PRO formula is a good candidate for potential preventive and/or therapeutic implementation in IBD.

DNA Nanopatch-Specific Modification of Probiotics for Ultrasound-Triggered Inflammatory Bowel Disease Therapy.

Probiotics offer promising results for treating inflammatory bowel disease, yet precision therapy remains challenging, particularly in manipulating probiotics spatially and temporally and shielding them from oxidative stress. To address these limitations, herein we synthesized bacteria-specific DNA nanopatches to modify ultrasound-triggered engineered Escherichia coli Nissle 1917. These probiotics produced the anti-inflammatory cytokine interleukin-10 when stimulated by ultrasound and were fortified with DNPs for oxidative stress resistance. The DNPs were composed of rectangular DNA origami nanosheets with reactive oxygen species' scavenging ability and bacterial targeting ligands of maltodextrin molecules. We systematically demonstrated that the DNPs could selectively attach to bacterial surface but not mammalian cell surface via the maltodextrin transporter pathway. To further enhance the bioavailability of engineered probiotics in the gastrointestinal tract, we employed a self-assembly strategy to encapsulate them using chitosan and sodium alginate. In a murine model of ulcerative colitis, this system significantly improved the gut barrier integrity and reduced inflammation. Our results indicate that this DNA nanopatch-bacteria system holds substantial promise for mitigating oxidative stress, correcting microbiota dysbiosis, and enhancing the intestinal barrier function in colitis.

Narrative Review: Advancing Dysbiosis Treatment in Onco-Hematology with Microbiome-Based Therapeutic Approach

This review explores the complex relationship between gut dysbiosis and hematological malignancies, focusing on graft-versus-host disease (GvHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. We discuss how alterations in microbial diversity and composition can influence disease development, progression, and treatment outcomes in blood cancers. The mechanisms by which the gut microbiota impacts these conditions are examined, including modulation of immune responses, production of metabolites, and effects on intestinal barrier function. Recent advances in microbiome-based therapies for treating and preventing GvHD are highlighted, with emphasis on full ecosystem standardized donor-derived products. Overall, this review underscores the growing importance of microbiome research in hematology–oncology and its potential to complement existing treatments and improve outcomes for thousands of patients worldwide.

A Novel Synbiotic Protects Against DSS-Induced Colitis in Mice via Anti-inflammatory and Microbiota-Balancing Properties.

Inflammatory bowel disease (IBD) is a chronic immune-inflammatory disease. Gut microbes, intestinal immunity, and gut barrier function play a critical role in IBD. Growing evidence suggests that synbiotic may offer therapeutic benefits for individuals with colitis, suggesting an alternative therapy against colitis. With this in mind, we creatively prepared a new synbiotic combination consisting of a probiotic strain (Limosilactobacillus reuteri) along with one prebiotic chitooligosaccharides (COS). The protective effects of the synbiotic on DSS-induced colitis and the underlying mechanisms were investigated. We demonstrated that the synbiotic ameliorated colitis in mice, as evidenced by a significant remission in body weight loss and colon shortening, and a decreased disease activity index (DAI). Notably, synbiotic reduced the intestinal inflammation and injury by synergistically decreasing inflammatory factors, inhibiting TLR4/Myd88/NF-κB/NLRP3 signaling, preventing macrophage infiltration, and enhancing the integrity of the intestinal barrier. Moreover, synbiotic selectively promoted the growth of beneficial bacteria (e.g., Akkermansia, Lactobacillus) but decreased the pathogenic bacteria (e.g., Helicobacter). BugBase's analysis supported its ameliorated role in reducing pathogenic bacteria. Collectively, our findings revealed the novel synbiotic had a potential to treat colitis, which was associated with its anti-inflammatory and microbiota-balancing properties. This study will contribute to the development of functional synbiotic products for IBD therapy and will provide valuable insights into their mechanisms.

Utilizing the apical-out enteroids in vitro model to investigate intestinal glucose transport, barrier function, oxidative stress, and inflammatory responses in broiler chickens

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.

Multi-Omics Reveal the Improvements of Nutrient Digestion, Absorption, and Metabolism and Intestinal Function via GABA Supplementation in Weanling Piglets

The nonprotein amino acid γ-aminobutyric acid (GABA) can enhance intestinal function in piglets; however, the mechanisms involved are not yet fully understood. To explore the effects of GABA and its underlying mechanisms, weanling piglets were randomly assigned to three groups, receiving either a basal diet or a basal diet supplemented with GABA (80 mg/kg or 120 mg/kg). The results demonstrated that dietary GABA improved growth performance and reduced diarrhea incidence (p < 0.05). Additionally, GABA supplementation decreased the serum and intestinal levels of pro-inflammatory cytokines (p < 0.05), and improved intestinal morphology. Multi-omics analyses were employed to explore the alterations caused by GABA supplementation and elucidate the related mechanisms. Microbiota profiling revealed improved beta-diversity and changes in the composition of ileal bacteria and fungi. Amino acid metabolism, lipid metabolism, and digestive processes were primarily enriched in the GABA group according to metabolomics analysis. A transcriptome analysis showed significant enrichment in ion transmembrane transport and nutrition absorption and digestion pathways in the ileum. Furthermore, increased lipase and trypsin activity, along with the elevated expression of tight junction proteins confirmed the beneficial effects of GABA on intestinal nutrient metabolism and barrier function. In conclusion, dietary 80 mg/kg GABA supplementation improved nutrient digestion and absorption and intestinal function in weanling piglets.

Correction: Ma et al. Perioperative Enteral Immunonutrition Support for the Immune Function and Intestinal Mucosal Barrier in Gastric Cancer Patients Undergoing Gastrectomy: A Prospective Randomized Controlled Study. Nutrients 2023, 15, 4566

In the original publication [...]

Novel hypothesis and therapeutic interventions for irritable bowel syndrome: interplay between metal dyshomeostasis, gastrointestinal dysfunction, and neuropsychiatric symptoms.

Irritable bowel syndrome is a gastrointestinal disorder due to multiple pathologies. While patients with this condition experience anxiety and depressed mood more frequently than healthy individuals, it is unclear how gastrointestinal dysfunction interacts with such neuropsychiatric symptoms. Data suggest that irritable bowel syndrome patients predominantly display a lower zinc intake, which presumably impairs enterochromaffin cells producing 5-hydroxytryptamine, gut bacteria fermenting short-chain fatty acids, and barrier system in the intestine, with the accompanying constipation, diarrhea, low-grade mucosal inflammation, and visceral pain. Dyshomeostasis of copper and zinc concentrations as well as elevated pro-inflammatory cytokine levels in the blood can disrupt blood-cerebrospinal fluid barrier function, leading to locus coeruleus neuroinflammation and hyperactivation with resultant amygdalar overactivation and dorsolateral prefrontal cortex hypoactivation as found in neuropsychiatric disorders. The dysregulation between the dorsolateral prefrontal cortex and amygdala is likely responsible for visceral pain-related anxiety, depressed mood caused by anticipatory anxiety, and visceral pain catastrophizing due to catastrophic thinking or cognitive distortion. Collectively, these events can result in a spiral of gastrointestinal symptoms and neuropsychiatric signs, prompting the progression of irritable bowel syndrome. Given that the negative feedback mechanism in regulation of the hypothalamic-pituitary-adrenal axis is preserved in a subset of neuropsychiatric cases, dorsolateral prefrontal cortex abnormality accompanied by neuropsychiatric symptoms may be a more significant contributing factor in brain-gut axis malfunction than activation of the hypothalamic corticotropin-releasing hormone system. The proposed mechanistic model could predict novel therapeutic interventions for comorbid irritable bowel syndrome and neuropsychiatric disorders.

Adaptive distributed dynamic average consensus with prescribed performance

AbstractA novel adaptive distributed estimation algorithm is developed for dynamic average consensus problem. The algorithm enables a group of agents to accurately track the average value of signals that are available locally to each agent. Unlike most of existing approaches that rely on error transformation techniques, our algorithm employs an adaptive‐gain based barrier function to simultaneously meet prescribed performance specifications of transient and steady state. It is both simple and easy to implement and is not dependent on bounded reference signals and their derivatives. Additionally, it can operate under less strict assumptions than those that assume absolute bounds on the signals. Simulation results are presented to demonstrate the effectiveness of the developed algorithm.

In Vitro Degradation of Collagen-Based Membranes for Guided Bone Regeneration After Zn-Ions or Doxycycline Functionalization

Collagen-based membrane is the most commonly used biomaterial for guided bone and tissue regeneration; however, its barrier function can be threatened by its rapid degradation pattern, affecting the success of the regeneration process. Differences in the origin and functionalization of the membrane to obtain better properties can alter the degradation rate. The objective of this study was to examine the biodegradation pattern of two commercially available collagen membranes (Jason® and Collprotect®) manufactured using porcine pericardium or dermis, doped or not with zinc-ions or doxycycline, in a period up to 21 days. The membrane specimens were subjected to hydrolytic and bacterial degradation tests. The different immersion times were carried out from 12 h up to 21 days. At each time point, quantitative measurements of thickness and weight were made using a digital caliper and an analytic microbalance, respectively. ANOVA and Student–Newman–Keuls tests were carried out for comparison purposes (p < 0.05). The differences between time-points within the same membranes and solutions were assessed by pairwise comparisons (p < 0.001). Unfunctionalized Jason membrane made of porcine pericardium attained the highest resistance to both degradation tests. The functionalization of the membranes did not alter the biodegradation patterns. All the membranes completely degraded before 48 h in the bacterial collagenase solution, which was the most aggressive test.

Protean Cutaneous Manifestation Caused by ABCA12 variants: Erythrokeratodermia Variabilis-like Ichthyosis and Unique Palmoplantar Keratoderma.

ABCA12 is crucial for skin barrier function and traditionally linked to severe congenital ichthyosis, such as harlequin ichthyosis. However, its genotype-phenotype relationship may be more nuanced. Using whole-exome sequencing and Sanger sequencing, we identified four cases of mild ichthyosis with biallelic ABCA12 pathogenic variants. In addition to a milder phenotype, the palmoplantar keratoderma (PPK) in these cases had a distinct "mosaic-tile like" pattern. Two cases with missense variants in the N-terminus of ABCA12 also presented an annular ichthyosis pattern resembling erythrokeratodermia variabilis et progressiva (EKVP). Our findings suggest a correlation between ABCA12 missense variant location and clinical presentation, expanding the phenotype spectrum associated with ABCA12 variants and highlighting the potential for annular patterns or "mosaic-tile like" PPK in these patients.

Highly Elastic Full Hydrocarbon Ultralong RTP Polymers with Visible Light Excitable S0→T1 Population

AbstractHighly elastic ultralong organic room temperature phosphorescence (RTP) polymers are highly desired in wearable optoelectronic fields, but they are hardly realized in rubbers since chain segment motions deactivate triplet excitons. In the current work, it is revealed that polystyrene (PS) can inhibit triplet thermal deactivation of coronene (Cor), and it is the serious oxygen diffusion and quenching that disables RTP emission of Cor/polymers. In view of oxygen barrier function of rubbers, PS−polyisoprene−PS tri‐block elastomers (SIS) are used as Cor's doping matrices. The results show that Cor/SIS sheets show bright and ultralong afterglow with RTP lifetime up to 3.64 s in air after brief 365 nm light excitation. More impressively, Cor/SIS and its red fluorescent dye doped sheets all exhibit ultralong room temperature afterglow under large dynamic elastic deformation. Further, all these sheets exhibit long‐wave blue light excited afterglow despite Cor/SIS having no visible light absorption band, and the unique photoexcitation and emission mechanism is verified. This work not only provides the development strategy of the latest elastic RTP materials, but also will evoke a fresh understanding on organic doped RTP polymers.